Note: Descriptions are shown in the official language in which they were submitted.
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PLUS D'UN TOME.
CECI EST LE TOME 1 DE 2
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VOLUME
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CONTAINING PAGES 1 TO 360
NOTE: For additional volumes, please contact the Canadian Patent Office
NOM DU FICHIER / FILE NAME:
NOTE POUR LE TOME / VOLUME NOTE:
CA 02767377 2012-01-04
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METHOD FOR GENOME EDITING
REFERENCE TO SEQUENCE LISTING
[0001] A paper copy of the sequence listing and a computer
readable form of the same sequence listing are appended below and herein
incorporated by reference. The information recorded in computer readable form
is identical to the written sequence listing, according to 37 C.F.R. 1.821
(f).
FIELD OF THE INVENTION
[0002] The invention encompasses a method for creating an animal
or cell with at least one chromosomal edit. In particular, the invention
relates to
the use of targeted zinc finger nucleases to edit chromosomal sequences.
BACKGROUND OF THE INVENTION
[0003] Rational genome engineering has enormous potential across
basic research, drug discovery, and cell-based medicines. Existing methods for
targeted gene knock-out or site-specific gene insertion rely on homologous
recombination. The low rate of spontaneous recombination in certain cell
types,
however, has been an enormous hurdle to universal genome editing. The scale
of screening effort and the time required to isolate the targeted event was
prohibitive. Thus, there exists a strong need for a technology that can
rapidly
achieve genomic editing in most cell types with high speed and efficiency, so
as
to greatly reduce the overall engineering effort.
SUMMARY OF THE INVENTION
[0004] One aspect of the present invention encompasses a method
for editing a chromosomal sequence. The method comprises, in part, (a)
introducing into a cell comprising the chromosomal sequence at least one
nucleic
acid encoding a zinc finger nuclease that recognizes a target sequence in the
chromosomal sequence and is able to cleave a cleavage site in the chromosomal
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sequence, and, optionally, (i) at least one donor polynucleotide comprising a
donor sequence for integration, an upstream sequence, and a downstream
sequence, wherein the donor sequence is flanked by the upstream sequence
and the downstream sequence, and wherein the upstream sequence and the
downstream sequence share substantial sequence identity with either side of
the
cleavage site, or (ii) at least one exchange polynucleotide comprising an
exchange sequence that is substantially identical to a portion of the
chromosomal
sequence at the cleavage site, and further comprising at least one nucleotide
change; and (b) culturing the cell to allow expression of the zinc finger
nuclease
such that the zinc finger nuclease introduces a double-stranded break into the
chromosomal sequence at the cleavage site, and wherein the double-stranded
break is repaired by (i) a non-homologous end-joining repair process such that
a
mutation is introduced into the chromosomal sequence, or optionally (ii) a
homology-directed repair process such that the donor sequence is integrated
into
the chromosomal sequence or the exchange sequence is exchanged with the
portion of the chromosomal sequence.
[0005] Another aspect of the present invention encompasses a non-
human animal. The non-human animal may be created in part, by (a) introducing
into a cell comprising the chromosomal sequence at least one nucleic acid
encoding a zinc finger nuclease that recognizes a target sequence in the
chromosomal sequence and is able to cleave a cleavage site in the chromosomal
sequence, and, optionally, (i) at least one donor polynucleotide comprising a
donor sequence for integration, an upstream sequence, and a downstream
sequence, wherein the donor sequence is flanked by the upstream sequence
and the downstream sequence, and wherein the upstream sequence and the
downstream sequence share substantial sequence identity with either side of
the
cleavage site, or (ii) at least one exchange polynucleotide comprising an
exchange sequence that is substantially identical to a portion of the
chromosomal
sequence at the cleavage site, and further comprising at least one nucleotide
change; and (b) culturing the cell to allow expression of the zinc finger
nuclease
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such that the zinc finger nuclease introduces a double-stranded break into the
chromosomal sequence at the cleavage site, and wherein the double-stranded
break is repaired by (i) a non-homologous end-joining repair process such that
a
mutation is introduced into the chromosomal sequence, or optionally (ii) a
homology-directed repair process such that the donor sequence is integrated
into
the chromosomal sequence or the exchange sequence is exchanged with the
portion of the chromosomal sequence.
[0006] Yet another aspect of the present invention encompasses a
cell. The cell may be created in part, by in part, by (a) introducing into the
cell
comprising the chromosomal sequence at least one nucleic acid encoding a zinc
finger nuclease that recognizes a target sequence in the chromosomal sequence
and is able to cleave a cleavage site in the chromosomal sequence, and,
optionally, (i) at least one donor polynucleotide comprising a donor sequence
for
integration, an upstream sequence, and a downstream sequence, wherein the
donor sequence is flanked by the upstream sequence and the downstream
sequence, and wherein the upstream sequence and the downstream sequence
share substantial sequence identity with either side of the cleavage site, or
(ii) at
least one exchange polynucleotide comprising an exchange sequence that is
substantially identical to a portion of the chromosomal sequence at the
cleavage
site, and further comprising at least one nucleotide change; and (b) culturing
the
cell to allow expression of the zinc finger nuclease such that the zinc finger
nuclease introduces a double-stranded break into the chromosomal sequence at
the cleavage site, and wherein the double-stranded break is repaired by (i) a
non-homologous end-joining repair process such that a mutation is introduced
into the chromosomal sequence, or optionally (ii) a homology-directed repair
process such that the donor sequence is integrated into the chromosomal
sequence or the exchange sequence is exchanged with the portion of the
chromosomal sequence.
[0007] A further aspect of the present invention encompasses an
embryo. Typcially, the embryo comprises at least one nucleic acid encoding a
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zinc finger nuclease that recognizes a target sequence in the chromosomal
sequence and is able to cleave a cleavage site in the chromosomal sequence,
and, optionally, (i) at least one donor polynucleotide comprising a donor
sequence for integration, an upstream sequence and a downstream sequence,
wherein the donor sequence is flanked by the upstream sequence and the
downstream sequence and wherein the upstream sequence and the downstream
sequence share substantial sequence identity with either side of the cleavage
site, or (ii) at least one exchange polynucleotide comprising an exchange
sequence that is substantially identical to a portion of the chromosomal
sequence
at the cleavage site and which further comprises at least one nucleotide
change.
[0008] Other aspects and iterations of the invention are described
more thoroughly below.
REFERENCE TO COLOR FIGURES
[0009] The application file contains at least one photograph
executed in color. Copies of this patent application publication with color
photographs will be provided by the Office upon request and payment of the
necessary fee.
BRIEF DESCRIPTION OF THE FIGURES
[0010] FIG. 1 is a schematic depicting the repair outcomes after a
targeted ZFN-induced double stranded break. Shaded bars represent the donor
fragment, whereas white bars depict target site for ZFN double stranded break.
[0011] FIG. 2 is a schematic depicting the construction of RFLP
donor plasmids. Shown, are the plasmid, and left and right PCR-amplified
fragments homologous to the integration target site. Restriction enzymes used
for cloning are denoted. The left fragment used Kpnl and Notl or Pmel. The
right
fragment used Notl or Pmel and Sacll.
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[0012] FIG. 3 is a schematic depicting the construction of GFP-
expressing donor plasmids. The GFP cassette was PCR amplified from an
existing plasmid and cloned into the Notl RFLP donor using a Notl site.
[0013] FIG. 4 is a schematic depicting methods of detecting (A) RFLP
integration and restriction enzyme digestion and (B) integration of the GFP
expression cassette using PCR amplification.
[0014] FIG. 5 is a photographic image of fluorescently stained PCR
fragments resolved on an agarose gel. The leftmost lane contains a DNA ladder.
Lanes 1 to 6 contain PCR fragments amplified using mouse Mdrl a-specific
primers from a whole or a fraction of a mouse blastocyst. Lanes 1 and 2 were
amplified from 5/6 and 1/6 of a blastocyst, respectively. Lane 3 was from one
whole blastocyst. Lanes 4 to 6 were from 1/2, 1/3, and 1 /6 of the same
blastocyst,
respective. Lane 7 contains a positive control PCR fragment amplified using
the
same primers from extracted mouse toe DNA.
[0015] FIG. 6 is a photographic image of fluorescently stained DNA
fragments resolved on an agarose gel. The leftmost lanes contain a DNA ladder.
(A) Lanes 1 to 39 contain PCR fragments amplified using mMdr1 a-specific
primers from 37 mouse embryos cultured in vitro after being microinjected with
ZFN RNA against mouse Mdrl a and RFLP donor with Notl site, along with one
positive and negative control for PCR amplification. (B) Lanes 1 to 39 contain
the PCR fragments in (A) after performing the Surveyor's mutation detection
assay.
[0016] FIG. 7 is a photographic image of fluorescently stained DNA
fragments resolved on an agarose gel. The leftmost and rightmost lanes contain
a DNA ladder. (A) Lanes contain PCR fragments amplified using mMdrla-
specific primers from mouse embryos in FIG 6, and digested with Notl without
purifying the PCR product. FIG. 7B is a longer run of the same gel in FIG. 7A.
The uncut PCR products are around 1.8 kb, and the digested products are two
bands around 900 bp.
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[0017] FIG. 8 is a photographic image of fluorescently stained DNA
fragments resolved on an agarose gel. The leftmost lane contains a DNA ladder.
Lanes 1 to 6 contain some of the PCR fragments from FIG 7 digested with Notl
after the PCR products were column purified so that Notl can work in its
optimal
buffer. Lines 7 and 8 are two of the samples digested with Notl as in FIG 7.
This
gel shows Notl digestion in PCR reactions was complete.
[0018] FIG. 9 is a photographic image of fluorescently stained PCR
fragments resolved on an agarose gel. The leftmost lane contains a DNA ladder.
Lanes 1 to 5 contain PCR fragments amplified using PXR-specific primers from
1, 1/2, 1/6, 1/10, 1/30 of a rat blastocyst. Lane 6 is a positive control
amplified
using the same primers from purified Sprague Dawley genomic DNA.
[0019] FIG. 10 is a photographic image of fluorescently stained
DNA fragments resolved on an agarose gel. The leftmost and rightmost lanes
contain a DNA ladder. (A) Lanes contain PCR fragments amplified from rat
embryos cultured in vitro after microinjection of PXR ZFN mRNA and the Notl
RFLP donor, using PXR-specific primers and digested with Notl. (B) Lanes
contain the same PCR fragments as in FIG. 10A after performing the Surveyor's
mutation detection assay.
[0020] FIG. 11 is a photographic image of fluorescently stained
DNA fragments resolved on an agarose gel. The first 4 lanes are PCR amplified
from 4 well developed fetus at 12.5 days post conception from embryos injected
with mMdr1 a ZFN mRNA with the Notl RFLP donor. The PCR was digested with
Notl. Lane 4 is positive one. Lanes 5-8 are 4 decidua, aborted implantations.
All
four were negative.
[0021] FIG. 12 is a schematic and photographic image of
fluorescently stained DNA fragments resolved on an agarose gel. (A) A
schematic showing the location of the primers used. Panels (B) and (C) show
results from primers PF and GR. Panels (D) and (E) show results from primers
PR + GF. Expected fragment size is 2.4kb. Two out of forty fetuses were
positive
for GFP.
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[0022] FIG. 13 is a photographic image of DNA fragments resolved
on an agarose gel. Lane 8 represents a 13 dpc fetus positive for the Notl
site.
[0023] FIG. 14 illustrates ZFN-mediated cleavage of SMAD4 in
human and feline cells, as detected by a Cel-1 surveyor nuclease assay. G =
GFP (no ZFN control). Z = SMAD4 ZFN (191160/19159). Arrows denote
cleavage products.
[0024] FIG. 15 depicts Cel-1 assays confirming SMAD4 ZFN
activity in cat embryos.
[0025] FIG. 16 illustrates cleavage of Fel dl in AKD cells.
Presented is Cel-1 screening of the Fel dl ZFN pair 17, 18 cleavage of chain 1-
exon 1.
[0026] FIG. 17 illustrates cleavage of Fel d1 chain 1-exon 2 in AKD
cells by the Fel dl ZFN pair 7, 9.
[0027] FIG. 18 depicts Cel-1 analysis of the Fel dl ZFN pair 12/13
cleavage of chain 1 -exon 2 in AKD cells.
[0028] FIG. 19 illustrates cleavage of Fel dl locus in cat embryos
by ZFN pairs 17, 18 and 12, 13. Lanes 1, 2, 7, and 8 contain samples from
individual blastocysts derived from embryos injected with 40 ng/pL of ZFNs.
Lane 3 presents a sample from a blastocyst derived an embryo injected with 20
ng/pL of ZFNs. Lanes 4, 9, and 10 contain samples from individual morulas
derived from embryos injected with 40 ng/pL of ZFNs. Lane 3 presents a sample
from a morula derived an embryo injected with 20 ng/pL of ZFNs. Lane 6
presents a sample from a control blastocyst.
[0029] FIG. 20 presents the DNA sequence of an edited Fel dl
locus comprising a 4541 bp deletion (SEQ ID NO:51) between the regions coding
for chain 2 and chain 1.
[0030] FIG. 21 aligns the edited Fel dl locus (designated by red
dotted line, labeled "sample 5") comprising the 4541 bp deletion with the
sequence of the wild-type Fel dl locus (SEQ ID NO:52). In the edited sample,
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the binding site for ZFN 13 is truncated (and the binding sire for ZFN 12 is
missing), but the binding site for ZFN pair 17, 18 is intact.
[0031] FIG. 22 depicts cleavage of the cauxin locus by cauxin ZFN
pair 1/2 (lane 2), ZFN pair 9/10 (lane 4), and ZFN pair 17/18 (lane 5) in AKD
cells. Lanes 1 and 3 contain samples from control (GFP) cells.
[0032] FIG. 23 illustrates cleavage of the cauxin locus by cauxin
ZFN pair 29/30 (lane 2). Lane 2 contains a control (GFP) sample.
[0033] FIG. 24 depicts integration at the TUBA1 B locus. (A) is a
schematic showing the chromosome sequence (SEQ ID NO:85) at the target
region for integration of the heterologous coding sequence, ZFN binding sites
(yellow sequence) on the chromosome target region, the ZFN cut site (yellow
arrow), and the integration site (green arrow). (B) presents schematics of the
TUBA1 B locus, site of integration, design of the SH2 biosensor, and the
proteins
expressed after successful integration. (C) presents an image of a Western
blot
of wild-type and integrated cells.
[0034] FIG. 25 depicts the map of a donor plasmid comprising the
SH2 biosensor sequence flanked by TUBAIA sequences at the target region.
[0035] FIG. 26 presents differential interference contrast (DIC) and
fluorescence microscopy images of individual isolated cell clones expressing
the
GFP-2xSH2-Grbl -2A protein. Fluorescent images show a time course of
biosensor translocation after exposure to 100 ng/mL of EGF.
[0036] FIG. 27 presents the map of a donor plasmid comprising the
SH2 biosensor sequence flanked by the ACTB sequences at the target region.
[0037] FIG. 28 depicts fluorescence microscopy images of
individual isolated cell clones expressing GFP-2xSH2-Grbl-2A (upper panels)
and RFP-(3-actin (lower panels). Presented is a time course after exposure to
100 ng/mL of EGF.
[0038] FIG. 29 presents the DNA sequences of two edited LRRK2
loci. The upper sequence (SEQ ID NO:92) has a 10 bp deletion in the target
sequence of exon 30, and the lower sequence (SEQ ID NO:93) has a 8 bp
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deletion in the target sequence of exon 30. The exon is shown in green; the
target site is presented in yellow, and the deletions are shown in dark blue.
[0039] FIG. 30 presents the DNA sequences of two edited ApoE
loci. The upper sequence (SEQ ID NO:1 14) has a 16 bp deletion in the target
sequence of exon 2, and the lower sequence (SEQ ID NO:115) has a 1 bp
deletion in the target sequence of exon 2. The exon sequence is shown in
green; the target site is presented in yellow, and the deletions are shown in
dark
blue.
[0040] FIG. 31 shows the DNA sequence of an edited leptin locus.
Presented is a region of the leptin locus (SEQ ID NO:1 16) in which 151 bp are
deleted from exon 1 and intron 1. The exon is shown in green; the target site
is
presented in yellow, and the deletion is shown in dark blue.
[0041] FIG. 32 presents the DNA sequences of edited APP loci in
two animals. (A) Shows a region of the rat APP locus (SEQ ID NO:127) in which
292 bp is deleted from exon 9. (B) Presents a region of the rat APP locus (SEQ
ID NO:128) in which there is a 309 bp deletion in exon 9. The exon is shown in
green; the target site is presented in yellow, and the deletion is shown in
dark
blue.
[0042] FIG. 33 presents the DNA sequences of edited Rag1 loci in
two animals. The upper sequence (SEQ ID NO:1 31) has a 808 bp deletion in
exon 2, and the lower sequence (SEQ ID NO:132) has a 29 bp deletion in exon
2. The exon sequence is shown in green; the target site is presented in
yellow,
and the deletions are shown in dark blue.
[0043] FIG. 34 presents the DNA sequences of edited Rag2 loci in
two animals. The upper sequence (SEQ ID NO:133) has a 13 bp deletion in the
target sequence in exon 3, and the lower sequence (SEQ ID NO:134) has a 2 bp
deletion in the target sequence in exon 2. The exon sequence is shown in
green;
the target site is presented in yellow, and the deletions are shown in dark
blue.
[0044] FIG. 35 presents the DNA sequences of edited Mdrl a loci in
two animals. The upper sequence (SEQ ID NO:157) has a 20 bp deletion in
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exon 7, and the lower sequence (SEQ ID NO:158) has a 15 bp deletion and a 3
bp insertion (GCT) in exon 7. The exon sequence is shown in green; the target
sequence is presented in yellow, and the deletions are shown in dark blue.
[0045] FIG. 36 illustrates knockout of the Mdrl a gene in rat.
Presented is a Western blot of varying amounts of a colon lysate from an Mdrl
a
knockout rat and a control cell lysate. The relative locations Mdrl a protein
and
actin protein are indicated to the left of the image
[0046] FIG. 37 presents the DNA sequences of edited Mrpl loci in
two animals. The upper sequence (SEQ ID NO:159) has a 43 bp deletion in
exon 11, and the lower sequence (SEQ ID NO:160) has a 14 bp deletion in exon
11. The exon sequence is shown in green; the target sequence is presented in
yellow, the deletions are shown in dark blue; and overlap between the target
sequence and the exon is shown in grey.
[0047] FIG. 38 shows the DNA sequence of an edited Mrp2 locus.
The sequence (SEQ ID NO:161) has a 726 bp deletion in exon 7. The exon is
shown in green; the target sequence is presented in yellow, and the deletion
is
shown in dark blue.
[0048] FIG. 39 presents the DNA sequences of edited BCRP loci in
two animals. (A) Shows a region of the rat BCRP locus (SEQ ID NO:162)
comprising a 588 bp deletion in exon 7. (B) Presents a region of the rat BCRP
locus (SEQ ID NO:163) comprising a 696 bp deletion in exon 7. The exon
sequence is shown in green; the target site is presented in yellow, and the
deletions are shown in dark blue.
[0049] FIG. 40 presents target sites and ZFN validation of Mdrl a,
and two additional genes, Jag1, and Notch3. (A) shows ZFN target sequences.
The ZFN binding sites are underlined. (B) shows results of a mutation
detection
assay in NIH 3T3 cells to validate the ZFN mRNA activity. Each ZFN mRNA pair
was cotransfected into NIH 3T3 cells. Transfected cells were harvested 24 h
later. Genomic DNA was analyzed with the mutation detection assay to detect
NHEJ products, indicative of ZFN activity. M, PCR marker; G (lanes 1, 3, and
5):
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GFP transfected control; Z (lanes 2, 4, and 6), ZFN transfected samples. Uncut
and cleaved bands are marked with respective sizes in base pairs.
[0050] FIG. 41 presents identification of genetically engineered
Mdrl a founders using a mutation detection assay. Uncut and cleaved bands are
marked with respective sizes in base pairs. Cleaved bands indicate a mutation
is
present at the target site. M, PCR marker. 1-44, 44 pups born from injected
eggs.
The numbers of founders are underlined.
[0051] FIG. 42 presents amplification of large deletions in Mdrl a
founders. PCR products were amplified using primers located 800 bp upstream
and downstream of the ZFN target site. Bands significantly smaller than the
1.6
kb wild-type band indicate large deletions in the target locus. Four founders
that
were not identified in Figure 7 are underlined.
[0052] FIG. 43 presents the results of a mutation detection assay at
the Mdrl b site in 44 Mdrl a ZFN injected pups. M, PCR marker; WT, toe DNA
from FVB/N mice that were not injected with Mdrl a ZFNs; 3T3, NIH 3T3 cells
transfected with Mdrl a ZFNs as a control.
[0053] FIG. 44 presents detection of Mdrl a expression by using
RT-PCR in Mdrl a-/- mice. (A) is a schematic illustration of Mdrl a genomic
and
mRNA structures around the target site. Exons are represented by open
rectangles with respective numbers. The size of each exon in base pairs is
labeled directly underneath. Intron sequences are represented by broken bars
with size in base pairs underneath. The ZFN target site in exon 7 is marked
with
a solid rectangle. The position of the 396 bp deletion in founder #23 is
labeled
above intron 6 and exon 7. RT-F and RT-R are the primers used in RT-PCR,
located in exons 5 and 9, respectively. In the RT reaction, 40 ng of total RNA
was
used as template. Normalization of the input RNA is confirmed by GAPDH
amplification with or without RT.
[0054] FIG. 45 presents the results of band isolation following
isolation and purification of the species at the wild-type size in the Mdrl a-
/-
samples, and then use as a template in a nested PCR.
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[0055] FIG. 46 shows the DNA sequences of edited BDNF loci in
two animals. The upper sequence (SEQ ID NO:21 1) has a 14 bp deletion in the
target sequence in exon 2, and the lower sequence (SEQ ID NO:212) has a 7 bp
deletion in the target sequence in exon 2. The exon is shown in green; the
target
site is presented in yellow, and the deletions are shown in dark blue.
[0056] FIG. 47 presents the DNA sequence of an edited DISC1
locus. Presented is a region of the rat DISC1 (SEQ ID NO:225) in which there
is
a 20 bp deletion in the target sequence in exon 5. The exon is shown in green;
the target site is presented in yellow, and the deletion is shown in dark
blue.
[0057] FIG. 48 illustrates editing of the p53 locus in rats. Presented
is a Cel-1 assay in which the presence of cleavage products indicated editing
of
the p53 gene.
[0058] FIG. 49 illustrates knockout of the p53 gene in rats.
Presented are Western blots of cytoplasmic and nuclear lysates of kidney (K)
and liver (L) samples from wild-type (WT 731 RP) and p53 knockout (KO 733RP)
animals. The relative locations p53 protein and actin protein are indicated to
the
right of each image.
DETAILED DESCRIPTION OF THE INVENTION
[0059] The present disclosure provides a method for creating a
genetically modified animal or animal cell comprising at least one edited
chromosomal sequence. The edited chromosomal sequence may be (1)
inactivated, (2) modified, or (3) comprise an integrated sequence. An
inactivated
chromosomal sequence is altered such that a functional protein is not made or
a
control sequence no longer functions the same as a wild-type control sequence.
Thus, a genetically modified animal comprising an inactivated chromosomal
sequence may be termed a "knock-out" or a "conditional knock-out." Similarly,
a
genetically modified animal comprising an integrated sequence may be termed a
"knock-in" or a "conditional knock-in." As detailed below, a knock-in animal
may
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be a humanized animal. Furthermore, a genetically modified animal comprising
a modified chromosomal sequence may comprise a targeted point mutation(s) or
other modification such that an altered protein product is produced. A
chromosomal sequence generally is edited using a zinc finger nuclease-
mediated process. Briefly, the process comprises introducing into a cell at
least
one nucleic acid encoding a targeted zinc finger nuclease and, optionally, at
least
one accessory polynucleotide. The method further comprises incubating the cell
to allow expression of the zinc finger nuclease, wherein a double-stranded
break
introduced into the targeted chromosomal sequence by the zinc finger nuclease
is repaired by an error-prone non-homologous end-joining DNA repair process or
a homology-directed DNA repair process. In an exemplary embodiment, the cell
is an embryo. The method of editing chromosomal sequences using targeted
zinc finger nuclease technology as described herein is rapid, precise, and
highly
efficient.
[0060] Additionally, the invention encompasses an animal or a cell
comprising at least one edited chromosomal sequence. A method of the
invention, an animal of the invention, a cell of the invention, and
applications
thereof are described in more detail below.
1. Method for Chromosomal Editing
[0061] One aspect of the present invention encompasses a method
for chromosomal editing. As used herein, "chromosomal editing" refers to
editing
a chromosomal sequence such that the sequence is (1) inactivated, (2)
modified,
or (3) comprises an integrated sequence. Generally speaking, a method for
editing a chromosomal sequence comprises: (a) introducing into a cell at least
one nucleic acid encoding a zinc finger nuclease that recognizes a target
sequence in the chromosomal sequence and is able to cleave a site in the
chromosomal sequence, and, optionally, (i) at least one donor polynucleotide
comprising a sequence for integration, the sequence flanked by an upstream
sequence and a downstream sequence that share substantial sequence identity
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with either side of the cleavage site, or (ii) at least one exchange
polynucleotide
comprising a sequence that is substantially identical to a portion of the
chromosomal sequence at the cleavage site and which further comprises at least
one nucleotide change; and (b) culturing the cell to allow expression of the
zinc
finger nuclease such that the zinc finger nuclease introduces a double-
stranded
break into the chromosomal sequence, and wherein the double-stranded break is
repaired by (i) a non-homologous end-joining repair process such that a
mutation
is introduced into the chromosomal sequence, or (ii) a homology-directed
repair
process such that the sequence in the donor polynucleotide is integrated into
the
chromosomal sequence or the sequence in the exchange polynucleotide is
exchanged with the portion of the chromosomal sequence.
[0062] Components of the zinc finger nuclease-mediated method of
editing a chromosomal sequence are described in more detail below.
(a) nucleic acid encoding a zinc finger nuclease
[0063] The method comprises, in part, introducing into a cell at least
one nucleic acid encoding a zinc finger nuclease. Typically, a zinc finger
nuclease comprises a DNA binding domain (i.e., zinc finger) and a cleavage
domain (i.e., nuclease). The DNA binding and cleavage domains are described
below. The nucleic acid encoding a zinc finger nuclease may comprise DNA or
RNA. For example, the nucleic acid encoding a zinc finger nuclease may
comprise mRNA. When the nucleic acid encoding a zinc finger nuclease
comprises mRNA, the mRNA molecule may be 5' capped. Similarly, when the
nucleic acid encoding a zinc finger nuclease comprises mRNA, the mRNA
molecule may be polyadenylated. An exemplary nucleic acid according to the
method is a capped and polyadenylated mRNA molecule encoding a zinc finger
nuclease. Methods for capping and polyadenylating mRNA are known in the art.
[0064] Generally speaking, a zinc finger nuclease of the invention,
once introduced into a cell, creates a double-stranded break in the
chromosomal
sequence. The double-stranded break may be repaired, in certain embodiments,
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by a non-homologous end-joining repair process of the cell, such that a
mutation
is introduced into the chromosomal sequence. In other embodiments, as
described below, a homology-directed repair process is used to edit the
chromosomal sequence.
(i) zinc finger binding domain
[0065] Zinc finger binding domains may be engineered to recognize
and bind to any nucleic acid sequence of choice. See, for example, Beerli et
al.
(2002) Nat. Biotechnol. 20:135-141; Pabo et al. (2001) Ann. Rev. Biochem.
70:313-340; Isalan et al. (2001) Nat. Biotechnol. 19:656-660; Segal et al.
(2001)
Curr. Opin. Biotechnol. 12:632-637; Choo et al. (2000) Curr. Opin. Struct.
Biol.
10:411-416; Zhang et al. (2000) J. Biol. Chem. 275(43):33850-33860; Doyon et
al. (2008) Nat. Biotechnol. 26:702-708; and Santiago et al. (2008) Proc. NatI.
Acad. Sci. USA 105:5809-5814. An engineered zinc finger binding domain may
have a novel binding specificity compared to a naturally-occurring zinc finger
protein. Engineering methods include, but are not limited to, rational design
and
various types of selection. Rational design includes, for example, using
databases comprising doublet, triplet, and/or quadruplet nucleotide sequences
and individual zinc finger amino acid sequences, in which each doublet,
triplet or
quadruplet nucleotide sequence is associated with one or more amino acid
sequences of zinc fingers which bind the particular triplet or quadruplet
sequence. See, for example, U.S. Patent Nos. 6,453,242 and 6,534,261, the
disclosures of which are incorporated by reference herein in their entireties.
As
an example, the algorithm described in U.S. Patent No. 6,453,242 may be used
to design a zinc finger binding domain to target a preselected sequence.
Alternative methods, such as rational design using a nondegenerate recognition
code table may also be used to design a zinc finger binding domain to target a
specific sequence (Sera et al. (2002) Biochemistry 41:7074-7081). Publically
available web-based tools for identifying potential target sites in DNA
sequences
and designing zinc finger binding domains may be found at
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www.zincfingertools.org and bindr.gdcb.iastate.edu/ZiFiT/, respectively
(Mandell
et al. (2006) Nuc. Acid Res. 34:W516-W523; Sander et al. (2007) Nuc. Acid Res.
35:W599-W605).
[0066] A zinc finger DNA binding domain may be designed to
recognize a DNA sequence ranging from about 3 nucleotides to about 21
nucleotides in length, or from about 8 to about 19 nucleotides in length. In
general, the zinc finger binding domains of the zinc finger nucleases
disclosed
herein comprise at least three zinc finger recognition regions (i.e., zinc
fingers).
In one embodiment, the zinc finger binding domain may comprise four zinc
finger
recognition regions. In another embodiment, the zinc finger binding domain may
comprise five zinc finger recognition regions. In still another embodiment,
the
zinc finger binding domain may comprise six zinc finger recognition regions. A
zinc finger binding domain may be designed to bind to any suitable target DNA
sequence. See for example, U.S. Patent Nos. 6,607,882; 6,534,261 and
6,453,242, the disclosures of which are incorporated by reference herein in
their
entireties.
[0067] Exemplary methods of selecting a zinc finger recognition
region may include phage display and two-hybrid systems, and are disclosed in
U.S. Patent. Nos. 5,789,538; 5,925,523; 6,007,988; 6,013,453; 6,410,248;
6,140,466; 6,200,759; and 6,242,568; as well as WO 98/37186; WO 98/53057;
WO 00/27878; WO 01/88197 and GB 2,338,237, each of which is incorporated
by reference herein in its entirety. In addition, enhancement of binding
specificity
for zinc finger binding domains has been described, for example, in WO
02/077227.
[0068] Zinc finger binding domains and methods for design and
construction of fusion proteins (and polynucleotides encoding same) are known
to those of skill in the art and are described in detail in U.S. Patent
Application
Publication Nos. 20050064474 and 20060188987, each incorporated by
reference herein in its entirety. Zinc finger recognition regions and/or multi-
fingered zinc finger proteins may be linked together using suitable linker
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sequences, including for example, linkers of five or more amino acids in
length.
See, U.S. Patent Nos. 6,479,626; 6,903,185; and 7,153,949, the disclosures of
which are incorporated by reference herein in their entireties, for non-
limiting
examples of linker sequences of six or more amino acids in length. The zinc
finger binding domain described herein may include a combination of suitable
linkers between the individual zinc fingers of the protein.
[0069] In some embodiments, the zinc finger nuclease may further
comprise a nuclear localization signal or sequence (NLS). A NLS is an amino
acid sequence which facilitates targeting the zinc finger nuclease protein
into the
nucleus to introduce a double stranded break at the target sequence in the
chromosome. Nuclear localization signals are known in the art. See, for
example, Makkerh et al. (1996) Current Biology 6:1025-1027.
(ii) cleavage domain
[0070] A zinc finger nuclease also includes a cleavage domain.
The cleavage domain portion of the zinc finger nucleases disclosed herein may
be obtained from any endonuclease or exonuclease. Non-limiting examples of
endonucleases from which a cleavage domain may be derived include, but are
not limited to, restriction endonucleases and homing endonucleases. See, for
example, 2002-2003 Catalog, New England Biolabs, Beverly, Mass.; and Belfort
et al. (1997) Nucleic Acids Res. 25:3379-3388 or www.neb.com. Additional
enzymes that cleave DNA are known (e.g., S1 Nuclease; mung bean nuclease;
pancreatic DNase I; micrococcal nuclease; yeast HO endonuclease). See also
Linn et al. (eds.) Nucleases, Cold Spring Harbor Laboratory Press, 1993. One
or
more of these enzymes (or functional fragments thereof) may be used as a
source of cleavage domains.
[0071] A cleavage domain also may be derived from an enzyme or
portion thereof, as described above, that requires dimerization for cleavage
activity. Two zinc finger nucleases may be required for cleavage, as each
nuclease comprises a monomer of the active enzyme dimer. Alternatively, a
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single zinc finger nuclease may comprise both monomers to create an active
enzyme dimer. As used herein, an "active enzyme dimer" is an enzyme dimer
capable of cleaving a nucleic acid molecule. The two cleavage monomers may
be derived from the same endonuclease (or functional fragments thereof), or
each monomer may be derived from a different endonuclease (or functional
fragments thereof).
[0072] When two cleavage monomers are used to form an active
enzyme dimer, the recognition sites for the two zinc finger nucleases are
preferably disposed such that binding of the two zinc finger nucleases to
their
respective recognition sites places the cleavage monomers in a spatial
orientation to each other that allows the cleavage monomers to form an active
enzyme dimer, e.g., by dimerizing. As a result, the near edges of the
recognition
sites may be separated by about 5 to about 18 nucleotides. For instance, the
near edges may be separated by about 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15,
16,
17 or 18 nucleotides. It will however be understood that any integral number
of
nucleotides or nucleotide pairs may intervene between two recognition sites
(e.g., from about 2 to about 50 nucleotide pairs or more). The near edges of
the
recognition sites of the zinc finger nucleases, such as for example those
described in detail herein, may be separated by 6 nucleotides. In general, the
site of cleavage lies between the recognition sites.
[0073] Restriction endonucleases (restriction enzymes) are present
in many species and are capable of sequence-specific binding to DNA (at a
recognition site), and cleaving DNA at or near the site of binding. Certain
restriction enzymes (e.g., Type IIS) cleave DNA at sites removed from the
recognition site and have separable binding and cleavage domains. For
example, the Type IIS enzyme Fok I catalyzes double-stranded cleavage of
DNA, at 9 nucleotides from its recognition site on one strand and 13
nucleotides
from its recognition site on the other. See, for example, U.S. Patent Nos.
5,356,802; 5,436,150 and 5,487,994; as well as Li et al. (1992) Proc. NatI.
Acad.
Sci. USA 89:4275-4279; Li et al. (1993) Proc. NatI. Acad. Sci. USA 90:2764-
18
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2768; Kim et al. (1994a) Proc. Natl. Acad. Sci. USA 91:883-887; Kim et al.
(1994b) J. Biol. Chem. 269:31, 978-31, 982. Thus, a zinc finger nuclease may
comprise the cleavage domain from at least one Type IIS restriction enzyme and
one or more zinc finger binding domains, which may or may not be engineered.
Exemplary Type IIS restriction enzymes are described for example in
International Publication WO 07/014,275, the disclosure of which is
incorporated
by reference herein in its entirety. Additional restriction enzymes also
contain
separable binding and cleavage domains, and these also are contemplated by
the present disclosure. See, for example, Roberts et al. (2003) Nucleic Acids
Res. 31:418-420.
[0074] An exemplary Type IIS restriction enzyme, whose cleavage
domain is separable from the binding domain, is Fok I. This particular enzyme
is
active as a dimer (Bitinaite et al. (1998) Proc. NatI. Acad. Sci. USA 95: 10,
570-
10, 575). Accordingly, for the purposes of the present disclosure, the portion
of
the Fok I enzyme used in a zinc finger nuclease is considered a cleavage
monomer. Thus, for targeted double-stranded cleavage using a Fok I cleavage
domain, two zinc finger nucleases, each comprising a Fokl cleavage monomer,
may be used to reconstitute an active enzyme dimer. Alternatively, a single
polypeptide molecule containing a zinc finger binding domain and two Fok I
cleavage monomers may also be used.
[0075] In certain embodiments, the cleavage domain may comprise
one or more engineered cleavage monomers that minimize or prevent
homodimerization, as described, for example, in U.S. Patent Publication Nos.
20050064474, 20060188987, and 20080131962, each of which is incorporated
by reference herein in its entirety. By way of non-limiting example, amino
acid
residues at positions 446, 447, 479, 483, 484, 486, 487, 490, 491, 496, 498,
499,
500, 531, 534, 537, and 538 of Fok I are all targets for influencing
dimerization of
the Fok I cleavage half-domains. Exemplary engineered cleavage monomers of
Fok I that form obligate heterodimers include a pair in which a first cleavage
monomer includes mutations at amino acid residue positions 490 and 538 of Fok
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I and a second cleavage monomer that includes mutations at amino-acid residue
positions 486 and 499.
[0076] Thus, in one embodiment, a mutation at amino acid position
490 replaces Glu (E) with Lys (K); a mutation at amino acid residue 538
replaces
Iso (I) with Lys (K); a mutation at amino acid residue 486 replaces GIn (Q)
with
Glu (E); and a mutation at position 499 replaces Iso (I) with Lys (K).
Specifically,
the engineered cleavage monomers may be prepared by mutating positions 490
from E to K and 538 from I to K in one cleavage monomer to produce an
engineered cleavage monomer designated "E490K:1538K" and by mutating
positions 486 from Q to E and 499 from I to L in another cleavage monomer to
produce an engineered cleavage monomer designated "Q486E:1499L." The
above described engineered cleavage monomers are obligate heterodimer
mutants in which aberrant cleavage is minimized or abolished. Engineered
cleavage monomers may be prepared using a suitable method, for example, by
site-directed mutagenesis of wild-type cleavage monomers (Fok I) as described
in U.S. Patent Publication No. 20050064474 (see Example 5).
[0077] The zinc finger nuclease described above may be
engineered to introduce a double stranded break at the targeted site of
integration. The double stranded break may be at the targeted site of
integration,
or it may be up to 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 100, or
1000
nucleotides away from the site of integration. In some embodiments, the double
stranded break may be up to 1, 2, 3, 4, 5, 10, 15, or 20 nucleotides away from
the site of integration. In other embodiments, the double stranded break may
be
up to 10, 15, 20, 25, 30, 35, 40, 45, or 50 nucleotides away from the site of
integration. In yet other embodiments, the double stranded break may be up to
50, 100, or 1000 nucleotides away from the site of integration.
(iii) exemplary zinc finger nuclease
[0078] Provided herein are non-limiting examples of zinc finger
nucleases that recognize and bind target sequences found in various animal
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chromosomal sequences. For instance, a zinc finger nuclease of the invention
may have an amino acid sequence that is at least 80% identical to a sequence
chosen from a zinc finger nuclease having a SEQ ID NO chosen from 53, 54, 57-
62, 69-76, 104-113, 123-126, 147-156, 201-210, 219-222, 223-224, 230-233,
240-243. In other embodiments, the sequence identity may be about 81, 82, 83,
84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100%.
[0079] Moreover, the zinc finger nucleases encoded by a SEQ ID
NO chosen from 53, 54, 57-62, 69-76, 104-113, 123-126, 147-156, 201-210,
219-222, 223-224, 230-233, 240-243 may recognize and bind a chromosomal
sequence having at least about 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91,
92,
93, 94, 95, 96, 97, 98, 99, or 100% sequence identity to a chromosomal SEQ ID
NO 55, 56, 63-68, 77-84, 86- 91, 94-103, 117-122, 129, 130, 135, 136, 137,
138,
139-146, 164-173, 213-218, 226-229, 234, 235, 236, 237, 238, 239.
(iv) additional methods for targeted cleavage
[0080] Any nuclease having a target site in a chromosome may be
used in the methods disclosed herein. For example, homing endonucleases and
meganucleases have very long recognition sequences, some of which are likely
to be present, on a statistical basis, once in a human-sized genome. Any such
nuclease having a unique target site in a genome may be used instead of, or in
addition to, a zinc finger nuclease, for targeted cleavage of a chromosome.
[0081] Non-limiting examples of homing endonucleases include I-
Scel, I-Ceul, PI-Pspl, PI-Sce, I-SceIV, I-Csml, I-Pant, I-Scell, I-Ppol, I-
Scelll, I-
Crel, I-Tevl, I-Tevll and I-Tevlll. The recognition sequences of these enzymes
are known in the art. See also U.S. Patent No. 5,420,032; U.S. Patent No.
6,833,252; Belfort et al. (1997) Nucleic Acids Res. 25:3379-3388; Dujon et al.
(1989) Gene 82:115-118; Perler et al. (1994) Nucleic Acids Res. 22, 1125-1127;
Jasin (1996) Trends Genet. 12:224-228; Gimble et al. (1996) J. Mol. Biol.
263:163-180; Argast et al. (1998) J. Mol. Biol. 280:345-353 and the New
England
Biolabs catalogue.
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[0082] Although the cleavage specificity of most homing
endonucleases is not absolute with respect to their recognition sites, the
sites are
of sufficient length that a single cleavage event per mammalian-sized genome
may be obtained by expressing a homing endonuclease in a cell containing a
single copy of its recognition site. It has also been reported that the
specificity of
homing endonucleases and meganucleases may be engineered to bind non-
natural target sites. See, for example, Chevalier et al. (2002) Molec. Cell
10:895-
905; Epinat et al. (2003) Nucleic Acids Res. 31:2952-2962; Ashworth et al.
(2006) Nature 441:656-659; Paques et al. (2007) Current Gene Therapy 7:49-66.
(b) optional exchange polynucleotide
[0083] A method for editing chromosomal sequences may further
comprise introducing into a cell at least one exchange polynucleotide
comprising
a sequence that is substantially identical to the chromosomal sequence at the
site of cleavage and which further comprises at least one specific nucleotide
change.
[0084] Typically, the exchange polynucleotide will be DNA. The
exchange polynucleotide may be a DNA plasmid, a bacterial artificial
chromosome (BAC), a yeast artificial chromosome (YAC), a viral vector, a
linear
piece of DNA, a PCR fragment, a naked nucleic acid, or a nucleic acid
complexed with a delivery vehicle such as a liposome or poloxamer. An
exemplary exchange polynucleotide may be a DNA plasmid.
[0085] The sequence in the exchange polynucleotide is
substantially identical to a portion of the chromosomal sequence at the site
of
cleavage. In general, the sequence of the exchange polynucleotide will share
enough sequence identity with the chromosomal sequence such that the two
sequences may be exchanged by homologous recombination. For example, the
sequence in the exchange polynucleotide may be at least about 80, 81, 82, 83,
84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical
to a
region of the chromosomal sequence.
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[0086] Importantly, the sequence in the exchange polynucleotide
comprises at least one specific nucleotide change with respect to the sequence
of the corresponding chromosomal sequence. For example, one nucleotide in a
specific codon may be changed to another nucleotide such that the codon codes
for a different amino acid. In one embodiment, the sequence in the exchange
polynucleotide may comprise one specific nucleotide change such that the
encoded protein comprises one amino acid change. In other embodiments, the
sequence in the exchange polynucleotide may comprise two, three, four, or more
specific nucleotide changes such that the encoded protein comprises one, two,
three, four, or more amino acid changes. In still other embodiments, the
sequence in the exchange polynucleotide may comprise a three nucleotide
deletion or insertion such that the reading frame of the coding reading is not
altered (and a functional protein may be produced). The expressed protein,
however, would comprise a single amino acid deletion or insertion.
[0087] The length of the sequence in the exchange polynucleotide
that is substantially identical to a portion of the chromosomal sequence at
the site
of cleavage can and will vary. In general, the sequence in the exchange
polynucleotide may range from about 25 bp to about 10,000 bp in length. In
various embodiments, the sequence in the exchange polynucleotide may be
about 50, 100, 200, 400, 600, 800, 1000, 1200, 1400, 1600, 1800, 2000, 2200,
2400, 2600, 2800, 3000, 3200, 3400, 3600, 3800, 4000, 4200, 4400, 4600, 4800,
or 5000 bp in length. In other embodiments, the sequence in the exchange
polynucleotide may be about 5500, 6000, 6500, 6000, 6500, 7000, 7500, 8000,
8500, 9000, 9500, or 10,000 bp in length.
[0088] One of skill in the art would be able to construct an
exchange polynucleotide as described herein using well-known standard
recombinant techniques (see, for example, Sambrook et al., 2001 and Ausubel et
al., 1996).
[0089] In the method detailed above for modifying a chromosomal
sequence, a double stranded break introduced into the chromosomal sequence
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by the zinc finger nuclease is repaired, via homologous recombination with the
exchange polynucleotide, such that the sequence in the exchange polynucleotide
may be exchanged with a portion of the chromosomal sequence. The presence
of the double stranded break facilitates homologous recombination and repair
of
the break. The exchange polynucleotide may be physically integrated or,
alternatively, the exchange polynucleotide may be used as a template for
repair
of the break, resulting in the exchange of the sequence information in the
exchange polynucleotide with the sequence information in that portion of the
chromosomal sequence. Thus, a portion of the endogenous chromosomal
sequence may be converted to the sequence of the exchange polynucleotide.
The changed nucleotide(s) may be at or near the site of cleavage.
Alternatively,
the changed nucleotide(s) may be anywhere in the exchanged sequences. As a
consequence of the exchange, however, the chromosomal sequence is modified.
(c) optional donor polynucleotide
[0090] A method for editing chromosomal sequences may
alternatively comprise introducing at least one donor polynucleotide
comprising a
sequence for integration into a cell. A donor polynucleotide comprises at
least
three components: the sequence to be integrated that is flanked by an upstream
sequence and a downstream sequence, wherein the upstream and downstream
sequences share sequence similarity with either side of the site of
integration in
the chromosome.
[0091] Typically, the donor polynucleotide will be DNA. The donor
polynucleotide may be a DNA plasmid, a bacterial artificial chromosome (BAC),
a
yeast artificial chromosome (YAC), a viral vector, a linear piece of DNA, a
PCR
fragment, a naked nucleic acid, or a nucleic acid complexed with a delivery
vehicle such as a liposome or poloxamer. An exemplary donor polynucleotide
may be a DNA plasmid.
[0092] The donor polynucleotide comprises a sequence for
integration. The sequence for integration may be a sequence endogenous to the
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animal or cell or it may be an exogenous sequence. The sequence for
integration may encode a protein or a non-coding RNA (e.g., a microRNA).
Thus, the sequence for integration may be operably linked to an appropriate
control sequence or sequences. Alternatively, the sequence for integration may
provide a regulatory function. Accordingly, the size of the sequence for
integration can and will vary. In general, the sequence for integration may
range
from about one nucleotide to several million nucleotides.
[0093] The donor polynucleotide also comprises upstream and
downstream sequence flanking the sequence to be integrated. The upstream
and downstream sequences in the donor polynucleotide are selected to promote
recombination between the chromosomal sequence of interest and the donor
polynucleotide. The upstream sequence, as used herein, refers to a nucleic
acid
sequence that shares sequence similarity with the chromosomal sequence
upstream of the targeted site of integration. Similarly, the downstream
sequence
refers to a nucleic acid sequence that shares sequence similarity with the
chromosomal sequence downstream of the targeted site of integration. The
upstream and downstream sequences in the donor polynucleotide may share
about 75%, 80%, 85%, 90%, 95%, or 100% sequence identity with the targeted
chromosomal sequence. In other embodiments, the upstream and downstream
sequences in the donor polynucleotide may share about 95%, 96%, 97%, 98%,
99%, or 100% sequence identity with the targeted chromosomal sequence. In an
exemplary embodiment, the upstream and downstream sequences in the donor
polynucleotide may share about 99% or 100% sequence identity with the
targeted chromosomal sequence.
[0094] An upstream or downstream sequence may comprise from
about 20 bp to about 2500 bp. In various embodiments, an upstream or
downstream sequence may comprise about 50, 100, 200, 300, 400, 500, 600,
700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900,
2000, 2100, 2200, 2300, 2400, or 2500 bp. An exemplary upstream or
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downstream sequence may comprise about 200 bp to about 2000 bp, about 600
bp to about 1000 bp, or more particularly about 700 bp to about 1000 bp.
[0095] In some embodiments, the donor polynucleotide may further
comprise a marker. Such a marker may make it easy to screen for targeted
integrations. Non-limiting examples of suitable markers include restriction
sites,
fluorescent proteins, or selectable markers.
[0096] One of skill in the art would be able to construct a donor
polynucleotide as described herein using well-known standard recombinant
techniques (see, for example, Sambrook et al., 2001 and Ausubel et al., 1996).
[0097] In the method detailed above for editing a chromosomal
sequence by integrating a sequence, the double stranded break introduced into
the chromosomal sequence by the zinc finger nuclease is repaired, via
homologous recombination with the donor polynucleotide, such that the
sequence is integrated into the chromosome. The presence of a double-
stranded break facilitates integration of the sequence. A donor polynucleotide
may be physically integrated or, alternatively, the donor polynucleotide may
be
used as a template for repair of the break, resulting in the introduction of
the
sequence as well as all or part of the upstream and downstream sequences of
the donor polynucleotide into the chromosome. Thus, the endogenous
chromosomal sequence may be converted to the sequence of the donor
polynucleotide.
(d) introducing nucleic acid into a cell
[0098] To mediate zinc finger nuclease genome editing, at least one
nucleic acid molecule encoding a zinc finger nuclease and, optionally, at
least
one exchange polynucleotide or at least one donor polynucleotide is introduced
into a cell. As used herein, the term "cell" encompasses any animal cell that
comprises a chromosomal sequence. In some embodiments, the term "cell" may
refer to an embryo. In certain exemplary embodiments, the embryo is a
fertilized
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one-cell stage embryo. In other exemplary embodiments, the embryo may be an
embryo of any stage.
[0099] Suitable methods of introducing the nucleic acids to the
embryo or cell may include microinjection, electroporation, sonoporation,
biolistics, calcium phosphate-mediated transfection, cationic transfection,
liposome transfection, dendrimer transfection, heat shock transfection,
nucleofection transfection, magnetofection, lipofection, impalefection,
optical
transfection, proprietary agent-enhanced uptake of nucleic acids, and delivery
via
liposomes, immunoliposomes, virosomes, or artificial virions. In one
embodiment, the nucleic acids may be introduced into an embryo by
microinjection. The nucleic acids may be microinjected into the nucleus or the
cytoplasm of the embryo. In another embodiment, the nucleic acids may be
introduced into a cell by nucleofection.
[0100] In embodiments in which both a nucleic acid encoding a zinc
finger nuclease and an exchange (or donor) polynucleotide are introduced into
an embryo or cell, the ratio of exchange (or donor) polynucleotide to nucleic
acid
encoding a zinc finger nuclease may range from about 1:10 to about 10:1. In
various embodiments, the ratio of exchange (or donor) polynucleotide to
nucleic
acid encoding a zinc finger nuclease may be about 1:10, 1:9, 1:8, 1:7, 1:6,
1:5,
1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, or 10:1. In one
embodiment, the ratio may be about 1:1.
[0101] In embodiments in which more than one nucleic acid
encoding a zinc finger nuclease and, optionally, more than one exchange (or
donor) polynucleotide is introduced into an embryo or cell, the nucleic acids
may
be introduced simultaneously or sequentially. For example, nucleic acids
encoding the zinc finger nucleases, each specific for a distinct recognition
sequence, as well as the optional exchange (or donor) polynucleotides, may be
introduced at the same time. Alternatively, each nucleic acid encoding a zinc
finger nuclease, as well as the optional exchange (or donor) polynucleotides,
may be introduced sequentially.
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[0102] In one embodiment, at least one nucleic acid molecule
encoding a zinc finger nuclease is introduced into a cell. In another
embodiment,
at least 2, 3, 4, 5, or more than 5 nucleic acid molecules encoding a zinc
finger
nuclease are introduced into a cell. In each of the above embodiments, one or
more corresponding donor or exchange polynucleotides may also be introduced
into the cell, in a ratio from about 1:10 to about 10:1 donor or exchange
polynucleotides to zinc finger nuclease nucleic acids, as described above.
(e) culturing the cell
[0103] A method for editing a chromosomal sequence using a zinc
finger nuclease-mediated process as described herein further comprises
culturing the cell comprising the introduced nucleic acid(s) to allow
expression of
the at least one zinc finger nuclease.
[0104] Cells comprising the introduced nucleic acids may be
cultured using standard procedures to allow expression of the zinc finger
nuclease. Standard cell culture techniques are described, for example, in
Santiago et al. (2008) PNAS 105:5809-5814; Moehle et al. (2007) PNAS
104:3055-3060; Urnov et al. (2005) Nature 435:646-651; and Lombardo et al
(2007) Nat. Biotechnology 25:1298-1306. Those of skill in the art appreciate
that
methods for culturing cells are known in the art and can and will vary
depending
on the cell type or cell species. Routine optimization may be used, in all
cases,
to determine the best techniques for a particular cell type.
[0105] In one embodiment where the cell is an embryo, the embryo
may be cultured in vitro (e.g., in cell culture). Typically, the embryo is
cultured for
a short period of time at an appropriate temperature and in appropriate media
with the necessary 02/CO2 ratio to allow the expression of the zinc finger
nuclease. A skilled artisan will appreciate that culture conditions can and
will
vary depending on the embryo species. Routine optimization may be used, in all
cases, to determine the best culture conditions for a particular species of
embryo.
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In some cases, a cell line may be derived from an in vitro-cultured embryo
(e.g.,
an embryonic stem cell line).
[0106] Preferably, the embryo will be cultured in vivo by transferring
the embryo into the uterus of a female host. Generally speaking, the female
host
is from the same or a similar species as the embryo. Preferably, the female
host
is pseudo-pregnant. Methods of preparing pseudo-pregnant female hosts are
known in the art. Additionally, methods of transferring an embryo into a
female
host are known. Culturing an embryo in vivo permits the embryo to develop and
may result in a live birth of an animal derived from the embryo. Such an
animal
generally will comprise the disrupted chromosomal sequence(s) in every cell of
its body.
[0107] Upon expression of the at least one zinc finger nuclease in a
cell, the chromosomal sequence of the cell may be edited. In cases in which
the
cell comprises an expressed zinc finger nuclease but no exchange (or donor)
polynucleotide, the zinc finger nuclease recognizes, binds, and cleaves the
target
sequence in the chromosomal sequence of interest. The double-stranded break
introduced by the zinc finger nuclease is repaired by an error-prone non-
homologous end-joining DNA repair process. Consequently, a deletion, or
insertion resulting in a missense or nonsense mutation may be introduced in
the
chromosomal sequence such that the sequence is inactivated.
[0108] In cases in which the embryo or cell comprises an expressed
zinc finger nuclease as well as an exchange (or donor) polynucleotide, the
zinc
finger nuclease recognizes, binds, and cleaves the target sequence in the
chromosome. The double-stranded break introduced by the zinc finger nuclease
is repaired, via homologous recombination with the exchange (or donor)
polynucleotide, such that a portion of the chromosomal sequence is converted
to
the sequence in the exchange polynucleotide or the sequence in the donor
polynucleotide is integrated into the chromosomal sequence. As a consequence,
the chromosomal sequence is edited.
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[0109] The genetically modified animals disclosed herein may be
crossbred to create animals comprising more than one edited chromosomal
sequence or to create animals that are homozygous for one or more edited
chromosomal sequences. Those of skill in the art will appreciate that many
combinations are possible. Moreover, the genetically modified animals
disclosed
herein may be crossed with other animals to combine the edited chromosomal
sequence with other genetic backgrounds. By way of non-limiting example,
suitable genetic backgrounds include wild-type, natural mutations giving rise
to
known phenotypes, targeted chromosomal integration, non-targeted integrations,
etc.
(f) types of chromosomal edits
[0110] As stated above, a method of the invention may be used to
(1) inactivate a chromosomal sequence, (2) modify a chromosomal sequence, or
(3) integrate a sequence into a chromosome. Each of these is discussed in more
detail below.
i. inactivate a sequence
[0111] In one embodiment, an edited chromosomal sequence may
be inactivated such that the sequence is not transcribed, the coded protein is
not
produced, or the sequence does not function as the wild-type sequence does.
For example, a protein coding sequence may be inactivated such that the
protein
is not produced. Alternatively, a microRNA coding sequence may be inactivated
such that the microRNA is not produced. Furthermore, a control sequence may
be inactivated such that it no longer functions as a control sequence. As used
herein, "control sequence" refers to any nucleic acid sequence that effects
the
transcription, translation, or accessibility of a nucleic acid sequence. By
way of
non-limiting example, a promoter, a transcription terminator, and an enhancer
are
control sequences. The inactivated chromosomal sequence may include a
deletion mutation (i.e., deletion of one or more nucleotides), an insertion
mutation
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(i.e., insertion of one or more nucleotides), or a nonsense mutation (i.e.,
substitution of a single nucleotide for another nucleotide such that a stop
codon
is introduced). In some embodiments, a chromosomal sequence that is
inactivated may be termed a "knock-out." In an interation of the invention, a
"knock-out" animal created by a method of the invention does not comprise any
exogenous sequence.
ii. modify a sequence
[0112] In another embodiment, an edited chromosomal sequence
may be modified such that it codes for an altered gene product or the function
of
the sequence is altered. A chromosomal sequence encoding a protein may be
modified to include at least one changed nucleotide such that the codon
comprising the changed nucleotide codes for a different amino acid. The
resultant protein, therefore, comprises at least one amino acid change.
Moreover, a protein coding sequence may be modified by insertions or deletions
such that the reading from of the sequence is not altered and a modified
protein
is produced. In such embodiments, the modified sequence may result in a
phenotype change.
[0113] Alternatively, a chromosomal sequence that functions as a
control sequence may be modified. For instance, a promoter may be modified
such that it is always active or is regulated by an exogenous signal.
[0114] In yet another embodiment, at least one chromosomal
sequence encoding a protein of interest may be edited such that the expression
pattern of the protein is altered. For example, regulatory regions controlling
the
expression of the protein, such as a promoter or transcription factor binding
site,
may be altered such that the protein of interest is over-produced, or the
tissue-
specific or temporal expression of the protein is altered, or a combination
thereof.
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N. Integrate a sequence
[0115] In yet another embodiment, an edited chromosomal
sequence may comprise an integrated sequence. Such a sequence may encode
an endogenous protein, an exogenous or heterologous protein, a wild-type
protein, a modified protein, a fusion protein, a microRNA, or the like. An
integrated protein coding sequence may be linked to a reporter sequence (the
reporter sequence may be linked 5' or 3' to the protein coding sequence). An
integrated protein coding sequence may also be placed under control of an
endogenous promoter, may be operably linked to an exogenous promoter, or
may be fused in-frame with an endogenous protein coding sequence.
Additionally, the integrated sequence may function as a control element.
Accordingly, the integrated sequence may be endogenous or exogenous to the
cell. An animal or cell comprising such an integrated sequence may be termed
"knock-in." In one iteration of the above embodiments, it should be understood
that no selectable marker is present.
[0116] In certain embodiments, a sequence may be integrated to
alter the expression pattern of a protein of interest. For instance, a
conditional
knock-out system may be created.
A. conditional mutations
[0117] In certain embodiments, a sequence may be edited to alter
the expression pattern of a protein of interest. For instance, a conditional
knock-
out system may be created.
[0118] As used herein, a "conditional knock-out" system is a model
where the expression of a nucleic acid molecule is disrupted in a particular
organ, tissue, or cell type, as opposed to the entire animal, and/or in a
temporally
controlled manner. A conditional knock-out allows, for example, the study of a
gene function even when global disruption of the gene is lethal.
[0119] A non-limiting example of a conditional knock-out system
includes a Cre-lox recombination system. A Cre-lox recombination system
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comprises a Cre recombinase enzyme, a site-specific DNA recombinase that can
catalyse the recombination of a nucleic acid sequence between specific sites
(lox
sites) in a nucleic acid molecule. Methods of using this system to produce
temporal and tissue specific expression are known in the art. In general, a
genetically modified cell is generated with lox sites flanking a chromosomal
sequence of interest. A genetically modified animal comprising a cell with the
lox-flanked chromosomal sequence of interest may then be crossed with another
genetically modified animal expressing Cre recombinase in one or more cells.
Progeny animals comprising one or more cells comprising a lox-flanked
chromosomal sequence and one or more cells comprising a Cre recombinase
are then produced. In the cells that comprise both a lox-flanked chromosomal
sequence and a Cre recombinase, the lox-flanked chromosomal sequence
encoding a protein of interest is recombined, leading to deletion or inversion
of
the chromosomal sequence encoding the protein of interest. Expression of Cre
recombinase may be temporally and conditionally regulated to effect temporally
and conditionally regulated recombination of the chromosomal sequence
encoding the protein of interest.
A. integrations that disrupt an endogenous locus
[0120] In another embodiment, a method of the invention may be
used to integrate a mutation that disrupts an endogenous locus. For instance,
a
chromosomal sequence may be disrupted by the substitution of an exogenous
sequence for an endogenous sequence, such that the exogenous sequence is
under the control of the endogenous promoter. In these embodiments, the
disrupted endogenous sequence would not be expressed, but the integrated
exogenous sequence would be expressed. The exogenous sequence may be a
homolog of the endogenous sequence. For instance, the exogenous sequence
may be a human sequence when the endogenous sequence is non-human. In
some embodiments, the exogenous sequence may be unrelated to the
endogenous sequence it is replacing. For instance, an endogenous sequence
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may be substituted for an exogenous marker such that when the endogenous
promoter is active, the marker is detectable. In some embodiments, the marker
may be an enzymatic marker that can amplify the detectable signal of the
marker.
[0121] Alternatively, in some embodiments a method of the
invention may be used to substitute an endogenous promoter or other regulatory
sequence with an exogenous promoter or regulator sequence. In these
embodiments, the expression pattern of the locus would be dictated by the
exogenous promoter or regulatory sequence, as opposed to the endogenous
promoter or regulatory sequence. Such an exogenous promoter or regulatory
sequence may be a homolog of the endogenous promoter or regulatory
sequence. For instance, the exogenous sequence may be a human sequence
when the endogenous sequence is non-human. In some embodiments, the
exogenous sequence may be unrelated to the endogenous sequence it is
replacing.
C. integration of an exogenous nucleic acid sequence
[0122] Alternatively, instead of disrupting a locus, a method of the
invention may be used to integrate an exogenous sequence, with or without a
promoter, into a chromosomal sequence without disrupting the expression of an
endogenous locus. In some embodiments, such integration may be in a "safe
harbor" locus, such as Rosa26 locus in the rat (or an equivalent in another
animal) or the HPRT locus on the X chromosome in the rat (or an equivalent in
another animal).
[0123] In one embodiment, a cassette comprising an exogenous
promoter operably linked to an exogenous nucleic acid sequence may be
integrated into a safe harbor locus. In certain embodiments, the exogenous
promoter may be conditional. For instance, a conditional promoter may be a
tissue-specific promoter, an organ specific promoter, or a cell-type specific
promoter (such as a stem cell promoter, a B-cell promoter, a hair cell
promoter,
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etc.) or an inducible promoter. An inducible promoter, as used herein, is a
promoter that is active only in the presence of a particular substance, such
as an
antibiotic, a drug, or other exogenous compound. In some embodiments, the
integration of a cassette comprising a conditional promoter may be used to
track
cell lineages.
[0124] In another embodiment, an exogenous nucleic acid
sequence may be integrated to serve as a detectable marker for a particular
nucleic acid sequence.
D. humanized
[0125] In an additional embodiment, the genetically modified animal
may be a "humanized" animal comprising at least one chromosomally integrated
sequence encoding a functional human protein. The functional human protein
may have no corresponding ortholog in the genetically modified animal.
Alternatively, the wild-type animal from which the genetically modified animal
is
derived may comprise an ortholog corresponding to the functional human
protein.
In this case, the orthologous sequence in the "humanized" animal is
inactivated
such that no endogenous functional protein is made and the "humanized" animal
comprises at least one chromosomally integrated sequence encoding the human
protein. Those of skill in the art appreciate that "humanized" animals may be
generated by crossing a knock-out animal with a knock-in animal comprising the
chromosomally integrated sequence.
(g) multiple chromosomal edits
[0126] A further embodiment of the above invention comprises
performing a method of the invention serially, such that a cell is developed
with
more than one chromosomal edit. For instance, an embryo with a first edit may
be cultured to produce an animal comprising the first genomic edit. An embryo
deriving from this animal may then be used in a method of the invention to
create
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a second genomic edit. The same process may be repeated to create an embryo
with three, four, five, six, seven, eight, nine, ten or more than ten genomic
edits.
[0127] Alternatively, a cell with multiple genomic edits may be
developed by simultaneoulsy introducing more than one zinc finger nuclease,
each specific for a distinct edit site. A corresponding number of donor and/or
exchange polynucleotides may optionally be introduced as well. The number of
zinc finger nucleases and optional corresponding donor or exchange
polynucleotides introduced into a cell may be two, three, four, five or more
than
five.
II. Applications Derived From a Method of the Invention
[0128] A method of the invention may be used to create an animal
or cell comprising an edited chromosomal sequence. Such an animal or cell may
be used for several different applications, including, for instance, research
applications, livestock applications, companion animal applications, or
biomolecule production applications. Non-limiting examples of such
applications
are detailed in sections (a) - (d) below.
(a) research applications
[0129] In certain embodiments, a method of the invention may be
used to create an animal or cell that may be used in research applications.
Such
applications may include disease models, pharmacological models,
developmental models, cellular function models, and humanized models, each of
which are detailed below.
i. disease models
[0130] A method of the invention may be used to create an animal
or cell that may be used as a disease model. As used herein, "disease" refers
to
a disease, disorder, or indication in a subject. For instance, in one
embodiment, a
method of the invention may be used to create an animal or cell that comprises
a
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chromosomal edit in one or more nucleic acid sequences associated with a
disease. Such a nucleic acid sequence may encode a disease associated protein
sequence or may be a disease associated control sequence.
[0131] In one embodiment, an animal or cell created by a method of
the invention may be used to study the effects of mutations on the animal or
cell
and development and/or progression of the disease using measures commonly
used in the study of the disease. Alternatively, such an animal or cell may be
used to study the effect of a pharmaceutically active compound on the disease.
[0132] In another embodiment, an animal or cell created by a
method of the invention may be used to assess the efficacy of a potential gene
therapy strategy. That is, a chromosomal sequence encoding a protein
associated with a disease may be modified such that the disease development
and/or progression is inhibited or reduced. In particular, the method
comprises
editing a chromosomal sequence encoding a protein associated with the disease
such that an altered protein is produced and, as a result, the animal or cell
has
an altered response. Accordingly, in some embodiments, a genetically modified
animal may be compared with an animal predisposed to development of the
disease such that the effect of the gene therapy event may be assessed.
[0133] In certain embodiments, a method of the invention may be
used to create an animal or cell that maybe used as a disease model for a
disease listed in Table A. Such an animal or cell may comprise a chromosomal
edit in a gene listed in Table A. In another embodiment, a method of the
invention may be used to create an animal or cell that maybe used as a disease
model for a disease listed in Table B. Such an animal or cell may comprise a
chromosomal edit in a gene listed in Table B. In Table B, a six-digit number
following an entry in the Disease/Disorder/Indication column is an OMIM number
(Online Mendelian Inheritance in Man, OMIM (TM). McKusick-Nathans Institute
of Genetic Medicine, Johns Hopkins University (Baltimore, MD) and National
Center for Biotechnology Information, National Library of Medicine (Bethesda,
MD), available on the World Wide Web. A number in parentheses after the
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name of each disorder indicates whether the mutation was positioned by
mapping the wildtype gene (1), by mapping the disease phenotype itself (2), or
by both approaches (3). For example, a "(3)", includes mapping of the wildtype
gene combined with demonstration of a mutation in that gene in association
with
the disorder."
TABLE A
DISEASE/DISORDERS GENE(S)
PTEN; ATM; ATR; EGFR; ERBB2; ERBB3; ERBB4;
Notch1; Notch2; Notch3; Notch4; AKT; AKT2; AKT3; HIF;
HIF1a; HIF3a; Met; HRG; Bc12; PPAR alpha; PPAR
gamma; WT1 (Wilms Tumor); FGF Receptor Family
members (5 members: 1, 2, 3, 4, 5); CDKN2a; APC; RB
Neoplasia (retinoblastoma); MEN1; VHL; BRCA1; BRCA2; AR
(Androgen Receptor); TSG101; IGF; IGF Receptor; lgf1 (4
variants); lgf2 (3 variants); lgf 1 Receptor; lgf 2 Receptor;
Bax; Bc12; caspases family (9 members:
1,2,3,4,6,7,8,9,12); Kras; Apc
Age-related Macular Abcr; Cc12; Cc2; cp (ceruloplasmin); Timp3; cathepsinD;
Degeneration VIdlr; Ccr2
Neuregulin1 (Nrgl); Erb4 (receptor for Neuregulin);
Complexin1 (Cplxl); Tphl Tryptophan hydroxylase; Tph2
Schizophrenia Tryptophan hydroxylase 2; Neurexin 1; GSK3; GSK3a;
GSK3b
5-HTT (Slc6a4); COMT; DRD (Drdla); SLC6A3; DAOA;
Disorders DTNBP1; Dao (Daol)
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TABLE A
DISEASE/DISORDERS GENE(S)
HTT (Huntington's Dx); SBMA/SMAX1/AR (Kennedy's
Dx); FXN/X25 (Friedrich's Ataxia); ATX3 (Machado-
Trinucleotide Repeat Joseph's Dx); ATXN1 and ATXN2 (spinocerebellar
Disorders ataxias); DMPK (myotonic dystrophy); Atrophin-1 and Atn1
(DRPLA Dx); CBP (Creb-BP - global instability); VLDLR
(Alzheimer's); Atxn7; Atxn10
Fragile X Syndrome FMR2; FXR1; FXR2; mGLUR5
Secretase Related APH-1 (alpha and beta); Presenilin (Psen1); nicastrin
Disorders (Ncstn); PEN-2
Others Nos1; Parp1; Nat1; Nat2
Prion - related disorders Prp
SOD1; ALS2; STEX; FUS; TARDBP; VEGF (VEGF-a;
ALS VEGF-b; VEGF-c)
Prkce (alcohol); Drd2; Drd4; ABAT (alcohol); GRIA2;
Drug addiction Grm5; Grin1; Htr1b; Grin2a; Drd3; Pdyn; Grial (alcohol)
Mecp2; BZRAP1; MDGA2; Sema5A; Neurexin 1; Fragile X
Autism (FMR2 (AFF2); FXR1; FXR2; Mglur5)
El; CHIP; UCH; UBB; Tau; LRP; PICALM; Clusterin; PS1;
Alzheimer's Disease SORL1; CR1; VIdIr; Ubal; Uba3; CHIP28 (Agp1,
Aquaporin 1); Uchll; Uch13; APP
IL-10; IL-1 (IL-1a; IL-1b); IL-13; IL-17 (IL-17a (CTLA8); IL-
17b; IL-17c; IL-17d; IL-17f); 11-23; Cx3cr1; ptpn22; TNFa;
Inflammation NOD2/CARD15 for IBD; IL-6; IL-12 (IL-12a; IL-12b);
CTLA4; Cx3cll
Parkinson's Disease x-Synuclein; DJ-1; LRRK2; Parkin; PINK1
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
17,20-lyase deficiency, isolated, 202110 (3) CYP17A1, CYP17, P450C17
17-alpha-hydroxylase/17,20-lyase CYP17A1, CYP17, P450C17
deficiency, 202110 (3)
2-methyl-3-hydroxybutyryl-CoA HAD H2, ERAB
dehydrogenase deficiency, 300438 (3)
2-methylbutyrylglycinuria (3) ACADSB
3-beta-hydroxysteroid dehydrogenase, type HSD3B2
II, deficiency (3)
3-hydroxyacyl-CoA dehydrogenase HADHSC, SCHAD
deficiency, 609609 (3)
3-Methyl crotonyl-CoA carboxylase 1 MCCC1, MCCA
deficiency, 210200 (3)
3-Methyl crotonyl-CoA carboxylase 2 MCCC2, MCCB
deficiency, 210210 (3)
3-methylglutaconic aciduria, type I, 250950 AUH
(3)
3-methylglutaconicaciduria, type III, 258501 OPA3, MGA3
(3)
3-M syndrome, 273750 (3) CUL7
6-mercaptopurine sensitivity (3) TPMT
Aarskog-Scott syndrome (3) FGD1, FGDY, AAS
Abacavir hypersensitivity, susceptibility to HLA-B
(3)
ABCD syndrome, 600501 (3) EDNRB, HSCR2, ABCDS
Abetalipoproteinemia, 200100 (3) MTP
Abetalipoproteinemia (3) APOB, FLDB
Acampomelic campolelic dysplasia, 114290 SOX9, CMD1, SRA1
(3)
Acatalasemia (3) CAT
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Accelerated tumor formation, susceptibility MDM2
to (3)
Achalasia-addisonianism-alacrimia AAAS, AAA
syndrome, 231550 (3)
Acheiropody, 200500 (3) C7orf2, ACHP, LMBR1
Achondrogenesis-hypochondrogenesis, COL2A1
type II, 200610 (3)
Achondrogenesis Ib, 600972 (3) SLC26A2, DTD, DTDST, D5S1708,
EDM4
Achondroplasia, 100800 (3) FGFR3, ACH
Achromatopsia-2, 216900 (3) CNGA3, CNG3, ACHM2
Achromatopsia-3, 262300 (3) CNGB3, ACHM3
Achromatopsia-4 (3) GNAT2, ACHM4
Acid-labile subunit, deficiency of (3) IGFALS, ALS
Acquired long QT syndrome, susceptibility KCNH2, LQT2, HERG
to (3)
Acrocallosal syndrome, 200990 (3) GL13, PAPA, PAPB, ACLS
Acrocapitofemoral dysplasia, 607778 (3) IHH, BDA1
Acrodermatitis enteropathica, 201100 (3) SLC39A4, ZIP4
Acrokeratosis verruciformis, 101900 (3) ATP2A2, ATP2B, DAR
Acromegaly, 102200 (3) GNAS, GNAS1, GPSA, POH, PHP1B,
PHP1A, AHO
Acromegaly, 102200 (3) SSTR5
Acromesomelic dysplasia, Hunter- GDF5, CDMP1
Thompson type, 201250 (3)
Acromesomelic dysplasia, Maroteaux type, NPR2, ANPRB, AMDM
602875 (3)
Acyl-CoA dehydrogenase, long chain, ACADL, LCAD
deficiency of (3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Acyl-CoA dehydrogenase, medium chain, ACADM, MCAD
deficiency of, 201450 (3)
Acyl-CoA dehydrogenase, short-chain, ACADS, SCAD
deficiency of, 201470 (3)
Adenocarcinoma of lung, response to EGFR
tyrosine kinase inhibitor in, 211980 (3)
Adenocarcinoma of lung, somatic, 211980 BRAF
(3)
Adenocarcinoma of lung, somatic, 211980 ERBB2, NGL, NEU, HER2
(3)
Adenocarcinoma of lung, somatic, 211980 PRKN, PARK2, PDJ
(3)
Adenocarcinoma, ovarian, somatic (3) PRKN, PARK2, PDJ
Adenoma, periampullary (3) APC, GS, FPC
Adenomas, multiple colorectal, 608456 (3) MUTYH
Adenomas, salivary gland pleomorphic, PLAG1, SGPA, PSA
181030 (3)
Adenomatous polyposis coli (3) APC, GS, FPC
Adenomatous polyposis coli, attenuated (3) APC, GS, FPC
Adenosine deaminase deficiency, partial, ADA
102700 (3)
Adenylosuccinase deficiency, 103050 (3) ADSL
Adiponectin deficiency (3) APM1, GBP28
Adrenal adenoma, sporadic (3) MEN1
Adrenal cortical carcinoma, 202300 (3) TP53, P53, LFS1
Adrenal hyperplasia, congenital, due to 11- CYP11B1, P450C11, FHI
beta-hydroxylase deficiency (3)
Adrenal hyperplasia, congenital, due to 21- CYP21A2, CYP21, CA21 H
hydroxylase deficiency (3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Adrenal hyperplasia, congenital, due to POR
combined P450C17 and P450C21
deficiency, 201750 (3)
Adrenal hypoplasia, congenital, with DAX1, AHC, AHX, NROB1
hypogonadotropic hypogonadism, 300200
(3)
Adrenocortical insufficiency without ovarian FTZF1, FTZ1, SF1
defect (3)
Adrenocortical tumor, somatic (3) PRKAR1A, TSE1, CNC1, CAR
Adrenocorticotropic hormone deficiency, TBS19
201400 (3)
Adrenoleukodystrophy, 300100 (3) ABCD1, ALD, AMN
Adrenoleukodystrophy, neonatal, 202370 PEX10, NALD
(3)
Adrenoleukodystrophy, neonatal, 202370 PEX13, ZWS, NALD
(3)
Adrenoleukodystrophy, neonatal, 202370 PEX1, ZWS1
(3)
Adrenoleukodystrophy, neonatal, 202370 PEX26
(3)
Adrenoleukodystrophy, neonatal, 202370 PXR1, PEX5, PTS1R
(3)
Adrenomyeloneuropathy, 300100 (3) ABCD1, ALD, AMN
Adult i phenotype with congenital cataract, GCNT2
110800 (3)
Adult i phenotype without cataract, 110800 GCNT2
(3)
ADULT syndrome, 103285 (3) TP73L, TP63, KET, EEC3, SHFM4,
LMS, RHS
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Advanced sleep phase syndrome, familial, PER2, FASPS, KIAA0347
604348 (3)
Afibrinogenemia, 202400 (3) FGA
Afibrinogenemia, congenital, 202400 (3) FGB
Agammaglobulinemia, 601495 (3) IGHM, MU
Agammaglobulinemia, autosomal recessive IGLL1, IGO, IGL5, VPREB2
(3)
Agammaglobulinemia, non-Bruton type, LRRC8, KIAA1437
601495 (3)
Agammaglobulinemia, type 1, X-linked (3) BTK, AGMX1, IMD1, XLA, AT
AGAT deficiency (3) GATM, AGAT
Agenesis of the corpus callosum with SLC12A6, KCC3A, KCC3B, KCC3,
peripheral neuropathy, 218000 (3) ACCPN
AICA-ribosiduria due to ATIC deficiency, ATIC, PURH, AICAR
608688 (3)
AIDS, delayed/rapid progression to (3) KIR3DL1, NKAT3, NKB1, AMB11,
KIR3DS1
AIDS, rapid progression to, 609423 (3) IFNG
AIDS, resistance to (3) CXCL12, SDF1
Alagille syndrome, 118450 (3) JAG1, AGS, AHD
Albinism, brown oculocutaneous, (3) OCA2, P, PED, D15S12, BOCA
Albinism, ocular, autosomal recessive (3) OCA2, P, PED, D15S12, BOCA
Albinism, oculocutaneous, type IA, 203100 TYR
(3)
Albinism, oculocutaneous, type IB, 606952 TYR
(3)
Albinism, oculocutaneous, type II (3) OCA2, P, PED, D15S12, BOCA
Albinism, rufous, 278400 (3) TYRP1, CAS2, GP75
Alcohol dependence, susceptibility to, HTR2A
103780 (3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Alcohol intolerance, acute (3) ALDH2
Alcoholism, susceptibility to, 103780 (3) GABRA2
Aldolase A deficiency (3) ALDOA
Aldosterone to renin ratio raised (3) CYP1 1 B2
Aldosteronism, glucocorticoid-remediable, CYP11B1, P450C11, FHI
103900 (3)
Alexander disease, 203450 (3) GFAP
Alexander disease, 203450 (3) NDUFV1, UQOR1
Alkaptonuria, 203500 (3) HGD, AKU
Allan-Herndon-Dudley syndrome, 300523 SLC16A2, DXS128, XPCT
(3)
Allergic rhinitis, susceptibility to, 607154 (3) IL13, ALRH
Alopecia universalis, 203655 (3) HR, AU
Alpers syndrome, 203700 (3) POLG, POLG1, POLGA, PEO
Alpha-l-antichymotrypsin deficiency (3) SERPINA3, AACT, ACT
Alpha-actinin-3 deficiency (3) ACTN3
Alpha-methylacetoacetic aciduria, 203750 ACAT1
(3)
Alpha-methylacyl-CoA racemase deficiency AMACR
(3)
Alpha-thalassemia/mental retardation ATRX, XH2, XNP, MRXS3, SHS
syndrome, 301040 (3)
Alpha-thalassemia myelodysplasia ATRX, XH2, XNP, MRXS3, SHS
syndrome, somatic, 300448 (3)
Alport syndrome, 301050 (3) COL4A5, ATS, ASLN
Alport syndrome, autosomal recessive, COL4A3
203780 (3)
Alport syndrome, autosomal recessive, COL4A4
203780 (3)
Alstrom syndrome, 203800 (3) ALMS1, ALSS, KIAA0328
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Alternating hemiplegia of childhood, 104290 ATP1A2, FHM2, MHP2
(3)
Alveolar soft-part sarcoma, 606243 (3) ASPCR1, RCC17, ASPL, ASPS
Alzheimer disease-1, APP-related (3) APP, AAA, CVAP, AD1
Alzheimer disease-2, 104310 (3) APOE, AD2
Alzheimer disease-4, 606889 (3) PSEN2, AD4, STM2
Alzheimer disease, late-onset, 104300 (3) APBB2, FE65L1
Alzheimer disease, late-onset, susceptibility NOS3
to, 104300 (3)
Alzheimer disease, late-onset, susceptibility PLAU, URK
to, 104300 (3)
Alzheimer disease, susceptibility to, 104300 ACE, DCP1, ACE1
(3)
Alzheimer disease, susceptibility to, 104300 MPO
(3)
Alzheimer disease, susceptibility to, 104300 PACIP1, PAXIPI L, PTIP
(3)
Alzheimer disease, susceptibility to (3) A2M
Alzheimer disease, susceptibility to (3) BLMH, BMH
Alzheimer disease, type 3, 607822 (3) PSEN1, AD3
Alzheimer disease, type 3, with spastic PSEN1, AD3
paraparesis and apraxia, 607822 (3)
Alzheimer disease, type 3, with spastic PSEN1, AD3
paraparesis and unusual plaques, 607822
(3)
Amelogenesis imperfecta 2, hypoplastic ENAM
local, 104500 (3)
Amelogenesis imperfecta, 301200 (3) AMELX, AMG, AIH1, AMGX
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Amelogenesis imperfecta, hypomaturation- DLX3, TDO
hypoplastic type, with taurodontism, 104510
(3)
Amelogenesis imperfecta, hypoplastic, and ENAM
openbite malocclusion, 608563 (3)
Amelogenesis imperfecta, pigmented KLK4, EMSP1, PRSS17
hypomaturation type, 204700 (3)
Amish infantile epilepsy syndrome, 609056 SIAT9, ST3GALV
(3)
AMP deaminase deficiency, erythrocytic (3) AMPD3
Amyloid neuropathy, familial, several allelic TTR, PALB
types (3)
Amyloidosis, 3 or more types (3) APOA1
Amyloidosis, cerebroarterial, Dutch type (3) APP, AAA, CVAP, AD1
Amyloidosis, Finnish type, 105120 (3) GSN
Amyloidosis, hereditary renal, 105200 (3) FGA
Amyloidosis, renal, 105200 (3) LYZ
Amyloidosis, senile systemic (3) TTR, PALB
Amyotrophic lateral sclerosis 8, 608627 (3) VAPB, VAPC, ALS8
Amyotrophic lateral sclerosis, due to SOD1 SOD1, ALS1
deficiency, 105400 (3)
Amyotrophic lateral sclerosis, juvenile, ALS2, ALSJ, PLSJ, IAHSP
205100 (3)
Amyotrophic lateral sclerosis, susceptibility DCTN1
to, 105400 (3)
Amyotrophic lateral sclerosis, susceptibility NEFH
to, 105400 (3)
Amyotrophic lateral sclerosis, susceptibility PRPH
to, 105400 (3)
Analbuminemia (3) ALB
47
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Analgesia from kappa-opioid receptor MC1 R
agonist, female-specific (3)
Anderson disease, 607689 (3) SARA2, SARI B, CMRD
Androgen insensitivity, 300068 (3) AR, DHTR, TFM, SBMA, KD, SMAX1
Anemia, congenital dyserythropoietic, type I, CDAN1, CDA1
224120 (3)
Anemia, Diamond-Blackfan, 105650 (3) RPS19, DBA
Anemia, hemolytic, due to PK deficiency (3) PKLR, PK1
Anemia, hemolytic, due to UMPH1 NT5C3, UMPH1, PSN1
deficiency, 266120 (3)
Anemia, hemolytic, Rh-null, regulator type, RHAG, RH50A
268150 (3)
Anemia, hypochromic microcytic, 206100 NRAMP2
(3)
Anemia, neonatal hemolytic, fatal and near- SPTB
fatal (3)
Anemia, sideroblastic/hypochromic (3) ALAS2, ANH1, ASB
Anemia, sideroblastic, with ataxia, 301310 ABCB7, ABC7, ASAT
(3)
Aneurysm, familial arterial (3) COL3A1
Angelman syndrome, 105830 (3) MECP2, RTT, PPMX, MRX16, MRX79
Angelman syndrome, 105830 (3) UBE3A, ANCR
Angioedema, hereditary, 106100 (3) C1NH, HAE1, HAE2, SERPING1
Angioedema induced by ACE inhibitors, XPNPEP2
susceptibility to (3)
Angiofibroma, sporadic (3) MEN1
Angiotensin I-converting enzyme, benign ACE, DCP1, ACE1
serum increase (3)
Anhaptoglobinemia (3) HP
Aniridia, type 11, 106210 (3) PAX6, AN2, MGDA
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Ankylosing spoldylitis, susceptibility to, HLA-B
106300 (3)
Anophthalmia 3, 206900 (3) SOX2, ANOP3
Anorexia nervosa, susceptibility to, 606788 HTR2A
(3)
Anterior segment anomalies and cataract EYA1, BOR
(3)
Anterior segment mesenchymal dysgenesis, FOXE3, FKHL12, ASMD
107250 (3)
Anterior segment mesenchymal dysgenesis FOXC1, FKHL7, FREAC3
(3)
Anterior segment mesenchymal dysgenesis PITX3
and cataract, 107250 (3)
Antithrombin III deficiency (3) AT3
Antley-Bixler syndrome, 207410 (3) POR
Anxiety-related personality traits (3) SLC6A4, HTT, OCD1
Aortic aneurysm, ascending, and dissection FBN1, MFS1, WMS
(3)
Apert syndrome, 101200 (3) FGFR2, BEK, CFD1, JWS
Aplasia of lacrimal and salivary glands, FGF10
180920 (3)
Aplastic anemia, 609135 (3) IFNG
Aplastic anemia, 609135 (3) TERC, TRC3, TR
Aplastic anemia, susceptibility to, 609135 TERT, TCS1, EST2
(3)
Apnea, postanesthetic (3) BCHE, CHE1
ApoA-I and apoC-III deficiency, combined APOA1
(3)
Apolipoprotein A-II deficiency (3) APOA2
Apolipoprotein C3 deficiency (3) APOC3
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Apolipoprotein H deficiency (3) APOH
Apparent mineralocorticoid excess, HSD11132, HSD1 1 K
hypertension due to (3)
Aquaporin-1 deficiency (3) AQP1, CHIP28, CO
ARC syndrome, 208085 (3) VPS33B
Argininemia, 207800 (3) ARG1
Argininosuccinic aciduria, 207900 (3) ASL
Aromatase deficiency (3) CYP19A1, CYP19, ARO
Aromatic L-amino acid decarboxylase DDC
deficiency, 608643 (3)
Arrhythmogenic right ventricular dysplasia 2, RYR2, VTSIP
600996 (3)
Arrhythmogenic right ventricular dysplasia 8, DSP, KPPS2, PPKS2
607450 (3)
Arrhythmogenic right ventricular dysplasia, PKP2, ARVD9
familial, 9, 609040 (3)
Arthrogryposis multiplex congenita, distal, TPM2, TMSB, AMCD1, DA1
type 1, 108120 (3)
Arthrogryposis multiplex congenita, distal, TNN12, AMCD2B, DA2B, FSSV
type 2B, 601680 (3)
Arthropathy, progressive WISP3, PPAC, PPD
pseudorheumatoid, of childhood, 208230 (3)
Arthyrgryposis multiplex congenita, distal, TNNT3, AMCD2B, DA2B, FSSV
type 2B, 601680 (3)
Aspartylglucosaminuria (3) AGA
Asperger syndrome, 300494 (3) NLGN3
Asperger syndrome, 300497 (3) NLGN4, KIAA1260, AUTSX2
Asthma, 600807 (3) PHF11, NYREN34
Asthma, atopic, susceptibility to (3) MS4A2, FCER1 B
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Asthma, dimished response to ALOX5
antileukotriene treatment in, 600807 (3)
Asthma, nocturnal, susceptibility to (3) ADRB2
Asthma, susceptibility to, 1, 607277 (3) PTGDR, AS1
Asthma, susceptibility to, 2, 608584 (3) GPR154, GPRA, VRR1, PGR14
Asthma, susceptibility to (3) HNMT
Asthma, susceptibility to, 600807 (3) IL12B, NKSF2
Asthma, susceptibility to, 600807 (3) IL13, ALRH
Asthma, susceptibility to, 600807 (3) PLA2G7, PAFAH
Asthma, susceptibility to, 600807 (3) SCGB3A2, UGRP1
Asthma, susceptibility to, 600807 (3) TNF, TNFA
Asthma, susceptibility to, 600807 (3) UGB, CC10, CCSP, SCGB1A1
Ataxia, cerebellar, Cayman type, 601238 (3) ATCAY, CLAC, KIAA1872
Ataxia, early-onset, with oculomotor apraxia APTX, AOA, AOA1
and hypoalbuminemia, 208920 (3)
Ataxia, episodic (3) CACNB4, EJM
Ataxia-ocular apraxia-2, 606002 (3) SETX, SCAR1, AOA2
Ataxia-telangiectasia, 208900 (3) ATM, ATA, AT1
Ataxia-telangiectasia-like disorder, 604391 MRE1 1A, MRE1 1, ATLD
(3)
Ataxia with isolated vitamin E deficiency, TTPA, TTP1, AVED
277460 (3)
Atelosteogenesis II, 256050 (3) SLC26A2, DTD, DTDST, D5S1708,
EDM4
Atelostogenesis, type I, 108720 (3) FLNB, SCT, AOI
Athabaskan brainstem dysgenesis HOXA1, HOX1F, BSAS
syndrome, 601536 (3)
Atherosclerosis, susceptibility to (3) ALOX5
Atopy, 147050 (3) SPINK5, LEKTI
Atopy, resistance to, 147050 (3) HAVCR1, HAVCR
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Atopy, susceptibility to, 147050 (3) PLA2G7, PAFAH
Atopy, susceptibility to, 147050 (3) SELP, GRMP
Atopy, susceptibility to (3) IL4R, IL4RA
Atransferrinemia, 209300 (3) TF
Atrial fibrillation, familial, 607554 (3) KCNE2, MIRP1, LQT6
Atrial fibrillation, familial, 607554 (3) KCNQ1, KCNA9, LQT1, KVLQT1,
ATFB1
Atrial septal defect-2, 607941 (3) GATA4
Atrial septal defect 3 (3) MYH6, ASD3, MYHCA
Atrial septal defect with atrioventricular NKX2E, CSX
conduction defects, 108900 (3)
Atrichia with papular lesions, 209500 (3) HR, AU
Atrioventricular block, idiopathic second- NKX2E, CSX
degree (3)
Atrioventricular septal defect, 600309 (3) GJA1, CX43, ODDD, SDTY3, ODOD
Atrioventricular septal defect, partial, with CRELD1, AVSD2
heterotaxy syndrome, 606217 (3)
Atrioventricular septal defect, susceptibility CRELD1, AVSD2
to, 2, 606217 (3)
Attention deficit-hyperactivity disorder, DRD5, DRD1 B, DRD1 L2
susceptibility to, 143465 (3)
Autism, susceptibility to, 209850 (3) GLO1
Autism, X-linked, 300425 (3) MECP2, RTT, PPMX, MRX16, MRX79
Autism, X-linked, 300425 (3) NLGN3
Autism, X-linked, 300495 (3) NLGN4, KIAA1260, AUTSX2
Autoimmune lymphoproliferative syndrome, TNFRSF6, APT1, FAS, CD95, ALPS1A
601859 (3)
Autoimmune lymphoproliferative syndrome, TNFRSF6, APT1, FAS, CD95, ALPS1A
type IA, 601859 (3)
52
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Autoimmune lymphoproliferative syndrome, CASP10, MCH4, ALPS2
type II, 603909 (3)
Autoimmune lymphoproliferative syndrome, CASP8, MCH5
type 1113, 607271 (3)
Autoimmune polyglandular disease, type I, AIRE, APECED
240300 (3)
Autoimmune thyroid disease, susceptibility TG, AITD3
to 3, 608175 (3)
Autonomic nervous system dysfunction (3) DRD4
Axenfeld anomaly (3) FOXC1, FKHL7, FREAC3
Azoospermia (3) USP9Y, DFFRY
Azoospermia due to perturbations of SYCP3, SCP3, COR1
meiosis, 270960 (3)
Bamforth-Lazarus syndrome, 241850 (3) FOXE1, FKHL15, TITF2, TTF2
Bannayan-Riley-Ruvalcaba syndrome, PTEN, MMAC1
153480 (3)
Bannayan-Zonana syndrome, 153480 (3) PTEN, MMAC1
Bardet-Biedl syndrome 1, 209900 (3) BBS1
Bardet-Biedl syndrome 1, modifier of, ARL6, BBS3
209900 (3)
Bardet-Biedl syndrome, 209900 (3) BBS7
Bardet-Biedl syndrome 2, 209900 (3) BBS2
Bardet-Biedl syndrome 3, 600151 (3) ARL6, BBS3
Bardet-Biedl syndrome 4, 209900 (3) BBS4
Bardet-Biedl syndrome 5, 209900 (3) BBS5
Bardet-Biedl syndrome 6, 209900 (3) MKKS, HMCS, KMS, MKS, BBS6
Bardet-Biedl syndrome 8, 209900 (3) TTC8, BBS8
Bare lymphocyte syndrome, type I, 604571 TAPBP, TPSN
(3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Bare lymphocyte syndrome, type I, due to TAP2, ABCB3, PSF2, RING1 1
TAP2 deficiency, 604571 (3)
Bare lymphocyte syndrome, type II, MHC2TA, C2TA
complementation group A, 209920 (3)
Bare lymphocyte syndrome, type II, RFX5
complementation group C, 209920 (3)
Bare lymphocyte syndrome, type II, RFXAP
complementation group D, 209920 (3)
Bare lymphocyte syndrome, type II, RFX5
complementation group E, 209920 (3)
Barth syndrome, 302060 (3) TAZ, EFE2, BTHS, CMD3A, LVNCX
Bart-Pumphrey syndrome, 149200 (3) GJB2, CX26, DFNB1, PPK, DFNA3,
KID, HID
Bartter syndrome, type 1, 601678 (3) SLC12A1, NKCC2
Bartter syndrome, type 2, 241200 (3) KCNJ1, ROMK1
Bartter syndrome, type 3, 607364 (3) CLCNKB
Bartter syndrome, type 4, 602522 (3) BSND
Bartter syndrome, type 4, digenic, 602522 CLCNKA
(3)
Bartter syndrome, type 4, digenic, 602522 CLCNKB
(3)
Basal cell carcinoma (3) RASA1, GAP, CMAVM, PKWS
Basal cell carcinoma, somatic, 605462 (3) PTCH2
Basal cell carcinoma, somatic, 605462 (3) PTCH, NBCCS, BCNS, HPE7
Basal cell carcinoma, sporadic (3) SMOH, SMO
Basal cell nevus syndrome, 109400 (3) PTCH, NBCCS, BCNS, HPE7
Basal ganglia disease, adult-onset, 606159 FTL
(3)
Basal ganglia disease, biotin-responsive, SLC19A3
607483 (3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
B-cell non-Hodgkin lymphoma, high-grade BCL7A, BCL7
(3)
BCG infection, generalized familial (3) IFNGR1
Beare-Stevenson cutis gyrata syndrome, FGFR2, BEK, CFD1, JWS
123790 (3)
Becker muscular dystrophy, 300376 (3) DMD, BMD
Becker muscular dystrophy modifier, MYF6
310200 (3)
Beckwith-Wiedemann syndrome, 130650 CDKNIC, KIP2, BWS
(3)
Beckwith-Wiedemann syndrome, 130650 H19, D11S813E, ASM1, BWS
(3)
Beckwith-Wiedemann syndrome, 130650 KCNQ1 OT1, LIT1
(3)
Beckwith-Wiedemann syndrome, 130650 NSD1, ARA267, STO
(3)
Benzene toxicity, susceptibility to (3) NQO1, DIA4, NMOR1
Bernard-Soulier syndrome, 231200 (3) GP1 BA
Bernard-Soulier syndrome, type B, 231200 GP1 BB
(3)
Bernard-Soulier syndrome, type C (3) GP9
Beryllium disease, chronic, susceptibility to HLA-DPB1
(3)
Beta-2-adrenoreceptor agonist, reduced ADRB2
response to (3)
Beta-u reidopropionase deficiency (3) UPB1, BUP1
Bethlem myopathy, 158810 (3) COL6A1, OPLL
Bethlem myopathy, 158810 (3) COL6A2
Bethlem myopathy, 158810 (3) COL6A3
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Bietti crystalline corneoretinal dystrophy, CYP4V2, BCD
210370 (3)
Bile acid malabsorption, primary (3) SLC10A2, NTCP2
Biotinidase deficiency, 253260 (3) BTD
Bipolar disorder, susceptibility to, 125480 XBP1, XBP2
(3)
Birt-Hogg-Dube syndrome, 135150 (3) FLCN, BHD
Bladder cancer, 109800 (3) FGFR3, ACH
Bladder cancer, 109800 (3) KRAS2, RASK2
Bladder cancer, 109800 (3) RB1
Bladder cancer, somatic, 109800 (3) HRAS
Blau syndrome, 186580 (3) CARD15, NOD2, IBD1, CD, ACUG,
PSORAS1
Bleeding disorder due to defective TBXA2R
thromboxane A2 receptor (3)
Bleeding due to platelet ADP receptor P2RX1, P2X1
defect, 600515 (3)
Blepharophimosis, epicanthus inversus, and FOXL2, BPES, BPES1, PFRK, POF3
ptosis, type 1, 110100 (3)
Blepharophimosis, epicanthus inversus, and FOXL2, BPES, BPES1, PFRK, POF3
ptosis, type 2, 110100 (3)
Blepharospasm, primary benign, 606798 (3) DRD5, DRD1 B, DRD1 L2
Blood group, ABO system (3) ABO
Blood group, Auberger system (3) LU, AU, BCAM
Blood group, Colton, 110450 (3) AQP1, CHIP28, CO
Blood group Cromer (3) DAF
Blood group, Diego, 110500 (3) SLC4A1, AE1, EPB3
Blood group, Dombrock (3) ART4, DO
Blood group, Gerbich (3) GYPC, GE, GPC
Blood group GIL, 607457 (3) AQP3
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Blood group, Ii, 110800 (3) GCNT2
Blood group, Indian system (3) CD44, MDU2, MDU3, MIC4
Blood group, Kell (3) KEL
Blood group, Kidd (3) SLC14A1, JK, UTE, UT1
Blood group, Knops system, 607486 (3) CR1, C3BR
Blood group, Landsteiner-Wiener (3) LW
Blood group, Lewis (3) FUT3, LE
Blood group, Lutheran system (3) LU, AU, BCAM
Blood group, MN (3) GYPA, MN, GPA
Blood group, OK, 111380 (3) BSG
Blood group, P system, 111400 (3) A4GALT, PK
Blood group, P system, 111400 (3) B3GALT3, GLCT3, P
Blood group, Rhesus (3) RHCE
Blood group, Ss (3) GYPB, SS, MNS
Blood group, Waldner, 112010 (3) SLC4A1, AE1, EPB3
Blood group, Wright, 112050 (3) SLC4A1, AE1, EPB3
Blood group, XG system (3) XG
Blood group, Yt system, 112100 (3) ACHE, YT
Bloom syndrome, 210900 (3) RECQL3, RECQ2, BLM, BS
Blue-cone monochromacy, 303700 (3) OPN1LW, RCP, CBP, CBBM
Blue-cone monochromacy, 303700 (3) OPN1MW, GCP, CBD, CBBM
Bombay phenotype (3) FUT1, H, HH
Bombay phenotype (3) FUT2, SE
Bone mineral density variability 1, 601884 LRP5, BMND1, LRP7, LR3, OPPG,
(3) VBCH2
Borjeson-Forssman-Lehmann syndrome, PHF6, BFLS
301900 (3)
Bosley-Salih-Alorainy syndrome, 601536 (3) HOXA1, HOX1F, BSAS
Bothnia retinal dystrophy, 607475 (3) RLBP1
Brachydactyly, type Al, 112500 (3) IHH, BDA1
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Brachydactyly, type A2, 112600 (3) BMPR1 B, ALK6
Brachydactyly, type B1, 113000 (3) ROR2, BDB1, BDB, NTRKR2
Brachydactyly, type C, 113100 (3) GDF5, CDMP1
Brachydactyly, type D, 113200 (3) HOXD13, HOX41, SPD
Brachydactyly, type E, 113300 (3) HOXD13, HOX41, SPD
Bradyopsia, 608415 (3) R9AP, RGS9, PERRS
Bradyopsia, 608415 (3) RGS9, PERRS
Branchiootic syndrome (3) EYA1, BOR
Branchiootorenal syndrome, 113650 (3) EYA1, BOR
Branchiootorenal syndrome with cataract, EYA1, BOR
113650 (3)
Breast and colorectal cancer, susceptibility CHEK2, RAD53, CHK2, CDS1, LFS2
to (3)
Breast cancer, 114480 (3) PIK3CA
Breast cancer, 114480 (3) PPM1 D, WIP1
Breast cancer, 114480 (3) SLC22A1L, BWSCR1A, IMPT1
Breast cancer, 114480 (3) TP53, P53, LFS1
Breast cancer-1 (3) BRCA1, PSCP
Breast cancer 2, early onset (3) BRCA2, FANCD1
Breast cancer (3) TSG101
Breast cancer, early-onset, 114480 (3) BRIP1, BACH1, FANCJ
Breast cancer, invasive intraductal (3) RAD54L, HR54, HRAD54
Breast cancer, lobular (3) CDH1, UVO
Breast cancer, male, susceptibility to, BRCA2, FANCD1
114480 (3)
Breast cancer, male, with Reifenstein AR, DHTR, TFM, SBMA, KD, SMAX1
syndrome (3)
Breast cancer, somatic, 114480 (3) KRAS2, RASK2
Breast cancer, somatic, 114480 (3) RB1CC1, CC1, KIAA0203
Breast cancer, sporadic (3) PHB
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Breast cancer, susceptibility to, 114480 (3) ATM, ATA, AT1
Breast cancer, susceptibility to, 114480 (3) BARD 1
Breast cancer, susceptibility to, 114480 (3) CHEK2, RAD53, CHK2, CDS1, LFS2
Breast cancer, susceptibility to, 114480 (3) RAD51A, RECA
Breast cancer, susceptibility to (3) XRCC3
Breast-ovarian cancer (3) BRCA1, PSCP
Brody myopathy, 601003 (3) ATP2A1, SERCA1
Bruck syndrome 2, 609220 (3) PLOD2
Brugada syndrome, 601144 (3) SCN5A, LQT3, IVF, HB1, SSS1
Brunner syndrome (3) MAOA
Burkitt lymphoma, 113970 (3) MYC
Buschke-Ollendorff syndrome, 166700 (3) LEMD3, MAN1
Butterfly dystrophy, retinal, 169150 (3) RDS, RP7, PRPH2, PRPH, AVMD,
AOFMD
C 1 q deficiency, type A (3) C1QA
Clq deficiency, type B (3) C1QB
Clq deficiency, type C (3) C1QG
Cis deficiency, isolated (3) C1S
C2 deficiency (3) C2
C3b inactivator deficiency (3) IF
C3 deficiency (3) C3
C4 deficiency (3) C4A, C4S
C4 deficiency (3) C4B, C4F
C6 deficiency (3) C6
C7 deficiency (3) C7
C8 deficiency, type II (3) C8B
C9 deficiency (3) C9
C9 deficiency with dermatomyositis (3) C9
Cafe-au-lait spots, multiple, with leukemia, MSH2, COCA1, FCC1, HNPCC1
114030 (3)
59
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Cafe-au-lait spots with glioma or leukemia, MLH1, COCA2, HNPCC2
114030 (3)
Caffey disease, 114000 (3) COL1A1
Calcinosis, tumoral, 211900 (3) FGF23, ADHR, HPDR2, PHPTC
Calcinosis, tumoral, 211900 (3) GALNT3
Campomelic dysplasia, 114290 (3) SOX9, CMD1, SRA1
Campomelic dysplasia with autosomal sex SOX9, CMD1, SRA1
reversal, 114290 (3)
Cam ptod actyly-a rth ro path y-coxa vara- PRG4, CACP, MSF, SZP, HAPO
pericarditis syndrome, 208250 (3)
Camurati-Engelmann disease, 131300 (3) TGFB1, DPD1, CED
Canavan disease, 271900 (3) ASPA
Cancer progression/metastasis (3) FGFR4
Cancer susceptibility (3) MSH6, GTBP, HNPCC5
Capillary malformation-arteriovenous RASA1, GAP, CMAVM, PKWS
malformation, 608354 (3)
Carbamoylphosphate synthetase I CPS1
deficiency, 237300 (3)
Carbohydrate-deficient glycoprotein PMM2, CDG1
syndrome, type I, 212065 (3)
Carbohydrate-deficient glycoprotein MPI, PM11
syndrome, type Ib, 602579 (3)
Carbohydrate-deficient glycoprotein MGAT2, CDGS2
syndrome, type 11, 212066 (3)
Carboxypeptidase N deficiency, 212070 (3) CPN1, SCPN, CPN
Carcinoid tumor of lung (3) MEN1
Carcinoid tumors, intestinal, 114900 (3) SDHD, PGL1
Cardioencephalomyopathy, fatal infantile, SC02
due to cytochrome c oxidase deficiency,
604377 (3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Cardiomyopathy, Familial hypertrophic, 8, MYL3, CMH8
608751 (3)
Cardiomyopathy, dilated, 115200 (3) ACTC
Cardiomyopathy, dilated, 115200 (3) MYH7, CMH1, MPD1
Cardiomyopathy, dilated, 1A, 115200 (3) LMNA, LMN1, EMD2, FPLD, CMD1A,
HGPS, LGMD1 B
Cardiomyopathy, dilated, 1 D, 601494 (3) TNNT2, CMH2, CMD1D
Cardiomyopathy, dilated, 1G, 604145 (3), TTN, CMD1G, TMD, LGMD2J
Tibial muscular dystrophy, tardive, 600334
(3)
Cardiomyopathy, dilated, 11, 604765 (3) DES, CMD11
Cardiomyopathy, dilated, 1J,605362(3) EYA4, DFNA10, CMD1J
Cardiomyopathy, dilated, 1L,606685(3) SGCD, SGD, LGMD2F, CMD1 L
Cardiomyopathy, dilated, 1 M, 607482 (3) CSRP3, CRP3, CLP, CMD1M
Cardiomyopathy, dilated, 1N,607487(3) TCAP, LGMD2G, CMD1N
Cardiomyopathy, dilated, with ventricular ABCC9, SUR2
tachycardia, 608569 (3)
Cardiomyopathy, dilated, X-linked, 302045 DMD, BMD
(3)
Cardiomyopathy, familial hypertrophic, 10, MYL2, CMH10
608758 (3)
Cardiomyopathy, familial hypertrophic, 1, MYH7, CMH1, MPD1
192600 (3)
Cardiomyopathy, familial hypertrophic, ACTC
192600 (3)
Cardiomyopathy, familial hypertrophic, CAV3, LGMD1C
192600 (3)
Cardiomyopathy, familial hypertrophic, MYH6, ASD3, MYHCA
192600 (3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Cardiomyopathy, familial hypertrophic, TNNC1
192600 (3) ()
Cardiomyopathy, familial hypertrophic, 2, TNNT2, CMH2, CMD1 D
115195 (3)
Cardiomyopathy, familial hypertrophic, 3, TPM1, CMH3
115196 (3)
Cardiomyopathy, familial hypertrophic (3) TNN13
Cardiomyopathy, familial hypertrophic, 4, MYBPC3, CMH4
115197 (3)
Cardiomyopathy, familial hypertrophic, 9 (3) TTN, CMD1G, TMD, LGMD2J
Cardiomyopathy, familial restrictive, 115210 TNN13
(3)
Cardiomyopathy, hypertrophic, early-onset COX1 5
fatal (3)
Cardiomyopathy, hypertrophic, mid-left MYL2, CMH10
ventricular chamber type, 608758 (3)
Cardiomyopathy, hypertrophic, MYLK2, MLCK
midventricular, digenic, 192600 (3)
Cardiomyopathy, hypertrophic, with WPW, PRKAG2, WPWS
600858 (3)
Cardiomyopathy, idiopathic dilated, 115200 PLN, PLB
(3)
Cardiomyopathy, X-linked dilated, 300069 TAZ, EFE2, BTHS, CMD3A, LVNCX
(3)
Carney complex, type 1, 160980 (3) PRKAR1A, TSE1, CNC1, CAR
Carney complex variant, 608837 (3) MYH8
Carnitine-acylcarnitine translocase SLC25A20, CACT, CAC
deficiency (3)
Carnitine deficiency, systemic primary, SLC22A5, OCTN2, CDSP, SCD
212140 (3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Carpal tunnel syndrome, familial (3) TTR, PALB
Cartilage-hair hypoplasia, 250250 (3) RMRP, RMRPR, CHH
Cataract, autosomal dominant nuclear (3) CRYAA, CRYA1
Cataract, cerulean, type 2, 601547 (3) CRYBB2, CRYB2
Cataract, congenital (3) PITX3
Cataract, congenital, 604219 (3) BFSP2, CP49, CP47
Cataract, congenital progressive, autosomal CRYAA, CRYA1
recessive (3)
Cataract, congenital, with late-onset corneal PAX6, AN2, MGDA
dystrophy (3)
Cataract, congenital zonular, with sutural CRYBA1, CRYB1
opacities, 600881 (3)
Cataract, Coppock-like, 604307 (3) CRYGC, CRYG3, CCL
Cataract, cortical pulverulent, late-onset (3) LIM2, MP19
Cataract, crystalline aculeiform, 115700 (3) CRYGD, CRYG4
Cataract, juvenile-onset, 604219 (3) BFSP2, CP49, CP47
Cataract, lamellar, 116800 (3) HSF4, CTM
Cataract, Marner type, 116800 (3) HSF4, CTM
Cataract, polymorphic and lamellar, 604219 MIP, AQPO
(3)
Cataract, posterior polar 2 (3) CRYAB, CRYA2, CTPP2
Cataract, pulverulent (3) CRYBB1
Cataracts, punctate, progressive juvenile- CRYGD, CRYG4
onset (3)
Cataract, sutural, with punctate and CRYBB2, CRYB2
cerulean opacities, 607133 (3)
Cataract, variable zonular pulverulent (3) CRYGC, CRYG3, CCL
Cataract, zonular central nuclear, autosomal CRYAA, CRYA1
dominant (3)
Cataract, zonular pulverulent-1, 116200 (3) GJA8, CX50, CAE1
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Cataract, zonular pulverulent-3, 601885 (3) GJA3, CX46, CZP3, CAE3
Cavernous malformations of CNS and CCM1, CAM, KRIT1
retina, 116860 (3)
CD59 deficiency (3) CD59, MIC1 1
CD8 deficiency, familial, 608957 (3) CD8A
Central core disease, 117000 (3) RYR1, MHS, CCO
Central core disease, one form (3) () MYH7, CMH1, MPD1
Central hypoventilation syndrome, 209880 GDNF
(3)
Central hypoventilation syndrome, BDNF
congenital, 209880 (3)
Central hypoventilation syndrome, EDN3
congenital, 209880 (3)
Central hypoventilation syndrome, PMX2B, NBPHOX, PHOX2B
congenital, 209880 (3)
Central hypoventilation syndrome, RET, MEN2A
congenital, 209880 (3)
Cerebellar ataxia, 604290 (3) CP
Cerebellar ataxia, pure (3) CACNA1A, CACNL1A4, SCA6
Cerebellar hypoplasia, VLDLR-associated, VLDLR, VLDLRCH
224050 (3)
Cerebral amyloid angiopathy, 105150 (3) ABCA1, ABC1, HDLDT1, TGD
Cerebral amyloid angiopathy, 105150 (3) CST3
Cerebral arteriopathy with subcortical NOTCH3, CADASIL, CASIL
infarcts and leukoencephalopathy, 125310
(3)
Cerebral cavernous malformations-1, CCM1, CAM, KRIT1
116860 (3)
Cerebral cavernous malformations-2, C7orf22, CCM2, MGC4067
603284 (3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Cerebral cavernous malformations 3, PDCD10, TFAR15, CCM3
603285 (3)
Cerebral dysgenesis, neuropathy, SNAP29, CEDNIK
ichthyosis, and palmoplantar keratoderma
syndrome, 609528 (3)
Cerebrooculofacioskeletal syndrome, ERCC2, EM9
214150 (3)
Cerebrooculofacioskeletal syndrome, ERCC5, XPG
214150 (3)
Cerebrooculofacioskeletal syndrome ERCC6, CKN2, COFS, CSB
214150 (3)
Cerebrotendinous xanthomatosis, 213700 CYP27A1, CYP27, CTX
(3)
Cerebrovascular disease, occlusive (3) SERPINA3, AACT, ACT
Ceroid lipofuscinosis, neuronal-1, infantile, PPT1, CLN1
256730 (3)
Ceroid-lipofuscinosis, neuronal 2, classic CLN2
late infantile, 204500 (3)
Ceroid-lipofuscinosis, neuronal-3, juvenile, CLN3, BTS
204200 (3)
Ceroid-lipofuscinosis, neuronal-5, variant CLN5
late infantile, 256731 (3)
Ceroid-lipofuscinosis, neuronal-6, variant CLN6
late infantile, 601780 (3)
Ceroid lipofuscinosis, neuronal 8, 600143 CLN8, EPMR
(3)
Ceroid lipofuscinosis, neuronal, variant PPT1, CLN1
juvenile type, with granular osmiophilic
deposits (3)
Cervical cancer, somatic, 603956 (3) FGFR3, ACH
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
CETP deficiency, 607322 (3) CETP
Chanarin-Dorfman syndrome, 275630 (3) ABHD5, CG158, IECN2, NCIE2
Charcot-Marie-Tooth disease, axonal, type HSPB1, HSP27, CMT2F
2F,606595(3)
Charcot-Marie-Tooth disease, dominant MPZ, CMT1 B, CMTD13, CHM, DSS
intermediate 3, 607791 (3)
Charcot-Marie-Tooth disease, dominant DNM2
intermediate B, 606482 (3)
Charcot-Marie-Tooth disease, foot deformity HOXD10, HOX4D
of (3)
Charcot-Marie-Tooth disease, mixed axonal GDAP1, CMT4A, CMT2K, CMT2G
and demyelinating type, 214400 (3)
Charcot-Marie-Tooth disease, type 1A, PMP22, CMT1A, CMT1 E, DSS
118220 (3)
Charcot-Marie-Tooth disease, type 1 B, MPZ, CMT1 B, CMTD13, CHM, DSS
118200 (3)
Charcot-Marie-Tooth disease, type 1C, LITAF, CMT1 C
601098 (3)
Charcot-Marie-Tooth disease, type 1 D, EGR2, KROX20
607678 (3)
Charcot-Marie-Tooth disease, type 1 E, PMP22, CMT1A, CMT1 E, DSS
118300 (3)
Charcot-Marie-Tooth disease, type 1 F, NEFL, CMT2E, CMT1 F
607734 (3)
Charcot-Marie-Tooth disease, type 2A1, KIF1 B, CMT2A, CMT2A1
118210 (3)
Charcot-Marie-Tooth disease, type 2A2, MFN2, KIAA0214, CMT2A2
609260 (3)
Charcot-Marie-Tooth disease, type 2B, RAB7, CMT2B, PSN
600882 (3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Charcot-Marie-Tooth disease, type 2D, GARS, SMAD1, CMT2D
601472 (3)
Charcot-Marie-Tooth disease, type 2E, NEFL, CMT2E, CMT1 F
607684 (3)
Charcot-Marie-Tooth disease, type 2G, GDAP1, CMT4A, CMT2K, CMT2G
607706 (3)
Charcot-Marie-Tooth disease, type 21, MPZ, CMT1 B, CMTD13, CHM, DSS
607677 (3)
Charcot-Marie-Tooth disease, type 2J, MPZ, CMT1 B, CMTD13, CHM, DSS
607736 (3)
Charcot-Marie-Tooth disease, type 2K, GDAP1, CMT4A, CMT2K, CMT2G
607831 (3)
Charcot-Marie-Tooth disease, type 4A, GDAP1, CMT4A, CMT2K, CMT2G
214400 (3)
Charcot-Marie-Tooth disease, type 4B1, MTMR2, CMT4B1
601382 (3)
Charcot-Marie-Tooth disease, type 4B2, SBF2, MTMR13, CMT4B2
604563 (3)
Charcot-Marie-Tooth disease, type 4B2, SBF2, MTMR13, CMT4B2
with early-onset glaucoma, 607739 (3)
Charcot-Marie-Tooth disease, type 4C, KIAA1985
601596 (3)
Charcot-Marie-Tooth disease, type 4D, NDRG1, HMSNL, CMT4D
601455 (3)
Charcot-Marie-Tooth neuropathy, X-linked GJB1, CX32, CMTX1
dominant, 1, 302800 (3)
CHARGE syndrome, 214800 (3) CHD7
Char syndrome, 169100 (3) TFAP2B, CHAR
Chediak-Higashi syndrome, 214500 (3) CHS1, LYST
Cherubism, 118400 (3) SH3BP2, CRPM
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
CHILD syndrome, 308050 (3) NSDHL
Chitotriosidase deficiency (3) CHIT
Chloride diarrhea, congenital, Finnish type, SLC26A3, DRA, CLD
214700 (3)
Cholelithiasis, 600803 (3) ABCB4, PGY3, MDR3
Cholestasis, benign recurrent intrahepatic, ATP8B1, FIC1, BRIC, PFIC1
243300 (3)
Cholestasis, familial intrahepatic, of ABCB4, PGY3, MDR3
pregnancy, 147480 (3)
Cholestasis, progressive familial ATP8B1, FIC1, BRIC, PFIC1
intrahepatic 1, 211600 (3)
Cholestasis, progressive familial ABCB11, BSEP, SPGP, PFIC2
intrahepatic 2, 601847 (3)
Cholestasis, progressive familial ABCB4, PGY3, MDR3
intrahepatic 3, 602347 (3)
Cholestasis, progressive familial HSD3B7, PFIC4
intrahepatic 4, 607765 (3)
Cholesteryl ester storage disease (3) LIPA
Chondrocalcinosis 2, 118600 (3) ANKH, HANK, ANK, CMDJ, CCAL2,
CPPDD
Chondrodysplasia, Grebe type, 200700 (3) GDF5, CDMP1
Chondrodysplasia punctata, rhizomelic, type GNPAT, DHAPAT
2,222765(3)
Chondrodysplasia punctata, X-linked EBP, CDPX2, CPXD, CPX
dominant, 302960 (3)
Chondrodysplasia punctata, X-linked ARSE, CDPX1, CDPXR
recessive, 302950 (3)
Chondrosarcoma, 215300 (3) EXT1
Chondrosarcoma, extraskeletal myxoid (3) CSMF
Chondrosarcoma, extraskeletal myxoid (3) EWSR1, EWS
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Chorea, hereditary benign, 118700 (3) TITF1, NKX2A, TTF1
Choreoacanthocytosis, 200150 (3) VPS13A, CHAC
Choreoathetosis, hypothyroidism, and TITF1, NKX2A, TTF1
respiratory distress (3)
Choroideremia, 303100 (3) CHM, TCD
Chromosome 22q13.3 deletion syndrome, PSAP2, PROSAP2, KIAA1650
606232 (3)
Chronic granulomatous disease, autosomal, CYBA
due to deficiency of CYBA, 233690 (3)
Chronic granulomatous disease due to NCF1
deficiency of NCF-1, 233700 (3)
Chronic granulomatous disease due to NCF2
deficiency of NCF-2, 233710 (3)
Chronic granulomatous disease, X-linked, CYBB, CGD
306400 (3)
Chronic infections, due to opsonin defect (3) MBL2, MBL, MBP1
Chudley-Lowry syndrome, 309490 (3) ATRX, XH2, XNP, MRXS3, SHS
Chylomicronemia syndrome, familial (3) LPL, LIPD
Chylomicron retention disease, 246700 (3) SARA2, SARI B, CMRD
Chylomicron retention disease with SARA2, SARI B, CMRD
Marinesco-Sjogren syndrome, 607692 (3)
Ciliary dyskinesia, primary, 1, 242650 (3) DNAI1, CILD1, ICS, PCD
Ciliary dyskinesia, primary, 3 608644 (3) DNAH5, HL1, PCD, CILD3
CINCA syndrome, 607115 (3) CIAS1, C1orf7, FCU, FCAS
Cirrhosis, cryptogenic (3) KRT18
Cirrhosis, cryptogenic (3) KRT8
Cirrhosis, noncryptogenic, susceptibility to, KRT18
215600 (3)
Cirrhosis, noncryptogenic, susceptibility to, KRT8
215600 (3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Cirrhosis, North American Indian childhood CIRHIA, NAIC, TEX292, KIAA1988
type, 604901 (3)
Citrullinemia, 215700 (3) ASS
Citrullinemia, adult-onset type II, 603471 (3) SLC25A13, CTLN2
Citrullinemia, type II, neonatal-onset, SLC25A13, CTLN2
605814 (3)
Cleft lip/palate ectodermal dysplasia HVEC, PVRL1, PVRR1, PRR1
syndrome, 225000 (3)
Cleft lip/palate, nonsyndromic, 608874 (3) MSX1, HOX7, HYD1, OFC5
Cleft palate with ankyloglossia, 303400 (3) TBX22, CPX
Cleidocranial dysplasia, 119600 (3) RUNX2, CBFA1, PEBP2A1, AML3
Coats disease, 300216 (3) NDP, ND
Cockayne syndrome, type A, 216400 (3) ERCC8, CKN1, CSA
Cockayne syndrome, type B, 133540 (3) ERCC6, CKN2, COFS, CSB
Codeine sensitivity (3) CYP2D@, CYP2D, P450C2D
Coffin-Lowry syndrome, 303600 (3) RPS6KA3, RSK2, MRX19
Cohen syndrome, 216550 (3) COH1
Colchicine resistance (3) ABCB1, PGY1, MDR1
Cold-induced autoinflammatory syndrome, CIAS1, C1orf7, FCU, FCAS
familial, 120100 (3)
Cold-induced sweating syndrome, 272430 CRLF1, CISS
(3)
Coloboma, ocular, 120200 (3) PAX6, AN2, MGDA
Coloboma, ocular, 120200 (3) SHH, HPE3, HLP3, SMMCI
Colon adenocarcinoma (3) RAD54B
Colon adenocarcinoma (3) RAD54L, HR54, HRAD54
Colon cancer (3) BCL10
Colon cancer (3) PTPN12, PTPG1
Colon cancer (3) TGFBR2, HNPCC6
Colon cancer, advanced (3) SRC, ASV, SRC1
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Colon cancer, hereditary nonpolypopsis, MLH3, HNPCC7
type 7 (3)
Colon cancer, somatic, 114500 (3) PTPRJ, DEP1
Colonic adenoma recurrence, reduced risk ODC1
of, 114500 (3)
Colonic aganglionosis, total, with small RET, MEN2A
bowel involvement (3)
Colorblindness, deutan (3) OPN1MW, GCP, CBD, CBBM
Colorblindness, protan (3) OPN1LW, RCP, CBP, CBBM
Colorblindness, tritan (3) OPN1SW, BCP, CBT
Colorectal adenomatous polyposis, MUTYH
autosomal recessive, with pilomatricomas,
132600 (3)
Colorectal cancer, 114500 (3) AXIN2
Colorectal cancer, 114500 (3) BUB1 B, BUBR1
Colorectal cancer, 114500 (3) EP300
Colorectal cancer, 114500 (3) PDGFRL, PDGRL, PRLTS
Colorectal cancer, 114500 (3) PIK3CA
Colorectal cancer, 114500 (3) TP53, P53, LFS1
Colorectal cancer (3) APC, GS, FPC
Colorectal cancer (3) BAX
Colorectal cancer (3) CTNNB1
Colorectal cancer (3) DCC
Colorectal cancer (3) MCC
Colorectal cancer (3) NRAS
Colorectal cancer, hereditary nonpolyposis, MSH2, COCA1, FCC1, HNPCC1
type 1, 120435 (3)
Colorectal cancer, hereditary nonpolyposis, MLH1, COCA2, HNPCC2
type 2, 609310 (3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Colorectal cancer, hereditary nonpolyposis, PMS1, PMSL1, HNPCC3
type 3 (3)
Colorectal cancer, hereditary nonpolyposis, PMS2, PMSL2, HNPCC4
type 4 (3)
Colorectal cancer, hereditary nonpolyposis, MSH6, GTBP, HNPCC5
type 5 (3)
Colorectal cancer, hereditary nonpolyposis, TGFBR2, HNPCC6
type 6 (3)
Colorectal cancer, somatic, 109800 (3) FGFR3, ACH
Colorectal cancer, somatic, 114500 (3) FLCN, BHD
Colorectal cancer, somatic, 114500 (3) MLH3, HNPCC7
Colorectal cancer, somatic (3) BRAF
Colorectal cancer, somatic (3) DLC1
Colorectal cancer, sporadic, 114500 (3) PLA2G2A, PLA2B, PLA2L, MOM1
Colorectal cancer, susceptibility to (3) CCND1, PRAD1, BCL1
Colorectal cancer with chromosomal BUB1
instability (3)
Combined C6/C7 deficiency (3) C6
Combined factor V and VIII deficiency, LMAN1, ERGIC53, F5F8D, MCFD1
227300 (3)
Combined hyperlipemia, familial (3) LPL, LIPD
Combined immunodeficiency, X-linked, IL2RG, SCIDX1, SCIDX, IMD4
moderate, 312863 (3)
Combined oxidative phosphorylation GFM1, EFG1, GFM
deficiency, 609060 (3)
Combined SAP deficiency (3) PSAP, SAP1
Complex I, mitochondrial respiratory chain, NDUFS6
deficiency of, 252010 (3)
Complex V, mitochondrial respiratory chain, ATPAF2, ATP12
deficiency of, 604273 (3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Cone dystrophy-1, 304020 (3) RPGR, RP3, CRD, RP15, COD1
Cone dystrophy-3, 602093 (3) GUCAIA, GCAP
Cone-rod dystrophy, 300029 (3) RPGR, RP3, CRD, RP15, COD1
Cone-rod dystrophy 3 (3) ABCA4, ABCR, STGD1, FFM, RP19
Cone-rod dystrophy (3) AIPL1, LCA4
Cone-rod dystrophy 6, 601777(3) GUCY2D, GUC2D, LCA1, CORD6
Cone-rod dystrophy 9, 608194 (3) RPGRIP1, LCA6, CORD9
Cone-rod retinal dystrophy-2, 120970 (3) CRX, CORD2, CRD
Congenital bilateral absence of vas CFTR, ABCC7, CF, MRP7
deferens, 277180 (3)
Congenital cataracts, facial dysmorphism, CTDP1, FCP1, CCFDN
and neuropathy, 604168 (3)
Congenital disorder of glycosylation, type Ic, ALG6
603147(3)
Congenital disorder of glycosylation, type Id, ALG3, NOT56L, CDGS4
601110(3)
Congenital disorder of glycosylation, type le, DPM1, MPDS, CDGIE
608799 (3)
Congenital disorder of glycosylation, type If, MPDU1, SL15, CDGIF
609180(3)
Congenital disorder of glycosylation, type Ig, ALG12
607143(3)
Congenital disorder of glycosylation, type Ih, ALG8
608104(3)
Congenital disorder of glycosylation, type Ii, ALG2, CDGII
607906 (3)
Congenital disorder of glycosylation, type II, DIBD1, ALG9
608776 (3)
Congenital disorder of glycosylation, type SLC35C1, FUCT1
Ilc, 266265 (3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Congenital disorder of glycosylation, type B4GALT1, GGTB2, GT1, GTB
Ild, 607091 (3)
Congenital disorder of glycosylation, type COG7, CDG2E
Ile, 608779 (3)
Congenital disorder of glycosylation, type Ij, DPAGT2, DGPT
608093 (3)
Congenital disorder of glycosylation, type Ik, ALG1, HMAT1, HMT1
608540 (3)
Congestive heart failure, susceptibility to (3) ADRA2C, ADRA2L2
Congestive heart failure, susceptibility to (3) ADRB1, ADRB1 R, RHR
Conjunctivitis, ligneous, 217090 (3) PLG
Conotruncal anomaly face syndrome, TBX1, DGS, CTHM, CAFS, TGA,
217095 (3) DORV, VCFS, DGCR
Contractural arachnodactyly, congenital (3) FBN2, CCA
Convulsions, familial febrile, 4, 604352 (3) MASS1, VLGR1, KIAA0686, FEB4,
USH2C
COPD, rate of decline of lung function in, MMP1, CLG
606963 (3)
Coproporphyria (3) CPO
Corneal clouding, autosomal recessive (3) APOA1
Corneal dystrophy, Avellino type, 607541 TGFBI, CSD2, CDGG1, CSD, BIGH3,
(3) CDG2
Corneal dystrophy, gelatinous drop-like, TACSTD2, TROP2, M1S1
204870 (3)
Corneal dystrophy, Groenouw type I, TGFBI, CSD2, CDGG1, CSD, BIGH3,
121900 (3) CDG2
Corneal dystrophy, hereditary polymorphous VSX1, RINX, PPCD, PPD, KTCN
posterior, 122000 (3)
Corneal dystrophy, hereditary polymorphous COL8A2, FECD, PPCD2
posterior, 2, 122000 (3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Corneal dystrophy, lattice type I, 122200 (3) TGFBI, CSD2, CDGG1, CSD, BIGH3,
CDG2
Corneal dystrophy, lattice type IIIA, 608471 TGFBI, CSD2, CDGG1, CSD, BIGH3,
(3) CDG2
Corneal dystrophy, Reis-Bucklers type, TGFBI, CSD2, CDGG1, CSD, BIGH3,
608470 (3) CDG2
Corneal dystrophy, Thiel-Behnke type, TGFBI, CSD2, CDGG1, CSD, BIGH3,
602082 (3) CDG2
Corneal fleck dystrophy, 121850 (3) PIP5K3, CFD
Cornea plana congenita, recessive, 217300 KERA, CNA2
(3)
Cornelia de Lange syndrome, 122470 (3) NIPBL, CDLS
Coronary artery disease, autosomal MEF2A, ADCAD1
dominant, 1, 608320 (3)
Coronary artery disease in familial ABCA1, ABC1, HDLDT1, TGD
hypercholesterolemia, protection against,
143890 (3)
Coronary artery disease, susceptibility to (3) KL
Coronary artery disease, susceptibility to (3) POW, PON, ESA
Coronary artery disease, susceptibility to (3) PON2
Coronary artery spasm, susceptibility to (3) PON1, PON, ESA
Coronary heart disease, susceptibility to (3) MMP3, STMY1
Coronary spasms, susceptibility to (3) NOS3
Corpus callosum, agenesis of, with mental IGBP1
retardation, ocular coloboma and
micrognathia, 300472 (3)
Cortisol resistance (3) NR3C1, GCR, GRL
Cortisone reductase deficiency, 604931 (3) GDH
Cortisone reductase deficiency, 604931 (3) HSD11B1, HSD11, HSD11L
Costello syndrome, 218040 (3) HRAS
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Coumarin resistance, 122700 (3) CYP2A6, CYP2A3, CYP2A, P450C2A
Cowden disease, 158350 (3) PTEN, MMAC1
Cowden-like syndrome, 158350 (3) BMPR1A, ACVRLK3, ALK3
CPT deficiency, hepatic, type IA, 255120 (3) CPT1A
CPT deficiency, hepatic, type II, 600649 (3) CPT2
CPT II deficiency, lethal neonatal, 608836 CPT2
(3)
Cramps, familial, potassium-aggravated (3) SCN4A, HYPP, NAC1A
Craniofacial anomalies, empty sella turcica, VSX1, RINX, PPCD, PPD, KTCN
corneal endothelial changes, and abnormal
retinal and auditory bipolar cells (3)
Craniofacial-deafness-hand syndrome, PAX3, WS1, HUP2, CDHS
122880 (3)
Craniofacial-skeletal-dermatologic dysplasia FGFR2, BEK, CFD1, JWS
(3)
Craniofrontonasal dysplasia, 304110 (3) EFNB1, EPLG2, CFNS, CFND
Craniometaphyseal dysplasia, 123000 (3) ANKH, HANK, ANK, CMDJ, CCAL2,
CPPDD
Craniosynostosis, nonspecific (3) FGFR2, BEK, CFD1, JWS
Craniosynostosis, type 2, 604757 (3) MSX2, CRS2, HOX8
CRASH syndrome, 303350 (3) L1 CAM, CAML1, HSAS1
Creatine deficiency syndrome, X-linked, SLC6A8, CRTR
300352 (3)
Creatine phosphokinase, elevated serum, CAV3, LGMD1C
123320 (3)
Creatine phosphokinase, elevated serum, CAV3, LGMD1C
123320 (3)
Creutzfeldt-Jakob disease, 123400 (3) PRNP, PRIP
Creutzfeldt-Jakob disease, variant, HLA-DQB1
resistance to, 123400 (3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Crigler-Najjar syndrome, type I, 218800 (3) UGT1A1, UGT1, GNT1
Crigler-Najjar syndrome, type II, 606785 (3) UGT1A1, UGT1, GNT1
Crohn disease, susceptibility to, 266600 (3) CARD15, NOD2, IBD1, CD, ACUG,
PSORAS1
Crohn disease, susceptibility to, 266600 (3) DLG5, PDLG, KIAA0583
Crouzon syndrome, 123500 (3) FGFR2, BEK, CFD1, JWS
Crouzon syndrome with acanthosis FGFR3, ACH
nigricans (3)
Cryptorchidism, bilateral, 219050 (3) LGR8, GREAT
Cryptorchidism, idiopathic, 219050 (3) INSL3
Currarino syndrome, 176450 (3) HLXB9, HOXHB9, SCRA1
Cutis laxa, AD, 123700 (3) ELN
Cutis laxa, autosomal dominant, 123700 (3) FBLN5, ARMD3
Cutis laxa, autosomal recessive, 219100 (3) FBLN5, ARMD3
Cutis laxa, neonatal (3) ATP7A, MNK, MK, OHS
Cyclic ichthyosis with epidermolytic KRT1
hyperkeratosis, 607602 (3)
Cylindromatosis, familial, 132700 (3) CYLD1, CDMT, EAC
Cystathioninuria, 219500 (3) CTH
Cystic fibrosis, 219700 (3) CFTR, ABCC7, CF, MRP7
Cystinosis, atypical nephropathic (3) CTNS
Cystinosis, late-onset juvenile or adolescent CTNS
nephropathic, 219900 (3)
Cystinosis, nephropathic, 219800 (3) CTNS
Cystinosis, ocular nonnephropathic, 219750 CTNS
(3)
Cystinuria, 220100 (3) SLC3A1, ATR1, D2H, NBAT
Cystinuria, type II (3) SLC7A9, CSNU3
Cystinuria, type III (3) SLC7A9, CSNU3
D-2-hydroxyglutaric aciduria, 600721 (3) D2HGD
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Darier disease, 124200 (3) ATP2A2, ATP2B, DAR
D-bifunctional protein deficiency, 261515 (3) HSD17B4
Deafness, autosomal dominant 10, 601316 EYA4, DFNA10, CMD1J
(3)
Deafness, autosomal dominant 1, 124900 DIAPH1, DFNA1, LFHL1
(3)
Deafness, autosomal dominant 11, MYO7A, USH1B, DFNB2, DFNA11
neurosensory, 601317 (3)
Deafness, autosomal dominant 12, 601842 TECTA, DFNA8, DFNA12, DFNB21
(3)
Deafness, autosomal dominant 13, 601868 COL11A2, STL3, DFNA13
(3)
Deafness, autosomal dominant 15, 602459 POU4F3, BRN3C
(3)
Deafness, autosomal dominant 17, 603622 MYH9, MHA, FTNS, DFNA17
(3)
Deafness, autosomal dominant 20/26, ACTG1, DFNA20, DFNA26
604717 (3)
Deafness, autosomal dominant 22, 606346 MYO6, DFNA22, DFNB37
(3)
Deafness, autosomal dominant 2, 600101 GJB3, CX31, DFNA2
(3)
Deafness, autosomal dominant 2, 600101 KCNQ4, DFNA2
(3)
Deafness, autosomal dominant 28, 608641 TFCP2L3, DFNA28
(3)
Deafness, autosomal dominant 3, 601544 GJB2, CX26, DFNB1, PPK, DFNA3,
(3) KID, HID
Deafness, autosomal dominant 3, 601544 GJB6, CX30, DFNA3, HED, ED2
(3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Deafness, autosomal dominant 36, 606705 TMC1, DFNB7, DFNB11, DFNA36
(3)
Deafness, autosomal dominant 36, with DSPP, DPP, DG11, DFNA39, DTDP2
dentinogenesis, 605594 (3)
Deafness, autosomal dominant 40 (3) CRYM, DFNA40
Deafness, autosomal dominant 4, 600652 MYH14, KIAA2034, DFNA4
(3)
Deafness, autosomal dominant 5 (3) DFNA5
Deafness, autosomal dominant 8, 601543 TECTA, DFNA8, DFNA12, DFNB21
(3)
Deafness, autosomal dominant 9, 601369 COCH, DFNA9
(3)
Deafness, autosomal dominant MYO1A
nonsyndromic sensorineural, 607841 (3)
Deafness, autosomal dominant, with GJB3, CX31, DFNA2
peripheral neuropathy (3)
Deafness, autosomal recessive 10, TMPRSS3, ECHOS1, DFNB8, DFNB10
congenital, 605316 (3)
Deafness, autosomal recessive 1, 220290 GJB2, CX26, DFNB1, PPK, DFNA3,
(3) KID, HID
Deafness, autosomal recessive 12, 601386 CDH23, USH1D
(3)
Deafness, autosomal recessive 12, modifier ATP2B2, PMCA2
of, 601386 (3)
Deafness, autosomal recessive 16, 603720 STRC, DFNB16
(3)
Deafness, autosomal recessive 18, 602092 USH1C, DFNB18
(3)
Deafness, autosomal recessive 21, 603629 TECTA, DFNA8, DFNA12, DFNB21
(3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Deafness, autosomal recessive 22, 607039 OTOA, DFNB22
(3)
Deafness, autosomal recessive 23, 609533 PCDH15, DFNB23
(3)
Deafness, autosomal recessive 29 (3) CLDN14, DFNB29
Deafness, autosomal recessive 2, MYO7A, USH1B, DFNB2, DFNA11
neurosensory, 600060 (3)
Deafness, autosomal recessive 30, 607101 MYO3A, DFNB30
(3)
Deafness, autosomal recessive 31, 607084 WHRN, CIP98, KIAA1526, DFNB31
(3)
Deafness, autosomal recessive 3, 600316 MYO15A, DFNB3
(3)
Deafness, autosomal recessive 36, 609006 ESPN
(3)
Deafness, autosomal recessive 37, 607821 MYO6, DFNA22, DFNB37
(3)
Deafness, autosomal recessive (3) GJB3, CX31, DFNA2
Deafness, autosomal recessive 4, 600791 SLC26A4, PDS, DFNB4
(3)
Deafness, autosomal recessive 61 (3) PRES, DFNB61, SLC26A5
Deafness, autosomal recessive 6, 600971 TMIE, DFNB6
(3)
Deafness, autosomal recessive 7, 600974 TMC1, DFNB7, DFNB11, DFNA36
(3)
Deafness, autosomal recessive 8, childhood TMPRSS3, ECHOS1, DFNB8, DFNB10
onset, 601072 (3)
Deafness, autosomal recessive 9, 601071 OTOF, DFNB9, NSRD9
(3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Deafness, congenital heart defects, and JAG1, AGS, AHD
posterior embryotoxon (3)
Deafness, nonsyndromic (3) () KIAA1199
Deafness, nonsyndromic neurosensory, GJB6, CX30, DFNA3, HED, ED2
digenic (3)
Deafness, sensorineural, with hypertrophic MYO6, DFNA22, DFNB37
cardiomyopathy, 606346 (3)
Deafness, X-linked 1, progressive (3) TIMM8A, DFN1, DDP, MTS, DDP1
Deafness, X-linked 3, conductive, with POU3F4, DFN3
stapes fixation, 304400 (3)
Debrisoquine sensitivity (3) CYP2D@, CYP2D, P450C2D
Dejerine-Sottas disease, 145900 (3) PMP22, CMT1A, CMT1 E, DSS
Dejerine-Sottas neuropathy, 145900 (3) EGR2, KROX20
Dejerine-Sottas neuropathy, autosomal PRX, CMT4F
recessive, 145900 (3)
Dejerine-Sottas syndrome, 145900 (3) MPZ, CMT1 B, CMTDI3, CHM, DSS
Delayed sleep phase syndrome, AANAT, SNAT
susceptibility to (3)
Dementia, familial British, 176500 (3) ITM2B, BRI, ABRI, FBD
Dementia, familial Danish, 117300 (3) ITM2B, BRI, ABRI, FBD
Dementia, frontotemporal, 600274 (3) PSEN1, AD3
Dementia, frontotemporal, with MAPT, MTBT1, DDPAC, MSTD
parkinsonism, 600274 (3)
Dementia, Lewy body, 127750 (3) SNCA, NACP, PARK1, PARK4
Dementia, Lewy body, 127750 (3) SNCB
Dementia, Pick disease-like, 172700 (3) MAPT, MTBT1, DDPAC, MSTD
Dementia, vascular, susceptibility to (3) TNF, TNFA
Dengue fever, protection against (3) CD209, CDSIGN
Dental anomalies, isolated (3) RUNX2, CBFA1, PEBP2A1, AML3
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Dentatorubro-palIidol uysian atrophy, 125370 DRPLA
(3)
Dent disease, 300009 (3) CLCN5, CLCK2, NPHL2, DENTS
Dentin dysplasia, type II, 125420 (3) DSPP, DPP, DG11, DFNA39, DTDP2
Dentinogenesis imperfecta, Shields type 11, DSPP, DPP, DG11, DFNA39, DTDP2
125490 (3)
Dentinogenesis imperfecta, Shields type 111, DSPP, DPP, DG11, DFNA39, DTDP2
125500 (3)
Dent syndrome, 300009 (3) OCRL, LOCR, OCRL1, NPHL2
Denys-Drash syndrome, 194080 (3) WT1
Dermatofibrosarcoma protuberans (3) PDGFB, SIS
De Sanctis-Cacchione syndrome, 278800 ERCC6, CKN2, COFS, CSB
(3)
Desmoid disease, hereditary, 135290 (3) APC, GS, FPC
Desmosterolosis, 602398 (3) DHCR24, KIAA0018
Diabetes insipidus, nephrogenic, 304800 (3) AVPR2, DIR, D11, ADHR
Diabetes insipidus, nephrogenic, autosomal AQP2
dominant, 125800 (3)
Diabetes insipidus, nephrogenic, autosomal AQP2
recessive, 222000 (3)
Diabetes insipidus, neurohypophyseal, AVP, AVRP, VP
125700 (3)
Diabetes mellitus, 125853 (3) ABCC8, SUR, PHHI, SUR1
Diabetes mellitus, insulin-dependent, TCF1, HNF1A, MODY3
222100 (3)
Diabetes mellitus, insulin-dependent, 5, SUMO4, IDDM5
600320 (3)
Diabetes mellitus, insulin-dependent, PTPN8, PEP, PTPN22, LYP
susceptibility to, 222100 (3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Diabetes mellitus, insulin-resistant, with INSR
acanthosis nigricans (3)
Diabetes mellitus, insulin-resistant, with PPARG, PPARG1, PPARG2
acanthosis nigricans and hypertension,
604367 (3)
Diabetes mellitus, neonatal-onset, 606176 GCK
(3)
Diabetes mellitus, noninsulin-dependent, GCGR
125853 (3)
Diabetes mellitus, noninsulin-dependent, GPD2
125853 (3)
Diabetes mellitus, noninsulin-dependent, HNF4A, TCF14, MODY1
125853 (3)
Diabetes mellitus, noninsulin-dependent, I RS2
125853 (3)
Diabetes mellitus, noninsulin-dependent, MAPK81P1, 1131
125853 (3)
Diabetes mellitus, noninsulin-dependent, NEUROD1, NIDDM
125853 (3)
Diabetes mellitus, noninsulin-dependent, TCF2, HNF2
125853 (3)
Diabetes mellitus, noninsulin-dependent, 2, TCF1, HNF1A, MODY3
125853 (3)
Diabetes mellitus, noninsulin-dependent (3) IRS1
Diabetes mellitus, noninsulin-dependent (3) SLC2A2, GLUT2
Diabetes mellitus, noninsulin-dependent (3) SLC2A4, GLUT4
Diabetes mellitus, noninsulin-dependent, CAPN10
601283 (3)
Diabetes mellitus, non-insulin-dependent, ENPP1, PDNP1, NPPS, M6S1, PCA1
susceptibility to, 125853 (3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Diabetes mellitus, noninsulin-dependent, RETN, RSTN, FIZZ3
susceptibility to, 125853 (3)
Diabetes mellitus, permanent neonatal, with PTF1A
cerebellar agenesis, 609069 (3)
Diabetes mellitus, permanent neonatal, with KCNJ11, BIR, PHHI
neurologic features, 606176 (3)
Diabetes mellitus, type II, 125853 (3) AKT2
Diabetes mellitus, type II, susceptibility to, IPF1
125853 (3)
Diabetes mellitus, type I, susceptibility to, FOXP3, IPEX, AIID, XPID, PIDX
222100 (3)
Diabetes, permanent neonatal, 606176 (3) KCNJ11, BIR, PHHI
Diabetic nephropathy, susceptibility to, ACE, DCP1, ACE1
603933 (3)
Diabetic retinopathy, NIDDM-related, VEGF
susceptibility to, 125853 (3)
Diastrophic dysplasia, 222600 (3) SLC26A2, DTD, DTDST, D5S1708,
EDM4
Diastrophic dysplasia, broad bone- SLC26A2, DTD, DTDST, D5S1708,
platyspondylic variant (3) EDM4
DiGeorge syndrome, 188400 (3) TBX1, DGS, CTHM, CAFS, TGA,
DORV, VCFS, DGCR
Dihydropyrimidinuria (3) DPYS, DHP
Dilated cardiomyopathy with woolly hair and DSP, KPPS2, PPKS2
keratoderma, 605676 (3)
Dimethylglycine dehydrogenase deficiency, DMGDH, DMGDHD
605850 (3)
Disordered steroidogenesis, isolated (3) POR
Dissection of cervical arteries (3) COL1A1
DNA ligase I deficiency (3) LIG1
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
DNA topoisomerase I, camptothecin- TOP1
resistant (3)
DNA topoisomerase II, resistance to TOP2A, TOP2
inhibition of, by amsacrine (3)
Dopamine-beta-hydroxylase activity levels, DBH
plasma (3)
Dopamine beta-hydroxylase deficiency, DBH
223360 (3)
Dosage-sensitive sex reversal, 300018 (3) DAX1, AHC, AHX, NROB1
Double-outlet right ventricle, 217095 (3) CFC1, CRYPTIC, HTX2
Down syndrome, risk of, 190685 (3) MTR
Doyne honeycomb degeneration of retina, EFEMP1, FBNL, DHRD
126600 (3)
Drug addiction, susceptibility to (3) FAAH
Duane-radial ray syndrome, 607323 (3) SALL4, HSAL4
Dubin-Johnson syndrome, 237500 (3) ABCC2, CMOAT
Duchenne muscular dystrophy, 310200 (3) DMD, BMD
Dyggve-Melchior-Clausen disease, 223800 DYM, FLJ90130, DMC, SMC
(3)
Dysalbuminemic hyperthyroxinemia (3) ALB
Dysautonomia, familial, 223900 (3) IKBKAP, IKAP
Dyschromatosis symmetrica hereditaria, ADAR, DRADA, DSH, DSRAD
127400 (3)
Dyserythropoietic anemia with GATA1, GF1, ERYF1, NFE1
thrombocytopenia, 300367 (3)
Dysfibrinogenemia, alpha type, causing FGA
bleeding diathesis (3)
Dysfibrinogenemia, alpha type, causing FGA
recurrent thrombosis (3)
Dysfibrinogenemia, beta type (3) FGB
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Dysfibrinogenemia, gamma type (3) FGG
Dyskeratosis congenita-1, 305000 (3) DKC1, DKC
Dyskeratosis congenita, autosomal TERC, TRC3, TR
dominant, 127550 (3)
Dyslexia, susceptibility to, 1, 127700 (3) DYX1C1, DYXC1, DYX1
Dyslexia, susceptibility to, 2, 600202 (3) KIAA0319, DYX2, DYLX2, DLX2
Dysprothrombinemia (3) F2
Dyssegmental dysplasia, Silverman- HSPG2, PLC, SJS, SJA, SJS1
Handmaker type, 224410 (3)
Dystonia-12, 128235 (3) ATP1A3, DYT12, RDP
Dystonia-1, torsion, 128100 (3) DYT1, TOR1A
Dystonia, DOPA-responsive, 128230 (3) GCH1, DYT5
Dystonia, early-onset atypical, with DYT1, TOR1A
myoclonic features (3)
Dystonia, myoclonic, 159900 (3) DRD2
Dystonia, myoclonic, 159900 (3) SGCE, DYT11
Dystonia, primary cervical (3) DRD5, DRD1 B, DRD1 L2
Dystransthyretinemic hyperthyroxinemia(3) TTR, PALB
EBD, Bart type, 132000 (3) COL7A1
EBD, localisata variant (3) COL7A1
Ectodermal dysplasia-1, anhidrotic, 305100 ED1, EDA, HED
(3)
Ectodermal dysplasia 2, hidrotic, 129500 (3) GJB6, CX30, DFNA3, HED, ED2
Ectodermal dysplasia, anhidrotic, 224900 EDARADD
(3)
Ectodermal dysplasia, anhidrotic, IKBKG, NEMO, FIP3, IP2
lymphedema and immunodeficiency, 300301
(3)
Ectodermal dysplasia, anhidrotic, with T-cell NFKBIA, IKBA
immunodeficiency (3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Ectodermal dysplasia, hypohidrotic, EDAR, DL, ED3, EDA3
autosomal dominant, 129490 (3)
Ectodermal dysplasia, hypohidrotic, EDAR, DL, ED3, EDA3
autosomal recessive, 224900 (3)
Ectodermal dysplasia, hypohidrotic, with IKBKG, NEMO, FIP3, IP2
immune deficiency, 300291 (3)
Ectodermal dysplasia, Margarita Island type, HVEC, PVRL1, PVRR1, PRR1
225060 (3)
Ectodermal dysplasia/skin fragility PKP1
syndrome, 604536 (3)
Ectopia lentis, familial, 129600 (3) FBN1, MFS1, WMS
Ectopia pupillae, 129750 (3) PAX6, AN2, MGDA
Ectrodactyly, ectodermal dysplasia, and TP73L, TP63, KET, EEC3, SHFM4,
cleft lip/palate syndrome 3, 604292 (3) LMS, RHS
Ehlers-Danlos due to tenascin X deficiency, TNXB, TNX, TNXB1, TNXBS, TNXB2
606408 (3)
Ehlers-Danlos syndrome, hypermobility TNXB, TNX, TNXB1, TNXBS, TNXB2
type, 130020 (3)
Ehlers-Danlos syndrome, progeroid form, B4GALT7, XGALT1, XGPT1
130070 (3)
Ehlers-Danlos syndrome, type I, 130000 (3) COL1A1
Ehlers-Danlos syndrome, type I, 130000 (3) COL5A1
Ehlers-Danlos syndrome, type I, 130000 (3) COL5A2
Ehlers-Danlos syndrome, type II, 130010 (3) COL5A1
Ehlers-Danlos syndrome, type III, 130020 COL3A1
(3)
Ehlers-Danlos syndrome, type IV, 130050 COL3A1
(3)
Ehlers-Danlos syndrome, type VI, 225400 PLOD, PLOD1
(3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Ehlers-Danlos syndrome, type VII, 130060 COL1A1
(3)
Ehlers-Danlos syndrome, type VIIA2, COL1A2
130060 (3)
Ehlers-Danlos syndrome, type VI IC, 225410 ADAMTS2, NPI
(3)
Elite sprint athletic performance (3) ACTN3
Elliptocytosis-1 (3) EPB41, EL1
Elliptocytosis-2 (3) SPTA1
Elliptocytosis-3 (3) SPTB
Elliptocytosis, Malaysian-Melanesian type SLC4A1, AE1, EPB3
(3)
Ellis-van Creveld syndrome, 225500 (3) EVC
Ellis-van Creveld syndrome, 225500 (3) LBN, EVC2
Emery-Dreifuss muscular dystrophy, EMD, EDMD, STA
310300 (3)
Emery-Dreifuss muscular dystrophy, AD, LMNA, LMN1, EMD2, FPLD, CMD1A,
181350 (3) HGPS, LGMD1 B
Emery-Dreifuss muscular dystrophy, AR, LMNA, LMN1, EMD2, FPLD, CMD1A,
604929 (3) HGPS, LGMD1 B
Emphysema (3) PI, AAT
Emphysema-cirrhosis (3) PI, AAT
Encephalopathy, familial, with neuroserpin SERPINI1, P112
inclusion bodies, 604218 (3)
Encephalopathy, progressive mitochondrial, COX10
with proximal renal tubulopathy due to
cytochrome c oxidase deficiency (3)
Enchondromatosis, Ollier type, 166000 (3) PTHR1, PTHR
Endometrial carcinoma (3) CDH1, UVO
Endometrial carcinoma (3) MSH3
88
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Endometrial carcinoma (3) MSH6, GTBP, HNPCC5
Endometrial carcinoma (3) PTEN, MMAC1
Endotoxin hyporesponsiveness (3) TLR4
Endplate acetylcholinesterase deficiency, COLQ, EAD
603034 (3)
Enhanced S-cone syndrome, 268100 (3) NR2E3, PNR, ESCS
Enlarged vestibular aqueduct, 603545 (3) SLC26A4, PDS, DFNB4
Enolase-beta deficiency (3) ENO3
Enterokinase deficiency, 226200 (3) PRSS7, ENTK
Eosinophil peroxidase deficiency, 261500 EPX
(3)
Epidermodysplasia verruciformis, 226400 EVER1, EV1
(3)
Epidermodysplasia verruciformis, 226400 EVER2, EV2
(3)
Epidermolysis bullosa dystrophica, AD, COL7A1
131750 (3)
Epidermolysis bullosa dystrophica, AR, COL7A1
226600 (3)
Epidermolysis bullosa, generalized atrophic COL17A1, BPAG2
benign, 226650 (3)
Epidermolysis bullosa, generalized atrophic ITGB4
benign, 226650 (3)
Epidermolysis bullosa, generalized atrophic LAMA3, LOCS
benign, 226650 (3)
Epidermolysis bullosa, generalized atrophic LAMB3
benign, 226650 (3)
Epidermolysis bullosa, generalized atrophic LAMC2, LAMNB2, LAMB2T
benign, 226650 (3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Epidermolysis bullosa, Herlitz junctional LAMB3
type, 226700 (3)
Epidermolysis bullosa, Herlitz junctional LAMC2, LAMNB2, LAMB2T
type, 226700 (3)
Epidermolysis bullosa, junctional, Herlitz LAMA3, LOCS
type, 226700 (3)
Epidermolysis bullosa, junctional, with ITGB4
pyloric atresia, 226730 (3)
Epidermolysis bullosa, junctional, with ITGA6
pyloric stenosis, 226730 (3)
Epidermolysis bullosa, lethal acantholytic, DSP, KPPS2, PPKS2
609638 (3)
Epidermolysis bullosa of hands and feet, ITGB4
131800 (3)
Epidermolysis bullosa, pretibial, 131850 (3) COL7A1
Epidermolysis bullosa pruriginosa, 604129 COL7A1
(3)
Epidermolysis bullosa simplex, Koebner, KRT14
Dowling-Meara, and Weber-Cockayne types,
131900, 131760, 131800 (3)
Epidermolysis bullosa simplex, Koebner, KRT5
Dowling-Meara, and Weber-Cockayne types,
131900, 131760, 131800 (3)
Epidermolysis bullosa simplex, Ogna type, PLEC1, PLTN, EBS1
131950 (3)
Epidermolysis bullosa simplex, recessive, KRT14
601001 (3)
Epidermolysis bullosa simplex with mottled KRT5
pigmentation, 131960 (3)
Epidermolytic hyperkeratosis, 113800 (3) KRT10
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Epidermolytic hyperkeratosis, 113800 (3) KRT1
Epidermolytic palmoplantar keratoderma, KRT9, EPPK
144200 (3)
Epilepsy, benign, neonatal, type 1, 121200 KCNQ2, EBN1
(3)
Epilepsy, benign neonatal, type 2, 121201 KCNQ3, EBN2, BFNC2
(3)
Epilepsy, childhood absence, 607681 (3) GABRG2, GEFSP3, CAE2, ECA2
Epilepsy, childhood absence, 607682 (3) CLCN2, EGMA, ECA3, EG13
Epilepsy, childhood absence, evolving to JRK, JH8
juvenile myoclonic epilepsy (3)
Epilepsy, generalized idiopathic, 600669 (3) CACNB4, EJM
Epilepsy, generalized, with febrile seizures GABRG2, GEFSP3, CAE2, ECA2
plus, 604233 (3)
Epilepsy, generalized, with febrile seizures SCN1A, GEFSP2, SMEI
plus, type 2, 604233 (3)
Epilepsy, idopathic generalized, ME2
susceptibility to, 600669 (3)
Epilepsy, juvenile absence, 607631 (3) CLCN2, EGMA, ECA3, EG13
Epilepsy, juvenile myoclonic, 606904 (3) CACNB4, EJM
Epilepsy, juvenile myoclonic, 606904 (3) CLCN2, EGMA, ECA3, EG13
Epilepsy, juvenile myoclonic, 606904 (3) GABRA1, EJM
Epilepsy, myoclonic, Lafora type, 254780 EPM2A, MELF, EPM2
(3)
Epilepsy, myoclonic, Lafora type, 254780 NHLRC1, EPM2A, EPM2B
(3)
Epilepsy, neonatal myoclonic, with SLC25A22, GC1
suppression-burst pattern, 609304 (3)
Epilepsy, nocturnal frontal lobe, 1, 600513 CHRNA4, ENFL1
(3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Epilepsy, nocturnal frontal lobe, 3, 605375 CHRNB2, EFNL3
(3)
Epilepsy, partial, with auditory features, LGI1, EPT, ETL1
600512 (3)
Epilepsy, progressive myoclonic 1, 254800 CSTB, STFB, EPM1
(3)
Epilepsy, progressive myoclonic 2B, 254780 NHLRC1, EPM2A, EPM2B
(3)
Epilepsy, severe myoclonic, of infancy, SCN1A, GEFSP2, SMEI
607208 (3)
Epilepsy with grand mal seizures on CLCN2, EGMA, ECA3, EG13
awakening, 607628 (3)
Epilepsy, X-linked, with variable learning SYN1
disabilities and behavior disorders, 300491
(3)
Epiphyseal dysplasia, multiple 1, 132400 (3) COMP, EDM1, MED, PSACH
Epiphyseal dysplasia, multiple, 226900 (3) SLC26A2, DTD, DTDST, D5S1708,
EDM4
Epiphyseal dysplasia, multiple, 3, 600969 COL9A3, EDM3, IDD
(3)
Epiphyseal dysplasia, multiple, 5, 607078 MATN3, EDM5, HOA
(3)
Epiphyseal dysplasia, multiple, COL9A1- COL9A1, MED
related (3)
Epiphyseal dysplasia, multiple, type 2, COL9A2, EDM2
600204 (3)
Epiphyseal dysplasia, multiple, with COL9A3, EDM3, IDD
myopathy (3)
Episodic ataxia/myokymia syndrome, KCNA1, AEMK, EA1
160120 (3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Episodic ataxia, type 2, 108500 (3) CACNAIA, CACNL1A4, SCA6
Epithelial ovarian cancer, somatic, 604370 OPCML
(3)
Epstein syndrome, 153650 (3) MYH9, MHA, FTNS, DFNA17
Erythermalgia, primary, 133020 (3) SCN9A, NENA, PN1
Erythremias, alpha-(3) HBA1
Erythremias, beta-(3) HBB
Erythrocytosis (3) HBA2
Erythrocytosis, familial, 133100 (3) EPOR
Erythrokeratoderma, progressive symmetric, LOR
602036 (3)
Erythrokeratodermia variabilis, 133200 (3) GJB3, CX31, DFNA2
Erythrokeratodermia variabilis with GJB4, CX30.3
erythema gyratum repens, 133200 (3)
Esophageal cancer, 133239 (3) TGFBR2, HNPCC6
Esophageal carcinoma, somatic, 133239 (3) RNF6
Esophageal squamous cell carcinoma, LZTS1, F37, FEZ1
133239 (3)
Esophageal squamous cell carcinoma, WWOX, FOR
133239 (3)
Estrogen resistance (3) ESR1, ESR
Ethylmalonic encephalopathy, 602473 (3) ETHE1, HSCO, D83198
Ewing sarcoma (3) EWSR1, EWS
Exertional myoglobinuria due to deficiency LDHA, LDH1
of LDH-A (3)
Exostoses, multiple, type 1, 133700 (3) EXT1
Exostoses, multiple, type 2, 133701 (3) EXT2
Exudative vitreoretinopathy, 133780 (3) FZD4, EVR1
Exudative vitreoretinopathy, dominant, LRP5, BMND1, LRP7, LR3, OPPG,
133780 (3) VBCH2
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Exudative vitreoretinopathy, recessive, LRP5, BMND1, LRP7, LR3, OPPG,
601813 (3) VBCH2
Exudative vitreoretinopathy, X-linked, NDP, ND
305390 (3)
Eye anomalies, multiplex (3) PAX6, AN2, MGDA
Ezetimibe, nonresponse to (3) NPC1 L1
Fabry disease (3) GLA
Facioscapulohumeral muscular dystrophy- FSHMD1A, FSHD1A
1A (3)
Factor H and factor H-like 1 (3) HF1, CFH, HUS
Factor V and factor VIII, combined MCFD2
deficiency of, 227300 (3)
Factor VII deficiency (3) F7
Factor X deficiency (3) F10
Factor XI deficiency, autosomal dominant F11
(3)
Factor XI deficiency, autosomal recessive F11
(3)
Factor XII deficiency (3) F12, HAF
Factor XIIIA deficiency (3) F13A1, F13A
Factor XIIIB deficiency (3) F13B
Familial Mediterranean fever, 249100 (3) MEFV, MEF, FMF
Fanconi anemia, complementation group A, FANCA, FACA, FA1, FA, FAA
227650 (3)
Fanconi anemia, complementation group B, FAAP95, FAAP90, FLJ34064, FANCB
300514 (3)
Fanconi anemia, complementation group C FANCC, FACC
(3)
Fanconi anemia, complementation group BRCA2, FANCD1
D1,605724(3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Fanconi anemia, complementation group D2 FANCD2, FANCD, FACD, FAD
(3)
Fanconi anemia, complementation group E FANCE, FACE
(3)
Fanconi anemia, complementation group F FANCF
(3)
Fanconi anemia, complementation group G XRCC9, FANCG
(3)
Fanconi anemia, complementation group J, BRIP1, BACH1, FANCJ
609054 (3)
Fanconi anemia, complementation group L PHF9, FANCL
(3)
Fanconi anemia, complementation group M FANCM, KIAA1596
(3)
Fanconi-Bickel syndrome, 227810 (3) SLC2A2, GLUT2
Farber lipogranulomatosis (3) ASAH, AC
Fatty liver, acute, of pregnancy (3) HAD HA, MTPA
Favism (3) G6PD, G6PD1
Fechtner syndrome, 153640 (3) MYH9, MHA, FTNS, DFNA17
Feingold syndrome, 164280 (3) MYCN, NMYC, ODED, MODED
Fertile eunuch syndrome, 228300 (3) GNRHR, LHRHR
Fibrocalculous pancreatic diabetes, SPINK1, PSTI, PCTT, TATI
susceptibility to (3)
Fibromatosis, gingival, 135300 (3) SOS1, GINGF, GF1, HGF
Fibromatosis, juvenile hyaline, 228600 (3) ANTXR2, CMG2, JHF, ISH
Fibrosis of extraocular muscles, congenital, KIF21A, KIAA1708, FEOM1, CFEOM1
1,135700(3)
Fibrosis of extraocular muscles, congenital, PHOX2A, ARIX, CFEOM2
2,602078(3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Fibular hypoplasia and complex GDF5, CDMP1
brachydactyly, 228900 (3)
Fish-eye disease, 136120 (3) LCAT
Fish-odor syndrome, 602079 (3) FMO3
Fitzgerald factor deficiency (3) KNG
Fluorouracil toxicity, sensitivity to (3) DPYD, DPD
Focal cortical dysplasia, Taylor balloon cell TSC1, LAM
type, 607341 (3)
Follicle-stimulating hormone deficiency, FSHB
isolated, 229070 (3)
Forebrain defects (3) TDGF1
Foveal hypoplasia, isolated, 136520 (3) PAX6, AN2, MGDA
Foveomacular dystrophy, adult-onset, with RDS, RP7, PRPH2, PRPH, AVMD,
choroidal neovascularization, 608161 (3) AOFMD
Fragile X syndrome (3) FMR1, FRAXA
Fraser syndrome, 219000 (3) FRAS1
Fraser syndrome, 219000 (3) FREM2
Frasier syndrome, 136680 (3) WT1
Friedreich ataxia, 229300 (3) FRDA, FARR
Friedreich ataxia with retained reflexes, FRDA, FARR
229300 (3)
Frontometaphyseal dysplasia, 304120 (3) FLNA, FLN1, ABPX, NHBP, OPD1,
OPD2, FMD, MNS
Fructose-bisphosphatase deficiency (3) FBP1
Fructose intolerance (3) ALDOB
Fructosuria (3) KHK
Fuchs endothelial corneal dystrophy, COL8A2, FECD, PPCD2
136800 (3)
Fucosidosis (3) FUCA1
Fucosyltransferase-6 deficiency (3) FUT6
96
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Fumarase deficiency, 606812 (3) FH
Fundus albipunctatus, 136880 (3) RDH5
Fundus albipunctatus, 136880 (3) RLBP1
Fundus flavimaculatus, 248200 (3) ABCA4, ABCR, STGD1, FFM, RP19
G6PD deficiency (3) G6PD, G6PD1
GABA-transaminase deficiency (3) ABAT, GABAT
Galactokinase deficiency with cataracts, GALK1
230200 (3)
Galactose epimerase deficiency, 230350 (3) GALE
Galactosemia, 230400 (3) GALT
Galactosialidosis (3) PPGB, GSL, NGBE, GLB2, CTSA
GAMT deficiency (3) GAMT
Gardner syndrome (3) APC, GS, FPC
Gastric cancer, 137215 (3) APC, GS, FPC
Gastric cancer, 137215 (3) IRF1, MAR
Gastric cancer, familial diffuse, 137215 (3) CDH1, UVO
Gastric cancer risk after H. pylori infection, 11-1 13
137215 (3)
Gastric cancer risk after H. pylori infection, IL1 RN
137215 (3)
Gastric cancer, somatic, 137215 (3) CASP10, MCH4, ALPS2
Gastric cancer, somatic, 137215 (3) ERBB2, NGL, NEU, HER2
Gastric cancer, somatic, 137215 (3) FGFR2, BEK, CFD1, JWS
Gastric cancer, somatic, 137215 (3) KLF6, COPEB, BCD1, ZF9
Gastric cancer, somatic, 137215 (3) MUTYH
Gastrointestinal stromal tumor, somatic, KIT, PBT
606764 (3)
Gastrointestinal stromal tumor, somatic, PDGFRA
606764 (3)
Gaucher disease, 230800 (3) GBA
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Gaucher disease, variant form (3) PSAP, SAP1
Gaucher disease with cardiovascular GBA
calcification, 231005 (3)
Gaze palsy, horizontal, with progressive ROBO3, RBIG1, RIG1, HGPPS
scoliosis, 607313 (3)
Generalized epilepsy and paroxysmal KCNMA1, SLO
dyskinesia, 609446 (3)
Generalized epilepsy with febrile seizures SCN1 B, GEFSP1
plus, 604233 (3)
Germ cell tumor (3) BCL10
Germ cell tumors, 273300 (3) KIT, PBT
Gerstmann-Straussler disease, 137440 (3) PRNP, PRIP
Giant axonal neuropathy-1, 256850 (3) GAN, GAN1
Giant-cell fibroblastoma (3) PDGFB, SIS
Giant cell hepatitis, neonatal, 231100 (3) CYP7B1
Giant platelet disorder, isolated (3) GP1 BB
Gilbert syndrome, 143500 (3) UGT1A1, UGT1, GNT1
Gitelman syndrome, 263800 (3) SLC12A3, NCCT, TSC
Glanzmann thrombasthenia, type A, 273800 ITGA2B, GP2B, CD41 B
(3)
Glanzmann thrombasthenia, type B (3) ITGB3, GP3A
Glaucoma 1A, primary open angle, juvenile- MYOC, TIGR, GLC1A, JOAG, GPOA
onset, 137750 (3)
Glaucoma 1A, primary open angle, MYOC, TIGR, GLC1A, JOAG, GPOA
recessive (3)
Glaucoma 1 E, primary open angle, adult- OPTN, GLC1 E, FIP2, HYPL, NRP
onset, 137760 (3)
Glaucoma 3A, primary congenital, 231300 CYP1 B1, GLC3A
(3)
Glaucoma, early-onset, digenic (3) CYP1B1, GLC3A
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Glaucoma, early-onset, digenic (3) MYOC, TIGR, GLC1A, JOAG, GPOA
Glaucoma, normal tension, susceptibility to, OPA1, NTG, NPG
606657 (3)
Glaucoma, normal tension, susceptibility to, OPTN, GLC1 E, FIP2, HYPL, NRP
606657 (3)
Glaucoma, primary open angle, adult-onset, CYP1 B1, GLC3A
137760 (3)
Glaucoma, primary open angle, juvenile- CYP1 B1, GLC3A
onset, 137750 (3)
Glioblastoma, early-onset, 137800 (3) MSH2, COCA1, FCC1, HNPCC1
Glioblastoma multiforme, somatic, 137800 DMBT1
(3)
Glioblastoma, somatic, 137800 (3) ERBB2, NGL, NEU, HER2
Glioblastoma, somatic, 137800 (3) LGI1, EPT, ETL1
Glioblastoma, susceptibility to, 137800 (3) PPARG, PPARG1, PPARG2
Glomerulocystic kidney disease, TCF2, HNF2
hypoplastic, 137920 (3)
Glomerulosclerosis, focal segmental, 1, ACTN4, FSGS1, FSGS
603278 (3)
Glomerulosclerosis, focal segmental, 2, TRPC6, TRP6, FSGS2
603965 (3)
Glomerulosclerosis, focal segmental, 3, CD2AP, CMS
607832 (3)
Glomuvenous malformations, 138000 (3) GLML, GVM, VMGLOM
Glucocorticoid deficiency 2, 607398 (3) MRAP, FALP, C21 orf61
Glucocorticoid deficiency, due to ACTH MC2R
unresponsiveness, 202200 (3)
Glucose/galactose malabsorption, 606824 SLC5A1, SGLT1
(3)
99
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Glucose transport defect, blood-brain SLC2A1, GLUT1
barrier, 606777 (3)
Glucosidase I deficiency, 606056 (3) GCS1
Glutamate formiminotransferase deficiency, FTCD
229100 (3)
Glutaricaciduria, type I, 231670 (3) GCDH
Glutaricaciduria, type IIA, 231680 (3) ETFA, GA2, MADD
Glutaricaciduria, type IIB, 231680 (3) ETFB, MADD
Glutaricaciduria, type IIC, 231680 (3) ETFDH, MADD
Glutathione synthetase deficiency, 266130 GSS, GSHS
(3)
Glycerol kinase deficiency, 307030 (3) GK
Glycine encephalopathy, 605899 (3) AMT, NKH, GCE
Glycine encephalopathy, 605899 (3) GCSH, NKH
Glycine encephalopathy, 605899 (3) GLDC, HYGN1, GCSP, GCE, NKH
Glycine N-methyltransferase deficiency, GNMT
606664 (3)
Glycogenosis, hepatic, autosomal (3) PHKG2
Glycogenosis, X-linked hepatic, type I (3) PHKA2, PHK
Glycogenosis, X-linked hepatic, type II (3) PHKA2, PHK
Glycogen storage disease I (3) G6PC, G6PT
Glycogen storage disease Ib, 232220 (3) G6PT1
Glycogen storage disease Ic, 232240 (3) G6PT1
Glycogen storage disease II, 232300 (3) GAA
Glycogen storage disease Ilb, 300257 (3) LAMP2, LAMPB
Glycogen storage disease Illa (3) AGL, GDE
Glycogen storage disease Illb (3) AGL, GDE
Glycogen storage disease IV, 232500 (3) GBE1
Glycogen storage disease, type 0, 240600 GYS2
(3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Glycogen storage disease VI (3) PYGL
Glycogen storage disease VII (3) PFKM
GM1-gangliosidosis (3) GLB1
GM2-gangliosidosis, AB variant (3) GM2A
GM2-gangliosidosis, several forms, 272800 HEXA, TSD
(3)
Gnthodiaphyseal dysplasia, 166260 (3) TMEM16E, GDD1
Goiter, congenital (3) TPO, TPX
Goiter, nonendemic, simple (3) TG, AITD3
Gold berg-Sh pri ntzen megacolon syndrome, KIAA1 279
609460 (3)
Gonadal dysgenesis, 46XY, partial, with DHH
minifascicular neuropathy, 607080 (3)
Gonadal dysgenesis, XY type (3) SRY, TDF
GRACILE syndrome, 603358 (3) BCS1L, FLNMS, GRACILE
Graft-versus-host disease, protection IL10, CSIF
against (3)
Graves disease, susceptibility to, 275000 (3) CTLA4
Graves disease, susceptibility to, 3, 275000 GC, DBP
(3)
Greenberg dysplasia, 215140 (3) LBR, PHA
Greig cephalopolysyndactyly syndrome, GLI3, PAPA, PAPB, ACLS
175700 (3)
Griscelli syndrome, type 1, 214450 (3) MYO5A, MYH12, GS1
Griscelli syndrome, type 2, 607624 (3) RAB27A, RAM, GS2
Griscelli syndrome, type 3, 609227 (3) MLPH
Growth hormone deficient dwarfism (3) GHRHR
Growth hormone insensitivity with STAT5B
immunodeficiency, 245590 (3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Growth retardation with deafness and IGF1
mental retardation due to IGF1 deficiency,
608747 (3)
Guttmacher syndrome, 176305 (3) HOXA13, HOX1J
Gyrate atrophy of choroid and retina with OAT
ornithinemia, B6 responsive or unresponsive
(3)
Hailey-Hailey disease, 169600 (3) ATP2C1, BCPM, HHD
Haim-Munk syndrome, 245010 (3) CTSC, CPPI, PALS, PLS, HMS
Hand-foot-uterus syndrome, 140000 (3) HOXA13, HOX1J
Harderoporphyrinuria (3) CPO
HARP syndrome, 607236 (3) PANK2, NBIA1, PKAN, HARP
Hartnup disorder, 234500 (3) SLC6A19, HND
Hay-Wells syndrome, 106260 (3) TP73L, TP63, KET, EEC3, SHFM4,
LMS, RHS
HDL deficiency, familial, 604091 (3) ABCA1, ABC1, HDLDT1, TGD
HDL response to hormone replacement, ESR1, ESR
augmented (3)
Hearing loss, low-frequency sensorineural, WFS1, WFRS, WFS, DFNA6
600965 (3)
Heart block, nonprogressive, 113900 (3) SCN5A, LQT3, IVF, HB1, SSS1
Heart block, progressive, type I, 113900 (3) SCN5A, LQT3, IVF, HB1, SSS1
Heinz body anemia (3) HBA2
Heinz body anemias, alpha-(3) HBA1
Heinz body anemias, beta-(3) HBB
HELLP syndrome, maternal, of pregnancy HAD HA, MTPA
(3)
Hemangioblastoma, cerebellar, somatic (3) VHL
Hemangioma, capillary infantile, somatic, FLT4, VEGFR3, PCL
602089 (3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Hemangioma, capillary infantile, somatic, KDR
602089 (3)
Hematopoiesis, cyclic, 162800 (3) ELA2
Hematuria, familial benign (3) COL4A4
Heme oxygenase-1 deficiency (3) HMOX1
Hemiplegic migraine, familial, 141500 (3) CACNAIA, CACNL1A4, SCA6
Hemochromatosis (3) HFE, HLA-H, HFE1
Hemochromatosis, juvenile, 602390 (3) HAMP, LEAP1, HEPC, HFE2
Hemochromatosis, juvenile, digenic, 602390 HAMP, LEAP1, HEPC, HFE2
(3)
Hemochromatosis, type 2A, 602390 (3) HJV, HFE2A
Hemochromatosis, type 3, 604250 (3) TFR2, HFE3
Hemochromatosis, type 4, 606069 (3) SLC40A1, SLC11A3, FPN1, IREG1,
HFE4
Hemoglobin H disease (3) HBA2
Hemolytic anemia due to adenylate kinase AK1
deficiency (3)
Hemolytic anemia due to band 3 defect SLC4A1, AE1, EPB3
defect (3)
Hemolytic anemia due to BPGM
bisphosphoglycerate mutase deficiency (3)
Hemolytic anemia due to G6PD deficiency G6PD, G6PD1
(3)
Hemolytic anemia due to gamma- GCLC, GLCLC
glutamylcysteine synthetase deficiency,
230450 (3)
Hemolytic anemia due to glucosephosphate GPI
isomerase deficiency (3)
Hemolytic anemia due to glutathione GSS, GSHS
synthetase deficiency, 231900 (3)
103
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Hemolytic anemia due to hexokinase HK1
deficiency (3)
Hemolytic anemia due to PGK deficiency (3) PGK1, PGKA
Hemolytic anemia due to triosephosphate TP11
isomerase deficiency (3)
Hemolytic-uremic syndrome, 235400 (3) HF1, CFH, HUS
Hemophagocytic lymphohistiocytosis, PRF1, HPLH2
familial, 2, 603553 (3)
Hemophagocytic lymphohistiocytosis, UNC13D, MUNC13-4, HPLH3, HLH3,
familial, 3, 608898 (3) FHL3
Hemophilia A (3) F8, F8C, HEMA
Hemophilia B (3) F9, HEMB
Hemorrhagic diathesis due to P1, AAT
\'antithrombinV Pittsburgh (3)
Hemorrhagic diathesis due to factor V F5
deficiency (3)
Hemosiderosis, systemic, due to CP
aceruloplasminemia, 604290 (3)
Hepatic adenoma, 142330 (3) TCF1, HNF1A, MODY3
Hepatic failure, early onset, and neurologic SCOD1, SCO1
disorder (3)
Hepatic lipase deficiency (3) LIPC
Hepatoblastoma (3) CTNNB1
Hepatocellular cancer, 114550 (3) PDGFRL, PDGRL, PRLTS
Hepatocellular carcinoma, 114550 (3) AXIN1, AXIN
Hepatocellular carcinoma, 114550 (3) CTNNBI
Hepatocellular carcinoma, 114550 (3) TP53, P53, LFS1
Hepatocellular carcinoma (3) IGF2R, MPRI
Hepatocellular carcinoma, childhood type, MET
114550 (3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Hepatocellular carcinoma, somatic, 114550 CASP8, MCH5
(3)
Hereditary hemorrhagic telangiectasia-1, ENG, END, HHT1, ORW
187300 (3)
Hereditary hemorrhagic telangiectasia-2, ACVRL1, ACVRLK1, ALK1, HHT2
600376 (3)
Hereditary persistence of alpha-fetoprotein AFP, HPAFP
(3)
Hermansky-Pudlak syndrome, 203300 (3) HPS1
Hermansky-Pudlak syndrome, 203300 (3) HPS3
Hermansky-Pudlak syndrome, 203300 (3) HPS4
Hermansky-pudlak syndrome, 203300 (3) HPS5, RU2, KIAA1017
Hermansky-Pudlak syndrome, 203300 (3) HPS6, RU
Hermansky-Pudlak syndrome, 608233 (3) AP3B1, ADTB3A, HPS2
Hermansky-Pudlak syndrome 7, 203300 (3) DTNBP1, HPS7
Heterotaxy, visceral, 605376 (3) CFC1, CRYPTIC, HTX2
Heterotaxy, X-linked visceral, 306955 (3) ZIC3, HTX1, HTX
Heterotopia, periventricular, 300049 (3) FLNA, FLN1, ABPX, NHBP, OPD1,
OPD2, FMD, MNS
Heterotopia, periventricular, ED variant, FLNA, FLN1, ABPX, NHBP, OPD1,
300537 (3) OPD2, FMD, MNS
Heterotopia, periventricular nodular, with FLNA, FLN1, ABPX, NHBP, OPD1,
frontometaphyseal dysplasia, 300049 (3) OPD2, FMD, MNS
Hex A pseudodeficiency, 272800 (3) HEXA, TSD
High-molecular-weight kininogen deficiency KNG
(3)
Hirschsprung disease, 142623 (3) EDN3
Hirschsprung disease, 142623 (3) GDNF
Hirschsprung disease, 142623 (3) NRTN, NTN
Hirschsprung disease, 142623 (3) RET, MEN2A
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Hirschsprung disease-2, 600155 (3) EDNRB, HSCR2, ABCDS
Hirschsprung disease, cardiac defects, and ECE1
autonomic dysfunction (3)
Hirschsprung disease, short-segment, PMX2B, NBPHOX, PHOX2B
142623 (3)
Histidinemia, 235800 (3) HAL, HSTD
Histiocytoma (3) TP53, P53, LFS1
HIV-1 disease, delayed progression of (3) CCL5, SCYA5, D17S136E, TCP228
HIV-1 disease, rapid progression of (3) CCL5, SCYA5, D17S136E, TCP228
HIV-1, susceptibility to (3) IL10, CSIF
HIV infection, susceptibility/resistance to (3) CMKBR2, CCR2
HIV infection, susceptibility/resistance to (3) CMKBR5, CCCKR5
HMG-CoA lyase deficiency (3) HMGCL
HMG-CoA synthase-2 deficiency, 605911 HMGCS2
(3)
Holocarboxylase synthetase deficiency, HLCS, HCS
253270 (3)
Holoprosencephaly-2, 157170 (3) SIX3, HPE2
Holoprosencephaly-3, 142945 (3) SHH, HPE3, HLP3, SMMCI
Holoprosencephaly-4, 142946 (3) TGIF, HPE4
Holoprosencephaly-5, 609637 (3) ZIC2, HPE5
Holoprosencephaly-7 (3) PTCH, NBCCS, BCNS, HPE7
Holt-Oram syndrome, 142900 (3) TBX5
Homocysteine, total plasma, elevated (3) CTH
Homocystinuria, B6-responsive and CBS
nonresponsive types (3)
Homocystinuria due to MTHFR deficiency, MTHFR
236250 (3)
Homocystinuria-megaloblastic anemia, cbl E MTRR
type, 236270 (3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Homozygous 2p16 deletion syndrome, SLC3A1, ATR1, D2H, NBAT
606407 (3)
Hoyeraal-Hreidarsson syndrome, 300240 DKC1, DKC
(3)
HPFH, deletion type (3) HBB
HPFH, nondeletion type A (3) HBG1
HPFH, nondeletion type G (3) HBG2
HPRT-related gout, 300323 (3) HPRT1, HPRT
H. pylori infection, susceptibility to, 600263 IFNGR1
(3)
Huntington disease (3) HD, IT15
Huntington disease-like 1, 603218 (3) PRNP, PRIP
Huntington disease-like 2, 606438 (3) JPH3, JP3, HDL2
Huntington disease-like-4, 607136 (3) TBP, SCA17
Hyalinosis, infantile systemic, 236490 (3) ANTXR2, CMG2, JHF, ISH
Hydrocephalus due to aqueductal stenosis, L1 CAM, CAML1, HSAS1
307000 (3)
Hydrocephalus with congenital idiopathic L1 CAM, CAML1, HSAS1
intestinal pseudoobstruction, 307000 (3)
Hydrocephalus with Hirschsprung disease L1 CAM, CAML1, HSAS1
and cleft palate, 142623 (3)
Hyperalphalipoproteinemia, 143470 (3) CETP
Hyperammonemia with hypoornithinemia, PYCS, GSAS
hypocitrullinemia, hypoargininemia, and
hypoprolinemia (3)
Hyperandrogenism, nonclassic type, due to CYP21A2, CYP21, CA21 H
21-hydroxylase deficiency (3)
Hyperapobetalipoproteinemia, susceptibility PPARA, PPAR
to (3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Hyperbilirubinemia, familial transcient UGT1A1, UGT1, GNT1
neonatal, 237900 (3)
Hypercalciuria, absorptive, susceptibility to, SAC, HCA2
143870 (3)
Hypercholanemia, familial, 607748 (3) BRAT
Hypercholanemia, familial, 607748 (3) EPHX1
Hypercholanemia, familial, 607748 (3) TJP2, Z02
Hypercholesterolemia, due to ligand- APOB, FLDB
defective apo B, 144010 (3)
Hypercholesterolemia, familial, 143890 (3) LDLR, FHC, FH
Hypercholesterolemia, familial, 3, 603776 PCSK9, NARC1, HCHOLA3, FH3
(3)
Hypercholesterolemia, familial, autosomal ARH, FHCB2, FHCB1
recessive, 603813 (3)
Hypercholesterolemia, familial, due to LDLR EPHX2
defect, modifier of, 143890 (3)
Hypercholesterolemia, familial, modification APOA2
of, 143890 (3)
Hypercholesterolemia, susceptibility to, GSBS
143890 (3)
Hypercholesterolemia, susceptibility to, ITIH4, PK120, ITIHL1
143890 (3)
Hyperekplexia and spastic paraparesis (3) GLRA1, STHE
Hyperekplexia, autosomal recessive, GLRB
149400 (3)
Hypereosinophilic syndrome, idiopathic, PDGFRA
resistant to imatinib, 607685 (3)
Hyperferritinemia-cataract syndrome, FTL
600886 (3)
Hyper-IgD syndrome, 260920 (3) MVK, MVLK
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Hyperinsulinism, familial, 602485 (3) GCK
Hyperinsulinism-hyperammonemia GLUD1
syndrome, 606762 (3)
Hyperkalemic periodic paralysis, 170500 (3) SCN4A, HYPP, NAC1A
Hyperkeratotic cutaneous capillary-venous CCM1, CAM, KRIT1
malformations associated with cerebral
capillary malformations, 116860 (3)
Hyperlipidemia, familial combined, USF1, HYPLIP1
susceptibility to, 602491 (3)
Hyperlipoproteinemia, type Ib, 207750 (3) APOC2
Hyperlipoproteinemia, type III (3) APOE, AD2
Hyperlysinemia, 238700 (3) AASS
Hypermethioninemia, persistent, autosomal MAT1A, MATA1, SAMS1
dominant, due to methionine
adenosyltransferase I/III deficiency (3)
Hypermethioninemia with deficiency of S- AHCY, SAHH
adenosylhomocysteine hydrolase (3)
Hyperornithinemia-hyperammonemia- SLC25A15, ORNT1, HHH
homocitrullinemia syndrome, 238970 (3)
Hyperostosis, endosteal, 144750 (3) LRP5, BMND1, LRP7, LR3, OPPG,
VBCH2
Hyperoxaluria, primary, type 1, 259900 (3) AGXT, SPAT
Hyperoxaluria, primary, type II, 260000 (3) GRHPR, GLXR
Hyperparathyroidism, AD, 145000 (3) MEN1
Hyperparathyroidism, familial primary, HRPT2, C1orf28
145000 (3)
Hyperparathyroidism-jaw tumor syndrome, HRPT2, C1orf28
145001 (3)
Hyperparathyroidism, neonatal, 239200 (3) CASR, HHC1, PCAR1, FIH
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Hyperphenylalaninemia due to pterin-4a- PCBD, DCOH
carbinolamine dehydratase deficiency,
264070 (3)
Hyperphenylalaninemia, mild (3) PAH, PKU1
Hyperproinsulinemia, familial (3) INS
Hyperprolinemia, type I, 239500 (3) PRODH, PRODH2, SCZD4
Hyperprolinemia, type II, 239510 (3) ALDH4A1, ALDH4, P5CDH
Hyperproreninemia (3) REN
Hyperprothrombinemia (3) F2
Hypertension, diastolic, resistance to, KCNMB1
608622 (3)
Hypertension, early-onset, autosomal NR3C2, MLR, MCR
dominant, with exacerbation in pregnancy,
605115 (3)
Hypertension, essential, 145500 (3) AGTR1, AGTR1A, AT2R1
Hypertension, essential, 145500 (3) PTGIS, CYP8A1, PGIS, CYP8
Hypertension, essential, salt-sensitive, ADD1
145500 (3)
Hypertension, essential, susceptibility to, AGT, SERPINA8
145500 (3)
Hypertension, essential, susceptibility to, ECE1
145500 (3)
Hypertension, essential, susceptibility to, GNB3
145500 (3)
Hypertension, insulin resistance-related, RETN, RSTN, FIZZ3
susceptibility to, 125853 (3)
Hypertension, mild low-renin (3) HSD11132, HSD11 K
Hypertension, pregnancy-induced, 189800 NOS3
(3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Hypertension, salt-sensitive essential, CYP3A5, P450PCN3
susceptibility to, 145500 (3)
Hypertension, susceptibility to, 145500 (3) NOS3
Hyperthroidism, congenital (3) TSHR
Hyperthyroidism, congenital (3) TPO, TPX
Hypertriglyceridemia, one form (3) APOA1
Hypertriglyceridemia, susceptibility to, APOA5
145750 (3)
Hypertriglyceridemia, susceptibility to, LIPI, LPDL, PRED5
145750 (3)
Hypertriglyceridemia, susceptibility to, RP1, ORP1
145750 (3)
Hypertrypsinemia, neonatal (3) CFTR, ABCC7, CF, MRP7
Hyperuricemic nephropathy, familial UMOD, HNFJ, FJHN, MCKD2,
juvenile, 162000 (3) ADMCKD2
Hypoaldosteronism, congenital, due to CMO CYP1 1 B2
I deficiency, 203400 (3)
Hypoaldosteronism, congenital, due to CMO CYP1 1 B2
II deficiency (3)
Hypoalphalipoproteinemia (3) APOA1
Hypobetalipoproteinemia (3) APOB, FLDB
Hypocalcemia, autosomal dominant, CASR, HHC1, PCAR1, FIH
146200 (3)
Hypocalcemia, autosomal dominant, with CASR, HHC1, PCAR1, FIH
Bartter syndrome (3)
Hypocalciuric hypercalcemia, type I, 145980 CASR, HHC1, PCAR1, FIH
(3)
Hypoceruloplasminemia, hereditary, 604290 CP
(3)
Hypochondroplasia, 146000 (3) FGFR3, ACH
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Hypochromic microcytic anemia (3) HBA2
Hypodontia, 106600 (3) PAX9
Hypodontia, autosomal dominant, 106600 MSX1, HOX7, HYD1, OFC5
(3)
Hypodontia with orofacial cleft, 106600 (3) MSX1, HOX7, HYD1, OFC5
Hypofibrinogenemia, gamma type (3) FGG
Hypoglobulinemia and absent B cells (3) BLNK, SLP65
Hypoglycemia of infancy, leucine-sensitive, ABCC8, SUR, PHHI, SUR1
240800 (3)
Hypoglycemia of infancy, persistent ABCC8, SUR, PHHI, SUR1
hyperinsulinemic, 256450 (3)
Hypogonadism, hypergonadotropic (3) LHB
Hypogonadotropic hypogonadism, 146110 GPR54
(3)
Hypogonadotropic hypogonadism, 146110 NELF
(3)
Hypogonadotropic hypogonadism (3) GNRHR, LHRHR
Hypogonadotropic hypogonadism (3) LHCGR
Hypohaptoglobinemia (3) HP
Hypokalemic periodic paralysis, 170400 (3) CACNA1S, CACNL1A3, CCHL1A3
Hypokalemic periodic paralysis, 170400 (3) KCNE3, HOKPP
Hypokalemic periodic paralysis, 170400 (3) SCN4A, HYPP, NAC1A
Hypolactasia, adult type, 223100 (3) LCT, LAC, LPH
Hypolactasia, adult type, 223100 (3) MCM6
Hypomagnesemia-2, renal, 154020 (3) FXYD2, ATP1G1, HOMG2
Hypomagnesemia, primary, 248250 (3) CLDN16, PCLN1
Hypomagnesemia with secondary TRPM6, CHAK2
hypocalcemia, 602014 (3)
Hypoparathyroidism, autosomal dominant(3) PTH
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Hypoparathyroidism, autosomal recessive PTH
(3)
Hypoparathyroidism, familial isolated, GCMB
146200 (3)
Hypoparathyroidism-retardation- TBCE, KCS, KCS1, HRD
dysmorphism syndrome, 241410 (3)
Hypoparathyroidism, sensorineural GATA3, HDR
deafness, and renal dysplasia, 146255 (3)
Hypophosphatasia, childhood, 241510 (3) ALPL, HOPS, TNSALP
Hypophosphatasia, infantile, 241500 (3) ALPL, HOPS, TNSALP
Hypophosphatemia, type III (3) CLCN5, CLCK2, NPHL2, DENTS
Hypophosphatemia, X-linked, 307800 (3) PHEX, HYP, HPDR1
Hypophosphatemic rickets, autosomal FGF23, ADHR, HPDR2, PHPTC
dominant, 193100 (3)
Hypoplastic enamel pitting, localized, ENAM
608563 (3)
Hypoplastic left heart syndrome, 241550 (3) GJA1, CX43, ODDD, SDTY3, ODOD
Hypoprothrombinemia (3) F2
Hypothyroidism, autoimmune, 140300 (3) CTLA4
Hypothyroidism, congenital, 274400 (3) SLC5A5, NIS
Hypothyroidism, congenital, due to DUOX2 DUOX2, THOX2
deficiency, 607200 (3)
Hypothyroidism, congenital, due to thyroid PAX8
dysgenesis or hypoplasia, 218700 (3)
Hypothyroidism, congenital, due to TSH TSHR
resistance, 275200 (3)
Hypothyroidism, hereditary congenital (3) TG, AITD3
Hypothyroidism, nongoitrous (3) TSHB
Hypothyroidism, subclinical (3) TSHR
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Hypotrichosis, congential, with juvenile CDH3, CDHP, PCAD, HJMD
macular dystrophy, 601553 (3)
Hypotrichosis, localized, autosomal DSG4, LAH
recessive, 607903 (3)
Hypotrichosis-lymphedema-telangiectasia SOX18, HLTS
syndrome, 607823 (3)
Hypotrichosis simplex of scalp, 146520 (3) CDSN, HTSS
Hypouricemia, renal, 220150 (3) SLC22A12, OAT4L, URAT1
Hystrix-like ichthyosis with deafness, GJB2, CX26, DFNB1, PPK, DFNA3,
602540 (3) KID, HID
Ichthyosiform erythroderma, congenital, TGM1, ICR2, L11
242100 (3)
Ichthyosiform erythroderma, congenital, ALOX12B
nonbullous, 1, 242100 (3)
Ichthyosiform erythroderma, congenital, ALOXE3
nonbullous, 1, 242100 (3)
Ichthyosis bullosa of Siemens, 146800 (3) KRT2A, KRT2E
Ichthyosis, congenital, autosomal recessive ICHYN
(3)
Ichthyosis, cyclic, with epidermolytic KRT10
hyperkeratosis, 607602 (3)
Ichthyosis, harlequin, 242500 (3) ABCA12, ICR2B, L12
Ichthyosis histrix, Curth-Macklin type, KRT1
146590 (3)
Ichthyosis, lamellar 2, 601277 (3) ABCA12, ICR2B, L12
Ichthyosis, lamellar, autosomal recessive, TGM1, ICR2, L11
242300 (3)
Ichthyosis, X-linked (3) STS, ARSC1, ARSC, SSDD
ICOS deficiency, 607594 (3) ICOS, AILIM
IgE levels QTL, 147050 (3) PHF1 1, NYREN34
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
IgG2 deficiency, selective (3) IGHG2
IgG receptor I, phagocytic, familial FCGR1A, IGFR1, CD64
deficiency of (3)
Immunodeficiency-centromeric instability- DNMT3B, ICF
facial anomalies syndrome, 242860 (3)
Immunodeficiency due to defect in CD3- CD3E
epsilon (3)
Immunodeficiency due to defect in CD3- CD3G
gamma (3)
Immunodeficiency with hyper-IgM, type 2, AICDA, AID, HIGM2
605258 (3)
Immunodeficiency with hyper-IgM, type 3, TNFRSF5, CD40
606843 (3)
Immunodeficiency with hyper IgM, type 4, UNG, DGU, HIGM4
608106 (3)
Immunodeficiency, X-linked, with hyper-IgM, TNFSF5, CD40LG, HIGM1, IGM
308230 (3)
Immunodysregulation, polyendocrinopathy, FOXP3, IPEX, AIID, XPID, PIDX
and enteropathy, X-linked, 304790 (3)
Immunoglobulin A deficiency, 609529 (3) TNFRSF14B, TACI
Inclusion body myopathy-3, 605637 (3) MYH2
Inclusion body myopathy, autosomal GNE, GLCNE, IBM2, DMRV, NM
recessive, 600737 (3)
Inclusion body myopathy with early-onset VCP, IBMPFD
Paget disease and frontotemporal dementia,
167320 (3)
Incontinentia pigmenti, type II, 308300 (3) IKBKG, NEMO, FIP3, IP2
Infantile spasm syndrome, 308350 (3) ARX, ISSX, PRTS, MRXS1, MRX36,
MRX54
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Infundibular hypoplasia and hypopituitarism SOX3, MRGH
(3)
Inosine triphosphatase deficiency (3) ITPA
Insensitivity to pain, congenital, with NTRK1, TRKA, MTC
anhidrosis, 256800 (3)
Insomnia (3) () GABRB3
Insomnia, fatal familial, 600072 (3) PRNP, PRIP
Insulin resistance, severe, digenic, 604367 PPARG, PPARG1, PPARG2
(3)
Insulin resistance, severe, digenic, 604367 PPP1R3A, PPP1R3
(3)
Insulin resistance, susceptibility to (3) PTPN1, PTP1B
Interleukin-2 receptor, alpha chain, IL2RA, IL2R
deficiency of (3)
Intervertebral disc disease, susceptibility to, COL9A2, EDM2
603932 (3)
Intervertebral disc disease, susceptibility to, COL9A3, EDM3, IDD
603932 (3)
Intrauterine and postnatal growth retardation IGF1 R
(3)
Intrauterine and postnatal growth retardation IGF2
(3)
Intrinsic factor deficiency, 261000 (3) GIF, IF
IRAK4 deficiency, 607676 (3) IRAK4, REN64
Iridogoniodysgenesis, 601631 (3) FOXC1, FKHL7, FREAC3
Iridogoniodysgenesis syndrome-2, 137600 PITX2, IDG2, RIEG1, RGS, IGDS2
(3)
Iris hypoplasia and glaucoma (3) FOXC1, FKHL7, FREAC3
Iron deficiency anemia, susceptibility to (3) TF
Iron overload, autosomal dominant (3) FTH1, FTHL6
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Isolated growth hormone deficiency, Illig GH1, GHN
type with absent GH and Kowarski type with
bioinactive GH (3)
Isovaleric acidemia, 243500 (3) IVD
Jackson-Weiss syndrome, 123150 (3) FGFR1, FLT2, KAL2
Jackson-Weiss syndrome, 123150 (3) FGFR2, BEK, CFD1, JWS
Jensen syndrome, 311150 (3) TIMM8A, DFN1, DDP, MTS, DDP1
Jervell and Lange-Nielsen syndrome, KCNE1, JLNS, LQT5
220400 (3)
Jervell and Lange-Nielsen syndrome, KCNQ1, KCNA9, LQT1, KVLQT1,
220400 (3) ATFB1
Joubert syndrome, 213300 (3) NPHP1, NPH1, SLSN1
Joubert syndrome-3, 608629 (3) AH11
Juberg-Marsidi syndrome, 309590 (3) ATRX, XH2, XNP, MRXS3, SHS
Juvenile polyposis/hereditary hemorrhagic MADH4, DPC4, SMAD4, JIP
telangiectasia syndrome, 175050 (3)
Kallikrein, decreased urinary activity of (3) KLK1, KLKR
Kallmann syndrome 2, 147950 (3) FGFR1, FLT2, KAL2
Kallmann syndrome (3) KAL1, KMS, ADMLX
Kanzaki disease, 609242 (3) NAGA
Kaposi sarcoma, susceptibility to, 148000 IL6, IFNB2, BSF2
(3)
Kappa light chain deficiency (3) IGKC
Kartagener syndrome, 244400 (3) DNAH11, DNAHC11
Kartagener syndrome, 244400 (3) DNAH5, HL1, PCD, CILD3
Kartagener syndrome, 244400 (3) DNA11, CILD1, ICS, PCD
Kenny-Caffey syndrome-1, 244460 (3) TBCE, KCS, KCS1, HRD
Keratitis, 148190 (3) PAX6, AN2, MGDA
Keratitis-ichthyosis-deafness syndrome, GJB2, CX26, DFNB1, PPK, DFNA3,
148210(3) KID, HID
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DISEASE/DISORDER/INDICATION GENE(S)
Keratoconus, 148300 (3) VSX1, RINX, PPCD, PPD, KTCN
Keratoderma, palmoplantar, with deafness, GJB2, CX26, DFNB1, PPK, DFNA3,
148350 (3) KID, HID
Keratosis follicularis spinulosa decalvans, SAT, SSAT, KFSD
308800 (3)
Keratosis palmoplantaria striata, 148700 (3) KRT1
Keratosis palmoplantaris striata I, 148700 DSG1
(3)
Keratosis palmoplantaris striata II (3) DSP, KPPS2, PPKS2
Keratosis palmoplantaris striata III, 607654 KRT1
(3)
Ketoacidosis due to SCOT deficiency (3) SCOT, OXCT
Keutel syndrome, 245150 (3) MGP, NTI
Kindler syndrome, 173650 (3) KIND1, URP1, C20orf42
Kininogen deficiency (3) KNG
Klippel-Trenaunay syndrome, 149000 (3) VG5Q, HUS84971, FLJ10283
Kniest dysplasia, 156550 (3) COL2A1
Knobloch syndrome, 267750 (3) COL18A1, KNO
Krabbe disease, 245200 (3) GALC
L-2-hydroxyglutaric aciduria, 236792 (3) L2HGDH, C14orf160
Lactate dehydrogenase-B deficiency (3) LDHB
Lacticacidemia due to PDX1 deficiency, PDX1
245349 (3)
Langer mesomelic dysplasia, 249700 (3) SHOX, GCFX, SS, PHOG
Langer mesomelic dysplasia, 249700 (3) SHOXY
Laron dwarfism, 262500 (3) GHR
Larson syndrome, 150250 (3) FLNB, SCT, AOI
Laryngoonychocutaneous syndrome, LAMA3, LOCS
245660 (3)
Lathosterolosis, 607330 (3) SC5DL, ERG3
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DISEASE/DISORDER/INDICATION GENE(S)
LCHAD deficiency (3) HADHA, MTPA
Lead poisoning, susceptibility to (3) ALAD
Leanness, inherited (3) AGRP, ART, AGRT
Leber congenital amaurosis, 204000 (3) CRB1, RP12
Leber congenital amaurosis, 204000 (3) CRX, CORD2, CRD
Leber congenital amaurosis, 204000 (3) RPGRIP1, LCA6, CORD9
Leber congenital amaurosis-2, 204100 (3) RPE65, RP20
Leber congenital amaurosis, 604393 (3) AIPL1, LCA4
Leber congenital amaurosis, type I, 204000 GUCY2D, GUC2D, LCA1, CORD6
(3)
Leber congenital amaurosis, type III, RDH12, LCA3
604232 (3)
Left-right axis malformations (3) ACVR2B
Left-right axis malformations (3) EBAF, TGFB4, LEFTY2, LEFTA,
LEFTYA
Left ventricular noncompaction, familial DTNA, D18S892E, DRP3, LVNC1
isolated, 1, 604169 (3)
Left ventricular noncompaction with DTNA, D18S892E, DRP3, LVNC1
congenital heart defects, 606617 (3)
Legionaire disease, susceptibility to, 608556 TLR5, TIL3
(3)
Leigh syndrome, 256000 (3) BCS1L, FLNMS, GRACILE
Leigh syndrome, 256000 (3) DLD, LAD, PHE3
Leigh syndrome, 256000 (3) NDUFS3
Leigh syndrome, 256000 (3) NDUFS4, AQDQ
Leigh syndrome, 256000 (3) NDUFS7, PSST
Leigh syndrome, 256000 (3) NDUFS8
Leigh syndrome, 256000 (3) NDUFV1, UQOR1
Leigh syndrome, 256000 (3) SDHA, SDH2, SDHF
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DISEASE/DISORDER/INDICATION GENE(S)
Leigh syndrome, due to COX deficiency, SURF1
256000 (3)
Leigh syndrome due to cytochrome c COX15
oxidase deficiency, 256000 (3)
Leigh syndrome, French-Canadian type, LRPPRC, LRP130, LSFC
220111 (3)
Leigh syndrome, X-linked, 308930 (3) PDHA1, PHE1A
Leiomyomatosis and renal cell cancer, FH
605839 (3)
Leiomyomatosis, diffuse, with Alport COL4A6
syndrome, 308940 (3)
Leopard syndrome, 151100 (3) PTPN11, PTP2C, SHP2, NS1
Leprechaunism, 246200 (3) INSR
Leprosy, susceptibility to, 607572 (3) PRKN, PARK2, PDJ
Leri-Weill dyschondrosteosis, 127300 (3) SHOX, GCFX, SS, PHOG
Leri-Weill dyschondrosteosis, 127300 (3) SHOXY
Lesch-Nyhan syndrome, 300322, (3) HPRT1, HPRT
Leukemia-1, T-cell acute lymphocytic (3) TALI, TCL5, SCL
Leukemia-2, T-cell acute lymphoblastic (3) TAL2
Leukemia, acute lymphoblastic (3) FLT3
Leukemia, acute lymphoblastic (3) NBS1, NBS
Leukemia, acute lymphoblastic (3) ZNFN1A1, IK1, LYF1
Leukemia, acute lymphoblastic, HOXD4, HOX4B
susceptibility to (3)
Leukemia, acute lymphocytic (3) BCR, CIVIL, PHL, ALL
Leukemia, acute myeloblastic (3) ARNT
Leukemia, acute myelogenous (3) KRAS2, RASK2
Leukemia, acute myelogenous, 601626 (3) GMPS
Leukemia, acute myeloid, 601626 (3) AF10
Leukemia, acute myeloid, 601626 (3) ARHGEF12, LARG, KIAA0382
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DISEASE/DISORDER/INDICATION GENE(S)
Leukemia, acute myeloid, 601626 (3) CALM, CLTH
Leukemia, acute myeloid, 601626 (3) CEBPA, CEBP
Leukemia, acute myeloid, 601626 (3) CHIC2, BTL
Leukemia, acute myeloid, 601626 (3) FLT3
Leukemia, acute myeloid, 601626 (3) KIT, PBT
Leukemia, acute myeloid, 601626 (3) LPP
Leukemia, acute myeloid, 601626 (3) NPM1
Leukemia, acute myeloid, 601626 (3) NUP214, D9S46E, CAN, CAIN
Leukemia, acute myeloid, 601626 (3) RUNX1, CBFA2, AML1
Leukemia, acute myeloid, 601626 (3) WHSC1L1, NSD3
Leukemia, acute myeloid, reduced survival FLT3
in (3)
Leukemia, acute myelomonocytic (3) AF1Q
Leukemia, acute promyelocytic, NPM/RARA NPM1
type (3)
Leukemia, acute promyelocytic, NUMA1
NUMA/RARA type (3)
Leukemia, acute promyelocytic, ZNF145, PLZF
PL2F/RARA type (3)
Leukemia, acute promyelocytic, PML/RARA PML, MYL
type (3)
Leukemia, acute promyeloyctic, STAT5B
STAT5B/RARA type (3)
Leukemia, acute T-cell lymphoblastic (3) AF10
Leukemia, acute T-cell lymphoblastic (3) CALM, CLTH
Leukemia, chronic lymphatic, susceptibility ARL1 1, ARLTS1
to, 151400 (3)
Leukemia, chronic lymphatic, susceptibility P2RX7, P2X7
to, 151400 (3)
Leukemia, chronic myeloid, 608232 (3) BCR, CIVIL, PHL, ALL
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DISEASE/DISORDER/INDICATION GENE(S)
Leukemia, juvenile myelomonocytic, 607785 GRAF
(3)
Leukemia, juvenile myelomonocytic, 607785 NF1, VRNF, WSS, NFNS
(3)
Leukemia, juvenile myelomonocytic, 607785 PTPN1 1, PTP2C, SHP2, NS1
(3)
Leukemia/lymphoma, B-cell, 2 (3) BCL2
Leukemia/lymphoma, chronic B-cell, 151400 CCND1, PRAD1, BCL1
(3)
Leukemia/lymphoma, T-cell (3) TCRA
Leukemia, megakaryoblastic, of Down GATA1, GF1, ERYF1, NFE1
syndrome, 190685 (3)
Leukemia, megakaryoblastic, with or without GATA1, GF1, ERYF1, NFE1
Down syndrome, 190685 (3)
Leukemia, Philadelphia chromosome- ABL1
positive, resistant to imatinib (3)
Leukemia, post-chemotherapy, susceptibility NQO1, DIA4, NMOR1
to (3)
Leukemia, T-cell acute lymphoblastic (3) NUP214, D9S46E, CAN, CAIN
Leukocyte adhesion deficiency, 116920 (3) ITGB2, CD18, LCAMB, LAD
Leukoencephalopathy with vanishing white EIF2B1, EIF2BA
matter, 603896 (3)
Leukoencephalopathy with vanishing white EIF2B2
matter, 603896 (3)
Leukoencephalopathy with vanishing white EIF2B3
matter, 603896 (3)
Leukoencephalopathy with vanishing white EIF2B5, LVWM, CACH, CLE
matter, 603896 (3)
Leukoencephaly with vanishing white EIF2B4
matter, 603896 (3)
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DISEASE/DISORDER/INDICATION GENE(S)
Leydig cell adenoma, with precocious LHCGR
puberty (3)
Lhermitte-Duclos syndrome (3) PTEN, MMAC1
Liddle syndrome, 177200 (3) SCNN1 B
Liddle syndrome, 177200 (3) SCNNIG, PHA1
Li Fraumeni syndrome, 151623 (3) CDKN2A, MTS1, P16, MLM, CMM2
Li-Fraumeni syndrome, 151623 (3) TP53, P53, LFS1
Li-Fraumeni syndrome, 609265 (3) CHEK2, RAD53, CHK2, CDS1, LFS2
LIG4 syndrome, 606593 (3) LIG4
Limb-mammary syndrome, 603543 (3) TP73L, TP63, KET, EEC3, SHFM4,
LMS, RHS
Lipodystrophy, congenital generalized, type AGPAT2, LPAAB, BSCL, BSCL1
1,608594(3)
Lipodystrophy, congenital generalized, type BSCL2, SPG17
2,269700(3)
Lipodystrophy, familial partial, 151660 (3) LMNA, LMN1, EMD2, FPLD, CMD1A,
HGPS, LGMD1 B
Lipodystrophy, familial partial, 151660 (3) PPARG, PPARG1, PPARG2
Lipodystrophy, familial partial, with PPARGC1A, PPARGC1
decreased subcutaneous fat of face and
neck (3)
Lipoid adrenal hyperplasia, 201710 (3) STAR
Lipoid congenital adrenal hyperplasia, CYP1 1A, P450SCC
201710 (3)
Lipoid proteinosis, 247100 (3) ECM1
Lipoma (3) HMGA2, HMGIC, BABL, LIPO
Lipoma (3) LPP
Lipoma, sporadic (3) MEN1
Lipomatosis, mutiple, 151900 (3) HMGA2, HMGIC, BABL, LIPO
Lipoprotein lipase deficiency (3) LPL, LIPD
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DISEASE/DISORDER/INDICATION GENE(S)
Lissencephaly-1, 607432 (3) PAFAH1B1, LIS1
Lissencephaly syndrome, Norman-Roberts RELN, RL
type, 257320 (3)
Lissencephaly, X-linked, 300067 (3) DCX, DBCN, LISX
Lissencephaly, X-linked with ambiguous ARX, ISSX, PRTS, MRXS1, MRX36,
genitalia, 300215 (3) MRX54
Listeria monocytogenes, susceptibility to (3) CDH1, UVO
Loeys-Dietz syndrome, 609192 (3) TGFBR1
Loeys-Dietz syndrome, 609192 (3) TGFBR2, HNPCC6
Longevity, exceptional, 152430 (3) CETP
Longevity, reduced, 152430 (3) AKAP10
Long QT syndrome-1, 192500 (3) KCNQ1, KCNA9, LQT1, KVLQTI,
ATFB1
Long QT syndrome-2 (3) KCNH2, LQT2, HERG
Long QT syndrome-3, 603830 (3) SCN5A, LQT3, IVF, HB1, SSS1
Long QT syndrome 4, 600919 (3) ANK2, LQT4
Long QT syndrome-5 (3) KCNE1, JLNS, LQT5
Long QT syndrome-6 (3) KCNE2, MIRP1, LQT6
Long QT syndrome-7, 170390 (3) KCNJ2, HHIRK1, KIR2.1, IRK1, LQT7
Lower motor neuron disease, progressive, DCTN1
without sensory symptoms, 607641 (3)
Lowe syndrome, 309000 (3) OCRL, LOCR, OCRL1, NPHL2
Low renin hypertension, susceptibility to (3) CYP1 1 B2
LPA deficiency, congenital (3) LPA
Lumbar disc disease, susceptibility to, CILP
603932 (3)
Lung cancer, 211980 (3) KRAS2, RASK2
Lung cancer, 211980 (3) PPP2R1B
Lung cancer, 211980 (3) SLC22A1L, BWSCR1A, IMPT1
Lung cancer, somatic, 211980 (3) MAP3K8, COT, EST, TPL2
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DISEASE/DISORDER/INDICATION GENE(S)
Lupus nephritis, susceptibility to (3) FCGR2A, IGFR2, CD32
Lymphangioleiomyomatosis, 606690 (3) TSC1, LAM
Lymphangioleiomyomatosis, somatic, TSC2, LAM
606690 (3)
Lymphedema and ptosis, 153000 (3) FOXC2, FKHL14, MFH1
Lymphedema-distichiasis syndrome, FOXC2, FKHL14, MFH1
153400 (3)
Lymphedema-distichiasis syndrome with FOXC2, FKHL14, MFH1
renal disease and diabetes mellitus (3)
Lymphedema, hereditary I, 153100 (3) FLT4, VEGFR3, PCL
Lymphedema, hereditary II, 153200 (3) FOXC2, FKHL14, MFH1
Lymphocytic leukemia, acute T-cell (3) RAP1 GDS1
Lymphoma, B-cell non-Hodgkin, somatic (3) ATM, ATA, AT1
Lymphoma, diffuse large cell (3) BCL8
Lymphoma, follicular (3) BCL10
Lymphoma, MALT (3) BCL10
Lymphoma, mantle cell (3) ATM, ATA, AT1
Lymphoma, non-Hodgkin (3) RAD54B
Lymphoma, non-Hodgkin (3) RAD54L, HR54, HRAD54
Lymphoma, progression of (3) FCGR2B, CD32
Lymphoma, somatic (3) MAD1L1, TXBP181
Lymphoma, T-cell (3) MSH2, COCA1, FCC1, HNPCC1
Lymphoproliferative syndrome, X-linked, SH2D1A, LYP, IMD5, XLP, XLPD
308240 (3)
Lynch cancer family syndrome II, 114400 MSH2, COCA1, FCC1, HNPCC1
(3)
Lysinuric protein intolerance, 222700 (3) SLC7A7, LPI
Machado-Joseph disease, 109150 (3) ATXN3, MJD, SCA3
Macrocytic anemia, refractory, of 5q- IRF1, MAR
syndrome, 153550 (3)
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DISEASE/DISORDER/INDICATION GENE(S)
Macrothrombocytopenia, 300367 (3) GATA1, GF1, ERYF1, NFE1
Macular corneal dystrophy, 217800 (3) CHST6, MCDC1
Macular degeneration, age-related, 1, HF1, CFH, HUS
603075 (3)
Macular degeneration, age-related, 1, HMCN1, FBLN6, FIBL6
603075 (3)
Macular degeneration, age-related, 3, FBLN5, ARMD3
608895 (3)
Macular degeneration, juvenile, 248200 (3) CNGB3, ACHM3
Macular degeneration, X-linked atrophic (3) RPGR, RP3, CRD, RP15, COD1
Macular dystrophy (3) RDS, RP7, PRPH2, PRPH, AVMD,
AOFMD
Macular dystrophy, age-related, 2, 153800 ABCA4, ABCR, STGD1, FFM, RP19
(3)
Macular dystrophy, autosomal dominant, ELOVL4, ADMD, STGD2, STGD3
chromosome 6-linked, 600110 (3)
Macular dystrophy, vitelliform, 608161 (3) RDS, RP7, PRPH2, PRPH, AVMD,
AOFMD
Macular dystrophy, vitelliform type, 153700 VMD2
(3)
Maculopathy, bull's-eye, 153870 (3) VMD2
Major depressive disorder and accelerated FKBP5, FKBP51
response to antidepressant drug treatment,
608616 (3)
Malaria, cerebral, reduced risk of, 248310 CD36
(3)
Malaria, cerebral, susceptibility to, 248310 CD36
(3)
Malaria, cerebral, susceptibility to (3) ICAM1
Malaria, cerebral, susceptibility to (3) TNF, TNFA
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DISEASE/DISORDER/INDICATION GENE(S)
Malaria, resistance to, 248310 (3) GYPC, GE, GPC
Malaria, resistance to, 248310 (3) NOS2A, NOS2
Malignant hyperthermia susceptibility 1, RYR1, MHS, CCO
145600 (3)
Malignant hyperthermia susceptibility 5, CACNA1S, CACNL1A3, CCHL1A3
601887 (3)
Malonyl-CoA decarboxylase deficiency, MLYCD, MCD
248360 (3)
MALT lymphoma (3) MALT1, MLT
Mandibuloacral dysplasia with type B ZMPSTE24, FACE1, STE24, MADB
lipodystrophy, 608612 (3)
Mannosidosis, alpha-, types I and II, 248500 MAN2B1, MANB
(3)
Mannosidosis, beta, 248510 (3) MANBA, MANB1
Maple syrup urine disease, type la, 248600 BCKDHA, MSUD1
(3)
Maple syrup urine disease, type lb (3) BCKDHB, E113
Maple syrup urine disease, type II (3) DBT, BCATE2
Maple syrup urine disease, type III, 248600 DLD, LAD, PHE3
(3)
Marfan syndrome, 154700 (3) FBN1, MFS1, WMS
Marfan syndrome, atypical (3) COL1A2
Maroteaux-Lamy syndrome, several forms ARSB, MPS6
(3)
Marshall syndrome, 154780 (3) COL11A1, STL2
MASA syndrome, 303350 (3) L1CAM, CAML1, HSAS1
MASP2 deficiency (3) MASP2
MASS syndrome, 604308 (3) FBN1, MFS1, WMS
Mast cell leukemia (3) KIT, PBT
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DISEASE/DISORDER/INDICATION GENE(S)
Mastocytosis with associated hematologic KIT, PBT
disorder (3)
Mast syndrome, 248900 (3) ACP33, MAST, SPG21
May-Hegglin anomaly, 155100 (3) MYH9, MHA, FTNS, DFNA17
McArdle disease, 232600 (3) PYGM
McCune-Albright syndrome, 174800 (3) GNAS, GNAS1, GPSA, POH, PHP1B,
PHP1A, AHO
McKusick-Kaufman syndrome, 236700 (3) MKKS, HMCS, KMS, MKS, BBS6
McLeod syndrome (3) XK
McLeod syndrome with neuroacanthosis (3) XK
Medullary cystic kidney disease 2, 603860 UMOD, HNFJ, FJHN, MCKD2,
(3) ADMCKD2
Medullary thyroid carcinoma, 155240 (3) RET, MEN2A
Medullary thyroid carcinoma, familial, NTRK1, TRKA, MTC
155240 (3)
Medulloblastoma, 155255 (3) PTCH2
Medulloblastoma, desmoplastic, 155255 (3) SUFU, SUFUXL, SUFUH
Meesmann corneal dystrophy, 122100 (3) KRT12
Meesmann corneal dystrophy, 122100 (3) KRT3
Megakaryoblastic leukemia, acute (3) MKL1, AMKL, MAL
Megalencephalic leukoencephalopathy with MLC1, LVM, VL
subcortical cysts, 604004 (3)
Megaloblastic anemia-1, Finnish type, CUBN, IFCR, MGA1
261100 (3)
Megaloblastic anemia-1, Norwegian type, AMN
261100 (3)
Melanoma (3) CDK4, CMM3
Melanoma and neural system tumor CDKN2A, MTS1, P16, MLM, CMM2
syndrome, 155755 (3)
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DISEASE/DISORDER/INDICATION GENE(S)
Melanoma, cutaneous malignant, 2, 155601 CDKN2A, MTS1, P16, MLM, CMM2
(3)
Melanoma, cutaneous malignant, XRCC3
susceptibility to (3)
Melanoma, malignant sporadic (3) STK1 1, PJS, LKB1
Melanoma, melignant, somatic (3) BRAF
Meleda disease, 248300 (3) SLURP1, MDM
Melnick-Needles syndrome, 309350 (3) FLNA, FLN1, ABPX, NHBP, OPD1,
OPD2, FMD, MNS
Melorheostosis with osteopoikilosis, 155950 LEMD3, MAN1
(3)
Memory impairment, susceptibility to (3) BDNF
Meniere disease 156000 (3) () COCH, DFNA9
Meningioma, 607174 (3) MN1, MGCR
Meningioma, 607174 (3) PTEN, MMAC1
Meningioma, NF2-related, somatic, 607174 NF2
(3)
Meningioma, SIS-related (3) PDGFB, SIS
Meningococcal disease, susceptibility to (3) MBL2, MBL, MBP1
Menkes disease, 309400 (3) ATP7A, MNK, MK, OHS
Mental retardation, nonsyndromic, PRSS12, BSSP3
autosomal recessive, 249500 (3)
Mental retardation, nonsyndromic, CRBN, MRT2A
autosomal recessive, 2A, 607417 (3)
Mental retardation, X-linked, 300425 (3) NLGN4, KIAA1260, AUTSX2
Mental retardation, X-linked, 300458 (3) MECP2, RTT, PPMX, MRX16, MRX79
Mental retardation, X-linked 30, 300558 (3) PAK3, MRX30, MRX47
Mental retardation, X-linked, 34, 300426 (3) IL1RAPL, MRX34
Mental retardation, X-linked 36, 300430 (3) ARX, ISSX, PRTS, MRXS1, MRX36,
MRX54
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DISEASE/DISORDER/INDICATION GENE(S)
Mental retardation, X-linked (3) SLC6A8, CRTR
Mental retardation, X-linked-44, 300501 (3) FTSJ1, JM23, SPB1, MRX44, MRX9
Mental retardation, X-linked 45, 300498 (3) ZNF81, MRX45
Mental retardation, X-linked 54, 300419 (3) ARX, ISSX, PRTS, MRXS1, MRX36,
MRX54
Mental retardation, X-linked 58, 300218 (3) TM4SF2, MXS1, A15
Mental retardation, X-linked, 60, 300486 (3) OPHN1
Mental retardation, X-linked-9, 309549 (3) FTSJ1, JM23, SPB1, MRX44, MRX9
Mental retardation, X-linked, FRAXE type FMR2, FRAXE, MRX2
(3)
Mental retardation, X-linked, JARID1C- SMCX, MRXJ, DXS1272E, XE169,
related, 300534 (3) JARID1C
Mental retardation, X-linked nonspecific, GDI1, RABGD1A, MRX41, MRX48
309541 (3)
Mental retardation, X-linked nonspecific, 63, FACL4, ACS4, MRX63
300387 (3)
Mental retardation, X-linked nonspecific, RPS6KA3, RSK2, MRX19
type 19 (3)
Mental retardation, X-linked nonspecific, ARHGEF6, MRX46, COOL2
type 46, 300436 (3)
Mental retardation, X-linked nonsyndromic AGTR2
(3)
Mental retardation, X-linked nonsyndromic FGD1, FGDY, AAS
(3)
Mental retardation, X-linked nonsyndromic ZNF41
(3)
Meesmann corneal dystrophy, 122100 (3) KRT12
Meesmann corneal dystrophy, 122100 (3) KRT3
Megakaryoblastic leukemia, acute (3) MKL1, AMKL, MAL
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DISEASE/DISORDER/INDICATION GENE(S)
Megalencephalic leukoencephalopathy with MLC1, LVM, VL
subcortical cysts, 604004 (3)
Megaloblastic anemia-1, Finnish type, CUBN, IFCR, MGA1
261100(3)
Megaloblastic anemia-1, Norwegian type, AMN
261100(3)
Melanoma (3) CDK4, CMM3
Melanoma and neural system tumor CDKN2A, MTS1, P16, MLM, CMM2
syndrome, 155755 (3)
Melanoma, cutaneous malignant, 2, 155601 CDKN2A, MTS1, P16, MLM, CMM2
(3)
Melanoma, cutaneous malignant, XRCC3
susceptibility to (3)
Melanoma, malignant sporadic (3) STK11, PJS, LKB1
Melanoma, melignant, somatic (3) BRAF
Meleda disease, 248300 (3) SLURPI, MDM
Melnick-Needles syndrome, 309350 (3) FLNA, FLN1, ABPX, NHBP, OPD1,
OPD2, FMD, MNS
Melorheostosis with osteopoikilosis, 155950 LEMD3, MAN1
(3)
Memory impairment, susceptibility to (3) BDNF
Meniere disease 156000 (3) () COCH, DFNA9
Meningioma, 607174 (3) MN1, MGCR
Meningioma, 607174 (3) PTEN, MMAC1
Meningioma, NF2-related, somatic, 607174 NF2
(3)
Meningioma, SIS-related (3) PDGFB, SIS
Meningococcal disease, susceptibility to (3) MBL2, MBL, MBP1
Menkes disease, 309400 (3) ATP7A, MNK, MK, OHS
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DISEASE/DISORDER/INDICATION GENE(S)
Mental retardation, nonsyndromic, PRSS12, BSSP3
autosomal recessive, 249500 (3)
Mental retardation, nonsyndromic, CRBN, MRT2A
autosomal recessive, 2A, 607417 (3)
Mental retardation, X-linked, 300425 (3) NLGN4, KIAA1260, AUTSX2
Mental retardation, X-linked, 300458 (3) MECP2, RTT, PPMX, MRX16, MRX79
Mental retardation, X-linked 30, 300558 (3) PAK3, MRX30, MRX47
Mental retardation, X-linked, 34, 300426 (3) IL1RAPL, MRX34
Mental retardation, X-linked 36, 300430 (3) ARX, ISSX, PRTS, MRXS1, MRX36,
MRX54
Mental retardation, X-linked (3) SLC6A8, CRTR
Mental retardation, X-linked-44, 300501 (3) FTSJ1, JM23, SPB1, MRX44, MRX9
Mental retardation, X-linked 45, 300498 (3) ZNF81, MRX45
Mental retardation, X-linked 54, 300419 (3) ARX, ISSX, PRTS, MRXS1, MRX36,
MRX54
Mental retardation, X-linked 58, 300218 (3) TM4SF2, MXS1, A15
Mental retardation, X-linked, 60, 300486 (3) OPHN1
Mental retardation, X-linked-9, 309549 (3) FTSJ1, JM23, SPB1, MRX44, MRX9
Mental retardation, X-linked, FRAXE type FMR2, FRAXE, MRX2
(3)
Mental retardation, X-linked, JARIDIC- SMCX, MRXJ, DXS1272E, XE169,
related, 300534 (3) JARID1C
Mental retardation, X-linked nonspecific, GDI1, RABGD1A, MRX41, MRX48
309541 (3)
Mental retardation, X-linked nonspecific, 63, FACL4, ACS4, MRX63
300387 (3)
Mental retardation, X-linked nonspecific, RPS6KA3, RSK2, MRX19
type 19 (3)
Mental retardation, X-linked nonspecific, ARHGEF6, MRX46, COOL2
type 46, 300436 (3)
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DISEASE/DISORDER/INDICATION GENE(S)
Mental retardation, X-linked nonsyndromic AGTR2
(3)
Mental retardation, X-linked nonsyndromic FGD1, FGDY, AAS
(3)
Mental retardation, X-linked nonsyndromic ZNF41
(3)
Mental retardation, X-linked nonsyndromic, DLG3, NEDLG, SAP102, MRX
DLG3-related (3)
Mental retardation, X-linked, Snyder- SMS, SRS, MRSR
Robinson type, 309583 (3)
Mental retardation, X-linked, with isolated SOX3, MRGH
growth hormone deficiency, 300123 (3)
Mental retardation, X-linked, with MECP2, RTT, PPMX, MRX16, MRX79
progressive spasticity, 300279 (3)
Mental retardation, X-linked, with seizures SLC6A8, CRTR
and carrier manifestations, 300397 (3)
Mephenytoin poor metabolizer (3) CYP2C, CYP2C19
Merkel cell carcinoma, somatic (3) SDHD, PGL1
Mesangial sclerosis, isolated diffuse, WT1
256370 (3)
Mesothelioma (3) BCL10
Metachromatic leukodystrophy, 250100 (3) ARSA
Metachromatic leukodystrophy due to PSAP, SAP1
deficiency of SAP-1 (3)
Metaphyseal chondrodysplasia, Murk PTHR1, PTHR
Jansen type, 156400 (3)
Metaphyseal chondrodysplasia, Schmid COL1OA1
type (3)
Metaphyseal dysplasia without RMRP, RMRPR, CHH
hypotrichosis, 250460 (3)
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DISEASE/DISORDER/INDICATION GENE(S)
Methemoglobinemia due to cytochrome b5 CYB5
deficiency (3)
Methemoglobinemias, alpha-(3) HBA1
Methemoglobinemias, beta-(3) HBB
Methemoglobinemia, type I (3) DIA1
Methemoglobinemia, type 11 (3) DIA1
Methionine adenosyltransferase deficiency, MAT1A, MATA1, SAMS1
autosomal recessive (3)
Methylcobalamin deficiency, cblG type, MTR
250940 (3)
Methylmalonate semialdehyde ALDH6A1, MMSDH
dehydrogenase deficiency (3)
Methylmalonic aciduria, mut(0) type, 251000 MUT, MCM
(3)
Methylmalonic aciduria, vitamin B12- MMAA
responsive, 251100 (3)
Methylmalonic aciduria, vitamin B12- MMAB
responsive, due to defect in synthesis of
adenosylcobalamin, cb1B complementation
type, 251110 (3)
Mevalonicaciduria (3) MVK, MVLK
MHC class 11 deficiency, complementation RFXANK
group B, 209920 (3)
Microcephaly, Amish type, 607196 (3) SLC25A19, DNC, MUP1, MCPHA
Microcephaly, autosomal recessive 1, MCPH1
251200 (3)
Microcephaly, primary autosomal recessive, CDK5RAP2, KIAA1633, MCPH3
3,604804(3)
Microcephaly, primary autosomal recessive, ASPM, MCPH5
5,608716(3)
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DISEASE/DISORDER/INDICATION GENE(S)
Microcephaly, primary autosomal recessive, CEMPJ, CPAP, MCPH6
6,608393(3)
Microcoria-congenital nephrosis syndrome, LAMB2, LAMS
609049 (3)
Micropenis (3) LHCGR
Microphthalmia, cataracts, and iris CHX10, HOX10
abnormalities (3)
Microphthalmia, SIX6-related (3) SIX6
Microphthalmia with associated anomalies BCOR, KIAA1575, MAA2, ANOP2
2, 300412 (3)
Migraine, familial hemiplegic, 2, 602481 (3) ATP1A2, FHM2, MHP2
Migraine, resistance to, 157300 (3) EDNRA
Migraine, susceptibility to, 157300 (3) ESR1, ESR
Migraine without aura, susceptibility to, TNF, TNFA
157300 (3)
Miller-Dieker lissencephaly, 247200 (3) YWHAE, MDCR, MDS
Mitochondrial complex I deficiency, 252010 NDUFS1
(3)
Mitochondrial complex I deficiency, 252010 NDUFS2
(3)
Mitochondrial complex I deficiency, 252010 NDUFS4, AQDQ
(3)
Mitochondrial complex I deficiency, 252010 NDUFV1, UQOR1
(3)
Mitochondrial complex III deficiency, 124000 BCS1L, FLNMS, GRACILE
(3)
Mitochondrial complex III deficiency, 124000 UQCRB, UQBP, QPC
(3)
Mitochondrial DNA depletion myopathy, TK2
251880 (3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Mitochondrial DNA depletion syndrome, SUCLA2
251880 (3)
Mitochondrial DNA-depletion syndrome, DGUOK, DGK
hepatocerebral form, 251880 (3)
Mitochondrial myopathy and sideroblastic PUS1, MLASA
anemia, 600462 (3)
Mitochondrial respiratory chain complex II SDHA, SDH2, SDHF
deficiency, 252011 (3)
Miyoshi myopathy, 254130 (3) DYSF, LGMD2B
MODY5 with nephron agenesis (3) TCF2, HNF2
MODY5 with non-diabetic renal disease and TCF2, HNF2
Mullerian aplasia (3)
MODY, one form, 125850 (3) INS
MODY, type I, 125850 (3) HNF4A, TCF14, MODY1
MODY, type II, 125851 (3) GCK
MODY, type III, 600496 (3) TCF1, HNF1A, MODY3
MODY, type IV (3) IPF1
MODY, type V, 604284 (3) TCF2, HNF2
Mohr-Tranebjaerg syndrome, 304700 (3) TIMM8A, DFN1, DDP, MTS, DDP1
Molybdenum cofactor deficiency, type A, MOCS1, MOCOD
252150 (3)
Molybdenum cofactor deficiency, type B, MOCS2, MPTS
252150 (3)
Molybdenum cofactor deficiency, type C, GPH, KIAA1385, GEPH
252150 (3)
Monilethrix, 158000 (3) KRTHB1, HB1
Monilethrix, 158000 (3) KRTHB6, HB6
Morning glory disc anomaly (3) PAX6, AN2, MGDA
Mowat-Wilson syndrome, 235730 (3) ZFHX1B, SMADIP1, SIP1
Moyamoya disease 3 (3) MYMY3
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Muckle-Wells syndrome, 191900 (3) CIAS1, C1orf7, FCU, FCAS
Mucoepidermoid salivary gland carcinoma MAML2, MAM3
(3)
Mucoepidermoid salivary gland carcinoma MECT1, KIAA0616
(3)
Mucolipidosis IIIA, 252600 (3) GNPTAB, GNPTA
Mucolipidosis IIIC, 252605 (3) GNPTAG
Mucolipidosis IV, 252650 (3) MCOLN1, ML4
Mucopolysaccharidosis Ih, 607014 (3) IDUA, IDA
Mucopolysaccharidosis Ih/s, 607015 (3) IDUA, IDA
Mucopolysaccharidosis II (3) IDS, MPS2, SIDS
Mucopolysaccharidosis Is, 607016 (3) IDUA, IDA
Mucopolysaccharidosis IVA (3) GALNS, MPS4A
Mucopolysaccharidosis IVB (3) GLB1
Mucopolysaccharidosis type IIID, 252940 GNS, G6S
(3)
Mucopolysaccharidosis type IX, 601492 (3) HYAL1
Mucopolysaccharidosis VII (3) GUSB, MPS7
Muenke syndrome, 602849 (3) FGFR3, ACH
Muir-Torre syndrome, 158320 (3) MLH1, COCA2, HNPCC2
Muir-Torre syndrome, 158320 (3) MSH2, COCA1, FCC1, HNPCC1
Mulibrey nanism, 253250 (3) TRIM37, MUL, KIAA0898
Multiple cutaneous and uterine FH
leiomyomata, 150800 (3)
Multiple endocrine neoplasia I (3) MEN1
Multiple endocrine neoplasia IIA, 171400 (3) RET, MEN2A
Multiple endocrine neoplasia IIB, 162300 (3) RET, MEN2A
Multiple malignancy syndrome (3) TP53, P53, LFS1
Multiple myeloma (3) IRF4, LSIRF
Multiple myeloma, resistance to, 254500 (3) LIG4
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Multiple sclerosis, susceptibility to, 126200 MHC2TA, C2TA
(3)
Multiple sclerosis, susceptibility to, 126200 PTPRC, CD45, LCA
(3)
Multiple sulfatase deficiency, 272200 (3) SUMF1, FGE
Muscle-eye-brain disease, 253280 (3) POMGNT1, MEB
Muscle glycogenosis (3) PHKA1
Muscle hypertrophy (3) GDF8, MSTN
Muscular dystrophy, congenital, 1 C (3) FKRP, MDC1C, LGMD21
Muscular dystrophy, congenital, due to LAMA2, LAMM
partial LAMA2 deficiency, 607855 (3)
Muscular dystrophy, congenital merosin- LAMA2, LAMM
deficient, 607855 (3)
Muscular dystrophy, congenital, type 1 D, LARGE, KIAA0609, MDC1 D
608840 (3)
Muscular dystrophy, Fukuyama congenital, FCMD
253800 (3)
Muscular dystrophy, limb-girdle, type 1A, TTID, MYOT
159000 (3)
Muscular dystrophy, limb-girdle, type 2A, CAPN3, CANP3
253600 (3)
Muscular dystrophy, limb-girdle, type 2B, DYSF, LGMD2B
253601 (3)
Muscular dystrophy, limb-girdle, type 2C, SGCG, LGMD2C, DMDA1, SCG3
253700 (3)
Muscular dystrophy, limb-girdle, type 2D, SGCA, ADL, DAG2, LGMD2D, DMDA2
608099 (3)
Muscular dystrophy, limb-girdle, type 2E, SGCB, LGMD2E
604286 (3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Muscular dystrophy, limb-girdle, type 2F, SGCD, SGD, LGMD2F, CMD1 L
601287 (3)
Muscular dystrophy, limb-girdle, type 2G, TCAP, LGMD2G, CMD1 N
601954 (3)
Muscular dystrophy, limb-girdle, type 2H, TRIM32, HT2A, LGMD2H
254110 (3)
Muscular dystrophy, limb-girdle, type 21, FKRP, MDC1 C, LGMD21
607155 (3)
Muscular dystrophy, limb-girdle, type 2J, TTN, CMD1G, TMD, LGMD2J
608807 (3)
Muscular dystrophy, limb-girdle, type 2K, POMT1
609308 (3)
Muscular dystrophy, limb-girdle, type IC, CAV3, LGMD1 C
607801 (3)
Muscular dystrophy, rigid spine, 1, 602771 SEPN1, SELN, RSMD1
(3)
Muscular dystrophy with epidermolysis PLEC1, PLTN, EBS1
bullosa simplex, 226670 (3)
Myasthenia, familial infantile, 1, 605809 (3) CMS1A1, FIM1
Myasthenic syndrome (3) SCN4A, HYPP, NAC1A
Myasthenic syndrome, congenital, CHRNB1, ACHRB, SCCMS, CMS2A,
associated with acetylcholine receptor CMS1 D
deficiency, 608931 (3)
Myasthenic syndrome, congenital, CHRNE, SCCMS, CMS2A, FCCMS,
associated with acetylcholine receptor CMS1 E, CMS1 D
deficiency, 608931 (3)
Myasthenic syndrome, congenital, RAPSN, CMS1 D, CMS1 E
associated with acetylcholine receptor
deficiency, 608931 (3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Myasthenic syndrome, congenital, CHAT, CMS1A2
associated with episodic apnea, 254210 (3)
Myasthenic syndrome, congenital, RAPSN, CMS1 D, CMS1 E
associated with facial dysmorphism and
acetylcholine receptor deficiency, 608931 (3)
Myasthenic syndrome, fast-channel CHRNA1, ACHRD, CMS2A, SCCMS,
congenital, 608930 (3) FCCMS
Myasthenic syndrome, fast-channel CHRND, ACHRD, SCCMS, CMS2A,
congenital, 608930 (3) FCCMS
Myasthenic syndrome, fast-channel CHRNE, SCCMS, CMS2A, FCCMS,
congenital, 608930 (3) CMS1 E, CMS1 D
Myasthenic syndrome, slow-channel CHRNA1, ACHRD, CMS2A, SCCMS,
congenital, 601462 (3) FCCMS
Myasthenic syndrome, slow-channel CHRNB1, ACHRB, SCCMS, CMS2A,
congenital, 601462 (3) CMS1 D
Myasthenic syndrome, slow-channel CHRND, ACHRD, SCCMS, CMS2A,
congenital, 601462 (3) FCCMS
Myasthenic syndrome, slow-channel CHRNE, SCCMS, CMS2A, FCCMS,
congenital, 601462 (3) CMS1E, CMS1D
Mycobacterial and salmonella infections, IL12RB1
susceptibility to, 209950 (3)
Mycobacterial infection, atypical, familial IFNGR1
disseminated, 209950 (3)
Mycobacterial infection, atypical, familial IFNGR2, IFNGT1, IFGR2
disseminated, 209950 (3)
Mycobacterial infection, atypical, familial STAT1
disseminated, 209950 (3)
Mycobacterium tuberculosis, suceptibility to NRAMP1, NRAMP
infection by, 607948 (3)
Myelodysplasia syndrome-1 (3) MDS1
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Myelodysplastic syndrome (3) FACL6, ACS2
Myelodysplastic syndrome, preleukemic (3) IRF1, MAR
Myelofibrosis, idiopathic, 254450 (3) JAK2
Myelogenous leukemia, acute (3) FACL6, ACS2
Myelogenous leukemia, acute (3) IRF1, MAR
Myeloid leukemia, acute, M4Eo subtype (3) CBFB
Myeloid malignancy, predisposition to (3) CSF1 R, FMS
Myelokathexis, isolated (3) CXCR4, D2S201 E, NPY3R, WHIM
Myelomonocytic leukemia, chronic (3) PDGFRB, PDGFR
Myeloperoxidase deficiency, 254600 (3) MPO
Myeloproliferative disorder with eosinophilia, PDGFRB, PDGFR
131440 (3)
Myoadenylate deaminase deficiency (3) AMPD1
Myocardial infarction, decreased F7
susceptibility to (3)
Myocardial infarction susceptibility (3) APOE, AD2
Myocardial infarction, susceptibility to (3) ACE, DCP1, ACE1
Myocardial infarction, susceptibility to (3) ALOX5AP, FLAP
Myocardial infarction, susceptibility to (3) LGALS2
Myocardial infarction, susceptibility to (3) LTA, TNFB
Myocardial infarction, susceptibility to (3) OLR1, LOX1
Myocardial infarction, susceptibility to (3) THBD, THRM
Myocardial infarction, susceptibility to, GCLM, GLCLR
608446 (3)
Myocardial infarction, susceptibility to, TNFSF4, GP34, OX4OL
608446 (3)
Myoclonic epilepsy, juvenile, 1, 254770 (3) EFHC1, FLJ10466, EJM1
Myoclonic epilepsy, severe, of infancy, GABRG2, GEFSP3, CAE2, ECA2
607208 (3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Myoclonic epilepsy with mental retardation ARX, ISSX, PRTS, MRXS1, MRX36,
and spasticity, 300432 (3) MRX54
Myoglobinuria/hemolysis due to PGK PGK1, PGKA
deficiency (3)
Myokymia with neonatal epilepsy, 606437 KCNQ2, EBN1
(3)
Myoneurogastrointestinal ECGF1
encephalomyopathy syndrome, 603041 (3)
Myopathy, actin, congenital, with cores (3) ACTA1, ASMA, NEM3, NEM1
Myopathy, actin, congenital, with excess of ACTA1, ASMA, NEM3, NEM1
thin myofilaments, 161800 (3)
Myopathy, cardioskeletal, desmin-related, CRYAB, CRYA2, CTPP2
with cataract, 608810 (3)
Myopathy, centronuclear, 160150 (3) MYF6
Myopathy, congenital (3) ITGA7
Myopathy, desmin-related, cardioskeletal, DES, CMD11
601419 (3)
Myopathy, distal, with anterior tibial onset, DYSF, LGMD2B
606768 (3)
Myopathy, distal, with decreased caveolin 3 CAV3, LGMD1C
(3)
Myopathy due to CPT II deficiency, 255110 CPT2
(3)
Myopathy due to phosphoglycerate mutase PGAM2, PGAMM
deficiency (3)
Myopathy, Laing distal, 160500 (3) MYH7, CMH1, MPD1
Myopathy, myosin storage, 608358 (3) MYH7, CMH1, MPD1
Myopathy, nemaline, 3, 161800 (3) ACTA1, ASMA, NEM3, NEM1
Myotilinopathy, 609200 (3) TTID, MYOT
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Myotonia congenita, atypical, SCN4A, HYPP, NAC1A
acetazolamide-responsive, 608390 (3)
Myotonia congenita, dominant, 160800 (3) CLCN1
Myotonia congenita, recessive, 255700 (3) CLCN1
Myotonia levior, recessive (3) CLCN1
Myotonic dystrophy, 160900 (3) DMPK, DM, DMK
Myotonic dystrophy, type 2, 602668 (3) ZNF9, CNBP1, DM2, PROMM
Myotubular myopathy, X-linked, 310400 (3) MTM1, MTMX
Myxoid liposarcoma (3) DDIT3, GADD153, CHOP10
Myxoma, intracardiac, 255960 (3) PRKAR1A, TSE1, CNC1, CAR
N-acetylglutamate synthase deficiency, NAGS
237310 (3)
Nail-patella syndrome, 161200 (3) LMX1B, NPS1
Nail-patella syndrome with open-angle LMX1 B, NPS1
glaucoma, 137750 (3)
Nance-Horan syndrome, 302350 (3) NHS
Narcolepsy, 161400 (3) HCRT, OX
Nasopharyngeal carcinoma, 161550 (3) TP53, P53, LFS1
Nasu-Hakola disease, 221770 (3) TREM2
Nasu-Hakola disease, 221770 (3) TYROBP, PLOSL, DAP12
Naxos disease, 601214 (3) JUP, DP3, PDGB
Nemaline myopathy, 161800 (3) TPM2, TMSB, AMCD1, DA1
Nemaline myopathy 1, autosomal dominant, TPM3, NEM1
161800 (3)
Nemaline myopathy 2, autosomal recessive, NEB, NEM2
256030 (3)
Nemaline myopathy, Amish type, 605355 TNNT1, ANM
(3)
Neonatal ichthyosis-sclerosing cholangitis CLDN1, SEMP1
syndrome, 607626 (3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Nephrogenic syndrome of inappropriate AVPR2, DIR, D11, ADHR
antidiuresis, 300539 (3)
Nephrolithiasis, type I, 310468 (3) CLCN5, CLCK2, NPHL2, DENTS
Nephrolithiasis, uric acid, susceptibility to, ZNF365, UAN
605990 (3)
Nephronophthisis 2, infantile, 602088 (3) INVS, INV, NPHP2, NPH2
Nephronophthisis 4, 606966 (3) NPHP4, SLSN4
Nephronophthisis, adolescent, 604387 (3) NPHP3, NPH3
Nephronophthisis, juvenile, 256100 (3) NPHP1, NPH1, SLSN1
Nephropathy, chronic hypocomplementemic HF1, CFH, HUS
(3)
Nephropathy with pretibial epidermolysis CD151, PETA3, SFA1
bullosa and deafness, 609057 (3)
Nephrosis-1, congenital, Finnish type, NPHS1, NPHN
256300 (3)
Nephrotic syndrome, steroid-resistant, PDCN, NPHS2, SRN1
600995 (3)
Netherton syndrome, 256500 (3) SPIN KS, LEKTI
Neural tube defects, maternal risk of, MTHFD, MTHFC
601634 (3)
Neuroblastoma, 256700 (3) NME1, NM23
Neuroblastoma, 256700 (3) PMX2B, NBPHOX, PHOX2B
Neurodegeneration, pantothenate kinase- PANK2, NBIA1, PKAN, HARP
associated, 234200 (3)
Neuroectodermal tumors, supratentorial PMS2, PMSL2, HNPCC4
primitive, with cafe-au-lait spots, 608623 (3)
Neurofibromatosis, familial spinal, 162210 NF1, VRNF, WSS, NFNS
(3)
Neurofibromatosis-Noonan syndrome, NF1, VRNF, WSS, NFNS
601321 (3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Neurofibromatosis, type 1 (3) NF1, VRNF, WSS, NFNS
Neurofibromatosis, type 2, 101000 (3) NF2
Neurofibromatosis, type I, with leukemia, MSH2, COCA1, FCC1, HNPCC1
162200 (3)
Neurofibrosarcoma (3) MXI1
Neuropathy, congenital hypomyelinating, 1, EGR2, KROX20
605253 (3)
Neuropathy, congenital hypomyelinating, MPZ, CMT1 B, CMTD13, CHM, DSS
605253 (3)
Neuropathy, distal hereditary motor, 608634 HSPB1, HSP27, CMT2F
(3)
Neuropathy, distal hereditary motor, type 11, HSPB8, H11, E21G1, DHMN2
158590 (3)
Neuropathy, hereditary sensory and SPTLC1, LBC1, SPT1, HSN1, HSAN
autonomic, type 1, 162400 (3)
Neuropathy, hereditary sensory and NGFB, HSAN5
autonomic, type V, 608654 (3)
Neuropathy, hereditary sensory, type 11, HSN2
201300 (3)
Neuropathy, recurrent, with pressure PMP22, CMT1A, CMT1E, DSS
palsies, 162500 (3)
Neutropenia, alloimmune neonatal (3) FCGR3A, CD16, IGFR3
Neutropenia, congenital, 202700 (3) ELA2
Neutropenia, severe congenital, 202700 (3) GF11, ZNF163
Neutropenia, severe congenital, X-linked, WAS, IMD2, THC
300299 (3)
Neutrophil immunodeficiency syndrome, RAC2
608203 (3)
Nevo syndrome, 601451 (3) PLOD, PLOD1
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Nevus, epidermal, epidermolytic KRT10
hyperkeratotic type, 600648 (3)
Newfoundland rod-cone dystrophy, 607476 RLBP1
(3)
Nicotine addiction, protection from (3) CYP2A6, CYP2A3, CYP2A, P450C2A
Nicotine addiction, susceptibility to, 188890 CHRNA4, ENFL1
(3)
Nicotine dependence, susceptibility to, GPR51, GABBR2
188890 (3)
Niemann-Pick disease, type A, 257200 (3) SMPD1, NPD
Niemann-Pick disease, type B, 607616 (3) SMPD1, NPD
Niemann-Pick disease, type C1, 257220 (3) NPC1, NPC
Niemann-pick disease, type C2, 607625 (3) NPC2, HE1
Niemann-Pick disease, type D, 257220 (3) NPC1, NPC
Night blindness, congenital stationary (3) GNAT1
Night blindness, congenital stationary, type CSNB1, NYX
1,310500(3)
Night blindness, congenital stationary, type PDE6B, PDEB, CSNB3
3,163500(3)
Night blindness, congenital stationary, X- CACNA1 F, CSNB2
linked, type 2, 300071 (3)
Night blindness, congenital stationery, RHO, RP4, OPN2
rhodopsin-related (3)
Nijmegen breakage syndrome, 251260 (3) NBS1, NBS
Nonaka myopathy, 605820 (3) GNE, GLCNE, IBM2, DMRV, NM
Noncompaction of left ventricular TAZ, EFE2, BTHS, CMD3A, LVNCX
myocardium, isolated, 300183 (3)
Non-Hodgkin lymphoma, somatic, 605027 CASP10, MCH4, ALPS2
(3)
Nonsmall cell lung cancer (3) IRF1, MAR
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Nonsmall cell lung cancer, response to EGFR
tyrosine kinase inhibitor in, 211980 (3)
Nonsmall cell lung cancer, somatic (3) BRAF
Noonan syndrome 1, 163950 (3) PTPN11, PTP2C, SHP2, NS1
Norrie disease (3) NDP, ND
Norum disease, 245900 (3) LCAT
Norwalk virus infection, resistance to (3) FUT2, SE
Nucleoside phosphorylase deficiency, NP
immunodeficiency due to (3)
Obesity, adrenal insufficiency, and red hair POMC
(3)
Obesity, autosomal dominant, 601665 (3) MC4R
Obesity, hyperphagia, and developmental AKR1C2, DDH2, DD2, HAKRD
delay (3)
Obesity, hyperphagia, and developmental NTRK2, TRKB
delay (3)
Obesity, late-onset, 601665 (3) AGRP, ART, AGRT
Obesity, mild, early-onset, 601665 (3) NR0B2, SHP
Obesity, morbid, with hypogonadism (3) LEP, OB
Obesity, morbid, with hypogonadism (3) LEPR, OBR
Obesity, resistance to (3) PPARG, PPARG1, PPARG2
Obesity, severe, 601665 (3) PPARG, PPARG1, PPARG2
Obesity, severe, 601665 (3) SIM1
Obesity, severe, and type II diabetes, UCP3
601665 (3)
Obesity, severe, due to leptin deficiency (3) LEP, OB
Obesity, severe, susceptibility to, 601665 (3) MC3R
Obesity, susceptibility to, 300306 (3) SLC6A14, OBX
Obesity, susceptibility to, 601665 (3) ADRB2
Obesity, susceptibility to, 601665 (3) ADRB3
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Obesity, susceptibility to, 601665 (3) CART
Obesity, susceptibility to, 601665 (3) ENPP1, PDNP1, NPPS, M6S1, PCA1
Obesity, susceptibility to, 601665 (3) GHRL
Obesity, susceptibility to, 601665 (3) UCP1
Obesity, susceptibility to, 601665 (3) UCP2
Obestiy with impaired prohormone PCSK1, NEC1, PC1, PC3
processing, 600955 (3)
Obsessive-compulsive disorder 1, 164230 SLC6A4, HTT, OCD1
(3)
Obsessive-compulsive disorder, protection BDNF
against, 164230 (3)
Obsessive-compulsive disorder, HTR2A
susceptibility to, 164230 (3)
Occipital horn syndrome, 304150 (3) ATP7A, MNK, MK, OHS
Ocular albinism, Nettleship-Falls type (3) OA1
Oculocutaneous albinism, type II, modifier of MC1 R
(3)
Oculocutaneous albinism, type IV, 606574 MATP, AIM1
(3)
Oculodentodigital dysplasia, 164200 (3) GJA1, CX43, ODDD, SDTY3, ODOD
Oculofaciocardiodental syndrome, 300166 BCOR, KIAA1575, MAA2, ANOP2
(3)
Oculopharyngeal muscular dystorphy, PABPN1, PABP2, PAB2
164300 (3)
Oculopharyngeal muscular dystrophy, PABPN1, PABP2, PAB2
autosomal recessive, 257950 (3)
Odontohypophosphatasia, 146300 (3) ALPL, HOPS, TNSALP
Oguchi disease-1, 258100 (3) SAG
Oguchi disease-2, 258100 (3) RHOK, RK, GRK1
Oligodendroglioma, 137800 (3) PTEN, MMAC1
148
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Oligodontia, 604625 (3) PAX9
Oligodontia-colorectal cancer syndrome, AXIN2
608615 (3)
Omenn syndrome, 603554 (3) DCLRE1C, ARTEMIS, SCIDA
Omenn syndrome, 603554 (3) RAG1
Omenn syndrome, 603554 (3) RAG2
Opitz G syndrome, type I, 300000 (3) MID1, OGS1, BBBG1, FXY, OSX
Opremazole poor metabolizer (3) CYP2C, CYP2C19
Optic atrophy 1, 165500 (3) OPA1, NTG, NPG
Optic atrophy and cataract, 165300 (3) OPA3, MGA3
Optic nerve coloboma with renal disease, PAX2
120330 (3)
Optic nerve hypoplasia/aplasia, 165550 (3) PAX6, AN2, MGDA
Oral-facial-digital syndrome 1, 311200 (3) OFD1, CXorf5
Ornithine transcarbamylase deficiency, OTC
311250 (3)
Orofacial cleft 6, 608864 (3) IRF6, VWS, LPS, PIT, PPS, OFC6
Orolaryngeal cancer, multiple, (3) CDKN2A, MTS1, P16, MLM, CMM2
Oroticaciduria (3) UMPS, OPRT
Orthostatic intolerance, 604715 (3) SLC6A2, NAT1, NET1
OSMED syndrome, 215150 (3) COL11A2, STL3, DFNA13
Osseous heteroplasia, progressive, 166350 GNAS, GNAS1, GPSA, POH, PHP1 B,
(3) PHP1A, AHO
Ossification of posterior longitudinal ENPP1, PDNP1, NPPS, M6S1, PCA1
ligament of spine, 602475 (3)
Osteoarthritis, hand, susceptibility to, MATN3, EDM5, HOA
607850 (3)
Osteoarthritis of hip, female-specific, FRZB, FRZB1, SRFP3
susceptibility to, 165720 (3)
Osteoarthritis, susceptibility to, 165720 (3) ASPN, PLAP1
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Osteoarthrosis, 165720 (3) COL2A1
Osteogenesis imperfecta, 3 clinical forms, COL1A2
166200, 166210, 259420 (3)
Osteogenesis imperfecta, type I, 166200 (3) COL1A1
Osteogenesis imperfecta, type II, 166210 COL1A1
(3)
Osteogenesis imperfecta, type III, 259420 COL1A1
(3)
Osteogenesis imperfecta, type IV, 166220 COL1A1
(3)
Osteolysis, familial expansile, 174810 (3) TNFRSF11A, RANK, ODFR, OFE
Osteolysis, idiopathic, Saudi type, 605156 MMP2, CLG4A, MONA
(3)
Osteopetrosis, autosomal dominant, type I, LRP5, BMND1, LRP7, LR3, OPPG,
607634 (3) VBCH2
Osteopetrosis, autosomal dominant, type II, CLCN7, CLC7, OPTA2
166600 (3)
Osteopetrosis, autosomal recessive, OSTM1, GL
259700 (3)
Osteopetrosis, recessive, 259700 (3) CLCN7, CLC7, OPTA2
Osteopetrosis, recessive, 259700 (3) TCIRG1, TIRC7, OC116, OPTB1
Osteopoikilosis, 166700 (3) LEMD3, MAN1
Osteoporosis, 166710 (3) COL1A1
Osteoporosis, 166710 (3) LRP5, BMND1, LRP7, LR3, OPPG,
VBCH2
Osteoporosis (3) CALCA, CALC1
Osteoporosis, hypophosphatemic, (3) SLC17A2, NPT2
Osteoporosis, idiopathic, 166710 (3) COL1A2
Osteoporosis, postmenopausal, CALCR, CRT
susceptibility, 166710 (3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Osteoporosis-pseudoglioma syndrome, LRP5, BMND1, LRP7, LR3, OPPG,
259770 (3) VBCH2
Osteoporosis, susceptibility to, 166710 (3) RIL
Osteosarcoma (3) TP53, P53, LFS1
Osteosarcoma, somatic, 259500 (3) CHEK2, RAD53, CHK2, CDS1, LFS2
Otopalatodigital syndrome, type I, 311300 FLNA, FLN1, ABPX, NHBP, OPD1,
(3) OPD2, FMD, MNS
Otopalatodigital syndrome, type II, 304120 FLNA, FLN1, ABPX, NHBP, OPD1,
(3) OPD2, FMD, MNS
Ovarian cancer (3) BRCA1, PSCP
Ovarian cancer (3) MSH2, COCA1, FCC1, HNPCC1
Ovarian cancer, 604370 (3) PIK3CA
Ovarian cancer, endometrial type (3) MSH6, GTBP, HNPCC5
Ovarian cancer, somatic, (3) ERBB2, NGL, NEU, HER2
Ovarian carcinoma (3) CDH1, UVO
Ovarian carcinoma (3) RRAS2, TC21
Ovarian carcinoma, endometrioid type (3) CTNNB1
Ovarian dysgenesis 1, 233300 (3) FSHR, ODG1
Ovarian dysgenesis 2, 300510 (3) BMP15, GDF9B, ODG2
Ovarian hyperstimulation syndrome, FSHR, ODG1
gestational, 608115 (3)
Ovarian sex cord tumors (3) FSHR, ODG1
Ovarioleukodystrophy, 603896 (3) EIF2B2
Ovarioleukodystrophy, 603896 (3) EIF2B4
Ovarioleukodystrophy, 603896 (3) EIF2B5, LVWM, CACH, CLE
Pachyonychia congenita, Jackson-Lawler KRT17, PC2, PCHC1
type, 167210 (3)
Pachyonychia congenita, Jackson-Lawler KRT6B, PC2
type, 167210 (3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Pachyonychia congenita, Jadassohn- KRT16
Lewandowsky type, 167200 (3)
Pachyonychia congenita, Jadassohn- KRT6A
Lewandowsky type, 167200 (3)
Paget disease, juvenile, 239000 (3) TNFRSF11 B, OPG, OCIF
Paget disease of bone, 602080 (3) SQSTM1, P62, PDB3
Paget disease of bone, 602080 (3) TNFRSF11A, RANK, ODFR, OFE
Pallidopontonigral degeneration, 168610 (3) MAPT, MTBT1, DDPAC, MSTD
Pallister-Hall syndrome, 146510 (3) GI-13, PAPA, PAPB, ACLS
Palmoplantar keratoderma, KRT16
nonepidermolytic, 600962 (3)
Palmoplantar verrucous nevus, unilateral, KRT16
144200 (3)
Pancreatic agenesis, 260370 (3) IPF1
Pancreatic cancer, 260350 (3) ARMET, ARP
Pancreatic cancer, 260350 (3) BRCA2, FANCD1
Pancreatic cancer, 260350 (3) TP53, P53, LFS1
Pancreatic cancer (3) MADH4, DPC4, SMAD4, JIP
Pancreatic cancer/melanoma syndrome, CDKN2A, MTS1, P16, MLM, CMM2
606719 (3)
Pancreatic cancer, somatic (3) ACVR1 B, ACVRLK4, ALK4
Pancreatic cancer, sporadic (3) STK11, PJS, LKB1
Pancreatic carcinoma, somatic, 260350 (3) KRAS2, RASK2
Pancreatic carcinoma, somatic (3) RBBP8, RIM
Pancreatitis, hereditary, 167800 (3) PRSS1, TRY1
Pancreatitis, hereditary, 167800 (3) SPINK1, PSTI, PCTT, TATI
Pancreatitis, idiopathic (3) CFTR, ABCC7, CF, MRP7
Papillary serous carcinoma of the BRCA1, PSCP
peritoneum (3)
Papillon-Lefevre syndrome, 245000 (3) CTSC, CPPI, PALS, PLS, HMS
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Paraganglioma, familial malignant, 168000 SDHB, SDH1, SDHIP
(3)
Paragangliomas, familial central nervous SDHD, PGL1
system, 168000 (3)
Paragangliomas, familial nonchromaffin, 1, SDHD, PGL1
with and without deafness, 168000 (3)
Paragangliomas, familial nonchromaffin, 3, SDHC, PGL3
605373 (3)
Paraganglioma, sporadic corotid body, SDHD, PGL1
168000 (3)
Paramyotonia congenita, 168300 (3) SCN4A, HYPP, NAC1A
Parathyroid adenoma, sporadic (3) MEN1
Parathyroid adenoma with cystic changes, HRPT2, C1orf28
145001 (3)
Parathyroid carcinoma, 608266 (3) HRPT2, Clorf28
Parietal foramina 1, 168500 (3) MSX2, CRS2, HOX8
Parietal foramina 2, 168500 (3) ALX4, PFM2, FPP
Parietal foramina with cleidocranial MSX2, CRS2, HOX8
dysplasia, 168550 (3)
Parkes Weber syndrome, 608355 (3) RASA1, GAP, CMAVM, PKWS
Parkinson disease, 168600 (3) NR4A2, NURR1, NOT, TINUR
Parkinson disease, 168600 (3) SNCAIP
Parkinson disease, 168600 (3) TBP, SCA17
Parkinson disease 4, autosomal dominant SNCA, NACP, PARK1, PARK4
Lewy body, 605543 (3)
Parkinson disease 7, autosomal recessive DJ1, PARK7
early-onset, 606324 (3)
Parkinson disease-8, 607060 (3) LRRK2, PARK8
Parkinson disease, early onset, 605909 (3) PINK1, PARK6
Parkinson disease, familial, 168600 (3) UCHL1, PARKS
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Parkinson disease, familial, 168601 (3) SNCA, NACP, PARK1, PARK4
Parkinson disease, juvenile, type 2, 600116 PRKN, PARK2, PDJ
(3)
Parkinson disease, resistance to, 168600 DBH
(3)
Parkinson disease, susceptibility to, 168600 NDUFV2
(3)
Paroxysmal nocturnal hemoglobinuria (3) PIGA
Paroxysmal nonkinesigenic dyskinesia, MR1, TAHCCP2, KIPP1184, BRP17,
118800 (3) PNKD, FPD1, PDC, DYT8
Partington syndrome, 309510 (3) ARX, ISSX, PRTS, MRXS1, MRX36,
MRX54
PCWH, 609136 (3) SOX10, WS4
Pelger-Huet anomaly, 169400 (3) LBR, PHA
Pelizaeus-Merzbacher disease, 312080 (3) PLP1, PMD
Pelizaeus-Merzbacher-like disease, GJA12, CX47, PMLDAR
autosomal recessive, 608804 (3)
Pendred syndrome, 274600 (3) SLC26A4, PDS, DFNB4
Perineal hypospadias (3) AR, DHTR, TFM, SBMA, KD, SMAX1
Periodic fever, familial, 142680 (3) TNFRSF1A, TNFR1, TNFAR, FPF
Periodontitis, juvenile, 170650 (3) CTSC, CPPI, PALS, PLS, HMS
Periventricular heterotopia with ARFGEF2, BIG2
microcephaly, 608097 (3)
Peroxisomal biogenesis disorder, PEX6, PXAAA1, PAF2
complementation group 4 (3)
Peroxisomal biogenesis disorder, PEX6, PXAAA1, PAF2
complementation group 6 (3)
Peroxisome biogenesis factor 12 (3) PEX12
Persistent hyperinsulinemic hypoglycemia of KCNJ11, BIR, PHHI
infancy, 256450 (3)
154
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Persistent Mullerian duct syndrome, type I, AMH, MIF
261550 (3)
Persistent Mullerian duct syndrome, type II, AMHR2, AMHR
261550 (3)
Peters anomaly, 603807 (3) PAX6, AN2, MGDA
Peters anomaly, 604229 (3) CYP1B1, GLC3A
Peutz-Jeghers syndrome, 175200 (3) STK11, PJS, LKB1
Pfeiffer syndrome, 101600 (3) FGFR1, FLT2, KAL2
Pfeiffer syndrome, 101600 (3) FGFR2, BEK, CFD1, JWS
Phenylketonuria (3) PAH, PKU1
Phenylketonuria due to dihydropteridine QDPR, DHPR
reductase deficiency (3)
Phenylketonuria due to PTS deficiency (3) PTS
Phenylthiocarbamide tasting, 171200 (3) TAS2R38, T2R61, PTC
Pheochromocytoma, 171300 (3) SDHD, PGL1
Pheochromocytoma, 171300 (3) VHL
Pheochromocytoma, extraadrenal, and SDHB, SDH1, SDHIP
cervical paraganglioma, 115310 (3)
Phosphoglycerate dehydrogenase PHGDH
deficiency, 601815 (3)
Phosphoribosyl pyrophosphate synthetase- PRPS1
related gout (3)
Phosphorylase kinase deficiency of liver and PHKB
muscle, autosomal recessive, 261750 (3)
Phosphoserine phosphatase deficiency (3) PSP
Pick disease, 172700 (3) PSEN1, AD3
Piebaldism (3) KIT, PBT
Pigmentation of hair, skin, and eyes, MATP, AIM1
variation in (3)
155
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Pigmented adrenocortical disease, primary PRKAR1A, TSE1, CNC1, CAR
isolated, 160980 (3)
Pigmented paravenous chorioretinal CRB1, RP12
atrophy, 172870 (3)
Pilomatricoma, 132600 (3) CTNNB1
Pituitary ACTH-secreting adenoma (3) GNA12, GNA12B, GIP
Pituitary ACTH secreting adenoma (3) GNAS, GNAS1, GPSA, POH, PHP1 B,
PHP1A, AHO
Pituitary adenoma, nonfunctioning (3) THRA, ERBA1, THRA1
Pituitary anomalies with holoprosencephaly- GL12
like features (3)
Pituitary hormone deficiency, combined (3) POU1F1, PIT1
Pituitary hormone deficiency, combined (3) PROP1
Pituitary hormone deficiency, combined, HESX1, RPX
HESX1-related, 182230 (3)
Pituitary hormone deficiency, combined, LHX3
with rigid cervical spine, 262600 (3)
Pituitary tumor, invasive (3) PRKCA, PKCA
Placental abruption (3) NOS3
Placental steroid sulfatase deficiency (3) STS, ARSC1, ARSC, SSDD
Plasmin inhibitor deficiency (3) PLI, SERPINF2
Plasminogen Tochigi disease (3) PLG
Platelet-activating factor acetylhydrolase PLA2G7, PAFAH
deficiency (3)
Platelet ADP receptor defect (3) P2RY12, P2Y12
Platelet disorder, familial, with associated RUNX1, CBFA2, AML1
myeloid malignancy, 601399 (3)
Platelet glycoprotein IV deficiency, 608404 CD36
(3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Pneumonitis, desquamative interstitial, SFTPC, SFTP2
263000 (3)
Pneumothorax, primary spontaneous, FLCN, BHD
173600 (3)
Polycystic kidney and hepatic disease, FCYT, PKHD1, ARPKD
263200 (3)
Polycystic kidney disease, adult type I, PKD1
173900 (3)
Polycystic kidney disease, adult, type 11 (3) PKD2, PKD4
Polycystic kidney disease, infantile severe, PKDTS
with tuberous sclerosis (3)
Polycystic liver disease, 174050 (3) PRKCSH, G19P1, PCLD
Polycystic liver disease, 174050 (3) SEC63
Polycythemia, benign familial, 263400 (3) VHL
Polycythemia vera, 263300 (3) JAK2
Polydactyly, postaxial, types Al and B, GI-13, PAPA, PAPB, ACLS
174200 (3)
Polydactyly, preaxial, type IV, 174700 (3) GI-13, PAPA, PAPB, ACLS
Polymicrogyria, bilateral frontoparietal, GPR56, TM7XN1, BFPP
606854 (3)
Polyposis, juvenile intestinal, 174900 (3) BMPR1A, ACVRLK3, ALK3
Polyposis, juvenile intestinal, 174900 (3) MADH4, DPC4, SMAD4, JIP
Popliteal pterygium syndrome, 119500 (3) IRF6, VWS, LPS, PIT, PPS, OFC6
Porencephaly, 175780 (3) COL4A1
Porphyria, acute hepatic (3) ALAD
Porphyria, acute intermittent (3) HMBS, PBGD, UPS
Porphyria, acute intermittent, nonerythroid HMBS, PBGD, UPS
variant (3)
Porphyria, congenital erythropoietic, 263700 UROS
(3)
157
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Porphyria cutanea tarda (3) UROD
Porphyria, hepatoerythropoietic (3) UROD
Porphyria variegata, 176200 (3) HFE, HLA-H, HFE1
Porphyria variegata, 176200 (3) PPOX
PPM-X syndrome, 300055 (3) MECP2, RTT, PPMX, MRX16, MRX79
Prader-Willi syndrome, 176270 (3) NDN
Prader-Willi syndrome, 176270 (3) SNRPN
Precocious puberty, male, 176410 (3) LHCGR
Preeclampsia/eclampsia 4 (3) STOX1, PEE4
Preeclampsia, susceptibility to, 189800 (3) EPHX1
Preeclampsia, susceptibility to (3) AGT, SERPINA8
Prekallikrein deficiency (3) KLKB1, KLK3
Premature chromosome condensation with MCPH1
microcephaly and mental retardation,
606858 (3)
Premature ovarian failure, 300511 (3) DIAPH2, DIA, POF2
Premature ovarian failure 3, 608996 (3) FOXL2, BPES, BPES1, PFRK, POF3
Primary lateral sclerosis, juvenile, 606353 ALS2, ALSJ, PLSJ, IAHSP
(3)
Prion disease with protracted course, PRNP, PRIP
606688 (3)
Progressive external ophthalmoplegia with ClOorf2, TWINKLE, PEO1, PEO
mitochondrial DNA deletions, 157640 (3)
Progressive external ophthalmoplegia with POLG, POLG1, POLGA, PEO
mitochondrial DNA deletions, 157640 (3)
Progressive external ophthalmoplegia with SLC25A4, ANTI, T1, PEO3
mitochondrial DNA deletions, 157640 (3)
Proguanil poor metabolizer (3) CYP2C, CYP2C19
Prolactinoma, hyperparathyroidism, MEN1
carcinoid syndrome (3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Prolidase deficiency (3) PEPD
Properdin deficiency, X-linked, 312060 (3) PFC, PFD
Propionicacidemia, 606054 (3) PCCA
Propionicacidemia, 606054 (3) PCCB
Prostate cancer 1, 176807, 601518 (3) RNASEL, RNS4, PRCA1, HPC1
Prostate cancer, 176807 (3) BRCA2, FANCD1
Prostate cancer, 176807 (3) PTEN, MMAC1
Prostate cancer (3) AR, DHTR, TFM, SBMA, KD, SMAX1
Prostate cancer, familial, 176807 (3) CHEK2, RAD53, CHK2, CDS1, LFS2
Prostate cancer, hereditary, 176807 (3) MSR1
Prostate cancer, progression and EPHB2, EPHT3, DRT, ERK
metastasis of, 176807 (3)
Prostate cancer, somatic, 176807 (3) KLF6, COPEB, BCD1, ZF9
Prostate cancer, somatic, 176807 (3) MAD1L1, TXBP181
Prostate cancer, susceptibility to, 176807 AR, DHTR, TFM, SBMA, KD, SMAX1
(3)
Prostate cancer, susceptibility to, 176807 ATBF1
(3)
Prostate cancer, susceptibility to, 176807 ELAC2, HPC2
(3)
Prostate cancer, susceptibility to, 176807 MXI1
(3)
Protein S deficiency (3) PROS1
Proteinuria, low molecular weight, with CLCN5, CLCK2, NPHL2, DENTS
hypercalciuric nephrocalcinosis (3)
Protoporphyria, erythropoietic (3) FECH, FCE
Protoporphyria, erythropoietic, recessive, FECH, FCE
with liver failure (3)
Proud syndrome, 300004 (3) ARX, ISSX, PRTS, MRXS1, MRX36,
MRX54
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Pseudoachondroplasia, 177170 (3) COMP, EDM1, MED, PSACH
Pseudohermaphroditism, male, with HSD17B3, EDH17B3
gynecomastia, 264300 (3)
Pseudohermaphroditism, male, with Leydig LHCGR
cell hypoplasia (3)
Pseudohypoaldosteronism, type I, 264350 SCNN1A
(3)
Pseudohypoaldosteronism, type I, 264350 SCNN1B
(3)
Pseudohypoaldosteronism, type I, 264350 SCNN1G, PHA1
(3)
Pseudohypoaldosteronism type I, autosomal NR3C2, MLR, MCR
dominant, 177735 (3)
Pseudohypoaldosteronism type II (3) WNK4, PRKWNK4, PHA2B
Pseudohypoaldosteronism, type IIC, 145260 WNK1, PRKWNK1, KDP, PHA2C
(3)
Pseudohypoparathyroidism, type la, 103580 GNAS, GNAS1, GPSA, POH, PHP1 B,
(3) PHP1A, AHO
Pseudohypoparathyroidism, type Ib, 603233 GNAS, GNAS1, GPSA, POH, PHP1 B,
(3) PHP1A, AHO
Pseudovaginal perineoscrotal hypospadias, SRD5A2
264600 (3)
Pseudovitamin D deficiency rickets 1 (3) CYP27B1, PDDR, VDD1
Pseudoxanthoma elasticum, autosomal ABCC6, ARA, ABC34, MLP1, PXE
dominant, 177850 (3)
Pseudoxanthoma elasticum, autosomal ABCC6, ARA, ABC34, MLP1, PXE
recessive, 264800 (3)
Psoriasis, susceptibility to, 177900 (3) PSORS6
Psoriatic arthritis, susceptibility to, 607507 CARD15, NOD2, IBD1, CD, ACUG,
(3) PSORAS1
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Pulmonary alveolar proteinosis, 265120 (3) CSF2RB
Pulmonary alveolar proteinosis, 265120 (3) SFTPC, SFTP2
Pulmonary alveolar proteinosis, congenital, SFTPB, SFTB3
265120 (3)
Pulmonary fibrosis, idiopathic, familial, SFTPC, SFTP2
178500 (3)
Pulmonary fibrosis, idiopathic, susceptibility SFTPA1, SFTP1
to, 178500 (3)
Pulmonary hypertension, familial primary, BMPR2, PPH1
178600 (3)
Pycnodysostosis, 265800 (3) CTSK
Pyloric stenosis, infantile hypertrophic, NOS1
susceptibility to, 179010 (3)
Pyogenic sterile arthritis, pyoderma PSTPIP1, PSTPIP, CD2BP1, PAPAS
gangrenosum, and acne, 604416 (3)
Pyropoikilocytosis (3) SPTA1
Pyruvate carboxylase deficiency, 266150 (3) PC
Pyruvate dehydrogenase deficiency (3) PDHA1, PHE1A
Pyruvate dehydrogenase El-beta deficiency PDHB
(3)
Rabson-Mendenhall syndrome, 262190 (3) INSR
Radioulnar synostosis with amegakaryocytic HOXA1 1, HOX1 I
thrombocytopenia, 605432 (3)
RAPADILINO syndrome, 266280 (3) RECQL4, RTS, RECQ4
Rapid progression to AIDS from HIV1 CX3CR1, GPR13, V28
infection (3)
Rapp-Hodgkin syndrome, 129400 (3) TP73L, TP63, KET, EEC3, SHFM4,
LMS, RHS
Red hair/fair skin (3) MC1 R
Refsum disease, 266500 (3) PEX7, RCDP1
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DISEASE/DISORDER/INDICATION GENE(S)
Refsum disease, 266500 (3) PHYH, PAHX
Refsum disease, infantile, 266510 (3) PEX1, ZWS1
Refsum disease, infantile form, 266510 (3) PEX26
Refsum disease, infantile form, 266510 (3) PXMP3, PAF1, PMP35, PEX2
Renal carcinoma, chromophobe, somatic, FLCN, BHD
144700 (3)
Renal cell carcinoma, 144700 (3) TRC8, RCA1, HRCA1
Renal cell carcinoma, clear cell, somatic, OGG1
144700 (3)
Renal cell carcinoma, papillary, 1, 605074 PRCC, RCCP1
(3)
Renal cell carcinoma, papillary, 1, 605074 TFE3
(3)
Renal cell carcinoma, papillary, familial and MET
sporadic, 605074 (3)
Renal cell carcinoma, somatic (3) VHL
Renal glucosuria, 233100 (3) SLC5A2, SGLT2
Renal hypoplasia, isolated (3) PAX2
Renal tubular acidosis, distal, 179800, SLC4A1, AE1, EPB3
602722 (3)
Renal tubular acidosis, distal, autosomal ATP6VOA4, ATP6N 1 B, VPP2, RTA1 C,
recessive, 602722 (3) RTADR
Renal tubular acidosis-osteopetrosis CA2
syndrome (3)
Renal tubular acidosis, proximal, with ocular SLC4A4, NBC1, KNBC, SLC4A5
abnormalities, 604278 (3)
Renal tubular acidosis with deafness, ATP6B1, VPP3
267300 (3)
Renal tubular dysgenesis, 267430 (3) ACE, DCP1, ACE1
Renal tubular dysgenesis, 267430 (3) AGTR1, AGTR1A, AT2R1
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Renal tubular dysgenesis, 267430 (3) AGT, SERPINA8
Renal tubular dysgenesis, 267430 (3) REN
Renpenning syndrome, 309500 (3) PQBP1, NPW38, SHS, MRX55,
MRXS3, RENS1, MRXS8
Response to morphine-6-glucuronide (3) OPRM1
Resting heart rate, 607276 (3) ADRB1, ADRB1R, RHR
Restrictive dermopathy, lethal, 275210 (3) ZMPSTE24, FACE1, STE24, MADB
Retinal degeneration, autosomal recessive, NRL, D14S46E, RP27
clumped pigment type (3)
Retinal degeneration, autosomal recessive, PROM1, PROML1, AC133
prominin-related (3)
Retinal degeneration, late-onset, autosomal CIQTNF5, CTRP5, LORD
dominant, 605670 (3)
Retinal dystrophy, early-onset severe (3) LRAT
Retinitis pigmentosa-10, 180105 (3) IMPDH1
Retinitis pigmentosa-11, 600138 (3) PRPF31, PRP31
Retinitis pigmentosa-1, 180100 (3) RP1, ORP1
Retinitis pigmentosa-12, autosomal CRB1, RP12
recessive, 600105 (3)
Retinitis pigmentosa-13, 600059 (3) PRPF8, PRPC8, RP13
Retinitis pigmentosa-14, 600132 (3) TULP1, RP14
Retinitis pigmentosa-17, 600852 (3) CA4, RP17
Retinitis pigmentosa-18, 601414 (3) HPRP3, RP18
Retinitis pigmentosa-19, 601718 (3) ABCA4, ABCR, STGD1, FFM, RP19
Retinitis pigmentosa-20 (3) RPE65, RP20
Retinitis pigmentosa-2 (3) RP2
Retinitis pigmentosa-26, 608380 (3) CERKL
Retinitis pigmentosa-27 (3) NRL, D14S46E, RP27
Retinitis pigmentosa-30, 607921 (3) FSCN2, RFSN
Retinitis pigmentosa-3, 300389 (3) RPGR, RP3, CRD, RP15, COD1
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Retinitis pigmentosa-4, autosomal dominant RHO, RP4, OPN2
(3)
Retinitis pigmentosa-7, 608133 (3) RDS, RP7, PRPH2, PRPH, AVMD,
AOFMD
Retinitis pigmentosa-9, 180104 (3) RP9
Retinitis pigmentosa, AR, 268000 (3) RLBP1
Retinitis pigmentosa, AR, without hearing USH2A
loss, 268000 (3)
Retinitis pigmentosa, autosomal dominant RGR
(3)
Retinitis pigmentosa, autosomal recessive, CNGB1, CNCG3L, CNCG2
268000 (3)
Retinitis pigmentosa, autosomal recessive CNGA1, CNCG1
(3)
Retinitis pigmentosa, autosomal recessive PDE6A, PDEA
(3)
Retinitis pigmentosa, autosomal recessive PDE6B, PDEB, CSNB3
(3)
Retinitis pigmentosa, autosomal recessive RGR
(3)
Retinitis pigmentosa, autosomal recessive RHO, RP4, OPN2
(3)
Retinitis pigmentosa, digenic (3) ROM1, ROSP1
Retinitis pigmentosa, digenic, 608133 (3) RDS, RP7, PRPH2, PRPH, AVMD,
AOFMD
Retinitis pigmentosa, juvenile (3) AIPL1, LCA4
Retinitis pigmentosa, late onset, 268000 (3) NR2E3, PNR, ESCS
Retinitis pigmentosa, late-onset dominant, CRX, CORD2, CRD
268000 (3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Retinitis pigmentosa, MERTK-related, MERTK
268000 (3)
Retinitis pigmentosa, X-linked with deafness RPGR, RP3, CRD, RP15, COD1
and sinorespiratory infections, 300455 (3)
Retinitis pigmentosa, X-linked, with RPGR, RP3, CRD, RP15, COD1
recurrent respiratory infections, 300455 (3)
Retinitis punctata albescens, 136880 (3) RDS, RP7, PRPH2, PRPH, AVMD,
AOFMD
Retinitis punctata albescens, 136880 (3) RLBP1
Retinoblastoma (3) RB1
Retinol binding protein, deficiency of (3) RBP4
Retinoschisis (3) RS1, XLRS1
Rett syndrome, 312750 (3) MECP2, RTT, PPMX, MRX16, MRX79
Rett syndrome, atypical, 312750 (3) CDKL5, STK9
Rett syndrome, preserved speech variant, MECP2, RTT, PPMX, MRX16, MRX79
312750 (3)
Rhabdoid predisposition syndrome, familial SMARCB1, SNF5, IN11, RDT
(3)
Rhabdoid tumors (3) SMARCB1, SNF5, IN11, RDT
Rhabdomyosarcoma, 268210 (3) SLC22A1L, BWSCR1A, IMPT1
Rhabdomyosarcoma, alveolar, 268220 (3) FOXO1A, FKHR
Rhabdomyosarcoma, alveolar, 268220 (3) PAX3, WS1, HUP2, CDHS
Rhabdomyosarcoma, alveolar, 268220 (3) PAX7
Rheumatoid arthritis, progression of, IL10, CSIF
180300 (3)
Rheumatoid arthritis, susceptibility to, MHC2TA, C2TA
180300 (3)
Rheumatoid arthritis, susceptibility to, NFKBIL1
180300 (3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Rheumatoid arthritis, susceptibility to, PAD14, PAD15, PAD
180300 (3)
Rheumatoid arthritis, susceptibility to, PTPN8, PEP, PTPN22, LYP
180300 (3)
Rheumatoid arthritis, susceptibility to, RUNX1, CBFA2, AML1
180300 (3)
Rheumatoid arthritis, susceptibility to, SLC22A4, OCTN1
180300 (3)
Rheumatoid arthritis, systemic juvenile, MIF
susceptibility to, 604302 (3)
Rhizomelic chondrodysplasia punctata, type PEX7, RCDP1
1, 215100 (3)
Rhizomelic chondrodysplasia punctata, type AGPS, ADHAPS
3, 600121 (3)
Rh-mod syndrome (3) RHAG, RH50A
Rh-negative blood type (3) RHD
Rh-null disease, amorph type (3) RHCE
Ribose 5-phosphate isomerase deficiency, RPIA, RPI
608611 (3)
Rickets due to defect in vitamin D 25- CYP2R1
hydroxylation, 600081 (3)
Rickets, vitamin D-resistant, type IIA, VDR
277440 (3)
Rickets, vitamin D-resistant, type IIB, VDR
277420 (3)
Rieger anomaly (3) FOXC1, FKHL7, FREAC3
Rieger syndrome, 180500 (3) PITX2, IDG2, RIEG1, RGS, IGDS2
Ring dermoid of cornea, 180550 (3) PITX2, IDG2, RIEG1, RGS, IGDS2
Rippling muscle disease, 606072 (3) CAV3, LGMD1C
Roberts syndrome, 268300 (3) ESCO2
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Robinow syndrome, autosomal recessive, ROR2, BDB1, BDB, NTRKR2
268310 (3)
Rokitansky-Kuster-Hauser syndrome, WNT4
277000 (3)
Rothmund-Thomson syndrome, 268400 (3) RECQL4, RTS, RECQ4
Roussy-Levy syndrome, 180800 (3) MPZ, CMT1 B, CMTD13, CHM, DSS
Roussy-Levy syndrome, 180800 (3) PMP22, CMT1A, CMT1E, DSS
Rubenstein-Taybi syndrome, 180849 (3) CREBBP, CBP, RSTS
Rubinstein-Taybi syndrome, 180849 (3) EP300
Saethre-Chotzen syndrome, 101400 (3) FGFR2, BEK, CFD1, JWS
Saethre-Chotzen syndrome, 101400 (3) TWIST, ACS3, SCS
Saethre-Chotzen syndrome with eyelid TWIST, ACS3, SCS
anomalies, 101400 (3)
Salivary adenoma (3) HMGA2, HMGIC, BABL, LIPO
Salla disease, 604369 (3) SLC17A5, SIASD, SLD
Sandhoff disease, infantile, juvenile, and HEXB
adult forms, 268800 (3)
Sanfilippo syndrome, type A, 252900 (3) SGSH, MPS3A, SFMD
Sanfilippo syndrome, type B (3) NAGLU
Sarcoidosis, early-onset, 181000 (3) CARD15, NOD2, IBD1, CD, ACUG,
PSORAS1
Sarcoidosis, susceptibility to, 181000 (3) BTNL2
Sarcoidosis, susceptibility to, 181000 (3) HLA-DR1 B
Sarcoma, synovial (3) SSX1, SSRC
Sarcoma, synovial (3) SSX2
SARS, progression of (3) ACE, DCP1, ACE1
Schimke immunoosseous dysplasia, SMARCAL1, HARP, SIOD
242900 (3)
Schindler disease, type 1, 609241 (3) NAGA
Schindler disease, type III, 609241 (3) NAGA
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Schizencephaly, 269160 (3) EMX2
Schizoaffective disorder, susceptibility to, DISC1
181500 (3)
Schizophrenia 5, 603175 (3) TRAR4
Schizophrenia, chronic (3) APP, AAA, CVAP, AD1
Schizophrenia, susceptibility to, 181500 (3) COMT
Schizophrenia, susceptibility to, 181500 (3) DISC1
Schizophrenia, susceptibility to, 181500 (3) HTR2A
Schizophrenia, susceptibility to, 181500 (3) RTN4R, NOGOR
Schizophrenia, susceptibility to, 181500 (3) SYN2
Schizophrenia, susceptibility to, 181510 (3) EPN4, EPNR, KIAA0171, SCZD1
Schizophrenia, susceptibility to, 4 600850 PRODH, PRODH2, SCZD4
(3)
Schwannomatosis, 162091 (3) NF2
Schwartz-Jampel syndrome, type 1, 255800 HSPG2, PLC, SJS, SJA, SJS1
(3)
SCID, autosomal recessive, T-negative/B- JAK3, JAKL
positive type (3)
Sclerosteosis, 269500 (3) SOST
Scurvy (3) GULOP, GULO
Sea-blue histiocyte disease, 269600 (3) APOE, AD2
Seasonal affective disorder, susceptibility to, HTR2A
608516 (3)
Sebastian syndrome, 605249 (3) MYH9, MHA, FTNS, DFNA17
Seckel syndrome 1, 210600 (3) ATR, FRP1, SCKL
Segawa syndrome, recessive (3) TH, TYH
Seizures, afebrile, 604233 (3) SCN2A1, SCN2A
Seizures, benign familial neonatal-infantile, SCN2A1, SCN2A
607745 (3)
Selective T-cell defect (3) ZAP70, SRK, STD
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Self-healing collodion baby, 242300 (3) TGM1, ICR2, LI1
SEMD, Pakistani type (3) PAPSS2, ATPSK2
Senior-Loken syndrome-1, 266900 (3) NPHP1, NPH1, SLSN1
Senior-Loken syndrome 4, 606996 (3) NPHP4, SLSN4
Senior-Loken syndrome 5, 609254 (3) IQCB1, NPHP5, KIAA0036
Sensory ataxic neuropathy, dysarthria, and POLG, POLG1, POLGA, PEO
ophthalmoparesis, 157640 (3)
Sepiapterin reductase deficiency (3) SPR
Sepsis, susceptibility to (3) CASP12, CASP12P1
Septic shock, susceptibility to (3) TNF, TNFA
Septooptic dysplasia, 182230 (3) HESX1, RPX
Sertoli cell-only syndrome, susceptibility to, USP26
305700 (3)
Severe combined immunodeficiency, DCLREIC, ARTEMIS, SCIDA
Athabascan type, 602450 (3)
Severe combined immunodeficiency, B cell- RAG1
negative, 601457 (3)
Severe combined immunodeficiency, B cell- RAG2
negative, 601457 (3)
Severe combined immunodeficiency due to ADA
ADA deficiency, 102700 (3)
Severe combined immunodeficiency due to PTPRC, CD45, LCA
PTPRC deficiency (3)
Severe combined immunodeficiency, T-cell IL7R
negative, B-cell/natural killer cell-positive
type, 600802 (3)
Severe combined immunodeficiency, T- CD3D, T3D
negative/B-positive type, 600802 (3)
Severe combined immunodeficiency, X- IL2RG, SCIDX1, SCIDX, IMD4
linked, 300400 (3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Sex reversal, XY, with adrenal failure (3) FTZF1, FTZ1, SF1
Sezary syndrome (3) BCL10
Shah-Waardenburg syndrome, 277580 (3) EDN3
Short stature, autosomal dominant, with GHR
normal serum growth hormone binding
protein (3)
Short stature, idiopathic (3) GHR
Short stature, idiopathic familial, 604271 (3) SHOX, GCFX, SS, PHOG
Short stature, idiopathic familial, 604271 (3) SHOXY
Short stature, pituitary and cerebellar LHX4
defects, and small sella turcica, 606606 (3)
Shprintzen-Goldberg syndrome, 182212 (3) FBN1, MFS1, WMS
Shwachman-Diamond syndrome, 260400 SBDS, SDS
(3)
Sialic acid storage disorder, infantile, SLC17A5, SIASD, SLD
269920 (3)
Sialidosis, type I, 256550 (3) NEU1, NEU, SIAL1
Sialidosis, type II, 256550 (3) NEU1, NEU, SIAL1
Sialuria, 269921 (3) GNE, GLCNE, IBM2, DMRV, NM
Sickle cell anemia (3) HBB
Sick sinus syndrome, 608567 (3) SCN5A, LQT3, IVF, HB1, SSS1
Silver spastic paraplegia syndrome, 270685 BSCL2, SPG17
(3)
Simpson-Golabi-Behmel syndrome, type 1, GPC3, SDYS, SGBS1
312870 (3)
Sitosterolemia, 210250 (3) ABCG5
Sitosterolemia, 210250 (3) ABCG8
Situs ambiguus (3) NODAL
Situs inversus viscerum, 270100 (3) DNAH11, DNAHC11
Sjogren-Larsson syndrome, 270200 (3) ALDH3A2, ALDH10, SLS, FALDH
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Skin fragility-woolly hair syndrome, 607655 DSP, KPPS2, PPKS2
(3)
Slow acetylation (3) NAT2, AAC2
Slowed nerve conduction velocity, AD, ARHGEF10, KIAA0294
608236 (3)
Small patella syndrome, 147891 (3) TBX4
SMED Strudwick type, 184250 (3) COL2A1
Smith-Fineman-Myers syndrome, 309580 ATRX, XH2, XNP, MRXS3, SHS
(3)
Smith-Lemli-Opitz syndrome, 270400 (3) DHCR7, SLOS
Smith-Magenis syndrome, 182290 (3) RAI1, SMCR, SMS
Smith-McCort dysplasia, 607326 (3) DYM, FLJ90130, DMC, SMC
Solitary median maxillary central incisor, SHH, HPE3, HLP3, SMMCI
147250 (3)
Somatotrophinoma (3) GNAS, GNAS1, GPSA, POH, PHP1B,
PHP1A, AHO
Sorsby fundus dystrophy, 136900 (3) TIMP3, SFD
Sotos syndrome, 117550 (3) NSD1, ARA267, STO
Spastic ataxia, Charlevoix-Saguenay type, SACS, ARSACS
270550 (3)
Spastic paralysis, infantile onset ascending, ALS2, ALSJ, PLSJ, IAHSP
607225 (3)
Spastic paraplegia 10, 604187 (3) KIF5A, NKHC, SPG10
Spastic paraplegia-13, 605280 (3) HSPD1, SPG13, HSP60
Spastic paraplegia-2, 312920 (3) PLP1, PMD
Spastic paraplegia-3A, 182600 (3) SPG3A
Spastic paraplegia-4, 182601 (3) SPG4, SPAST
Spastic paraplegia-6, 600363 (3) NIPA1, SPG6
Spastic paraplegia-7, 607259 (3) PGN, SPG7, CMAR, CAR
Specific granule deficiency, 245480 (3) CEBPE, CRP1
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Speech-language disorder-1, 602081 (3) FOXP2, SPCH1, TNRC10, CAGH44
Spermatogenic failure, susceptibility to (3) DAZL, DAZH, SPGYLA
Spherocytosis-1 (3) SPTB
Spherocytosis-2 (3) ANK1, SPH2
Spherocytosis, hereditary (3) SLC4A1, AE1, EPB3
Spherocytosis, hereditary, Japanese type EPB42
(3)
Spherocytosis, recessive (3) SPTA1
Spina bifida, 601634 (3) MTHFD, MTHFC
Spina bifida, risk of, 601634, 182940(3) MTR
Spina bifida, risk of, 601634, 182940(3) MTRR
Spinal and bulbar muscular atrophy of AR, DHTR, TFM, SBMA, KD, SMAX1
Kennedy, 313200 (3)
Spinal muscrular atrophy, late-onset, Finkel VAPB, VAPC, ALS8
type, 182980 (3)
Spinal muscular atrophy-1, 253300 (3) SMN1, SMA1, SMA2, SMA3, SMA4
Spinal muscular atrophy-2, 253550 (3) SMN1, SMA1, SMA2, SMA3, SMA4
Spinal muscular atrophy-3, 253400 (3) SMN1, SMA1, SMA2, SMA3, SMA4
Spinal muscular atrophy-4, 271150 (3) SMN1, SMA1, SMA2, SMA3, SMA4
Spinal muscular atrophy, distal, type V, BSCL2, SPG17
600794 (3)
Spinal muscular atrophy, distal, type V, GARS, SMAD1, CMT2D
600794 (3)
Spinal muscular atrophy, juvenile (3) HEXB
Spinal muscular atrophy with respiratory IGHMBP2, SMUBP2, CATF1, SMARDI
distress, 604320 (3)
Spinocerebellar ataxia-10 (3) ATXN10, SCA10
Spinocerebellar ataxia-1, 164400 (3) ATXN1, ATX1, SCA1
Spinocerebellar ataxia 12, 604326 (3) PPP2R2B
Spinocerebellar ataxia 14, 605361 (3) PRKCG, PKCC, PKCG, SCA14
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Spinocerebellar ataxia 17, 607136 (3) TBP, SCA17
Spinocerebellar ataxia-2, 183090 (3) ATXN2, ATX2, SCA2
Spinocerebellar ataxia 25 (3) SCA25
Spinocerebellar ataxia-27, 609307 (3) FGF14, FHF4, SCA27
Spinocerebellar ataxia 4, pure Japanese PLEKHG4
type, 117210 (3)
Spinocerebellar ataxia-6, 183086 (3) CACNAIA, CACNL1A4, SCA6
Spinocerebellar ataxia-7, 164500 (3) ATXN7, SCA7, OPCA3
Spinocerebellar ataxia 8, 608768 (3) SCA8
Spinocerebellar ataxia, autosomal recessive TDP1
with axonal neuropathy, 607250 (3)
Split hand/foot malformation, type 3, 600095 SHFM3, DAC
(3)
Split-hand/foot malformation, type 4, 605289 TP73L, TP63, KET, EEC3, SHFM4,
(3) LMS, RHS
Spondylocarpotarsal synostosis syndrome, FLNB, SCT, AOI
272460 (3)
Spondylocostal dysostosis, autosomal DLL3, SCDO1
recessive, 1, 277300 (3)
Spondylocostal dysostosis, autosomal MESP2
recessive 2, 608681 (3)
Spondyloepimeta physeaI dysplasia, 608728 MATN3, EDM5, HOA
(3)
Spondyloepiphyseal dysplasia, Kimberley AGC1, CSPG1, MSK16, SEDK
type, 608361 (3)
Spondyloepiphyseal dysplasia, Omani type, CHST3, C6ST, C6ST1
608637 (3)
Spondyloepiphyseal dysplasia tarda, SEDL, SEDT
313400 (3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Spondyloepiphyseal dysplasia tarda with WISP3, PPAC, PPD
progressive arthropathy, 208230 (3)
Spondylometaphyseal dysplasia, Japanese COL1OA1
type (3)
Squamous cell carcinoma, burn scar- TNFRSF6, APT1, FAS, CD95, ALPS1A
related, somatic (3)
Squamous cell carcinoma, head and neck, ING1
601400 (3)
Squamous cell carcinoma, head and neck, TNFRSF10B, DR5, TRAILR2
601400 (3)
Stapes ankylosis syndrome without NOG, SYM1, SYNS1
symphalangism, 184460 (3)
Stargardt disease-1, 248200 (3) ABCA4, ABCR, STGD1, FFM, RP19
Stargardt disease 3, 600110 (3) ELOVL4, ADMD, STGD2, STGD3
Startle disease, autosomal recessive (3) GLRA1, STHE
Startle disease/hyperekplexia, autosomal GLRA1, STHE
dominant, 149400 (3)
STAT1 deficiency, complete (3) STAT1
Statins, attenuated cholesterol lowering by HMGCR
(3)
Steatocystoma multiplex, 184500 (3) KRT17, PC2, PCHC1
Stem-cell leukemia/lymphoma syndrome (3) ZNF198, SCLL, RAMP, FIM
Stevens-Johnson syndrome, HLA-B
carbamazepine-induced, susceptibility to,
608579 (3)
Stickler syndrome, type I, 108300 (3) COL2A1
Stickler syndrome, type II, 604841 (3) COL11A1, STL2
Stickler syndrome, type III, 184840 (3) COL11A2, STL3, DFNA13
Stomach cancer, 137215 (3) KRAS2, RASK2
Stroke, susceptibility to, 1, 606799 (3) PDE4D, DPDE3, STRK1
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Stroke, susceptibility to, 601367 (3) ALOX5AP, FLAP
Stuve-Wiedemann syndrome/Schwartz- LIFR, STWS, SWS, SJS2
Jampel type 2 syndrome, 601559 (3)
Subcortical laminal heteropia, X-linked, DCX, DBCN, LISX
300067 (3)
Subcortical laminar heterotopia (3) PAFAH1 B1, LIS1
Succinic semialdehyde dehydrogenase SSADH
deficiency (3)
Sucrose intolerance (3) SI
Sudden infant death with dysgenesis of the TSPYL1, TSPYL, SIDDT
testes syndrome, 608800 (3)
Sulfite oxidase deficiency, 272300 (3) SUOX
Superoxide dismutase, elevated SOD3
extracellular (3)
Supranuclear palsy, progressive, 601104 (3) MAPT, MTBT1, DDPAC, MSTD
Supranuclear palsy, progressive atypical, MAPT, MTBT1, DDPAC, MSTD
260540 (3)
Supravalvar aortic stenosis, 185500 (3) ELN
Surfactant deficiency, neonatal, 267450 (3) ABCA3, ABC3
Surfactant protein C deficiency (3) SFTPC, SFTP2
Sutherland-Haan syndrome-like, 300465 (3) ATRX, XH2, XNP, MRXS3, SHS
Sweat chloride elevation without CF (3) CFTR, ABCC7, CF, MRP7
Symphalangism, proximal, 185800 (3) NOG, SYM1, SYNS1
Syndactyly, type III, 186100 (3) GJA1, CX43, ODDD, SDTY3, ODOD
Synostoses syndrome, multiple, 1, 186500 NOG, SYM1, SYNS1
(3)
Synpolydactyly, 3/3'4, associated with FBLN1
metacarpal and metatarsal synostoses,
608180 (3)
Synpolydactyly, type II, 186000 (3) HOXD13, HOX41, SPD
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Synpolydactyly with foot anomalies, 186000 HOXD13, HOX41, SPD
(3)
Systemic lupus erythematosus, TNFSF6, APT1LG1, FASL
susceptibility, 152700 (3)
Systemic lupus erythematosus, DNASE1, DNL1
susceptibility to, 152700 (3)
Systemic lupus erythematosus, PTPN8, PEP, PTPN22, LYP
susceptibility to, 152700 (3)
Systemic lupus erythematosus, PDCD1, SLEB2
susceptibility to, 2, 605218, 152700 (3)
Tall stature, susceptibility to (3) MCM6
Tangier disease, 205400 (3) ABCA1, ABC1, HDLDT1, TGD
Tarsal-carpal coalition syndrome, 186570 NOG, SYM1, SYNS1
(3)
Tauopathy and respiratory failure (3) MAPT, MTBT1, DDPAC, MSTD
Tay-Sachs disease, 272800 (3) HEXA, TSD
T-cell acute lymphoblastic leukemia (3) BAX
T-cell immunodeficiency, congenital WHN
alopecia, and nail dystrophy (3)
T-cell prolymphocytic leukemia, sporadic (3) ATM, ATA, AT1
Temperature-sensitive apoptosis, cellular DAD1
(3)
Tetra-amelia, autosomal recessive, 273395 WNT3, INT4
(3)
Tetralogy of Fallot, 187500 (3) JAG1, AGS, AHD
Tetralogy of Fallot, 187500 (3) ZFPM2, FOG2
Tetrology of Fallot, 187500 (3) NKX2E, CSX
Thalassemia, alpha-(3) HBA2
Thalassemia-beta, dominant inclusion-body, HBB
603902 (3)
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DISEASE/DISORDER/INDICATION GENE(S)
Thalassemia, delta-(3) HBD
Thalassemia due to Hb Lepore (3) HBD
Thalassemia, Hispanic gamma-delta-beta LCRB
(3)
Thalassemias, alpha-(3) HBA1
Thalassemias, beta-(3) HBB
Thanatophoric dysplasia, types I and II, FGFR3, ACH
187600 (3)
Thiamine-responsive megaloblastic anemia SLC19A2, THTR1
syndrome, 249270 (3)
Thrombocythemia, essential, 187950 (3) JAK2
Thrombocythemia, essential, 187950 (3) THPO, MGDF, MPLLG, TPO
Thrombocytopenia-2, 188000 (3) FLJ14813, THC2
Thrombocytopenia, congenital MPL, TPOR, MPLV
amegakaryocytic, 604498 (3)
Thrombocytopenia, X-linked, 313900 (3) WAS, IMD2, THC
Thrombocytopenia, X-linked, intermittent, WAS, IMD2, THC
313900 (3)
Thromboembolism susceptibility due to F5
factor V Leiden (3)
Thrombophilia due to factor V Liverpool (3) F5
Thrombophilia due to heparin cofactor II HCF2, HC2, SERPIND1
deficiency (3)
Thrombophilia due to HRG deficiency (3) HRG
Thrombophilia due to protein C deficiency PROC
(3)
Thrombophilia due to thrombomodulin THBD, THRM
defect (3)
Thrombophilia, dysfibrinogenemic (3) FGB
Thrombophilia, dysfibrinogenemic (3) FGG
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DISEASE/DISORDER/INDICATION GENE(S)
Thrombosis, hyperhomocysteinemic (3) CBS
Thrombotic thrombocytopenic purpura, ADAMTS13, VWFCP, TTP
familial, 274150 (3)
Thrombycytosis, susceptibility to, 187950 MPL, TPOR, MPLV
(3)
Thymine-uraciluria (3) DPYD, DPD
Thyroid adenoma, hyperfunctioning (3) TSHR
Thyroid carcinoma (3) TP53, P53, LFS1
Thyroid carcinoma, follicular, 188470 (3) MINPP1, HIPER1
Thyroid carcinoma, follicular, 188470 (3) PTEN, MMAC1
Thyroid carcinoma, follicular, somatic, HRAS
188470 (3)
Thyroid carcinoma, papillary, 188550 (3) GOLGA5, RFG5, PTC5
Thyroid carcinoma, papillary, 188550 (3) NCOA4, ELE1, PTC3
Thyroid carcinoma, papillary, 188550 (3) PCM1, PTC4
Thyroid carcinoma, papillary, 188550 (3) PRKAR1A, TSE1, CNC1, CAR
Thyroid carcinoma, papillary, 188550 (3) TIF1G, RFG7, PTC7
Thyroid carcinoma, papillary, 188550 (3) TRIM24, TIF1, TIF1A, PTC6
Thyroid hormone organification defect IIA, TPO, TPX
274500 (3)
Thyroid hormone resistance, 188570 (3) THRB, ERBA2, THR1
Thyroid hormone resistance, autosomal THRB, ERBA2, THR1
recessive, 274300 (3)
Thyrotoxic periodic paralysis, susceptibility CACNA1S, CACNL1A3, CCHL1A3
to, 188580 (3)
Thyrotropin-releasing hormone resistance, TRHR
generalized (3)
Thyroxine-binding globulin deficiency (3) TBG
Tietz syndrome, 103500 (3) MITF, WS2A
Timothy syndrome, 601005 (3) CACNA1C, CACNL1A1, CCHL1A1, TS
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DISEASE/DISORDER/INDICATION GENE(S)
Toenail dystrophy, isolated, 607523 (3) COL7A1
Tolbutamide poor metabolizer (3) CYP2C9
Total iodide organification defect, 274500 TPO, TPX
(3)
Townes-Brocks branchiootorenal-like SALL1, HSAL1, TBS
syndrome, 107480 (3)
Townes-Brocks syndrome, 107480 (3) SALL1, HSAL1, TBS
Transaldolase deficiency, 606003 (3) TALDO1
Transcobalamin II deficiency (3) TCN2, TC2
Transient bullous of the newborn, 131705 COL7A1
(3)
Transposition of great arteries, dextro- CFC1, CRYPTIC, HTX2
looped, 217095 (3)
Transposition of the great arteries, dextro- THRAP2, PROSIT240, TRAP240L,
looped, 608808 (3) KIAA1025
Treacher Collins mandibulofacial TCOF1, MFD1
dysostosis, 154500 (3)
Tremor, familial essential, 2, 602134 (3) HS1BP3, FLJ14249, ETM2
Trichodontoosseous syndrome, 190320 (3) DLX3, TDO
Trichorhinophalangeal syndrome, type I, TRPS1
190350 (3)
Trichorhinophalangeal syndrome, type III, TRPS1
190351 (3)
Trichothiodystrophy (3) ERCC3, XPB
Trichothiodystrophy, 601675 (3) ERCC2, EM9
Trichothiodystrophy, complementation TGF2H5, TTDA, TFB5, C6orf175
group A, 601675 (3)
Trichothiodystrophy, non photosensitive 1, TTDN1, C7orfl1, ABHS
234050 (3)
Trifunctional protein deficiency, type 1 (3) HADHA, MTPA
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DISEASE/DISORDER/INDICATION GENE(S)
Trifunctional protein deficiency, type II (3) HADHB
Trismus-pseudocomptodactyly syndrome, MYH8
158300 (3)
Tropical calcific pancreatitis, 608189 (3) SPINK1, PSTI, PCTT, TATI
Troyer syndrome, 275900 (3) SPG20
TSC2 angiomyolipomas, renal, modifier of, IFNG
191100 (3)
Tuberculosis, susceptibility to (3) IFNGR1
Tuberculosis, susceptibility to, 607948 (3) IFNG
Tuberous sclerosis-1, 191100 (3) TSC1, LAM
Tuberous sclerosis-2, 191100 (3) TSC2, LAM
Turcot syndrome, 276300 (3) APC, GS, FPC
Turcot syndrome with glioblastoma, 276300 MLH1, COCA2, HNPCC2
(3)
Turcot syndrome with glioblastoma, 276300 PMS2, PMSL2, HNPCC4
(3)
Twinning, dizygotic, 276400 (3) FSHR, ODG1
Tyrosinemia, type I (3) FAH
Tyrosinemia, type II (3) TAT
Tyrosinemia, type III (3) HPD
Ullrich congenital muscular dystrophy, COL6A1, OPLL
254090 (3)
Ullrich congenital muscular dystrophy, COL6A3
254090 (3)
Ullrich scleroatonic muscular dystrophy, COL6A2
254090 (3)
Ulnar-mammary syndrome, 181450 (3) TBX3
Unipolar depression, susceptibility to, TPH2, NTPH
608516 (3)
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Unna-Thost disease, nonepidermolytic, KRT1
600962 (3)
Urolithiasis, 2,8-dihydroxyadenine (3) APRT
Urolithiasis, hypophosphatemic (3) SLC17A2, NPT2
Usher syndrome, type 1 B (3) MYO7A, USH1 B, DFNB2, DFNA11
Usher syndrome, type 1 C, 276904 (3) USH1 C, DFNB18
Usher syndrome, type 1 D, 601067 (3) CDH23, USH1D
Usher syndrome, type 1 F, 602083 (3) PCDH15, DFNB23
Usher syndrome, type 1 G, 606943 (3) SANS, USH 1 G
Usher syndrome, type 2A, 276901 (3) USH2A
Usher syndrome, type 3, 276902 (3) USH3A, USH3
Usher syndrome, type IIC, 605472 (3) MASS1, VLGR1, KIAA0686, FEB4,
USH2C
Uterine leiomyoma (3) HMGA2, HMGIC, BABL, LIPO
UV-induced skin damage, vulnerability to (3) MC1 R
van Buchem disease, type 2, 607636 (3) LRP5, BMND1, LRP7, LR3, OPPG,
VBCH2
van der Woude syndrome, 119300 (3) IRF6, VWS, LPS, PIT, PPS, OFC6
VATER association with hydrocephalus, PTEN, MMAC1
276950 (3)
Velocardiofacial syndrome, 192430 (3) TBX1, DGS, CTHM, CAFS, TGA,
DORV, VCFS, DGCR
Venous malformations, multiple cutaneous TEK, TIE2, VMCM
and mucosal, 600195 (3)
Venous thrombosis, susceptibility to (3) SERPINA10, ZPI
Ventricular fibrillation, idiopathic, 603829 (3) SCN5A, LQT3, IVF, HB1, SSS1
Ventricular tachycardia, idiopathic, 192605 GNAI2, GNAI2B, GIP
(3)
Ventricular tachycardia, stress-induced CASQ2
polymorphic, 604772 (3)
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DISEASE/DISORDER/INDICATION GENE(S)
Ventricular tachycardia, stress-induced RYR2, VTSIP
polymorphic, 604772 (3)
Vertical talus, congenital, 192950 (3) HOXD10, HOX4D
Viral infections, recurrent (3) FCGR3A, CD16, IGFR3
Viral infection, susceptibility to (3) OAS1, OIAS
Virilization, maternal and fetal, from CYP19A1, CYP19, ARO
placental aromatase deficiency (3)
Vitamin K-dependent clotting factors, VKORC1, VKOR, VKCFD2, FLJO0289
combined deficiency of, 2, 607473 (3)
Vitamin K-dependent coagulation defect, GGCX
277450 (3)
Vitelliform macular dystrophy, adult-onset, VMD2
608161 (3)
VLCAD deficiency, 201475 (3) ACADVL, VLCAD
Vohwinkel syndrome, 124500 (3) GJB2, CX26, DFNB1, PPK, DFNA3,
KID, HID
Vohwinkel syndrome with ichthyosis, LOR
604117 (3)
von Hippel-Lindau disease, modification of, CCND1, PRAD1, BCL1
193300 (3)
von Hippel-Lindau syndrome, 193300 (3) VHL
von Willebrand disease (3) VWF, F8VWF
Waardenburg-Shah syndrome, 277580 (3) EDNRB, HSCR2, ABCDS
Waardenburg-Shah syndrome, 277580 (3) SOX10, WS4
Waardenburg syndrome/albinism, digenic, TYR
103470 (3)
Waardenburg syndrome/ocular albinism, MITF, WS2A
digenic, 103470 (3)
Waardenburg syndrome, type I, 193500 (3) PAX3, WS1, HUP2, CDHS
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Waardenburg syndrome, type IIA, 193510 MITF, WS2A
(3)
Waardenburg syndrome, type III, 148820 (3) PAX3, WS1, HUP2, CDHS
Waardenburg syndrome, typ IID, 608890 (3) SNAI2, SLUG, WS2D
Wagner syndrome, 143200 (3) COL2A1
WAGR syndrome, 194072 (3) WT1
Walker-Warburg syndrome, 236670 (3) FCMD
Walker-Warburg syndrome, 236670 (3) POMT1
Warburg micro syndrome 1, 600118 (3) RAB3GAP, WARBM1, P130
Warfarin resistance, 122700 (3) VKORC1, VKOR, VKCFD2, FLJO0289
Warfarin sensitivity, 122700 (3) CYP2C9
Warfarin sensitivity (3) F9, HEMB
Watson syndrome, 193520 (3) NF1, VRNF, WSS, NFNS
Weaver syndrome, 277590 (3) NSD1, ARA267, STO
Wegener-like granulomatosis (3) TAP2, ABCB3, PSF2, RING1 1
Weill-Marchesani syndrome, dominant, FBN1, MFS1, WMS
608328 (3)
Weill-Marchesani syndrome, recessive, ADAMTS10, WMS
277600 (3)
Weissenbacher-Zweymuller syndrome, COL1 1A2, STL3, DFNA13
277610 (3)
Werner syndrome, 277700 (3) RECQL2, RECQ3, WRN
Wernicke-Korsakoff syndrome, susceptibility TKT
to, 277730 (3)
Weyers acrodental dysostosis, 193530 (3) EVC
WHIM syndrome, 193670 (3) CXCR4, D2S201 E, NPY3R, WHIM
White sponge nevus, 193900 (3) KRT13
White sponge nevus, 193900 (3) KRT4, CYK4
Williams-Beuren syndrome, 194050 (3) ELN
Wilms tumor, 194070 (3) BRCA2, FANCD1
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Wilms tumor, somatic, 194070 (3) GPC3, SDYS, SGBS1
Wilms tumor susceptibility-5, 601583 (3) POU6F2, WTSL, WT5
Wilms tumor, type 1, 194070 (3) WT1
Wilson disease, 277900 (3) ATP7B, WND
Wiskott-Aldrich syndrome, 301000 (3) WAS, IMD2, THC
Witkop syndrome, 189500 (3) MSX1, HOX7, HYD1, OFC5
Wolcott-Rallison syndrome, 226980 (3) EIF2AK3, PEK, PERK, WRS
Wolff-Parkinson-White syndrome, 194200 PRKAG2, WPWS
(3)
Wolfram syndrome, 222300 (3) WFS1, WFRS, WFS, DFNA6
Wolman disease (3) LIPA
Xanthinuria, type I, 278300 (3) XDH
Xeroderma pigmentosum, group A (3) XPA
Xeroderma pigmentosum, group B (3) ERCC3, XPB
Xeroderma pigmentosum, group C (3) XPC, XPCC
Xeroderma pigmentosum, group D, 278730 ERCC2, EM9
(3)
Xeroderma pigmentosum, group E, DDB- DDB2
negative subtype, 278740 (3)
Xeroderma pigmentosum, group F, 278760 ERCC4, XPF
(3)
Xeroderma pigmentosum, group G, 278780 ERCC5, XPG
(3)
Xeroderma pigmentosum, variant type, POLH, XPV
278750 (3)
X-inactivation, familial skewed, 300087 (3) XIC, XCE, XIST, SXI1
XLA and isolated growth hormone BTK, AGMX1, IMD1, XLA, AT
deficiency, 307200 (3)
Yellow nail syndrome, 153300 (3) FOXC2, FKHL14, MFH1
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TABLE B
DISEASE/DISORDER/INDICATION GENE(S)
Yemenite deaf-blind hypopigmentation SOX10, WS4
syndrome, 601706 (3)
Zellweger syndrome-1, 214100 (3) PEX1, ZWS1
Zellweger syndrome, 214100 (3) PEX10, NALD
Zellweger syndrome, 214100 (3) PEX13, ZWS, NALD
Zellweger syndrome, 214100 (3) PEX14
Zellweger syndrome, 214100 (3) PEX26
Zellweger syndrome, 214100 (3) PXF, HK33, D1S2223E, PEX19
Zellweger syndrome, 214100 (3) PXR1, PEX5, PTS1R
Zellweger syndrome-2 (3) ABCD3, PXMP1, PMP70
Zellweger syndrome-3 (3) PXMP3, PAF1, PMP35, PEX2
Zellweger syndrome, complementation PEX16
group 9 (3)
Zellweger syndrome, complementation PEX3
group G, 214100 (3)
Zlotogora-Ogur syndrome, 225000 (3) HVEC, PVRL1, PVRR1, PRR1
[0134] Further non-limiting examples of disease models created by
a method of the invention include a Parkinson's disease model, an addiction
model, an inflammation model, a cardiovascular disease model, an Alzheimer's
disease model, an autism spectrum disorder model, a macular degeneration
model, a schizophrenia model, a tumor suppression model, a trinucleotide
repeat
disorder model, a neurotransmission disorder model, a secretase-associated
disorder model, an ALS model, a prion disease model, on ABC transporter
protein - associated disorder model, and an immunodeficiency model. Each is
discussed in more detail below.
A. Parkinsons disease
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[0135] In one embodiment, a method of the invention may be used
to create an animal or cell in which at least one chromosomal sequence
associated with Parkinsons disease (PD) has been edited. Suitable chromosomal
edits may include, but are not limited to, the type of edits detailed in
section I(f)
above.
[0136] In some embodiments, one or more chromosomal
sequences encoding a protein or control sequence associated with PD may be
edited. A PD-associated protein or control sequence may typically be selected
based on an experimental association of the PD-associated protein or control
sequence to PD. By way of non-limiting example, the production rate or
circulating concentration of a PD-related protein may be elevated or depressed
in
a population having PD relative to a population not having PD. Differences in
protein levels may be assessed using proteomic or genomic analysis techniques
known in the art. By way of non-limiting example, proteins associated with
Parkinson's disease include but are not limited to a-synuclein, DJ-1, LRRK2,
PINK1, Parkin, UCHL1, Synphilin-1, and NURR1.
[0137] In certain embodiments, an animal created by a method of
the invention may be used to study the effects of mutations on the animal and
development and/or progression of PD using measures commonly used in the
study of PD. Methods for measuring and studying progression of PD in animals
are known in the art. Commonly used measures in the study of PD may include
without limit, amyloidogenesis or protein aggregation, dopamine response,
neurodegeneration, development of mitochondrial related dysfunction
phenotypes, as well as functional, pathological or biochemical assays. Other
relevant indicators regarding development or progression of PD include
coordination, balance, gait, motor impairment, tremors and twitches, rigidity,
hypokinesia, and cognitive impairments. Such assays may be made in
comparison to wild type littermates.
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B. addiction
[0138] Addiction, as used herein, is defined as a chronic disease of
brain reward, motivation, memory, and related neuronal circuitry contained
within
various brain structures. Specific examples of brain structures that may
experience dysfunction associated with an addiction disorder include nucleus
accumbens, ventral pallidum, dorsal thalamus, prefrontal cortex, striatum,
substantia nigra, pontine reticular formation, amygdala, and ventral tegmental
area. Dysfunction in these neural circuits may lead to various biological,
psychological, social and behavioral symptoms of addiction.
[0139] Biological symptoms of addiction may include
overproduction or underproduction of one or more addiction-related proteins;
redistribution of one or more addiction-related proteins within the brain; the
development of tolerance, reverse tolerance, or other changes in sensitivity
to
the effects of an addictive substance or a neurotransmitter within the brain;
high
blood pressure; and withdrawal symptoms such as insomnia, restlessness, loss
of appetite, depression, weakness, irritability, anger, pain, and craving.
[0140] Psychological symptoms of addiction may vary depending
on the particular addictive substance and the duration of the addiction. Non-
limiting examples of psychological symptoms of addiction include mood swings,
paranoia, insomnia, psychosis, schizophrenia, tachycardia panic attacks,
cognitive impairments, and drastic changes in the personality that can lead to
aggressive, compulsive, criminal and/or erratic behaviors.
[0141] Social symptoms of addiction may include low self-esteem,
verbal hostility, ignorance of interpersonal means, focal anxiety such as fear
of
crowds, rigid interpersonal behavior, grossly bizarre behavior,
rebelliousness,
and diminished recognition of significant problems with an individual's
behaviors
and interpersonal relationships.
[0142] Non-limiting examples of behavioral symptoms of addiction
include impairment in behavioral control, inability to consistently abstain
from the
use of addictive substances, cycles of relapse and remission, risk-taking
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behavior, pleasure-seeking behavior, novelty-seeking behavior, relief-seeking
behavior, and reward-seeking behavior.
[0143] Addictions may be substance addictions typically associated
with the ingestion of addictive substances. Addictive substances may include
psychoactive substances capable of crossing the blood-brain barrier and
temporarily altering the chemical milieu of the brain. Non-limiting examples
of
addictive substances include alcohol; opioid compounds such as opium and
heroin; sedative, hypnotic, or anxiolytic compounds such as benzodiazepine and
barbiturate compounds; cocaine and related compounds; cannabis and related
compounds; amphetamine and amphetamine-like compounds; hallucinogen
compounds; inhalants such as glue or aerosol propellants; phencyclidine or
phencyclidine-like compounds; and nicotine. In addition, addictions may be
behavioral addictions associated with compulsions that are not substance-
related, such as problem gambling and computer addiction.
[0144] In one embodiment, a method of the invention may be used
to create an animal or cell in which at least one addiction-related
chromosomal
sequence has been edited. Suitable edits may include, but are not limited to,
the
type of edits detailed in section I(f) above.
[0145] Addiction-related nucleic acid sequences are a diverse set of
sequences associated with susceptibility for developing an addiction, the
presence of an addiction, the severity of an addiction or any combination
thereof.
An addiction-related nucleic acid sequence may typically be selected based on
an experimental association of the addiction-related nucleic acid sequence to
an
addiction disorder. An addiction-related nucleic acid sequence may encode an
addiction-related protein or may be an addiction-related control sequence. By
way of non-limiting example, the production rate or circulating concentration
of an
addiction-related protein may be elevated or depressed in a population having
an
addiction disorder relative to a population lacking the addiction disorder.
Differences in protein levels may be assessed using proteomic or genomic
analysis techniques known in the art.
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[0146] Non-limiting examples of addiction-related proteins include
ABAT (4-aminobutyrate aminotransferase); ACN9 (ACN9 homolog (S.
cerevisae)); ADCYAP1 (Adenylate cyclase activating polypeptide 1); ADH1 B
(Alcohol dehydrogenase IB (class I), beta polypeptide); ADH1C (Alcohol
dehydrogenase 1 C (class I), gamma polypeptide); ADH4 (Alcohol
dehydrogenase 4); ADH7 (Alcohol dehydrogenase 7 (class IV), mu or sigma
polypeptide); ADORA1 (Adenosine Al receptor); ADRA1A (Adrenergic, alpha-
1A-, receptor); ALDH2 (Aldehyde dehydrogenase 2 family); ANKK1 (Ankyrin
repeat, Tagl Al allele); ARC (Activity-regulated cytoskeleton-associated
protein);
ATF2 (Corticotrophin-releasing factor); AVPR1A (Arginine vasopressin receptor
1A); BDNF (Brain-derived neurotrophic factor); BMAL1 (Aryl hydrocarbon
receptor nuclear translocator-like); CDK5 (Cyclin-dependent kinase 5); CHRM2
(Cholinergic receptor, muscarinic 2); CHRNA3 (Cholinergic receptor, nicotinic,
alpha 3); CHRNA4 (Cholinergic receptor, nicotinic, alpha 4); CHRNA5
(Cholinergic receptor, nicotinic, alpha 5); CHRNA7 (Cholinergic receptor,
nicotinic, alpha 7); CHRNB2 (Cholinergic receptor, nicotinic, beta 2); CLOCK
(Clock homolog (mouse)); CNR1 (Cannabinoid receptor 1); CNR2 (Cannabinoid
receptor type 2); COMT (Catechol-O-methyltransferase); CREB1 (cAMP
Responsive element binding protein 1); CREB2 (Activating transcription factor
2);
CRHR1 (Corticotropin releasing hormone receptor 1); CRY1 (Cryptochrome 1);
CSNK1 E (Casein kinase 1, epsilon); CSPG5 (Chondroitin sulfate proteoglycan
5); CTNNB1 (Catenin (cadherin-associated protein), beta 1, 88kDa); DBI
(Diazepam binding inhibitor); DDN (Dendrin); DRD1 (Dopamine receptor D1);
DRD2 (Dopamine receptor D2); DRD3 (Dopamine receptor D3); DRD4
(Dopamine receptor D4); EGR1 (Early growth response 1); ELTD1 (EGF,
latrophilin and seven transmembrane domain containing 1); FAAH (Fatty acid
amide hydrolase); FOSB (FBJ murine osteosarcoma viral oncogene homolog);
FOSB (FBJ murine osteosarcoma viral oncogene homolog B); GABBR2
(Gamma-aminobutyric acid (GABA) B receptor, 2); GABRA2 (Gamma-
aminobutyric acid (GABA) A receptor, alpha 2); GABRA4 (Gamma-aminobutyric
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acid (GABA) A receptor, alpha 4); GABRA6 (Gamma-aminobutyric acid (GABA)
A receptor, alpha 6); GABRB3 (Gamma-aminobutyric acid (GABA) A receptor,
alpha 3); GABRE (Gamma-aminobutyric acid (GABA) A receptor, epsilon);
GABRG1 (Gamma-aminobutyric acid (GABA) A receptor, gamma 1); GAD1
(Glutamate decarboxylase 1); GAD2 (Glutamate decarboxylase 2); GAL (Galanin
prepropeptide); GDNF (Glial cell derived neurotrophic factor); GRIA1
(Glutamate
receptor, ionotropic, AMPA 1); GRIA2 (Glutamate receptor, ionotropic, AMPA 2);
GRIN1 (Glutamate receptor, ionotropic, N-methyl D-aspartate 1); GRIN2A
(Glutamate receptor, ionotropic, N-methyl D-aspartate 2A); GRM2 (Glutamate
receptor, metabotropic 2, mGluR2); GRM5 (Metabotropic glutamate receptor 5);
GRM6 (Glutamate receptor, metabotropic 6); GRM8 (Glutamate receptor,
metabotropic 8); HTR1 B (5-Hydroxytryptamine (serotonin) receptor 1 B); HTR3A
(5-Hydroxytryptamine (serotonin) receptor 3A); IL1 (Interleukin 1); U5
(Interleukin 15); ILIA (Interleukin 1 alpha); IL1 B (Interleukin 1 beta);
KCNMA1
(Potassium large conductance calcium-activated channel, subfamily M, alpha
member 1); LGALS1 (lectin galactoside-binding soluble 1); MAOA (Monoamine
oxidase A); MAOB (Monoamine oxidase B); MAPK1 (Mitogen-activated protein
kinase 1); MAPK3 (Mitogen-activated protein kinase 3); MBP (Myelin basic
protein); MC2R (Melanocortin receptor type 2); MGLL (Monoglyceride lipase);
MOBP (Myelin-associated oligodendrocyte basic protein); NPY (Neuropeptide Y);
NR4A1 (Nuclear receptor subfamily 4, group A, member 1); NR4A2 (Nuclear
receptor subfamily 4, group A, member 2); NRXN1 (Neurexin 1); NRXN3
(Neurexin 3); NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2); NTRK2
(Tyrosine kinase B neurotrophin receptor); OPRD1 (delta-Opioid receptor);
OPRK1 (kappa-Opioid receptor); OPRM1 (mu-Opioid receptor); PDYN
(Dynorphin); PENK (Enkephalin); PER2 (Period homolog 2 (Drosophila));
PKNOX2 (PBX/knotted 1 homeobox 2); PLP1 (Proteolipid protein 1); POMC
(Proopiomelanocortin); PRKCE (Protein kinase C, epsilon); PROKR2
(Prokineticin receptor 2); RGS9 (Regulator of G-protein signaling 9); RIMS2
(Regulating synaptic membrane exocytosis 2); SCN9A (sodium channel voltage-
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gated type IX alpha subunit); SLC1 7A6 (Solute carrier family 17 (sodium-
dependent inorganic phosphate cotransporter), member 6); SLC17A7 (Solute
carrier family 17 (sodium-dependent inorganic phosphate cotransporter),
member 7); SLC1A2 (Solute carrier family 1 (glial high affinity glutamate
transporter), member 2); SLC1A3 (Solute carrier family 1 (glial high affinity
glutamate transporter), member 3); SLC29A1 (solute carrier family 29
(nucleoside transporters), member 1); SLC4A7 (Solute carrier family 4, sodium
bicarbonate cotransporter, member 7); SLC6A3 (Solute carrier family 6
(neurotransmitter transporter, dopamine), member 3); SLC6A4 (Solute carrier
family 6 (neurotransmitter transporter, serotonin), member 4); SNCA
(Synuclein,
alpha (non A4 component of amyloid precursor)); TFAP2B (Transcription factor
AP-2 beta); and TRPV1 (Transient receptor potential cation channel, subfamily
V, member 1).
[0147] Preferred addiction-related proteins may include ABAT (4-
aminobutyrate aminotransferase), DRD2 (Dopamine receptor D2), DRD3
(Dopamine receptor D3), DRD4 (Dopamine receptor D4), GRIA1 (Glutamate
receptor, ionotropic, AMPA 1), GRIA2 (Glutamate receptor, ionotropic, AMPA 2),
GRIN1 (Glutamate receptor, ionotropic, N-methyl D-aspartate 1), GRIN2A
(Glutamate receptor, ionotropic, N-methyl D-aspartate 2A), GRM5 (Metabotropic
glutamate receptor 5), HTR1 B (5-Hydroxytryptamine (serotonin) receptor 1 B),
PDYN (Dynorphin), PRKCE (Protein kinase C, epsilon), LGALS1 (lectin
galactoside-binding soluble 1), TRPV1 (transient receptor potential cation
channel subfamily V member 1), SCN9A (sodium channel voltage-gated type IX
alpha subunit), OPRD1 (opioid receptor delta 1), OPRK1 (opioid receptor kappa
1), OPRM1 (opioid receptor mu 1), and any combination thereof.
[0148] In certain embodiments, an animal created by a method of
the invention may be used as a model for indications of addiction disorders by
comparing the measurements of an assay obtained from a genetically modified
animal comprising at least one edited chromosomal sequence encoding an
addiction-related protein to the measurements of the assay using a wild-type
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animal. Non-limiting examples of assays used to assess for indications of an
addictive disorder include behavioral assays, physiological assays, whole
animal
assays, tissue assays, cell assays, biomarker assays, and combinations
thereof.
The indications of addiction disorders may occur spontaneously, or may be
promoted by exposure to exogenous agents such as addictive substances or
addiction-related proteins. Alternatively, the indications of addiction
disorders
may be induced by withdrawal of an addictive substance or other compound
such as an exogenously administered addiction-related protein.
[0149] An additional aspect of the present disclosure encompasses
a method of assessing the efficacy of a treatment for inhibiting addictive
behaviors and/or reducing withdrawal symptoms of a genetically modified animal
comprising at least one edited chromosomal sequence associated with addiction.
Treatments for addiction that may be assessed include the administering of one
or more novel candidate therapeutic compounds, a novel combination of
established therapeutic compounds, a novel therapeutic method, and any
combination thereof. Novel therapeutic methods may include various drug
delivery mechanisms, nanotechnology applications in drug therapy, surgery, and
combinations thereof.
[0150] Behavioral testing of a genetically modified animal
comprising at least one edited addiction-related protein and/or a wild-type
animal
may be used to assess the side effects of a therapeutic compound or
combination of therapeutic agents. The genetically modified animal and
optionally a wild-type animal may be treated with the therapeutic compound or
combination of therapeutic agents and subjected to behavioral testing. The
behavioral testing may assess behaviors including but not limited to learning,
memory, anxiety, depression, addiction, and sensory-motor functions.
[0151] An additional aspect provides a method for assessing the
therapeutic potential of an agent in an animal that may include contacting a
genetically modified animal comprising at least one edited chromosomal
sequence encoding an addiction-related protein, and comparing results of a
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selected parameter to results obtained from a wild-type animal with no contact
with the same agent. Selected parameters include but are not limited to a)
spontaneous behaviors; b) performance during behavioral testing; c)
physiological anomalies; d) abnormalities in tissues or cells; e) biochemical
function; and f) molecular structures.
C. inflammation
[0152] In one embodiment, a method of the invention may be used
to create an animal or cell in which at least one chromosomal sequence
associated with inflammation has been edited. Suitable chromosomal edits may
include, but are not limited to, the type of edits detailed in section I(f)
above.
[0153] In each of the above embodiments, one or more
chromosomal sequences associated with inflammation may be edited. An
inflammation-related chromosomal sequence may typically be selected based on
an experimental association of the inflammation-related sequence to an
inflammation disorder. An inflammation-related sequence may encode an
inflammation-related protein or may be an inflammation-related control
sequence. For example, the production rate or circulating concentration of an
inflammation-related protein may be elevated or depressed in a population
having an inflammation disorder relative to a population lacking the
inflammation
disorder. Differences in protein levels may be assessed using proteomic or
genomic analysis techniques known in the art.
[0154] Non-limiting examples of inflammation-related proteins
whose chromosomal sequence may be edited include the monocyte
chemoattractant protein-1 (MCP1) encoded by the Ccr2 gene, the C-C
chemokine receptor type 5 (CCR5) encoded by the Ccr5 gene, the IgG receptor
IIB (FCGR2b, also termed CD32) encoded by the Fcgr2b gene, the Fc epsilon
R1g (FCER1g) protein encoded by the Fcerlg gene, the forkhead box Ni
transcription factor (FOXN1) encoded by the FOXN1 gene, Interferon-gamma
(IFN-y) encoded by the IFNg gene, interleukin 4 (IL-4) encoded by the IL-4
gene,
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perforin-1 encoded by the PRF-1 gene, the cyclooxygenase 1 protein (COX1)
encoded by the COX1 gene, the cyclooxygenase 2 protein (COX2) encoded by
the COX2 gene, the T-box transcription factor (TBX21) protein encoded by the
TBX21 gene, the SH2-B PH domain containing signaling mediator 1 protein
(SH2BPSM1) encoded by the SH2B1 gene (also termed SH2BPSM1), the
fibroblast growth factor receptor 2 (FGFR2) protein encoded by the FGFR2 gene,
the solute carrier family 22 member 1 (SLC22A1) protein encoded by the OCT1
gene (also termed SLC22A1), the peroxisome proliferator-activated receptor
alpha protein (PPAR-alpha, also termed the nuclear receptor subfamily 1, group
C, member 1; NR1 Cl) encoded by the PPARA gene, the phosphatase and
tensin homolog protein (PTEN) encoded by the PTEN gene, interleukin 1 alpha
(IL-1 a) encoded by the IL-1A gene, interleukin 1 beta (IL-113) encoded by the
IL-
1B gene, interleukin 6 (IL-6) encoded by the IL-6 gene, interleukin 10 (IL-10)
encoded by the IL-10 gene, interleukin 12 alpha (IL-12a) encoded by the IL-12A
gene, interleukin 12 beta (IL-1213) encoded by the IL-12B gene, interleukin 13
(IL-
13) encoded by the IL-13 gene, interleukin 17A(IL-17A, also termed CTLA8)
encoded by the IL-17A gene, interleukin 17B(IL-17B) encoded by the IL-17B
gene, interleukin 17C (IL-17C) encoded by the IL-17C gene interleukin 17D (IL-
17D) encoded by the IL-17D gene interleukin 17F (IL-17F) encoded by the IL-
17F gene, interleukin 23 (IL-23) encoded by the IL-23 gene, the chemokine (C-
X3-C motif) receptor 1 protein (CX3CR1) encoded by the CX3CR1 gene, the
chemokine (C-X3-C motif) ligand 1 protein (CX3CL1) encoded by the CX3CL1
gene, the recombination activating gene 1 protein (RAG1) encoded by the RAG1
gene, the recombination activating gene 2 protein (RAG2) encoded by the RAG2
gene, the protein kinase, DNA-activated, catalytic polypeptidel (PRKDC)
encoded by the PRKDC (DNAPK) gene, the protein tyrosine phosphatase non-
receptor type 22 protein (PTPN22) encoded by the PTPN22 gene, tumor
necrosis factor alpha (TNFa) encoded by the TNFA gene, the nucleotide-binding
oligomerization domain containing 2 protein (NOD2) encoded by the NOD2 gene
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(also termed CARD15), or the cytotoxic T-lymphocyte antigen 4 protein (CTLA4,
also termed CD152) encoded by the CTLA4 gene.
[0155] In certain embodiments, an animal created by a method of
the invention may be used to study the effects of mutations on the animal and
development and/or progression of inflammation using measures commonly
used in the study of inflammation. Alternatively, an animal created by a
method
of the invention may be used to study the effects of the mutations on the
progression of a disease state or disorder associated with inflammation-
related
proteins using measures commonly used in the study of said disease state or
disorder. Non-limiting examples of measures that may be used include
spontaneous behaviors of the genetically modified animal, performance during
behavioral testing, physiological anomalies, differential responses to a
compound, abnormalities in tissues or cells, and biochemical or molecular
differences between genetically modified animals and wild type animals.
D. cardiovascular disease
[0156] Cardiovascular diseases generally include high blood
pressure, heart attacks, heart failure, and stroke and TIA. In one embodiment,
a
method of the invention may be used to create an animal or cell in which at
least
one chromosomal sequence associated with cardiovascular disease has been
edited. Suitable chromosomal edits may include, but are not limited to, the
type
of edits detailed in section I(f) above.
[0157] Any chromosomal sequence involved in cardiovascular
disease or the protein encoded by any chromosomal sequence involved in
cardiovascular disease may be utilized in a method of the invention. A
cardiovascular-related sequence may typically be selected based on an
experimental association of the cardiovascular-related sequence to the
development of cardiovascular disease. A cardiovascular-related nucleic acid
sequence may encode a cardiovascular-related protein or may be a
cardiovascular-related control sequence. For example, the production rate or
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circulating concentration of a cardiovascular-related protein may be elevated
or
depressed in a population having a cardiovascular disorder relative to a
population lacking the cardiovascular disorder. Differences in protein levels
may
be assessed using proteomic or genomic analysis techniques known in the art.
[0158] By way of example, the chromosomal sequence may
comprise, but is not limited to, IL1B (interleukin 1, beta), XDH (xanthine
dehydrogenase), TP53 (tumor protein p53), PTGIS (prostaglandin 12
(prostacyclin) synthase), MB (myoglobin),IL4 (interleukin 4), ANGPT1
(angiopoietin 1), ABCG8 (ATP-binding cassette, sub-family G (WHITE), member
8), CTSK (cathepsin K), PTGIR (prostaglandin 12 (prostacyclin) receptor (IP)),
KCNJ1 1 (potassium inwardly-rectifying channel, subfamily J, member 11), INS
(insulin), CRP (C-reactive protein, pentraxin-related), PDGFRB (platelet-
derived
growth factor receptor, beta polypeptide), CCNA2 (cyclin A2), PDGFB (platelet-
derived growth factor beta polypeptide (simian sarcoma viral (v-sis) oncogene
homolog)), KCNJ5 (potassium inwardly-rectifying channel, subfamily J, member
5), KCNN3 (potassium intermediate/small conductance calcium-activated
channel, subfamily N, member 3), CAPN10 (calpain 10), PTGES (prostaglandin
E synthase), ADRA2B (adrenergic, alpha-2B-, receptor), ABCG5 (ATP-binding
cassette, sub-family G (WHITE), member 5), PRDX2 (peroxiredoxin 2), CAPN5
(calpain 5), PARP14 (poly (ADP-ribose) polymerase family, member 14), MEX3C
(mex-3 homolog C (C. elegans)), ACE angiotensin I converting enzyme (peptidyl-
dipeptidase A) 1), TNF (tumor necrosis factor (TNF superfamily, member 2)),
IL6
(interleukin 6 (interferon, beta 2)), STN (statin), SERPINE1 (serpin peptidase
inhibitor, Glade E (nexin, plasminogen activator inhibitor type 1), member 1),
ALB
(albumin), ADIPOQ (adiponectin, C1 Q and collagen domain containing), APOB
(apolipoprotein B (including Ag(x) antigen)), APOE (apolipoprotein E), LEP
(leptin), MTHFR (5,10-m ethyl enetetrahydrofolate reductase (NADPH)), APOA1
(apolipoprotein A-I), EDN1 (endothelin 1), NPPB (natriuretic peptide precursor
B), NOS3 (nitric oxide synthase 3 (endothelial cell)), PPARG (peroxisome
proliferator-activated receptor gamma), PLAT (plasminogen activator, tissue),
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PTGS2 (prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase
and cyclooxygenase)), CETP (cholesteryl ester transfer protein, plasma), AGTR1
(angiotensin II receptor, type 1), HMGCR (3-hydroxy-3-methylglutaryl-Coenzyme
A reductase), IGF1 (insulin-like growth factor 1 (somatomedin C)), SELE
(selectin E), REN (renin), PPARA (peroxisome proliferator-activated receptor
alpha), PON1 (paraoxonase 1), KNG1 (kininogen 1), CCL2 (chemokine (C-C
motif) ligand 2), LPL (lipoprotein lipase), VWF (von Willebrand factor), F2
(coagulation factor II (thrombin)), ICAM1 (intercellular adhesion molecule 1),
TGFB1 (transforming growth factor, beta 1), NPPA (natriuretic peptide
precursor
A), IL10 (interleukin 10), EPO (erythropoietin), SOD1 (superoxide dismutase 1,
soluble), VCAM1 (vascular cell adhesion molecule 1), IFNG (interferon, gamma),
LPA (lipoprotein, Lp(a)), MPO (myeloperoxidase), ESR1 (estrogen receptor 1),
MAPK1 (mitogen-activated protein kinase 1), HP (haptoglobin), F3 (coagulation
factor III (thromboplastin, tissue factor)), CST3 (cystatin C), COG2
(component of
oligomeric golgi complex 2), MMP9 (matrix metallopeptidase 9 (gelatinase B,
92kDa gelatinase, 92kDa type IV collagenase)), SERPINC1 (serpin peptidase
inhibitor, Glade C (antithrombin), member 1), F8 (coagulation factor VIII,
procoagulant component), HMOX1 (heme oxygenase (decycling) 1), APOC3
(apolipoprotein C-III), IL8 (interleukin 8), PROM (prokineticin 1), CBS
(cystathionine-beta-synthase), NOS2 (nitric oxide synthase 2, inducible), TLR4
(toll-like receptor 4), SELP (selectin P (granule membrane protein 140kDa,
antigen CD62)), ABCA1 (ATP-binding cassette, sub-family A (ABC1), member
1), AGT (angiotensinogen (serpin peptidase inhibitor, Glade A, member 8)),
LDLR
(low density lipoprotein receptor), GPT (glutamic-pyruvate transaminase
(alanine
aminotransferase)), VEGFA (vascular endothelial growth factor A), NR3C2
(nuclear receptor subfamily 3, group C, member 2), IL18 (interleukin 18
(interferon-gamma-inducing factor)), NOS1 (nitric oxide synthase 1
(neuronal)),
NR3C1 (nuclear receptor subfamily 3, group C, member 1 (glucocorticoid
receptor)), FGB (fibrinogen beta chain), HGF (hepatocyte growth factor
(hepapoietin A; scatter factor)), IL1A (interleukin 1, alpha), RETN
(resistin), AKT1
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(v-akt murine thymoma viral oncogene homolog 1), LIPC (lipase, hepatic),
HSPD1 (heat shock 60kDa protein 1 (chaperonin)), MAPK14 (mitogen-activated
protein kinase 14), SPP1 (secreted phosphoprotein 1), ITGB3 (integrin, beta 3
(platelet glycoprotein Ilia, antigen CD61)), CAT (catalase), UTS2 (urotensin
2),
THBD (thrombomodulin), F10 (coagulation factor X), CP (ceruloplasmin
(ferroxidase)), TNFRSF1 1 B (tumor necrosis factor receptor superfamily,
member
11 b), EDNRA (endothelin receptor type A), EGFR (epidermal growth factor
receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian)),
MMP2 (matrix metallopeptidase 2 (gelatinase A, 72kDa gelatinase, 72kDa type
IV collagenase)), PLG (plasminogen), NPY (neuropeptide Y), RHOD (ras
homolog gene family, member D), MAPK8 (mitogen-activated protein kinase 8),
MYC (v-myc myelocytomatosis viral oncogene homolog (avian)), FN1 (fibronectin
1), CMA1 (chymase 1, mast cell), PLAU (plasminogen activator, urokinase),
GNB3 (guanine nucleotide binding protein (G protein), beta polypeptide 3),
ADRB2 (adrenergic, beta-2-, receptor, surface), APOA5 (apolipoprotein A-V),
SOD2 (superoxide dismutase 2, mitochondrial), F5 (coagulation factor V
(proaccelerin, labile factor)), VDR (vitamin D (1,25- dihydroxyvitamin D3)
receptor), ALOX5 (arachidonate 5-lipoxygenase), HLA-DRB1 (major
histocompatibility complex, class II, DR beta 1), PARP1 (poly (ADP-ribose)
polymerase 1), CD40LG (CD40 ligand), PON2 (paraoxonase 2), AGER
(advanced glycosylation end product-specific receptor), IRS1 (insulin receptor
substrate 1), PTGS1 (prostaglandin-endoperoxide synthase 1 (prostaglandin G/H
synthase and cyclooxygenase)), ECE1 (endothelin converting enzyme 1), F7
(coagulation factor VII (serum prothrombin conversion accelerator)), IL1 RN
(interleukin 1 receptor antagonist), EPHX2 (epoxide hydrolase 2, cytoplasmic),
IGFBP1 (insulin-like growth factor binding protein 1), MAPK10 (mitogen-
activated
protein kinase 10), FAS (Fas (TNF receptor superfamily, member 6)), ABCB1
(ATP-binding cassette, sub-family B (MDR/TAP), member 1), JUN (jun
oncogene), IGFBP3 (insulin-like growth factor binding protein 3), CD14 (CD14
molecule), PDE5A (phosphodiesterase 5A, cGMP-specific), AGTR2 (angiotensin
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II receptor, type 2), CD40 (CD40 molecule, TNF receptor superfamily member 5),
LCAT (lecithin-cholesterol acyltransferase), CCR5 (chemokine (C-C motif)
receptor 5), MMP1 (matrix metallopeptidase 1 (interstitial collagenase)),
TIMP1
(TIMP metallopeptidase inhibitor 1), ADM (adrenomedullin), DYT10 (dystonia
10), STAT3 (signal transducer and activator of transcription 3 (acute-phase
response factor)), MMP3 (matrix metallopeptidase 3 (stromelysin 1,
progelatinase)), ELN (elastin), USF1 (upstream transcription factor 1), CFH
(complement factor H), HSPA4 (heat shock 70kDa protein 4), MMP1 2 (matrix
metallopeptidase 12 (macrophage elastase)), MME (membrane metallo-
endopeptidase), F2R (coagulation factor II (thrombin) receptor), SELL
(selectin
L), CTSB (cathepsin B), ANXA5 (annexin A5), ADRB1 (adrenergic, beta-l-,
receptor), CYBA (cytochrome b-245, alpha polypeptide), FGA (fibrinogen alpha
chain), GGT1 (gamma-glutamyltransferase 1), LIPG (lipase, endothelial), HIF1A
(hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix
transcription
factor)), CXCR4 (chemokine (C-X-C motif) receptor 4), PROC (protein C
(inactivator of coagulation factors Va and Villa)), SCARB1 (scavenger receptor
class B, member 1), CD79A (CD79a molecule, immunoglobulin-associated
alpha), PLTP (phospholipid transfer protein), ADD1 (adducin 1 (alpha)), FGG
(fibrinogen gamma chain), SAA1 (serum amyloid Al), KCNH2 (potassium
voltage-gated channel, subfamily H (eag-related), member 2), DPP4 (dipeptidyl-
peptidase 4), G6PD (glucose-6-phosphate dehydrogenase), NPR1 (natriuretic
peptide receptor A/guanylate cyclase A (atrionatriuretic peptide receptor A)),
VTN
(vitronectin), KIAA0101 (KIAA0101), FOS (FBJ murine osteosarcoma viral
oncogene homolog), TLR2 (toll-like receptor 2), PPIG (peptidylprolyl isomerase
G (cyclophilin G)), IL1 R1 (interleukin 1 receptor, type I), AR (androgen
receptor),
CYP1A1 (cytochrome P450, family 1, subfamily A, polypeptide 1), SERPINA1
(serpin peptidase inhibitor, ciade A (alpha-1 antiproteinase, antitrypsin),
member
1), MTR (5-methyltetrahydrofolate-homocysteine methyltransferase), RBP4
(retinol binding protein 4, plasma), APOA4 (apolipoprotein A-IV), CDKN2A
(cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)), FGF2
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(fibroblast growth factor 2 (basic)), EDNRB (endothelin receptor type B),
ITGA2
(integrin, alpha 2 (CD49B, alpha 2 subunit of VLA-2 receptor)), CABIN1
(calcineurin binding protein 1), SHBG (sex hormone-binding globulin), HMGB1
(high-mobility group box 1), HSP90B2P (heat shock protein 90kDa beta (Grp94),
member 2 (pseudogene)), CYP3A4 (cytochrome P450, family 3, subfamily A,
polypeptide 4), GJA1 (gap junction protein, alpha 1, 43kDa), CAV1 (caveolin 1,
caveolae protein, 22kDa), ESR2 (estrogen receptor 2 (ER beta)), LTA
(lymphotoxin alpha (TNF superfamily, member 1)), GDF15 (growth differentiation
factor 15), BDNF (brain-derived neurotrophic factor), CYP2D6 (cytochrome
P450, family 2, subfamily D, polypeptide 6), NGF (nerve growth factor (beta
polypeptide)), SP1 (Spl transcription factor), TGIF1 (TGFB-induced factor
homeobox 1), SRC (v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene
homolog (avian)), EGF (epidermal growth factor (beta-urogastrone)), PIK3CG
(phosphoinositide-3-kinase, catalytic, gamma polypeptide), HLA-A (major
histocompatibility complex, class I, A), KCNQ1 (potassium voltage-gated
channel, KQT-like subfamily, member 1), CNR1 (cannabinoid receptor 1 (brain)),
FBN1 (fibrillin 1), CHKA (choline kinase alpha), BEST1 (bestrophin 1), APP
(amyloid beta (A4) precursor protein), CTNNB1 (catenin (cadherin-associated
protein), beta 1, 88kDa), IL2 (interleukin 2), CD36 (CD36 molecule
(thrombospondin receptor)), PRKAB1 (protein kinase, AMP-activated, beta 1
non-catalytic subunit), TPO (thyroid peroxidase), ALDH7A1 (aldehyde
dehydrogenase 7 family, member Al), CX3CR1 (chemokine (C-X3-C motif)
receptor 1), TH (tyrosine hydroxylase), F9 (coagulation factor IX), GH1
(growth
hormone 1), TF (transferrin), HFE (hemochromatosis), IL17A (interleukin 17A),
PTEN (phosphatase and tensin homolog), GSTM1 (glutathione S-transferase mu
1), DMD (dystrophin), GATA4 (GATA binding protein 4), F13A1 (coagulation
factor XIII, Al polypeptide), TTR (transthyretin), FABP4 (fatty acid binding
protein
4, adipocyte), PON3 (paraoxonase 3), APOC1 (apolipoprotein C-I), INSR (insulin
receptor), TNFRSF1 B (tumor necrosis factor receptor superfamily, member 1 B),
HTR2A (5-hydroxytryptamine (serotonin) receptor 2A), CSF3 (colony stimulating
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factor 3 (granulocyte)), CYP2C9 (cytochrome P450, family 2, subfamily C,
polypeptide 9), TXN (thioredoxin), CYP1 1 B2 (cytochrome P450, family 11,
subfamily B, polypeptide 2), PTH (parathyroid hormone), CSF2 (colony
stimulating factor 2 (granulocyte-macrophage)), KDR (kinase insert domain
receptor (a type III receptor tyrosine kinase)), PLA2G2A (phospholipase A2,
group IIA (platelets, synovial fluid)), B2M (beta-2-microglobulin), THBS1
(thrombospondin 1), GCG (glucagon), RHOA (ras homolog gene family, member
A), ALDH2 (aldehyde dehydrogenase 2 family (mitochondrial)), TCF7L2
(transcription factor 7-like 2 (T-cell specific, HMG-box)), BDKRB2 (bradykinin
receptor B2), NFE2L2 (nuclear factor (erythroid-derived 2)-like 2), NOTCH1
(Notch homolog 1, translocation-associated (Drosophila)), UGT1A1 (UDP
glucuronosyltransferase 1 family, polypeptide Al), IFNA1 (interferon, alpha
1),
PPARD (peroxisome proliferator-activated receptor delta), SIRT1 (sirtuin
(silent
mating type information regulation 2 homolog) 1 (S. cerevisiae)), GNRH1
(gonadotropin-releasing hormone 1 (luteinizing-releasing hormone)), PAPPA
(pregnancy-associated plasma protein A, pappalysin 1), ARR3 (arrestin 3,
retinal
(X-arrestin)), NPPC (natriuretic peptide precursor C), AHSP (alpha hemoglobin
stabilizing protein), PTK2 (PTK2 protein tyrosine kinase 2), IL13 (interleukin
13),
MTOR (mechanistic target of rapamycin (serine/threonine kinase)), ITGB2
(integrin, beta 2 (complement component 3 receptor 3 and 4 subunit)), GSTT1
(glutathione S-transferase theta 1), IL6ST (interleukin 6 signal transducer
(gp130,
oncostatin M receptor)), CPB2 (carboxypeptidase B2 (plasma)), CYP1A2
(cytochrome P450, family 1, subfamily A, polypeptide 2), HNF4A (hepatocyte
nuclear factor 4, alpha), SLC6A4 (solute carrier family 6 (neurotransmitter
transporter, serotonin), member 4), PLA2G6 (phospholipase A2, group VI
(cytosolic, calcium-independent)), TNFSF1 1 (tumor necrosis factor (ligand)
superfamily, member 11), SLC8A1 (solute carrier family 8 (sodium/calcium
exchanger), member 1), F2RL1 (coagulation factor II (thrombin) receptor-like
1),
AKR1A1 (aldo-keto reductase family 1, member Al (aldehyde reductase)),
ALDH9A1 (aldehyde dehydrogenase 9 family, member Al), BGLAP (bone
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gamma-carboxyglutamate (gla) protein), MTTP (microsomal triglyceride transfer
protein), MTRR (5-methyltetrahydrofolate-homocysteine methyltransferase
reductase), SULT1A3 (sulfotransferase family, cytosolic, 1A, phenol-
preferring,
member 3), RAGE (renal tumor antigen), C4B (complement component 4B
(Chido blood group), P2RY12 (purinergic receptor P2Y, G-protein coupled, 12),
RNLS (renalase, FAD-dependent amine oxidase), CREB1 (cAMP responsive
element binding protein 1), POMC (proopiomelanocortin), RAC1 (ras-related C3
botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1)),
LMNA
(lamin A/C), CD59 (CD59 molecule, complement regulatory protein), SCN5A
(sodium channel, voltage-gated, type V, alpha subunit), CYP1 B1 (cytochrome
P450, family 1, subfamily B, polypeptide 1), MIF (macrophage migration
inhibitory factor (glycosylation-inhibiting factor)), MMP1 3 (matrix
metallopeptidase 13 (collagenase 3)), TIMP2 (TIMP metallopeptidase inhibitor
2),
CYP19A1 (cytochrome P450, family 19, subfamily A, polypeptide 1), CYP21A2
(cytochrome P450, family 21, subfamily A, polypeptide 2), PTPN22 (protein
tyrosine phosphatase, non-receptor type 22 (lymphoid)), MYH14 (myosin, heavy
chain 14, non-muscle), MBL2 (mannose-binding lectin (protein C) 2, soluble
(opsonic defect)), SELPLG (selectin P ligand), AOC3 (amine oxidase, copper
containing 3 (vascular adhesion protein 1)), CTSL1 (cathepsin L1), PCNA
(proliferating cell nuclear antigen), IGF2 (insulin-like growth factor 2
(somatomedin A)), ITGB1 (integrin, beta 1 (fibronectin receptor, beta
polypeptide,
antigen CD29 includes MDF2, MSK12)), CAST (calpastatin), CXCL12
(chemokine (C-X-C motif) ligand 12 (stromal cell-derived factor 1)), IGHE
(immunoglobulin heavy constant epsilon), KCNE1 (potassium voltage-gated
channel, Isk-related family, member 1), TFRC (transferrin receptor (p90,
CD71)),
COL1A1 (collagen, type I, alpha 1), COL1A2 (collagen, type I, alpha 2), IL2RB
(interleukin 2 receptor, beta), PLA2G10 (phospholipase A2, group X), ANGPT2
(angiopoietin 2), PROCR (protein C receptor, endothelial (EPCR)), NOX4
(NADPH oxidase 4), HAMP (hepcidin antimicrobial peptide), PTPN1 1 (protein
tyrosine phosphatase, non-receptor type 11), SLC2A1 (solute carrier family 2
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(facilitated glucose transporter), member 1), IL2RA (interleukin 2 receptor,
alpha), CCL5 (chemokine (C-C motif) ligand 5), IRF1 (interferon regulatory
factor
1), CFLAR (CASP8 and FADD-like apoptosis regulator), CALCA (calcitonin-
related polypeptide alpha), EIF4E (eukaryotic translation initiation factor
4E),
GSTP1 (glutathione S-transferase pi 1), JAK2 (Janus kinase 2), CYP3A5
(cytochrome P450, family 3, subfamily A, polypeptide 5), HSPG2 (heparan
sulfate proteoglycan 2), CCL3 (chemokine (C-C motif) ligand 3), MYD88 (myeloid
differentiation primary response gene (88)), VIP (vasoactive intestinal
peptide),
SOAT1 (sterol 0-acyltransferase 1), ADRBK1 (adrenergic, beta, receptor kinase
1), NR4A2 (nuclear receptor subfamily 4, group A, member 2), MMP8 (matrix
metallopeptidase 8 (neutrophil collagenase)), NPR2 (natriuretic peptide
receptor
B/guanylate cyclase B (atrionatriuretic peptide receptor B)), GCH1 (GTP
cyclohydrolase 1), EPRS (glutamyl-prolyl-tRNA synthetase), PPARGC1A
(peroxisome proliferator-activated receptor gamma, coactivator 1 alpha), F12
(coagulation factor XII (Hageman factor)), PECAM1 (platelet/endothelial cell
adhesion molecule), CCL4 (chemokine (C-C motif) ligand 4), SERPINA3 (serpin
peptidase inhibitor, Glade A (alpha-1 antiproteinase, antitrypsin), member 3),
CASR (calcium-sensing receptor), GJA5 (gap junction protein, alpha 5, 40kDa),
FABP2 (fatty acid binding protein 2, intestinal), TTF2 (transcription
termination
factor, RNA polymerase II), PROS1 (protein S (alpha)), CTF1 (cardiotrophin 1),
SGCB (sarcoglycan, beta (43kDa dystrophin-associated glycoprotein)), YME1 L1
(YME1 -like 1 (S. cerevisiae)), CAMP (cathelicidin antimicrobial peptide),
ZC3H12A (zinc finger CCCH-type containing 12A), AKR1 131 (aldo-keto reductase
family 1, member 131 (aldose reductase)), DES (desmin), MMP7 (matrix
metallopeptidase 7 (matrilysin, uterine)), AHR (aryl hydrocarbon receptor),
CSF1
(colony stimulating factor 1 (macrophage)), HDAC9 (histone deacetylase 9),
CTGF (connective tissue growth factor), KCNMA1 (potassium large conductance
calcium-activated channel, subfamily M, alpha member 1), UGT1A (UDP
glucuronosyltransferase 1 family, polypeptide A complex locus), PRKCA (protein
kinase C, alpha), COMT (catechol-O-methyltransferase), S100B (S100 calcium
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binding protein B), EGR1 (early growth response 1), PRL (prolactin), U5
(interleukin 15), DRD4 (dopamine receptor D4), CAMK2G (calcium/calmodulin-
dependent protein kinase II gamma), SLC22A2 (solute carrier family 22 (organic
cation transporter), member 2), CCL1 1 (chemokine (C-C motif) ligand 11), PGF
(8321 placental growth factor), THPO (thrombopoietin), GP6 (glycoprotein VI
(platelet)), TACR1 (tachykinin receptor 1), NTS (neurotensin), HNF1A (HNF1
homeobox A), SST (somatostatin), KCND1 (potassium voltage-gated channel,
Shal-related subfamily, member 1), LOC646627 (phospholipase inhibitor),
TBXAS1 (thromboxane A synthase 1 (platelet)), CYP2J2 (cytochrome P450,
family 2, subfamily J, polypeptide 2), TBXA2R (thromboxane A2 receptor),
ADH1C (alcohol dehydrogenase 1C (class I), gamma polypeptide), ALOX12
(arachidonate 12-lipoxygenase), AHSG (alpha-2-HS-glycoprotein), BHMT
(betaine-homocysteine methyltransferase), GJA4 (gap junction protein, alpha 4,
37kDa), SLC25A4 (solute carrier family 25 (mitochondrial carrier; adenine
nucleotide translocator), member 4), ACLY (ATP citrate lyase), ALOX5AP
(arachidonate 5-lipoxygenase-activating protein), NUMA1 (nuclear mitotic
apparatus protein 1), CYP27B1 (cytochrome P450, family 27, subfamily B,
polypeptide 1), CYSLTR2 (cysteinyl leukotriene receptor 2), SOD3 (superoxide
dismutase 3, extracellular), LTC4S (leukotriene C4 synthase), UCN (urocortin),
GHRL (ghrelin/obestatin prepropeptide), APOC2 (apolipoprotein C-II), CLEC4A
(C-type lectin domain family 4, member A), KBTBD10 (kelch repeat and BTB
(POZ) domain containing 10), TNC (tenascin C), TYMS (thymidylate synthetase),
SHC1 (SHC (Src homology 2 domain containing) transforming protein 1), LRP1
(low density lipoprotein receptor-related protein 1), SOCS3 (suppressor of
cytokine signaling 3), ADH1 B (alcohol dehydrogenase 1 B (class I), beta
polypeptide), KLK3 (kallikrein-related peptidase 3), HSD1 1 B1 (hydroxysteroid
(11-beta) dehydrogenase 1), VKORC1 (vitamin K epoxide reductase complex,
subunit 1), SERPINB2 (serpin peptidase inhibitor, Glade B (ovalbumin), member
2), TNS1 (tensin 1), RNF19A (ring finger protein 19A), EPOR (erythropoietin
receptor), ITGAM (integrin, alpha M (complement component 3 receptor 3
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subunit)), PITX2 (paired-like homeodomain 2), MAPK7 (mitogen-activated
protein kinase 7), FCGR3A (Fc fragment of IgG, low affinity Ilia, receptor
(CD16a)), LEPR (leptin receptor), ENG (endoglin), GPX1 (glutathione peroxidase
1), GOT2 (glutamic-oxaloacetic transaminase 2, mitochondrial (aspartate
aminotransferase 2)), HRH1 (histamine receptor H1), NR112 (nuclear receptor
subfamily 1, group I, member 2), CRH (corticotropin releasing hormone), HTR1A
(5-hydroxytryptamine (serotonin) receptor 1A), VDAC1 (voltage-dependent anion
channel 1), HPSE (heparanase), SFTPD (surfactant protein D), TAP2
(transporter 2, ATP-binding cassette, sub-family B (MDR/TAP)), RNF123 (ring
finger protein 123), PTK2B (PTK2B protein tyrosine kinase 2 beta), NTRK2
(neurotrophic tyrosine kinase, receptor, type 2), IL6R (interleukin 6
receptor),
ACHE (acetylcholinesterase (Yt blood group)), GLP1 R (glucagon-like peptide 1
receptor), GHR (growth hormone receptor), GSR (glutathione reductase), NQO1
(NAD(P)H dehydrogenase, quinone 1), NR5A1 (nuclear receptor subfamily 5,
group A, member 1), GJB2 (gap junction protein, beta 2, 26kDa), SLC9A1 (solute
carrier family 9 (sodium/hydrogen exchanger), member 1), MAOA (monoamine
oxidase A), PCSK9 (proprotein convertase subtilisin/kexin type 9), FCGR2A (Fc
fragment of IgG, low affinity Ila, receptor (CD32)), SERPINF1 (serpin
peptidase
inhibitor, Glade F (alpha-2 antiplasmin, pigment epithelium derived factor),
member 1), EDN3 (endothelin 3), DHFR (dihydrofolate reductase), GAS6 (growth
arrest-specific 6), SMPD1 (sphingomyelin phosphodiesterase 1, acid lysosomal),
UCP2 (uncoupling protein 2 (mitochondrial, proton carrier)), TFAP2A
(transcription factor AP-2 alpha (activating enhancer binding protein 2
alpha)),
C4BPA (complement component 4 binding protein, alpha), SERPINF2 (serpin
peptidase inhibitor, Glade F (alpha-2 antiplasmin, pigment epithelium derived
factor), member 2), TYMP (thymidine phosphorylase), ALPP (alkaline
phosphatase, placental (Regan isozyme)), CXCR2 (chemokine (C-X-C motif)
receptor 2), SLC39A3 (solute carrier family 39 (zinc transporter), member 3),
ABCG2 (ATP-binding cassette, sub-family G (WHITE), member 2), ADA
(adenosine deaminase), JAK3 (Janus kinase 3), HSPAIA (heat shock 70kDa
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protein 1A), FASN (fatty acid synthase), FGF1 (fibroblast growth factor 1
(acidic)), F11 (coagulation factor XI), ATP7A (ATPase, Cu++ transporting,
alpha
polypeptide), CR1 (complement component (3b/4b) receptor 1 (Knops blood
group)), GFAP (glial fibrillary acidic protein), ROCK1 (Rho-associated, coiled-
coil
containing protein kinase 1), MECP2 (methyl CpG binding protein 2 (Rett
syndrome)), MYLK (myosin light chain kinase), BCHE (butyrylcholinesterase),
LIPE (lipase, hormone-sensitive), PRDX5 (peroxiredoxin 5), ADORA1
(adenosine Al receptor), WRN (Werner syndrome, RecQ helicase-like), CXCR3
(chemokine (C-X-C motif) receptor 3), CD81 (CD81 molecule), SMAD7 (SMAD
family member 7), LAMC2 (laminin, gamma 2), MAP3K5 (mitogen-activated
protein kinase kinase kinase 5), CHGA (chromogranin A (parathyroid secretory
protein 1)), IAPP (islet amyloid polypeptide), RHO (rhodopsin), ENPP1
(ectonucleotide pyrophosphatase/phosphodiesterase 1), PTHLH (parathyroid
hormone-like hormone), NRG1 (neuregulin 1), VEGFC (vascular endothelial
growth factor C), ENPEP (glutamyl aminopeptidase (aminopeptidase A)), CEBPB
(CCAAT/enhancer binding protein (C/EBP), beta), NAGLU (N-
acetylglucosaminidase, alpha-), F2RL3 (coagulation factor II (thrombin)
receptor-
like 3), CX3CL1 (chemokine (C-X3-C motif) ligand 1), BDKRB1 (bradykinin
receptor B1), ADAMTS13 (ADAM metallopeptidase with thrombospondin type 1
motif, 13), ELANE (elastase, neutrophil expressed), ENPP2 (ectonucleotide
pyrophosphatase/phosphodiesterase 2), CISH (cytokine inducible SH2-
containing protein), GAST (gastrin), MYOC (myocilin, trabecular meshwork
inducible glucocorticoid response), ATP1A2 (ATPase, Na+/K+ transporting,
alpha 2 polypeptide), NF1 (neurofibromin 1), GJB1 (gap junction protein, beta
1,
32kDa), MEF2A (myocyte enhancer factor 2A), VCL (vinculin), BMPR2 (bone
morphogenetic protein receptor, type II (serine/threonine kinase)), TUBB
(tubulin,
beta), CDC42 (cell division cycle 42 (GTP binding protein, 25kDa)), KRT18
(keratin 18), HSF1 (heat shock transcription factor 1), MYB (v-myb
myeloblastosis viral oncogene homolog (avian)), PRKAA2 (protein kinase, AMP-
activated, alpha 2 catalytic subunit), ROCK2 (Rho-associated, coiled-coil
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containing protein kinase 2), TFPI (tissue factor pathway inhibitor
(lipoprotein-
associated coagulation inhibitor)), PRKG1 (protein kinase, cGMP-dependent,
type I), BMP2 (bone morphogenetic protein 2), CTNND1 (catenin (cadherin-
associated protein), delta 1), CTH (cystathionase (cystathionine gamma-
lyase)),
CTSS (cathepsin S), VAV2 (vav 2 guanine nucleotide exchange factor), NPY2R
(neuropeptide Y receptor Y2), IGFBP2 (insulin-like growth factor binding
protein
2, 36kDa), CD28 (CD28 molecule), GSTA1 (glutathione S-transferase alpha 1),
PPIA (peptidylprolyl isomerase A (cyclophilin A)), APOH (apolipoprotein H
(beta-
2-glycoprotein I)), S100A8 (S100 calcium binding protein A8), IL11
(interleukin
11), ALOX15 (arachidonate 15-lipoxygenase), FBLN1 (fibulin 1), NR1 H3 (nuclear
receptor subfamily 1, group H, member 3), SCD (stearoyl-CoA desaturase (delta-
9-desaturase)), GIP (gastric inhibitory polypeptide), CHGB (chromogranin B
(secretogranin 1)), PRKCB (protein kinase C, beta), SRD5A1 (steroid-5-alpha-
reductase, alpha polypeptide 1 (3-oxo-5 alpha-steroid delta 4-dehydrogenase
alpha 1)), HSD1 1 B2 (hydroxysteroid (11-beta) dehydrogenase 2), CALCRL
(calcitonin receptor-like), GALNT2 (UDP-N-acetyl-alpha-D-
galactosamine:polypeptide N-acetylgalactosaminyltransferase 2 (GaINAc-T2)),
ANGPTL4 (angiopoietin-like 4), KCNN4 (potassium intermediate/small
conductance calcium-activated channel, subfamily N, member 4), PIK3C2A
(phosphoinositide-3-kinase, class 2, alpha polypeptide), HBEGF (heparin-
binding
EGF-like growth factor), CYP7A1 (cytochrome P450, family 7, subfamily A,
polypeptide 1), HLA-DRB5 (major histocompatibility complex, class II, DR beta
5), BNIP3 (BCL2/adenovirus E1 B 19kDa interacting protein 3), GCKR
(glucokinase (hexokinase 4) regulator), S100A12 (S100 calcium binding protein
A12), PADI4 (peptidyl arginine deiminase, type IV), HSPA14 (heat shock 70kDa
protein 14), CXCR1 (chemokine (C-X-C motif) receptor 1), H19 (H19, imprinted
maternally expressed transcript (non-protein coding)), KRTAP19-3 (keratin
associated protein 19-3), IDDM2 (insulin-dependent diabetes mellitus 2), RAC2
(ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding
protein
Rac2)), RYR1 (ryanodine receptor 1 (skeletal)), CLOCK (clock homolog
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(mouse)), NGFR (nerve growth factor receptor (TNFR superfamily, member 16)),
DBH (dopamine beta-hydroxylase (dopamine beta-monooxygenase)), CHRNA4
(cholinergic receptor, nicotinic, alpha 4), CACNA1C (calcium channel, voltage-
dependent, L type, alpha 1C subunit), PRKAG2 (protein kinase, AMP-activated,
gamma 2 non-catalytic subunit), CHAT (choline acetyltransferase), PTGDS
(prostaglandin D2 synthase 21 kDa (brain)), NR1 H2 (nuclear receptor subfamily
1, group H, member 2), TEK (TEK tyrosine kinase, endothelial), VEGFB
(vascular endothelial growth factor B), MEF2C (myocyte enhancer factor 2C),
MAPKAPK2 (mitogen-activated protein kinase-activated protein kinase 2),
TNFRSF11A (tumor necrosis factor receptor superfamily, member 11a, NFKB
activator), HSPA9 (heat shock 70kDa protein 9 (mortalin)), CYSLTR1 (cysteinyl
leukotriene receptor 1), MAT1A (methionine adenosyltransferase I, alpha),
OPRL1 (opiate receptor-like 1), IMPA1 (inositol(myo)-1 (or 4)-monophosphatase
1), CLCN2 (chloride channel 2), DLD (dihydrolipoamide dehydrogenase), PSMA6
(proteasome (prosome, macropain) subunit, alpha type, 6), PSMB8 (proteasome
(prosome, macropain) subunit, beta type, 8 (large multifunctional peptidase
7)),
CHI3L1 (chitinase 3-like 1 (cartilage glycoprotein-39)), ALDH1 B1 (aldehyde
dehydrogenase 1 family, member B1), PARP2 (poly (ADP-ribose) polymerase 2),
STAR (steroidogenic acute regulatory protein), LBP (lipopolysaccharide binding
protein), ABCC6 (ATP-binding cassette, sub-family C (CFTR/MRP), member 6),
RGS2 (regulator of G-protein signaling 2, 24kDa), EFNB2 (ephrin-B2), GJB6
(gap junction protein, beta 6, 30kDa), APOA2 (apolipoprotein A-II), AMPD1
(adenosine monophosphate deaminase 1), DYSF (dysferlin, limb girdle muscular
dystrophy 2B (autosomal recessive)), FDFT1 (farnesyl-diphosphate
farnesyltransferase 1), EDN2 (endothelin 2), CCR6 (chemokine (C-C motif)
receptor 6), GJB3 (gap junction protein, beta 3, 31 kDa), IL1 RL1 (interleukin
1
receptor-like 1), ENTPD1 (ectonucleoside triphosphate diphosphohydrolase 1),
BBS4 (Bardet-Biedl syndrome 4), CELSR2 (cadherin, EGF LAG seven-pass G-
type receptor 2 (flamingo homolog, Drosophila)), F11 R (F11 receptor),
RAPGEF3 (Rap guanine nucleotide exchange factor (GEF) 3), HYAL1
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(hyaluronoglucosaminidase 1), ZNF259 (zinc finger protein 259), ATOX1 (ATX1
antioxidant protein 1 homolog (yeast)), ATF6 (activating transcription factor
6),
KHK (ketohexokinase (fructokinase)), SAT1 (spermidine/spermine N1-
acetyltransferase 1), GGH (gamma-glutamyl hydrolase (conjugase,
folylpolygammaglutamyl hydrolase)), TIMP4 (TIMP metallopeptidase inhibitor 4),
SLC4A4 (solute carrier family 4, sodium bicarbonate cotransporter, member 4),
PDE2A (phosphodiesterase 2A, cGMP-stimulated), PDE3B (phosphodiesterase
3B, cGMP-inhibited), FADS1 (fatty acid desaturase 1), FADS2 (fatty acid
desaturase 2), TMSB4X (thymosin beta 4, X-linked), TXNIP (thioredoxin
interacting protein), LIMS1 (LIM and senescent cell antigen-like domains 1),
RHOB (ras homolog gene family, member B), LY96 (lymphocyte antigen 96),
FOXO1 (forkhead box 01), PNPLA2 (patatin-like phospholipase domain
containing 2), TRH (thyrotropin-releasing hormone), GJC1 (gap junction
protein,
gamma 1, 45kDa), SLC17A5 (solute carrier family 17 (anion/sugar transporter),
member 5), FTO (fat mass and obesity associated), GJD2 (gap junction protein,
delta 2, 36kDa), PSRC1 (proline/serine-rich coiled-coil 1), CASP12 (caspase 12
(gene/pseudogene)), GPBARI (G protein-coupled bile acid receptor 1), PXK (PX
domain containing serine/threonine kinase), IL33 (interleukin 33), TRIB1
(tribbles
homolog 1 (Drosophila)), PBX4 (pre-B-cell leukemia homeobox 4), NUPR1
(nuclear protein, transcriptional regulator, 1), 15-Sep(15 kDa selenoprotein),
CILP2 (cartilage intermediate layer protein 2), TERC (telomerase RNA
component), GGT2 (gamma-glutamyltransferase 2), MT-CO1 (mitochondrially
encoded cytochrome c oxidase I), and UOX (urate oxidase, pseudogene).
[0159] In an additional embodiment, the chromosomal sequence
may further be selected from Pont (paraoxonase 1), LDLR (LDL receptor), ApoE
(Apolipoprotein E), Apo B-100 (Apolipoprotein B-100), ApoA
(Apolipoprotein(a)),
ApoA1 (Apolipoprotein Al), CBS (Cystathione B-synthase), Glycoprotein Ilb/Ilb,
MTHRF (5,10-m ethyl enetetrahydrofolate reductase (NADPH), and combinations
thereof. In one iteration, the chromosomal sequences and proteins encoded by
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chromosomal sequences involved in cardiovascular disease may be chosen from
Cacnal C, Sodl, Pten, Ppar(alpha), Apo E, Leptin, and combinations thereof.
[0160] In certain embodiments, an animal created by a method of
the invention may be used to study the effects of mutations on the animal and
development and/or progression of cardiovascular disease using measures
commonly used in the study of cardiovascular disease. For instance, suitable
disease measures may include behavioral, electrophysiological, neurochemical,
biochemical, or cellular dysfunctions which can be evaluated using any of a
number of well-known diagnostic tests or assays.
E. Alzheimer's disease
[0161] In one embodiment, a method of the invention may be used
to create an animal or cell in which at least one chromosomal sequence
associated with Alheimer's disease (AD) has been edited. Suitable chromosomal
edits may include, but are not limited to, the type of edits detailed in
section I(f)
above.
[0162] In some embodiments, one or more chromosomal
sequences associated with AD may be edited. The AD-related nucleic acid
sequence may typically be selected based on an experimental association of the
AD-related nucleic acid sequence to an AD disorder. An AD-related nucleic acid
sequence may encode an AD-related protein or may be an AD-related control
sequence. For example, the production rate or circulating concentration of an
AD-related protein may be elevated or depressed in a population having an AD
disorder relative to a population lacking the AD disorder. Differences in
protein
levels may be assessed using proteomic or genomic analysis techniques known
in the art.
[0163] By way of non-limiting example, proteins associated with AD
include but are not limited to the very low density lipoprotein receptor
protein
(VLDLR) encoded by the VLDLR gene, the ubiquitin-like modifier activating
enzyme 1 (UBA1) encoded by the UBAI gene, the NEDD8-activating enzyme El
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catalytic subunit protein (UBE1 C) encoded by the UBA3 gene, the aquaporin 1
protein (AQP1) encoded by the AQPI gene, the ubiquitin carboxyl-terminal
esterase L1 protein (UCHL1) encoded by the UCHLI gene, the ubiquitin
carboxyl-terminal hydrolase isozyme L3 protein (UCHL3) encoded by the UCHL3
gene, the ubiquitin B protein (UBB) encoded by the UBB gene, the microtubule-
associated protein tau (MAPT) encoded by the MAPT gene, the protein tyrosine
phosphatase receptor type A protein (PTPRA) encoded by the PTPRA gene, the
phosphatidylinositol binding clathrin assembly protein (PICALM) encoded by the
P/CALM gene, the clusterin protein (also known as apoplipoprotein J) encoded
by the CLU gene, the presenilin 1 protein encoded by the PSENI gene, the
presenilin 2 protein encoded by the PSEN2 gene, the sortilin-related receptor
L(DLR class) A repeats-containing protein (SORL1) protein encoded by the
SORLI gene, the amyloid precursor protein (APP) encoded by the APP gene,
the Apolipoprotein E precursor (APOE) encoded by the APOE gene, or the brain-
derived neurotrophic factor (BDNF) encoded by the BDNF gene, or combinations
thereof.
[0164] In certain embodiments, an animal created by a method of
the invention may be used to study the effects of mutations on the animal and
development and/or progression of AD using measures commonly used in the
study of AD. Commonly used measures in the study of AD include without limit,
learning and memory, anxiety, depression, addiction, and sensory-motor
functions, as well as functional, pathological, metabolic, or biochemical
assays.
Those of skill in the art are familiar with other suitable measures or
indicators of
AD. In general, such measures may be made in comparison to wild type
littermates.
[0165] Other measures of behavior may include assessments of
spontaneous behavior. Spontaneous behavior may be assessed using any one
or more methods of spontaneous behavioral observations known in the art. In
general, any spontaneous behavior within a known behavioral repertoire of an
animal may be observed, including movement, posture, social interaction,
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rearing, sleeping, blinking, eating, drinking, urinating, defecating, mating,
and
aggression. An extensive battery of observations for quantifying the
spontaneous behavior of mice and rats is well-known in the art, including but
not
limited to home-cage observations such as body position, respiration, tonic
involuntary movement, unusual motor behavior such as pacing or rocking,
catatonic behavior, vocalization, palpebral closure, mating frequency, running
wheel behavior, nest building, and frequency of aggressive interactions.
[0166] In another embodiment, the animals of the invention may be
used to study the effects of the mutations on the progression of a disease
state
or disorder other than AD, but which is also associated with AD-related
proteins,
using measures commonly used in the study of said disease state or disorder.
Non limiting examples of disease states or disorders other than AD that may be
associated with AD-related proteins include dementia, congenital cerebellar
ataxia, mental retardation such as learning and memory defects, lissencephaly,
tauopathy or fibrilization, amyloidosis, neurodegeneration, Parkinsonism,
progressive supranuclear palsy, Pick disease, male infertility, prostate and
breast
cancer, squamous cell carcinoma, lymphoma, leukemia, and atherosclerosis.
[0167] Yet another aspect encompasses a method for assessing
the efficacy of a potential gene therapy strategy. That is, a chromosomal
sequence encoding a protein associated with AD may be modified such that the
genetically modified animal may have an altered response to the development
and/or progression of AD as compared to a non treated animal. Stated another
way, a mutated gene that predisposes an animal to AD may be "corrected"
through gene therapy.
F. autism spectrum disorder
[0168] In one embodiment, a method of the invention may be used
to create an animal or cell in which at least one chromosomal sequence
associated with autism spectrum disorder (ASD) has been edited. Suitable
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chromosomal edits may include, but are not limited to, the type of edits
detailed
in section I(f) above.
[0169] In each of the above embodiments, one or more
chromosomal sequences associated with ASD may be edited. An ASD
associated protein or control sequence may typically be selected based on an
experimental association of the protein or control sequence to an incidence or
indication of an ASD. For example, the production rate or circulating
concentration of a protein associated with ASD may be elevated or depressed in
a population having an ASD relative to a population lacking the ASD.
Differences in protein levels may be assessed using proteomic or genomic
analysis techniques known in the art.
[0170] The identity of the protein associated with ASD whose
chromosomal sequence is edited can and will vary. In preferred embodiments,
the proteins associated with ASD whose chromosomal sequence is edited may
be the benzodiazapine receptor (peripheral) associated protein 1 (BZRAP1)
encoded by the BZRAPI gene, the AF4/FMR2 family member 2 protein (AFF2)
encoded by the AFF2 gene (also termed MFR2), the fragile X mental retardation
autosomal homolog 1 protein (FXR1) encoded by the FXR1 gene, the fragile X
mental retardation autosomal homolog 2 protein (FXR2) encoded by the FXR2
gene, the MAM domain containing glycosylphosphatidylinositol anchor 2 protein
(MDGA2) encoded by the MDGA2 gene, the methyl CpG binding protein 2
(MECP2) encoded by the MECP2 gene, the metabotropic glutamate receptor 5
(MGLUR5) encoded by the MGLUR5-1 gene (also termed GRM5), the neurexin
1 protein encoded by the NRXN1 gene, or the semaphorin-5A protein (SEMA5A)
encoded by the SEMA5A gene.
[0171] The edited or integrated chromosomal sequence may be
modified to encode an altered protein associated with ASD. Non-limiting
examples of mutations in proteins associated with ASD include the L18Q
mutation in neurexin 1 where the leucine at position 18 is replaced with a
glutamine, the R451 C mutation in neuroligin 3 where the arginine at position
451
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is replaced with a cysteine, the R87W mutation in neuroligin 4 where the
arginine
at position 87 is replaced with a tryptophan, and the 1425V mutation in
serotonin
transporter where the isoleucine at position 425 is replaced with a valine. A
number of other mutations and chromosomal rearrangements in ASD-related
chromosomal sequences have been associated with ASD and are known in the
art. See, for example, Freitag et al. (2010) Eur. Child. Adolesc. Psychiatry
19:169-178, and Bucan et al. (2009) PLoS Genetics 5: el000536, the disclosure
of which is incorporated by reference herein in its entirety.
[0172] In certain embodiments, an animal created by a method of
the invention may be used to study the effects of mutations on the animal and
development and/or progression of ASD using measures commonly used in the
study of ASD.
G. macular degeneration
[0173] In one embodiment, a method of the invention may be used
to create an animal or cell in which at least one chromosomal sequence
associated with macular degeneration (MD) has been edited. Suitable
chromosomal edits may include, but are not limited to, the type of edits
detailed
in section I(f) above.
[0174] In each of the above embodiments, one or more
chromosomal sequences associated with MD may be edited. A MD-associated
protein or control sequence may typically be selected based on an experimental
association of the protein associated with MD to an MD disorder. For example,
the production rate or circulating concentration of a protein associated with
MD
may be elevated or depressed in a population having an MD disorder relative to
a population lacking the MD disorder. Differences in protein levels may be
assessed using proteomic or genomic analysis techniques known in the art.
[0175] The identity of the protein associated with MD whose
chromosomal sequence is edited can and will vary. In preferred embodiments,
the proteins associated with MD whose chromosomal sequence is edited may be
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the ATP-binding cassette, sub-family A (ABC1) member 4 protein (ABCA4)
encoded by the ABCR gene, the apolipoprotein E protein (APOE) encoded by
the APOE gene, the chemokine (C-C motif) Ligand 2 protein (CCL2) encoded by
the CCL2 gene, the chemokine (C-C motif) receptor 2 protein (CCR2) encoded
by the CCR2 gene, the ceruloplasmin protein (CP) encoded by the CP gene, the
cathepsin D protein (CTSD) encoded by the CTSD gene, or the
metalloproteinase inhibitor 3 protein (TIMP3) encoded by the TIMP3 gene.
[0176] In certain embodiments, a genetically modified animal
created by a method of the invention may be used to study the effects of
mutations on the progression of MD using measures commonly used in the study
of MD. Alternatively, the genetically modified animals of the invention may be
used to study the effects of the mutations on the progression of a disease
state
or disorder associated with proteins associated with MD using measures
commonly used in the study of said disease state or disorder. Non-limiting
examples of measures that may be used include drusen accumulation, lipofuscin
accumulation, thickening of Bruch's membrane, retinal degeneration, choroidal
neovascularization, differential responses to a compound, abnormalities in
tissues or cells, biochemical or molecular differences between genetically
modified animals and wild type animals or a combination thereof.
H. schizophrenia
[0177] In one embodiment, a method of the invention may be used
to create an animal or cell in which at least one chromosomal sequence
associated with schizophrenia has been edited. Suitable chromosomal edits may
include, but are not limited to, the type of edits detailed in section I(f)
above.
[0178] In each of the above embodiments, one or more
chromosomal sequences associated with schizophrenia may be edited. A
schizophrenia-associated protein or control sequence may typically be selected
based on an experimental association of the protein associated with
schizophrenia to the development or progression of schizophrenia. For example,
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the production rate or circulating concentration of a protein associated with
schizophrenia may be elevated or depressed in a population having
schizophrenia relative to a population not having schizophrenia. Differences
in
protein levels may be assessed using proteomic or genomic analysis techniques
known in the art. Exemplary non-limiting examples of chromosomal sequences
associated with schizophrenia include NRG1, ErbB4, CPLX1, TPH1, TPH2,
NRXN1, GSK3A, BDNF, DISC1, GSK3B, and combinations thereof, each of
which is described in more detail below.
[0179] In certain embodiments, an animal created by a method of
the invention may be used to study the effects of mutations on the animal and
development and/or progression of MD using measures commonly used in the
study of MD.
[0180] The incidence or indication of the schizophrenia or related
disorder may occur spontaneously in the genetically modified animal.
Alternatively, the incidence or indication of the schizophrenia or related
disorder
may be promoted by exposure to a disruptive agent. Non-limiting examples of
disruptive agents include a protein associated with schizophrenia such as any
of
those described above, a drug, a toxin, a chemical, an activated retrovirus,
and
an environmental stress. Non-limiting examples of environmental stresses
include forced swimming, cold swimming, platform shaker stimuli, loud noises,
and immobilization stress.
1. tumor sumpresion
[0181] Tumor suppression genes are genes whose protein products
protect a cell from one step on the path to cancer. A mutation in a tumor
suppressor gene may cause a loss or reduction in the protective function of
its
protein product, thereby increasing the probability that a tumor will form,
leading
to cancer, usually in combination with other genetic changes. The proteins
encoded by tumor suppressor genes have a dampening or repressive effect on
the regulation of the cell cycle or promote apoptosis, and sometimes both.
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Tumor suppressor proteins are involved in the repression of genes essential
for
the continuing cell cycle; coupling the cell cycle to DNA damage so that the
cell
cycle can continue; initiating apoptosis in the cell if the damage cannot be
repaired; and cell adhesion to prevent tumors from dispersing, blocking a loss
of
contact inhibition, and inhibiting metastasis.
[0182] In one embodiment, a method of the invention may be used
to create an animal or cell in which at least one chromosomal sequence
associated with tumor suppresion has been edited. Suitable chromosomal edits
may include, but are not limited to, the type of edits detailed in section
I(f) above.
[0183] In each of the above embodiments, one or more
chromosomal sequences associated with tumor suppression may be edited. A
tumor suppression-associated protein or control sequence may typically
selected
based on an experimental association of the protein of interest with a cancer.
For example, the production rate or circulating concentration of a protein
associated with tumor suppression may be elevated or depressed in a population
having cancer relative to a population not having cancer. Differences in
protein
levels may be assessed using proteomic or genomic analysis techniques known
in the art.
[0184] By way of example, proteins involved in tumor suppression
may comprise, but are not limited to, TNF (tumor necrosis factor (TNF
superfamily, member 2)), TP53 (tumor protein p53), ERBB2 (v-erb-b2
erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived
oncogene homolog (avian)), FN1 (fibronectin 1), TSC1 (tuberous sclerosis 1),
PTGS2 (prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase
and cyclooxygenase)), PTEN (phosphatase and tensin homolog), PCNA
(proliferating cell nuclear antigen), COL18A1 (collagen, type XVIII, alpha 1),
TSSC4 (tumor suppressing subtransferable candidate 4), JUN (jun oncogene),
MAPK8 (mitogen-activated protein kinase 8), TGFB1 (transforming growth factor,
beta 1), IL6 (interleukin 6 (interferon, beta 2)), IFNG (interferon, gamma),
BRCA1
(breast cancer 1, early onset), TSPAN32 (tetraspanin 32), BCL2 (B-cell
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CLL/lymphoma 2), NF2 (neurofibromin 2 (merlin)), GJB1 (gap junction protein,
beta 1, 32kDa), MAPK1 (mitogen-activated protein kinase 1), CD44 (CD44
molecule (Indian blood group)), PGR (progesterone receptor), TNS1 (tensin 1),
PROK1 (prokineticin 1), SIAH1 (seven in absentia homolog 1 (Drosophila)), ENG
(endoglin), TP73 (tumor protein p73), APC (adenomatous polyposis coli), BAX
(BCL2-associated X protein), SRC (v-src sarcoma (Schmidt-Ruppin A-2) viral
oncogene homolog (avian)), VHL (von Hippel-Lindau tumor suppressor), FHIT
(fragile histidine triad gene), NFKB1 (nuclear factor of kappa light
polypeptide
gene enhancer in B-cells 1), IFNA1 (interferon, alpha 1), TGFBR1 (transforming
growth factor, beta receptor 1), PRKCD (protein kinase C, delta), TGIF1 (TGFB-
induced factor homeobox 1), DLC1 (deleted in liver cancer 1), SLC22A1 8
(solute
carrier family 22, member 18), VEGFA (vascular endothelial growth factor A),
MME (membrane metallo-endopeptidase), IL3 (interleukin 3 (colony-stimulating
factor, multiple)), MK167 (antigen identified by monoclonal antibody Ki-67),
HSPD1 (heat shock 60kDa protein 1 (chaperonin)), HSPB1 (heat shock 27kDa
protein 1), HSP90B2P (heat shock protein 90kDa beta (Grp94), member 2
(pseudogene)), MBL2 (mannose-binding lectin (protein C) 2, soluble (opsonic
defect)), ZFYVE9 (zinc finger, FYVE domain containing 9), TERT (telomerase
reverse transcriptase), PML (promyelocytic leukemia), SKP2 (S-phase kinase-
associated protein 2 (p45)), CYCS (cytochrome c, somatic), MAPK10 (mitogen-
activated protein kinase 10), PAX7 (paired box 7), YAP1 (Yes-associated
protein
1), PARP1 (poly (ADP-ribose) polymerase 1), MIR34A (microRNA 34a), PRKCA
(protein kinase C, alpha), FAS (Fas (TNF receptor superfamily, member 6)), SYK
(spleen tyrosine kinase), GSK3B (glycogen synthase kinase 3 beta), PRKCE
(protein kinase C, epsilon), CYP1 9A1 (cytochrome P450, family 19, subfamily
A,
polypeptide 1), ABCB1 (ATP-binding cassette, sub-family B (MDR/TAP), member
1), NFKBIA (nuclear factor of kappa light polypeptide gene enhancer in B-cells
inhibitor, alpha), RUNX1 (runt-related transcription factor 1), PRKCG (protein
kinase C, gamma), RELA (v-ref reticuloendotheliosis viral oncogene homolog A
(avian)), PLAU (plasminogen activator, urokinase), BTK (Bruton
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agammaglobulinemia tyrosine kinase), PRKCB (protein kinase C, beta), CSF1
(colony stimulating factor 1 (macrophage)), POMC (proopiomelanocortin),
CEBPB (CCAAT/enhancer binding protein (C/EBP), beta), ROCK1 (Rho-
associated, coiled-coil containing protein kinase 1), KDR (kinase insert
domain
receptor (a type III receptor tyrosine kinase)), NPM1 (nucleophosmin
(nucleolar
phosphoprotein B23, numatrin)), ROCK2 (Rho-associated, coiled-coil containing
protein kinase 2), PRKAB1 (protein kinase, AMP-activated, beta 1 non-catalytic
subunit), BAK1 (BCL2-antagonist/killer 1), AURKA (aurora kinase A), NTN1
(netrin 1), FLT1 (fms-related tyrosine kinase 1 (vascular endothelial growth
factor/vascular permeability factor receptor)), NBN (nibrin), DNM3 (dynamin
3),
PRDM10 (PR domain containing 10), PAX5 (paired box 5), EIF4G1 (eukaryotic
translation initiation factor 4 gamma, 1), KAT2B (K(lysine) acetyltransferase
2B),
TIMP3 (TIMP metallopeptidase inhibitor 3), CCL22 (chemokine (C-C motif) ligand
22), GRIN2B (glutamate receptor, ionotropic, N-methyl D-aspartate 2B), CD81
(CD81 molecule), CCL27 (chemokine (C-C motif) ligand 27), MAPK1 1 (mitogen-
activated protein kinase 11), DKK1 (dickkopf homolog 1 (Xenopus laevis)),
HYAL1 (hyaluronoglucosaminidase 1), CTSL1 (cathepsin L1), PKD1 (polycystic
kidney disease 1 (autosomal dominant)), BUB1 B (budding uninhibited by
benzimidazoles 1 homolog beta (yeast)), MPP1 (membrane protein,
palmitoylated 1, 55kDa), SIAH2 (seven in absentia homolog 2 (Drosophila)),
DUSP13 (dual specificity phosphatase 13), CCL21 (chemokine (C-C motif) ligand
21), RTN4 (reticulon 4), SMO (smoothened homolog (Drosophila)), CCL19
(chemokine (C-C motif) ligand 19), CSTF2 (cleavage stimulation factor, 3V pre-
RNA, subunit 2, 64kDa), RSF1 (remodeling and spacing factor 1), EZH2
(enhancer of zeste homolog 2 (Drosophila)), AK1 (adenylate kinase 1), CKM
(creatine kinase, muscle), HYAL3 (hyaluronoglucosaminidase 3), ALOX15B
(arachidonate 15-lipoxygenase, type B), PAG1 (phosphoprotein associated with
glycosphingolipid microdomains 1), MIR21 (microRNA 21), S100A2 (S100
calcium binding protein A2), HYAL2 (hyaluronoglucosaminidase 2), CSTF1
(cleavage stimulation factor, 3\' pre-RNA, subunit 1, 50kDa), PCGF2 (polycomb
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group ring finger 2), THSD1 (thrombospondin, type I, domain containing 1),
HOPX (HOP homeobox), SLC5A8 (solute carrier family 5 (iodide transporter),
member 8), EMB (embigin homolog (mouse)), PAX9 (paired box 9), ARMCX3
(armadillo repeat containing, X-linked 3), ARMCX2 (armadillo repeat
containing,
X-linked 2), ARMCX1 (armadillo repeat containing, X-linked 1), RASSF4 (Ras
association (RaIGDS/AF-6) domain family member 4), MIR34B (microRNA 34b),
MIR205 (microRNA 205), RB1 (retinoblastoma 1), DYT10 (dystonia 10),
CDKN2A (cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)),
CDKN1A (cyclin-dependent kinase inhibitor 1A (p21, Cip1)), CCND1 (cyclin D1),
AKT1 (v-akt murine thymoma viral oncogene homolog 1), MYC (v-myc
myelocytomatosis viral oncogene homolog (avian)), CTNNB1 (catenin (cadherin-
associated protein), beta 1, 88kDa), MDM2 (Mdm2 p53 binding protein homolog
(mouse)), SERPINB5 (serpin peptidase inhibitor, Glade B (ovalbumin), member
5), EGF (epidermal growth factor (beta-urogastrone)), FOS (FBJ murine
osteosarcoma viral oncogene homolog), NOS2 (nitric oxide synthase 2,
inducible), CDK4 (cyclin-dependent kinase 4), SOD2 (superoxide dismutase 2,
mitochondrial), SMAD3 (SMAD family member 3), CDKN1 B (cyclin-dependent
kinase inhibitor 1 B (p27, Kip1)), SOD1 (superoxide dismutase 1, soluble),
CCNA2 (cyclin A2), LOX (lysyl oxidase), SMAD4 (SMAD family member 4), HGF
(hepatocyte growth factor (hepapoietin A; scatter factor)), THBS1
(thrombospondin 1), CDK6 (cyclin-dependent kinase 6), ATM (ataxia
telangiectasia mutated), STAT3 (signal transducer and activator of
transcription 3
(acute-phase response factor)), HIF1A (hypoxia inducible factor 1, alpha
subunit
(basic helix-loop-helix transcription factor)), IGF1 R (insulin-like growth
factor 1
receptor), MTOR (mechanistic target of rapamycin (serine/threonine kinase)),
TSC2 (tuberous sclerosis 2), CDC42 (cell division cycle 42 (GTP binding
protein,
25kDa)), ODC1 (ornithine decarboxylase 1), SPARC (secreted protein, acidic,
cysteine-rich (osteonectin)), HDAC1 (histone deacetylase 1), CDK2 (cyclin-
dependent kinase 2), BARD1 (BRCA1 associated RING domain 1), CDH1
(cadherin 1, type 1, E-cadherin (epithelial)), EGR1 (early growth response 1),
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INSR (insulin receptor), IRF1 (interferon regulatory factor 1), PHB
(prohibitin),
PXN (paxillin), HSPA4 (heat shock 70kDa protein 4), TYR (tyrosinase
(oculocutaneous albinism IA)), CAV1 (caveolin 1, caveolae protein, 22kDa),
CDKN2B (cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4)), FOXO3
(forkhead box 03), HDAC9 (histone deacetylase 9), FBXW7 (F-box and WD
repeat domain containing 7), FOXO1 (forkhead box 01), E2F1 (E2F transcription
factor 1), STK1 1 (serine/threonine kinase 11), BMP2 (bone morphogenetic
protein 2), HSP90AAl (heat shock protein 90kDa alpha (cytosolic), class A
member 1), HNF4A (hepatocyte nuclear factor 4, alpha), CAMK2G
(calcium/calmodulin-dependent protein kinase II gamma), TP53BP1 (tumor
protein p53 binding protein 1), CRYAB (crystallin, alpha B), HMGCR (3-hydroxy-
3-methylglutaryl-Coenzyme A reductase), PLAUR (plasminogen activator,
urokinase receptor), MCL1 (myeloid cell leukemia sequence 1 (BCL2-related)),
NOTCH1 (Notch homolog 1, translocation-associated (Drosophila)), RASSF1
(Ras association (RaIGDS/AF-6) domain family member 1), GSN (gelsolin),
CADM1 (cell adhesion molecule 1), ATF2 (activating transcription factor 2),
IFNB1 (interferon, beta 1, fibroblast), DAPK1 (death-associated protein kinase
1),
CHFR (checkpoint with forkhead and ring finger domains), KITLG (KIT ligand),
NDUFA13 (NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 13), DPP4
(dipeptidyl-peptidase 4), GLB1 (galactosidase, beta 1), IKZF1 (IKAROS family
zinc finger 1 (Ikaros)), ST5 (suppression of tumorigenicity 5), TGFA
(transforming
growth factor, alpha), EIF4EBP1 (eukaryotic translation initiation factor 4E
binding protein 1), TGFBR2 (transforming growth factor, beta receptor II
(70/8OkDa)), EIF2AK2 (eukaryotic translation initiation factor 2-alpha kinase
2),
GJA1 (gap junction protein, alpha 1, 43kDa), MYD88 (myeloid differentiation
primary response gene (88)), IF127 (interferon, alpha-inducible protein 27),
RBMX (RNA binding motif protein, X-linked), EPHA1 (EPH receptor Al), TWSG1
(twisted gastrulation homolog 1 (Drosophila)), H2AFX (H2A histone family,
member X), LGALS3 (lectin, galactoside-binding, soluble, 3), MUC3A (mucin 3A,
cell surface associated), ILK (integrin-linked kinase), APAF1 (apoptotic
peptidase
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activating factor 1), MAOA (monoamine oxidase A), ERBB3 (v-erb-b2
erythroblastic leukemia viral oncogene homolog 3 (avian)), EIF2S1 (eukaryotic
translation initiation factor 2, subunit 1 alpha, 35kDa), PER2 (period homolog
2
(Drosophila)), IGFBP7 (insulin-like growth factor binding protein 7), KDM5B
(lysine (K)-specific demethylase 5B), SMARCA4 (SWI/SNF related, matrix
associated, actin dependent regulator of chromatin, subfamily a, member 4),
NME1 (non-metastatic cells 1, protein (NM23A) expressed in), F2RL1
(coagulation factor II (thrombin) receptor-like 1), ZFP36 (zinc finger protein
36,
C3H type, homolog (mouse)), HSPA8 (heat shock 70kDa protein 8), WNT5A
(wingless-type MMTV integration site family, member 5A), ITGB4 (integrin, beta
4), RARB (retinoic acid receptor, beta), VEGFC (vascular endothelial growth
factor C), CCL20 (chemokine (C-C motif) ligand 20), EPHB2 (EPH receptor B2),
CSNK2A1 (casein kinase 2, alpha 1 polypeptide), PSMD9 (proteasome
(prosome, macropain) 26S subunit, non-ATPase, 9), SERPINB2 (serpin
peptidase inhibitor, Glade B (ovalbumin), member 2), RHOB (ras homolog gene
family, member B), DUSP6 (dual specificity phosphatase 6), CDKN1C (cyclin-
dependent kinase inhibitor 1C (p57, Kip2)), SLIT2 (slit homolog 2
(Drosophila)),
CEACAM1 (carcinoembryonic antigen-related cell adhesion molecule 1 (biliary
glycoprotein)), UBC (ubiquitin C), STS (steroid sulfatase (microsomal),
isozyme
S), FST (follistatin), KRT1 (keratin 1), EIF6 (eukaryotic translation
initiation factor
6), JUP (junction plakoglobin), HDAC4 (histone deacetylase 4), NEDD4 (neural
precursor cell expressed, developmentally down-regulated 4), KRT14 (keratin
14), GLI2 (GLI family zinc finger 2), MYH11 (myosin, heavy chain 11, smooth
muscle), MAPKAPK5 (mitogen-activated protein kinase-activated protein kinase
5), MAD1 L1 (MAD1 mitotic arrest deficient-like 1 (yeast)), TNFAIP3 (tumor
necrosis factor, alpha-induced protein 3), WEE1 (WEE1 homolog (S. pombe)),
BTRC (beta-transducin repeat containing), NKX3-1 (NK3 homeobox 1), GPC3
(glypican 3), CREB3 (cAMP responsive element binding protein 3), PLCB3
(phospholipase C, beta 3 (phosphatidylinositol-specific)), DMPK (dystrophia
myotonica-protein kinase), BLNK (B-cell linker), PPIA (peptidylprolyl
isomerase A
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(cyclophilin A)), DAB2 (disabled homolog 2, mitogen-responsive phosphoprotein
(Drosophila)), KLF4 (Kruppel-like factor 4 (gut)), RUNX3 (runt-related
transcription factor 3), FLG (filaggrin), IVL (involucrin), CCT5 (chaperonin
containing TCP1, subunit 5 (epsilon)), LRPAP1 (low density lipoprotein
receptor-
related protein associated protein 1), IGF2R (insulin-like growth factor 2
receptor), PER1 (period homolog 1 (Drosophila)), BIK (BCL2-interacting killer
(apoptosis-inducing)), PSMC4 (proteasome (prosome, macropain) 26S subunit,
ATPase, 4), USF2 (upstream transcription factor 2, c-fos interacting), GAS1
(growth arrest-specific 1), LAMP2 (lysosomal-associated membrane protein 2),
PSMD10 (proteasome (prosome, macropain) 26S subunit, non-ATPase, 10),
IL24 (interleukin 24), GADD45G (growth arrest and DNA-damage-inducible,
gamma), ARHGAP1 (Rho GTPase activating protein 1), CLDN1 (claudin 1),
ANXA7 (annexin A7), CHN1 (chimerin (chimaerin) 1), TXNIP (thioredoxin
interacting protein), PEG3 (paternally expressed 3), EIF3A (eukaryotic
translation
initiation factor 3, subunit A), CASC5 (cancer susceptibility candidate 5),
TCF4
(transcription factor 4), CSNK2A2 (casein kinase 2, alpha prime polypeptide),
CSNK2B (casein kinase 2, beta polypeptide), CRY1 (cryptochrome 1
(photolyase-like)), CRY2 (cryptochrome 2 (photolyase-like)), EIF4G2
(eukaryotic
translation initiation factor 4 gamma, 2), LOXL2 (lysyl oxidase-like 2),
PSMD13
(proteasome (prosome, macropain) 26S subunit, non-ATPase, 13), ANP32A
(acidic (leucine-rich) nuclear phosphoprotein 32 family, member A), COL4A3
(collagen, type IV, alpha 3 (Goodpasture antigen)), SCGB1A1 (secretoglobin,
family 1A, member 1 (uteroglobin)), BNIP3L (BCL2/adenovirus E1 B 19kDa
interacting protein 3-like), MCC (mutated in colorectal cancers), EFNB3
(ephrin-
B3), RBBP8 (retinoblastoma binding protein 8), PALB2 (partner and localizer of
BRCA2), HBP1 (HMG-box transcription factor 1), MRPL28 (mitochondrial
ribosomal protein L28), KDM5A (lysine (K)-specific demethylase 5A), QSOX1
(quiescin Q6 sulfhydryl oxidase 1), ZFR (zinc finger RNA binding protein), MN1
(meningioma (disrupted in balanced translocation) 1), SMYD4 (SET and MYND
domain containing 4), USP7 (ubiquitin specific peptidase 7 (herpes virus-
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associated)), STK4 (serine/threonine kinase 4), THY1 (Thy-1 cell surface
antigen), PTPRG (protein tyrosine phosphatase, receptor type, G), E2F6 (E2F
transcription factor 6), STX11 (syntaxin 11), CDC42BPA (CDC42 binding protein
kinase alpha (DMPK-like)), MYOCD (myocardin), DAP (death-associated
protein), LOXL1 (lysyl oxidase-like 1), RNF139 (ring finger protein 139),
HTATIP2
(HIV-1 Tat interactive protein 2, 30kDa), AIM1 (absent in melanoma 1), BCCIP
(BRCA2 and CDKNIA interacting protein), LOXL4 (lysyl oxidase-like 4), WWC1
(WW and C2 domain containing 1), LOXL3 (lysyl oxidase-like 3), CENPN
(centromere protein N), TNS4 (tensin 4), SIK1 (salt-inducible kinase 1), PCGF6
(polycomb group ring finger 6), PHLDA3 (pleckstrin homology-like domain,
family
A, member 3), IL32 (interleukin 32), LATS1 (LATS, large tumor suppressor,
homolog 1 (Drosophila)), COMMD7 (COMM domain containing 7), CDHR2
(cadherin-related family member 2), LELP1 (late cornified envelope-like
proline-
rich 1), NCRNA00188 (non-protein coding RNA 188), and ENSG00000131023.
[0185] Exemplary non-limiting examples of tumor suppression
proteins include ATM (ataxia telangiectasia mutated), ATR (ataxia
telangiectasia
and Rad3 related), EGFR (epidermal growth factor receptor), ERBB2 (v-erb-b2
erythroblastic leukemia viral oncogene homolog 2), ERBB3 (v-erb-b2
erythroblastic leukemia viral oncogene homolog 3), ERBB4 (v-erb-b2
erythroblastic leukemia viral oncogene homolog 4), Notch 1, Notch2, Notch 3,
Notch 4, ATK1 (v-akt murine thymoma viral oncogene homolog 1), ATK2 (v-akt
murine thymoma viral oncogene homolog 2), ATK3 (v-akt murine thymoma viral
oncogene homolog 3), HIF1a (hypoxia-inducible factor 1a), HIF3a (hypoxia-
inducible factor 1 a), Met (met pronto-oncogene), HRG (histidine-rich
glycoprotein), Bc12 , PPAR(alpha) (peroxisome proliferator-activated receptor
alpha), Ppar(gamma) (peroxisome proliferator-activated receptor gamma), WT1
(Wilmus Tumor 1), FGF1 R(fibroblast growth factor 1 receptor) , FGF2R
(fibroblast growth factor 1 receptor), FGF3R (fibroblast growth factor 3
receptor),
FGF4R (fibroblast growth factor 4 receptor), FGF5R (fibroblast growth factor 5
receptor), CDKN2a (cyclin-dependent kinase inhibitor 2A), APC (adenomatous
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polyposis coli), Rbl (retinoblastoma 1), MEN1 (multiple endocrine neoplasial),
VHL (von-Hippel-Lindau tumor suppressor), BRCA1 (breast cancer 1), BRCA2
(breast cancer 2), AR (androgen receptor), TSG1 01 (tumor susceptibility gene
101), Igf1(insulin-like growth factor 1), Igf2 (insulin-like growth factor 2),
Igf 1 R
(insulin-like growth factor 1 receptor), Igf 2R(insulin-like growth factor 2
receptor)
Bax (BCL-2 associated X protein), CASP 1 (Caspase 1), CASP 2 (Caspase 2),
CASP 3 (Caspase 3), CASP 4(Caspase 4), CASP 6 (Caspase 6), CASP
7(Caspase 7), CASP 8 (Caspase 8), CASP 9 (Caspase 9), CASP 12 (Caspase
12), Kras (v-Ki-ras2 Kirsten rate sarcoma viral oncogene homolog), PTEN
(phosphate and tensin homolog), BCRP (breast cancer receptor protein), p53,
and combinations thereof.
[0186] In certain embodiments, an animal created by a method of
the invention may be used to study the effects of mutations on the animal and
on
tumor suppression using measures commonly used in the study of tumor
suppression. In one embodiment, a genetically modified animal comprising an
inactivated chromosomal sequence involved with tumor suppression may be
used to determine susceptibility to developing tumors. The method comprises
exposing the genetically modified animal comprising an inactivated tumor
suppressor sequence and a wild-type animal to a carcinogenic agent, and then
monitoring the development of tumors. The animal comprising the inactivated
tumor suppressor sequence may have an increased risk for tumor formation.
Moreover, an animal homozygous for the inactivated tumor suppressor sequence
may have increased risk relative to an animal heterozygous for the same
inactivated sequence, which in turn may have increased risk relative to a wild-
type animal. A similar method may be used to screen for spontaneous tumors,
wherein the animals described above are not exposed to a carcinogenic agent.
[0187] In another embodiment, an animal comprising an inactivated
chromosomal sequence associated with tumor suppression may be used to
evaluate the carcinogenic potential of a test agent. The method comprises
contacting the genetically modified animal comprising an inactivated tumor
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suppressor sequence and a wild-type animal to the test agent, and then
monitoring the development of tumors. If the animal comprising an inactivated
tumor suppressor sequence has an increased incidence of tumors relative to the
wild-type animal, the test agent may be carcinogenic.
J. secretase associated disorders
[0188] Secretases make up a diverse set of proteins that affect
susceptibility for numerous disorders, the presence of a disorder, the
severity of
a disorder, or any combination thereof. Secretases are enzymes that clip off
smaller pieces of another transmembrane protein. Secretases are implicated in
many disorders including, for example, Alzheimer's discase. In one embodiment,
a method of the invention may be used to create an animal or cell in which at
least one chromosomal sequence associated with secretase associated
disorders has been edited. Suitable chromosomal edits may include, but are not
limited to, the type of edits detailed in section I(f) above.
[0189] In each of the above embodiments, one or more
chromosomal sequences associated with a secretase associated disorder may
be edited. A secretase associated disorder-associated protein or control
sequence may typically be selected based on an experimental association of the
secretase-related proteins with the development of a secretase disorder. For
example, the production rate or circulating concentration of a protein
associated
with a secretase disorder may be elevated or depressed in a population with a
secretase disorder relative to a population without a secretase disorder.
Differences in protein levels may be assessed using proteomic or genomic
analysis techniques known in the art.
[0190] By way of non-limiting example, proteins associated with a
secretase disorder include PSENEN (presenilin enhancer 2 homolog (C.
elegans)), CTSB (cathepsin B), PSEN1 (presenilin 1), APP (amyloid beta (A4)
precursor protein), APH1 B (anterior pharynx defective 1 homolog B (C.
elegans)), PSEN2 (presenilin 2 (Alzheimer disease 4)), BACE1 (beta-site APP-
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cleaving enzyme 1), ITM2B (integral membrane protein 2B), CTSD (cathepsin
D), NOTCH1 (Notch homolog 1, translocation-associated (Drosophila)), TNF
(tumor necrosis factor (TNF superfamily, member 2)), INS (insulin), DYT10
(dystonia 10), ADAM17 (ADAM metallopeptidase domain 17), APOE
(apolipoprotein E), ACE (angiotensin I converting enzyme (peptidyl-dipeptidase
A) 1), STN (statin), TP53 (tumor protein p53), IL6 (interleukin 6 (interferon,
beta
2)), NGFR (nerve growth factor receptor (TNFR superfamily, member 16)), IL1 B
(interleukin 1, beta), ACHE (acetylcholinesterase (Yt blood group)), CTNNB1
(catenin (cadherin-associated protein), beta 1, 88kDa), IGF1 (insulin-like
growth
factor 1 (somatomedin C)), IFNG (interferon, gamma), NRG1 (neuregulin 1),
CASP3 (caspase 3, apoptosis-related cysteine peptidase), MAPK1 (mitogen-
activated protein kinase 1), CDH1 (cadherin 1, type 1, E-cadherin
(epithelial)),
APBB1 (amyloid beta (A4) precursor protein-binding, family B, member 1
(Fe65)), HMGCR (3-hydroxy-3-methylglutaryl-Coenzyme A reductase), CREB1
(cAMP responsive element binding protein 1), PTGS2 (prostaglandin-
endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)),
HES1 (hairy and enhancer of split 1, (Drosophila)), CAT (catalase), TGFB1
(transforming growth factor, beta 1), ENO2 (enolase 2 (gamma, neuronal)),
ERBB4 (v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian)),
TRAPPC10 (trafficking protein particle complex 10), MAOB (monoamine oxidase
B), NGF (nerve growth factor (beta polypeptide)), MMP12 (matrix
metallopeptidase 12 (macrophage elastase)), JAG1 (jagged 1 (Alagille
syndrome)), CD40LG (CD40 ligand), PPARG (peroxisome proliferator-activated
receptor gamma), FGF2 (fibroblast growth factor 2 (basic)), IL3 (interleukin 3
(colony-stimulating factor, multiple)), LRP1 (low density lipoprotein receptor-
related protein 1), NOTCH4 (Notch homolog 4 (Drosophila)), MAPK8 (mitogen-
activated protein kinase 8), PREP (prolyl endopeptidase), NOTCH3 (Notch
homolog 3 (Drosophila)), PRNP (prion protein), CTSG (cathepsin G), EGF
(epidermal growth factor (beta-urogastrone)), REN (renin), CD44 (CD44
molecule (Indian blood group)), SELP (selectin P (granule membrane protein
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140kDa, antigen CD62)), GHR (growth hormone receptor), ADCYAP1 (adenylate
cyclase activating polypeptide 1 (pituitary)), INSR (insulin receptor), GFAP
(glial
fibrillary acidic protein), MMP3 (matrix metallopeptidase 3 (stromelysin 1,
progelatinase)), MAPK10 (mitogen-activated protein kinase 10), SP1 (Spl
transcription factor), MYC (v-myc myelocytomatosis viral oncogene homolog
(avian)), CTSE (cathepsin E), PPARA (peroxisome proliferator-activated
receptor
alpha), JUN (jun oncogene), TIMP1 (TIMP metallopeptidase inhibitor 1), IL5
(interleukin 5 (colony-stimulating factor, eosinophil)), IL1A (interleukin 1,
alpha),
MMP9 (matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type
IV collagenase)), HTR4 (5-hydroxytryptamine (serotonin) receptor 4), HSPG2
(heparan sulfate proteoglycan 2), KRAS (v-Ki-ras2 Kirsten rat sarcoma viral
oncogene homolog), CYCS (cytochrome c, somatic), SMG1 (SMG1 homolog,
phosphatidylinositol 3-kinase-related kinase (C. elegans)), IL1 R1
(interleukin 1
receptor, type I), PROK1 (prokineticin 1), MAPK3 (mitogen-activated protein
kinase 3), NTRK1 (neurotrophic tyrosine kinase, receptor, type 1), IL13
(interleukin 13), MME (membrane metallo-endopeptidase), TKT (transketolase),
CXCR2 (chemokine (C-X-C motif) receptor 2), IGF1 R (insulin-like growth factor
1
receptor), RARA (retinoic acid receptor, alpha), CREBBP (CREB binding
protein), PTGS1 (prostaglandin-endoperoxide synthase 1 (prostaglandin G/H
synthase and cyclooxygenase)), GALT (galactose-1 -phosphate
uridylyltransferase), CHRM1 (cholinergic receptor, muscarinic 1), ATXN1
(ataxin
1), PAWR (PRKC, apoptosis, WT1, regulator), NOTCH2 (Notch homolog 2
(Drosophila)), M6PR (mannose-6-phosphate receptor (cation dependent)),
CYP46A1 (cytochrome P450, family 46, subfamily A, polypeptide 1), CSNK1 D
(casein kinase 1, delta), MAPK14 (mitogen-activated protein kinase 14), PRG2
(proteoglycan 2, bone marrow (natural killer cell activator, eosinophil
granule
major basic protein)), PRKCA (protein kinase C, alpha), L1 CAM (L1 cell
adhesion molecule), CD40 (CD40 molecule, TNF receptor superfamily member
5), NR1 12 (nuclear receptor subfamily 1, group I, member 2), JAG2 (jagged 2),
CTNND1 (catenin (cadherin-associated protein), delta 1), CDH2 (cadherin 2,
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type 1, N-cadherin (neuronal)), CMA1 (chymase 1, mast cell), SORT1 (sortilin
1),
DLK1 (delta-like 1 homolog (Drosophila)), THEM4 (thioesterase superfamily
member 4), JUP (junction plakoglobin), CD46 (CD46 molecule, complement
regulatory protein), CCL1 1 (chemokine (C-C motif) ligand 11), CAV3 (caveolin
3),
RNASE3 (ribonuclease, RNase A family, 3 (eosinophil cationic protein)), HSPA8
(heat shock 70kDa protein 8), CASP9 (caspase 9, apoptosis-related cysteine
peptidase), CYP3A4 (cytochrome P450, family 3, subfamily A, polypeptide 4),
CCR3 (chemokine (C-C motif) receptor 3), TFAP2A (transcription factor AP-2
alpha (activating enhancer binding protein 2 alpha)), SCP2 (sterol carrier
protein
2), CDK4 (cyclin-dependent kinase 4), HIF1A (hypoxia inducible factor 1, alpha
subunit (basic helix-loop-helix transcription factor)), TCF7L2 (transcription
factor
7-like 2 (T-cell specific, HMG-box)), IL1 R2 (interleukin 1 receptor, type
II),
B3GALTL (beta 1,3-galactosyltransferase-like), MDM2 (Mdm2 p53 binding
protein homolog (mouse)), RELA (v-rel reticuloendotheliosis viral oncogene
homolog A (avian)), CASP7 (caspase 7, apoptosis-related cysteine peptidase),
IDE (insulin-degrading enzyme), FABP4 (fatty acid binding protein 4,
adipocyte),
CASK (calcium/calmodulin-dependent serine protein kinase (MAGUK family)),
ADCYAP1 R1 (adenylate cyclase activating polypeptide 1 (pituitary) receptor
type
I), ATF4 (activating transcription factor 4 (tax-responsive enhancer element
B67)), PDGFA (platelet-derived growth factor alpha polypeptide), C21 orf33
(chromosome 21 open reading frame 33), SCG5 (secretogranin V (7B2 protein)),
RNF1 23 (ring finger protein 123), NFKB1 (nuclear factor of kappa light
polypeptide gene enhancer in B-cells 1), ERBB2 (v-erb-b2 erythroblastic
leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene
homolog (avian)), CAV1 (caveolin 1, caveolae protein, 22kDa), MMP7 (matrix
metallopeptidase 7 (matrilysin, uterine)), TGFA (transforming growth factor,
alpha), RXRA (retinoid X receptor, alpha), STX1A (syntaxin 1A (brain)), PSMC4
(proteasome (prosome, macropain) 26S subunit, ATPase, 4), P2RY2 (purinergic
receptor P2Y, G-protein coupled, 2), TNFRSF21 (tumor necrosis factor receptor
superfamily, member 21), DLG1 (discs, large homolog 1 (Drosophila)), NUMBL
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(numb homolog (Drosophila)-like), SPN (sialophorin), PLSCR1 (phospholipid
scramblase 1), UBQLN2 (ubiquilin 2), UBQLN1 (ubiquilin 1), PCSK7 (proprotein
convertase subtilisin/kexin type 7), SPON1 (spondin 1, extracellular matrix
protein), SILV (silver homolog (mouse)), QPCT (glutaminyl-peptide
cyclotransferase), HES5 (hairy and enhancer of split 5 (Drosophila)), GCC1
(GRIP and coiled-coil domain containing 1), and any combination thereof.
[0191] Preferred proteins associated with a secretase disorder
include APH-1A (anterior pharynx-defective 1, alpha), APH-1 B (anterior
pharynx-
defective 1, beta), PSEN-1 (presenilin-1), NCSTN (nicastrin), PEN-2
(presenilin
enhancer 2), and any combination thereof.
[0192] In certain embodiments, an animal created by a method of
the invention may be used to study the effects of mutations on the animal and
development and/or progression of a secretase associated disorder using
measures commonly used in the study of secretase disorders.
[0193] The incidence or indication of a secretase disorder may
occur spontaneously in the genetically modified animal. Alternatively, the
incidence or indication of the secretase disorder may be promoted by exposure
to a disruptive agent. Non-limiting examples of disruptive agents include a
protein associated with a secretase disorder such as any of those described
above, a drug, a toxin, a chemical, an activated retrovirus, and an
environmental
stress. Non-limiting examples of environmental stresses include forced
swimming, cold swimming, platform shaker stimuli, loud noises, and
immobilization stress.
K. amyotrophic lateral sclerosis
[0194] Certain nucleic acid sequences, and the proteins encoded
by them, are associated with motor neuron disorders. These sequences make
up a diverse set of sequences that affect susceptibility for developing a
motor
neuron disorder, the presence of the motor neuron disorder, the severity of
the
motor neuron disorder or any combination thereof. In one embodiment, a method
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of the invention may be used to create an animal or cell in which at least one
chromosomal sequence associated with a specific motor neuron disorder,
amyotrophic lateral sclerosis (ALS), has been edited. Suitable chromosomal
edits
may include, but are not limited to, the type of edits detailed in section
I(f) above.
[0195] In each of the above embodiments, one or more
chromosomal sequences associated with ALS may be edited. A chromosomal
sequence associated with ALS may typically be selected based on an
experimental association of an ALS-related sequence to ALS. An ALS-related
nucleic acid sequence may encode an ALS-related protein or may be an ALS-
related control sequence. For example, the production rate or circulating
concentration of a protein associated with ALS may be elevated or depressed in
a population with ALS relative to a population without ALS. Differences in
protein
levels may be assessed using proteomic or genomic analysis techniques known
in the art.
[0196] By way of non-limiting example, proteins associated with
ALS include but are not limited to SOD1 (superoxide dismutase 1), ALS2
(amyotrophic lateral sclerosis 2), FUS (fused in sarcoma), TARDBP (TAR DNA
binding protein), VAGFA (vascular endothelial growth factor A), VAGFB
(vascular
endothelial growth factor B), and VAGFC (vascular endothelial growth factor
C),
and any combination thereof.
[0197] In certain embodiments, an animal created by a method of
the invention may be used to study the effects of mutations on the animal and
development and/or progression of ALS using measures commonly used in the
study of ALS.
L. prion diseases
[0198] Prion disorders appear to be diseases of protein
conformation, which results in abnormal protein aggregation. In one
embodiment, a method of the invention may be used to create an animal or cell
in which at least one chromosomal sequence associated with a prion disease
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has been edited. Suitable chromosomal edits may include, but are not limited
to,
the type of edits detailed in section I(f) above.
[0199] In each of the above embodiments, one or more
chromosomal sequences encoding a protein or control sequence associated with
prion disorders may be edited. A prion disorder-related nucleic acid sequence
may typically be selected based on an experimental association of the prion
disorder-related nucleic acid sequence to a prion disorder. A prion disorder-
related nucleic acid sequence may encode a prion disorder-related protein or
isoform thereof, or may be a prion disorder-related control sequence. For
example, the production rate or circulating concentration of a prion disorder-
related protein or isoform may be elevated or depressed in a population having
a
prion disorder relative to a population lacking the prion disorder.
Differences in
protein or certain isoform levels may be assessed using proteomic techniques
including but not limited to Western blot, immunohistochemical staining,
enzyme
linked immunosorbent assay (ELISA), and mass spectrometry. Alternatively, the
prion disorder-related proteins may be identified by obtaining gene expression
profiles of the genes encoding the proteins using genomic techniques including
but not limited to DNA microarray analysis, serial analysis of gene expression
(SAGE), and quantitative real-time polymerase chain reaction (Q-PCR).
[0200] Non-limiting examples of prion disorder-related proteins
include PrPc and its isoforms, PrPsc and its isoforms, HECTD2 (e3-ubipuitin
ligase protein), ST11 (stress inducible protein 1), DPL (residue Doppel
protein,
encoded by Prnd), APOA1 (Apolipoprotein Al), BCL-2 (B-cell lymphoma 2),
HSP60 (Heat shock 60kDa protein), BAX- inhibiting peptide (Bcl-2-associated X
protein inhibitor), NRF2 (nuclear respiratory factor 2), NCAMs (neural cell-
adhesion molecules), heparin, laminin and laminin receptor.
[0201] Further, non-limiting examples of genes that may be related
to neurodegenerative conditions in prion disorders include A2M (Alpha-2-
Macroglobulin), AATF (Apoptosis antagonizing transcription factor), ACPP (Acid
phosphatase prostate), ACTA2 (Actin alpha 2 smooth muscle aorta), ADAM22
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(ADAM metallopeptidase domain), ADORA3 (Adenosine A3 receptor), ADRA1 D
(Alpha-1 D adrenergic receptor for Alpha-1 D adrenoreceptor), AHSG (Alpha-2-
HS-glycoprotein), AIF1 (Allograft inflammatory factor 1), ALAS2 (Delta-
aminolevulinate synthase 2), AMBP (Alpha-1-microglobulin/bikunin precursor),
ANK3 (Ankryn 3), ANXA3 (Annexin A3), APCS (Amyloid P component serum),
APOA1 (Apolipoprotein Al), APOA12 (Apolipoprotein A2), APOB (Apolipoprotein
B), APOC1 (Apolipoprotein Cl), APOE (Apolipoprotein E), APOH (Apolipoprotein
H), APP (Amyloid precursor protein), ARC (Activity-regulated cytoskeleton-
associated protein), ARF6 (ADP-ribosylation factor 6), ARHGAP5 (Rho GTPase
activating protein 5), ASCL1 (Achaete-scute homolog 1), B2M (Beta-2
microglobulin), B4GALNTI (Beta-1,4-N-acetyl-galactosaminyl transferase 1),
BAX (Bcl-2-associated X protein), BCAT (Branched chain amino-acid
transaminase 1 cytosolic), BCKDHA (Branched chain keto acid dehydrogenase
E1 alpha), BCKDK (Branched chain alpha-ketoacid dehydrogenase kinase),
BCL2 (B-cell lymphoma 2), BCL2L1 (BCL2-like 1), BDNF (Brain-derived
neurotrophic factor), BHLHE40 (Class E basic helix-loop-helix protein 40),
BHLHE41 (Class E basic helix-loop-helix protein 41), BMP2 (Bone
morphogenetic protein 2A), BMP3 (Bone morphogenetic protein 3), BMP5 (Bone
morphogenetic protein 5), BRD1 (Bromodomain containing 1), BTC
(Betacellulin), BTNL8 (Butyrophilin-like protein 8), CALB1 (Calbindin 1),
CALM1
(Calmodulin 1), CAMK1 (Calcium/calmodulin-dependent protein kinase type I),
CAMK4 (Calcium/calmodulin-dependent protein kinase type IV), CAMKIIB
(Calcium/calmodulin-dependent protein kinase type IIB), CAMKIIG
(Calcium/calmodulin-dependent protein kinase type IIG), CASP11 (Caspase-10),
CASP8 (Caspase 8 apoptosis-related cysteine peptidase), CBLN1 (cerebellin 1
precursor), CCL2 (Chemokine (C-C motif) ligand 2), CCL22 (Chemokine (C-C
motif) ligand 22), CCL3 (Chemokine (C-C motif) ligand 3), CCL8 (Chemokine (C-
C motif) ligand 8), CCNG1 (Cyclin-G1), CCNT2 (Cyclin T2), CCR4 (C-C
chemokine receptor type 4 (CD194)), CD58 (CD58), CD59 (Protectin), CD5L
(CD5 antigen-like), CD93 (CD93), CDKN2AIP (CDKN2A interacting protein),
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CDKN2B (Cyclin-dependent kinase inhibitor 2B), CDX1 (Homeobox protein CDX-
1), CEA (Carcinoembryonic antigen), CEBPA (CCAAT/enhancer-binding protein
alpha), CEBPB (CCAAT/enhancer binding protein C/EBP beta), CEBPB
(CCAAT/enhancer-binding protein beta), CEBPD (CCAAT/enhancer-binding
protein delta), CEBPG (CCAAT/enhancer-binding protein gamma), CENPB
(Centromere protein B), CGA (Glycoprotein hormone alpha chain), CGGBP1
(CGG triplet repeat-binding protein 1), CHGA (Chromogranin A), CHGB
(Secretoneurin), CHN2 (Beta-chimaerin), CHRD (Chordin), CHRM1 (Cholinergic
receptor muscarinic 1), CITED2 (Cbp/p300-interacting transactivator 2), CLEC4E
(C-type lectin domain family 4 member E), CMTM2 (CKLF-like MARVEL
transmembrane domain-containing protein 2), CNTN1 (Contactin 1), CNTNAP1
(Contactin-associated protein-like 1), CR1 (Erythrocyte complement receptor
1),
CREM (cAMP-responsive element modulator), CRH (Corticotropin-releasing
hormone), CRHR1 (Corticotropin releasing hormone receptor 1), CRKRS (Cell
division cycle 2-related protein kinase 7), CSDA (DNA-binding protein A), CSF3
(Granulocyte colony stimulating factor 3), CSF3R (Granulocyte colony-
stimulating factor 3 receptor), CSP (Chemosensory protein), CSPG4 (Chondroitin
sulfate proteoglycan 4), CTCF (CCCTC-binding factor zinc finger protein), CTGF
(Connective tissue growth factor), CXCL1 2 (Chemokine C-X-C motif ligand 12),
DAD1 (Defender against cell death 1), DAXX (Death associated protein 6), DBN1
(Drebrin 1), DBP (D site of albumin promoter-albumin D-box binding protein),
DDR1 (Discoidin domain receptor family member 1), DDX14 (DEAD/DEAN box
helicase), DEFA3 (Defensin alpha 3 neutrophil-specific), DVL3 (Dishevelled dsh
homolog 3), EDN1 (Endothelin 1), EDNRA (Endothelin receptor type A), EGF
(Epidermal growth factor), EGFR (Epidermal growth factor receptor), EGR1
(Early growth response protein 1), EGR2 (Early growth response protein 2),
EGR3 (Early growth response protein 3), EIF2AK2 (Eukaryotic translation
initiation factor 2-alpha kinase 2), ELANE (Elastase neutrophil expressed),
ELK1
(ELK1 member of ETS oncogene family), ELK3 (ELK3 ETS-domain protein (SRF
accessory protein 2)), EML2 (Echinoderm microtubule associated protein like
2),
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EPHA4 (EPH receptor A4), ERBB2 (V-erb-b2 erythroblastic leukemia viral
oncogene homolog 2), ERBB3 (Receptor tyrosine-protein kinase erbB-3), ESR2
(Estrogen receptor 2), ESR2 (Estrogen receptor 2), ETS1 (V-ets
erythroblastosis
virus E26 oncogene homolog 1), ETV6 (Ets variant 6), FASLG (Fas ligand TNF
superfamily member 6), FCAR (Fc fragment of IgA receptor), FCER1 G (Fc
fragment of IgE high affinity I receptor for gamma polypeptide), FCGR2A (Fc
fragment of IgG low affinity Ila receptor - CD32), FCGR3B (Fc fragment of IgG
low affinity Illb receptor - CD16b), FCGRT (Fc fragment of IgG receptor
transporter alpha), FGA (Basic fibrinogen), FGF1 (Acidic fibroblast growth
factor
1), FGF14 (Fibroblast growth factor 14), FGF16 (fibroblast growth factor 16),
FGF18 (Fibroblast growth factor 18), FGF2 (Basic fibroblast growth factor 2),
FIBP (Acidic fibroblast growth factor intracellular binding protein), FIGF (C-
fos
induced growth factor), FMR1 (Fragile X mental retardation 1), FOSB (FBJ
murine osteosarcoma viral oncogene homolog B), FOXO1 (Forkhead box 01),
FSHB (Follicle stimulating hormone beta polypeptide), FTH1 (Ferritin heavy
polypeptide 1), FTL (Ferritin light polypeptide), G1 P3 (Interferon alpha-
inducible
protein 6), G6S (N-acetylglucosamine-6-sulfatase), GABRA2 (Gamma-
aminobutyric acid A receptor alpha 2), GABRA3 (Gamma-aminobutyric acid A
receptor alpha 3), GABRA4 (Gamma-aminobutyric acid A receptor alpha 4),
GABRB1 (Gamma-aminobutyric acid A receptor beta 1), GABRG1 (Gamma-
aminobutyric acid A receptor gamma 1), GADD45A (Growth arrest and DNA-
damage-inducible alpha), GCLC (Glutamate-cysteine ligase catalytic subunit),
GDF15 (Growth differentiation factor 15), GDF9 (Growth differentiation factor
9),
GFRA1 (GDNF family receptor alpha 1), GIT1 (G protein-coupled receptor kinase
interactor 1), GNA13 (Guanine nucleotide-binding protein/G protein alpha 13),
GNAQ (Guanine nucleotide binding protein/G protein q polypeptide), GPR12 (G
protein-coupled receptor 12), GPR18 (G protein-coupled receptor 18), GPR22 (G
protein-coupled receptor 22), GPR26 (G protein-coupled receptor 26), GPR27 (G
protein-coupled receptor 27), GPR77 (G protein-coupled receptor 77), GPR85 (G
protein-coupled receptor 85), GRB2 (Growth factor receptor-bound protein 2),
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GRLF1 (Glucocorticoid receptor DNA binding factor 1), GST (Glutathione S-
transferase), GTF2B (General transcription factor IIB), GZMB (Granzyme B),
HAND1 (Heart and neural crest derivatives expressed 1), HAVCR1 (Hepatitis A
virus cellular receptor 1), HES1 (Hairy and enhancer of split 1), HES5 (Hairy
and
enhancer of split 5), HLA-DQA1 (Major histocompatibility complex class II DQ
alpha), HOXA2 (Homeobox A2), HOXA4 (Homeobox A4), HP (Haptoglobin),
HPGDS (Prostaglandin-D synthase), HSPA8 (Heat shock 70kDa protein 8),
HTR1A (5-hydroxytryptamine receptor 1A), HTR2A (5-hydroxytryptamine
receptor 2A), HTR3A (5-hydroxytryptamine receptor 3A), ICAM1 (Intercellular
adhesion molecule 1 (CD54)), IFIT2 (Interferon-induced protein with
tetratricopeptide repeats 2), IFNAR2 (Interferon alpha/beta/omega receptor 2),
IGF1 (Insulin-like growth factor 1), IGF2 (Insulin-like growth factor 2),
IGFBP2
(Insulin-like growth factor binding protein 2, 36kDa), IGFBP7 (Insulin-like
growth
factor binding protein 7), IL10 (Interleukin 10), IL1 ORA (Interleukin 10
receptor
alpha), IL11 (Interleukin 11), IL11 RA (Interleukin 11 receptor alpha), IL11
RB
(Interleukin 11 receptor beta), IL13 (Interleukin 13), IL15 (Interleukin 15),
IL17A
(Interleukin 17A), IL17RB (interleukin 17 receptor B), IL18 (Interleukin 18),
ILI8RAP (Interleukin 18 receptor accessory protein), IL1 R2 (Interleukin 1
receptor type II), IL1 RN (Interleukin 1 receptor antagonist), IL2RA
(Interleukin 2
receptor alpha), IL4R (Interleukin 4 receptor), IL6 (Interleukin 6), IL6R
(Interleukin
6 receptor), IL7 (Interleukin 7), IL8 (Interleukin 8), IL8RA (Interleukin 8
receptor
alpha), IL8RB (Interleukin 8 receptor beta), ILK (Integrin-linked kinase),
INPP4A
(Inositol polyphosphate-4-phosphatase type I, 107kDa), INPP4B (Inositol
polyphosphate-4-phosphatase type I beta), INS (Insulin), IRF2 (Interferon
regulatory factor 2), IRF3 (Interferon regulatory factor 3), IRF9 (Interferon
regulatory factor 9), IRS1 (Insulin receptor substrate 1), ITGA4 (integrin
alpha 4),
ITGA6 (Integrin alpha-6), ITGAE (Integrin alpha E), ITGAV (Integrin alpha-V),
JAG1 (Jagged 1), JAK1 (Janus kinase 1), JDP2 (Jun dimerization protein 2),
JUN (Jun oncogene), JUNB (Jun B proto-oncogene), KCNJ15 (Potassium
inwardly-rectifying channel subfamily J member 15), KIF5B (Kinesin family
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member 5B), KLRC4 (Killer cell lectin-like receptor subfamily C member 4),
KRT8 (Keratin 8), LAMP2 (Lysosomal-associated membrane protein 2), LEP
(Leptin), LHB (Luteinizing hormone beta polypeptide), LRRN3 (Leucine rich
repeat neuronal 3), MAL (Mal T-cell differentiation protein), MAN1A1
(Mannosidase alpha class 1A member 1), MAOB (Monoamine oxidase B),
MAP3K1 (Mitogen-activated protein kinase kinase kinase 1), MAPK1 (Mitogen-
activated protein kinase 1), MAPK3 (Mitogen-activated protein kinase 3),
MAPRE2 (Microtubule-associated protein RP/EB family member 2), MARCKS
(Myristoylated alanine-rich protein kinase C substrate), MAS1 (MAS1 oncogene),
MASL1 (MAS1 oncogene-like), MBP (Myelin basic protein), MCL1 (Myeloid cell
leukemia sequence 1), MDMX (MDM2-like p53-binding protein), MECP2 (Methyl
CpG binding protein 2), MFGE8 (Milk fat globule-EGF factor 8 protein), MIF
(Macrophage migration inhibitory factor), MMP2 (Matrix metal lopepticlase 2),
MOBP (Myelin-associated oligodendrocyte basic protein), MUC16 (Cancer
antigen 125), MX2 (Myxovirus (influenza virus) resistance 2), MYBBP1A (MYB
binding protein 1 a), NBN (Nibrin), NCAM1 (Neural cell adhesion molecule 1),
NCF4 (Neutrophil cytosolic factor 4 40kDa), NCOA1 (Nuclear receptor
coactivator 1), NCOA2 (Nuclear receptor coactivator 2), NEDD9 (Neural
precursor cell expressed developmentally down-regulated 9), NEUR
(Neuraminidase), NFATC1 (Nuclear factor of activated T-cells cytoplasmic
calcineurin-dependent 1), NFE2L2 (Nuclear factor erythroid-derived 2-like 2),
NFIC (Nuclear factor I/C), NFKBIA (Nuclear factor of kappa light polypeptide
gene enhancer in B-cells inhibitor alpha), NGFR (Nerve growth factor
receptor),
NIACR2 (niacin receptor 2), NLGN3 (Neuroligin 3), NPFFR2 (neuropeptide FF
receptor 2), NPY (Neuropeptide Y), NR3C2 (Nuclear receptor subfamily 3 group
C member 2), NRAS (Neuroblastoma RAS viral (v-ras) oncogene homolog),
NRCAM (Neuronal cell adhesion molecule), NRG1 (Neuregulin 1), NRTN
(Neurturin), NRXN1 (Neurexin 1), NSMAF (Neutral sphingomyelinase activation
associated factor), NTF3 (Neurotrophin 3), NTF5 (Neurotrophin 4/5), ODC1
(Ornithine decarboxylase 1), OR10A1 (Olfactory receptor 1 OA1), OR1A1
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(Olfactory receptor family 1 subfamily A member 1), OR1 N1 (Olfactory receptor
family 1 subfamily N member 1), OR3A2 (Olfactory receptor family 3 subfamily A
member 2), OR7A1 7 (Olfactory receptor family 7 subfamily A member 17),
ORM1 (Orosomucoid 1), OXTR (Oxytocin receptor), P2RY13 (Purinergic
receptor P2Y G-protein coupled 13), P2Y12 (Purinergic receptor P2Y G-protein
coupled 12), P70S6K (P70S6 kinase), PAK1 (P21 /Cdc42/Rac1-activated kinase
1), PAR1 (Prader-Willi/Angelman region-1), PBEF1 (Pre-B-cell colony enhancing
factor 1), PCAF (P300/CBP-associated factor), PDE4A (cAMP-specific 3',5'-
cyclic phosphodiesterase 4A), PDE4B (Phosphodiesterase 4B cAMP-specific),
PDE4B (Phosphodiesterase 4B cAMP-specific), PDE4D (Phosphodiesterase 4D
cAMP-specific), PDGFA (Platelet-derived growth factor alpha polypeptide),
PDGFB (Platelet-derived growth factor beta polypeptide), PDGFC (Platelet
derived growth factor C), PDGFRB (Beta-type platelet-derived growth factor
receptor), PDPN (Podoplanin), PENK (Enkephalin), PER1 (Period homolog 1),
PLA2 (Phospholipase A2), PLAU (Plasminogen activator urokinase), PLXNCI
(Plexin Cl), PMVK (Phosphomevalonate kinase), PNOC (Prepronociceptin),
POLH (Polymerase (DNA directed) eta), POMC (Proopiomelanocortin
(adrenocorticotropin/ beta-lipotropin/ alpha-melanocyte stimulating hormone/
beta-melanocyte stimulating hormone/ beta-endorphin)), POU2AF1 (POU
domain class 2 associating factor 1), PRKAA1 (5'-AMP-activated protein kinase
catalytic subunit alpha-1), PRL (Prolactin), PSCDBP (Cytohesin 1 interacting
protein), PSPN (Persephin), PTAFR (Platelet-activating factor receptor), PTGS2
(Prostaglandin-endoperoxide synthase 2), PTN (Pleiotrophin), PTPN11 (Protein
tyrosine phosphatase non-receptor type 11), PYY (Peptide YY), RAB11 B
(RAB11 B member RAS oncogene family), RAB6A (RAB6A member RAS
oncogene family), RAD17 (RAD17 homolog), RAF1 (RAF proto-oncogene
serine/threonine-protein kinase), RANBP2 (RAN binding protein 2), RAP1A
(RAP1A member of RAS oncogene family), RB1 (Retinoblastoma 1), RBL2
(Retinoblastoma-like 2 (p130)), RCVRN (Recoverin), REM2 (RAS/RAD/GEM-like
GTP binding 2), RFRP (RFamide-related peptide), RPS6KA3 (Ribosomal protein
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S6 kinase 90kDa polypeptide 3), RTN4 (Reticulon 4), RUNX1 (Runt-related
transcription factor 1), S100A4 (S100 calcium binding protein A4), S1 PR1
(Sphingosine-1 -phosphate receptor 1), SCG2 (Secretogranin II), SCYE1 (Small
inducible cytokine subfamily E member 1), SELENBP1 (Selenium binding protein
1), SGK (Serum/glucocorticoid regulated kinase), SKD1 (Suppressor of K+
transport growth defect 1), SLC14A1 (Solute carrier family 14 (urea
transporter)
member 1 (Kidd blood group)), SLC25A37 (Solute carrier family 25 member 37),
SMAD2 (SMAD family member 2), SMAD5 (SMAD family member 5), SNAP23
(Synaptosomal-associated protein 23kDa), SNOB (Synuclein beta), SNF1 LK
(SNP-like kinase), SORT1 (Sortilin 1), SSB (Sjogren syndrome antigen B),
STAT1 (Signal transducer and activator of transcription 1, 91 kDa), STAT5A
(Signal transducer and activator of transcription 5A), STAT5B (Signal
transducer
and activator of transcription 5B), STX16 (Syntaxin 16), TAC1 (Tachykinin
precursor 1), TBX1 (T-box 1), TEF (Thyrotrophic embryonic factor), TF
(Transferrin), TGFA (Transforming growth factor alpha), TGFB1 (Transforming
growth factor beta 1), TGFB2 (Transforming growth factor beta 2), TGFB3
(Transforming growth factor beta 3), TGFBR1 (Transforming growth factor beta
receptor I), TGM2 (Transglutaminase 2), THPO (Thrombopoietin), TIMP1 (TIMP
metallopeptidase inhibitor 1), TIMP3 (TIMP metallopeptidase inhibitor 3),
TMEM129 (Transmembrane protein 129), TNFRC6 (TNFR/NGFR cysteine-rich
region), TNFRSF10A (Tumor necrosis factor receptor superfamily member 1 Oa),
TNFRSF10C (Tumor necrosis factor receptor superfamily member 1 Oc decoy
without an intracellular domain), TNFRSF1A (Tumor necrosis factor receptor
superfamily member 1A), TOB2 (Transducer of ERBB2 2), TOP1
(Topoisomerase (DNA) I), TOPOII (Topoisomerase 2), TRAK2 (Trafficking
protein kinesin binding 2), TRH (Thyrotropin-releasing hormone), TSH (Thyroid-
stimulating hormone alpha), TUBAIA (Tubulin alpha 1a), TXK (TXK tyrosine
kinase), TYK2 (Tyrosine kinase 2), UCP1 (Uncoupling protein 1), UCP2
(Uncoupling protein 2), ULIP (Unc-33-like phosphoprotein), UTRN (Utrophin),
VEGF (Vascular endothelial growth factor), VGF (VGF nerve growth factor
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inducible), VIP (Vasoactive intestinal peptide), VNN1 (Vanin 1), VTN
(Vitronectin), WNT2 (Wingless-type MMTV integration site family member 2),
XRCC6 (X-ray repair cross-complementing 6), ZEB2 (Zinc finger E-box binding
homeobox 2), and ZNF461 (Zinc finger protein 461).
[0202] Exemplary prion disorder-related proteins, include PrPc and
isoforms thereof, PrPsc and isoforms thereof, HECTD2 (e3-ubipuitin ligase
protein), STI1 (stress inducible protein 1), DPL (residue Doppel protein,
encoded
by Prnd), APOA1 (Apolipoprotein Al), BCL-2 (B-cell lymphoma 2), HSP60 (Heat
shock 60kDa protein), BAX- inhibiting peptide (Bcl-2-associated X protein
inhibitor), NRF2 (nuclear respiratory factor 2), NCAMs (neural cell-adhesion
molecules), heparin, laminin and laminin receptor and any combination thereof.
[0203] In certain embodiments, an animal created by a method of
the invention may be used to study the effects of mutations on the animal and
development and/or progression of a prion disorder using measures commonly
used in the study of prion disorders.
M. immunodeficiency
[0204] In one embodiment, a method of the invention may be used
to create an animal or cell in which at least one chromosomal sequence
associated with immunodeficiency has been edited. Suitable chromosomal edits
may include, but are not limited to, the type of edits detailed in section
I(f) above.
[0205] In each of the above embodiments, one or more
chromosomal sequences associated with immunodeficiency may be edited. An
immunodeficiency protein or control sequence is a protein or control sequence
for which an alteration in activity is linked to an immunodeficiency, which
may be
the primary or a secondary symptom of an animal disease or condition,
preferably a mammalian, e.g., a human, disease or condition. An
immunodeficiency sequence may typically be selected based on an experimental
association of the immunodeficiency sequence to an immunodeficiency disease
or condition, especially a mammalian, e.g., a human, disease or condition. For
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example, the expression of an immunodeficiency protein in a particular tissue
may be elevated or depressed in a population having an immunodeficiency
disease or condition relative to a population lacking the disease or
condition.
Differences in protein levels may be assessed using proteomic or genomic
analysis techniques known in the art.
[0206] Non-limiting examples of human immunodeficiency genes
include A2M [alpha-2-macroglobulin]; AANAT [arylalkylamine N-
acetyltransferase]; ABCA1 [ATP-binding cassette, sub-family A (ABC1), member
1 ]; ABCA2 [ATP-binding cassette, sub-family A (ABC1), member 2]; ABCA3
[ATP-binding cassette, sub-family A (ABC1), member 3]; ABCA4 [ATP-binding
cassette, sub-family A (ABC1), member 4]; ABCB1 [ATP-binding cassette, sub-
family B (MDR/TAP), member 1]; ABCC1 [ATP-binding cassette, sub-family C
(CFTR/MRP), member 1]; ABCC2 [ATP-binding cassette, sub-family C
(CFTR/MRP), member 2]; ABCC3 [ATP-binding cassette, sub-family C
(CFTR/MRP), member 3]; ABCC4 [ATP-binding cassette, sub-family C
(CFTR/MRP), member 4]; ABCC8 [ATP-binding cassette, sub-family C
(CFTR/MRP), member 8]; ABCD2 [ATP-binding cassette, sub-family D (ALD),
member 2]; ABCD3 [ATP-binding cassette, sub-family D (ALD), member 3];
ABCG1 [ATP-binding cassette, sub-family G (WHITE), member 1]; ABCG2 [ATP-
binding cassette, sub-family G (WHITE), member 2]; ABCG5 [ATP-binding
cassette, sub-family G (WHITE), member 5]; ABCG8 [ATP-binding cassette, sub-
family G (WHITE), member 8]; ABHD2 [abhydrolase domain containing 2]; ABL1
[c-abl oncogene 1, receptor tyrosine kinase]; ABO [ABO blood group
(transferase
A, alpha 1-3-N-acetylgalactosaminyltransferase; transferase B, alpha 1-3-
galactosyltransferase)]; ABP1 [amiloride binding protein 1 (amine oxidase
(copper-containing))]; ACAA1 [acetyl-Coenzyme A acyltransferase 1]; ACACA
[acetyl-Coenzyme A carboxylase alpha]; ACAN [aggrecan]; ACAT1 [acetyl-
Coenzyme A acetyltransferase 1 ]; ACAT2 [acetyl-Coenzyme A acetyltransferase
2]; ACCN5 [amiloride-sensitive cation channel 5, intestinal]; ACE [angiotensin
I
converting enzyme (peptidyl-dipeptidase A) 1]; ACE2 [angiotensin I converting
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enzyme (peptidyl-dipeptidase A) 2]; ACHE [acetylcholinesterase (Yt blood
group)]; ACLY [ATP citrate lyase]; ACOT9 [acyl-CoA thioesterase 9]; ACOX1
[acyl-Coenzyme A oxidase 1, palmitoyl]; ACP1 [acid phosphatase 1, soluble];
ACP2 [acid phosphatase 2, lysosomal]; ACP5 [acid phosphatase 5, tartrate
resistant]; ACPP [acid phosphatase, prostate]; ACSL3 [acyl-CoA synthetase
long-chain family member 3]; ACSM3 [acyl-CoA synthetase medium-chain family
member 3]; ACTA1 [actin, alpha 1, skeletal muscle]; ACTA2 [actin, alpha 2,
smooth muscle, aorta]; ACTB [actin, beta]; ACTC1 [actin, alpha, cardiac muscle
1]; ACTG1 [actin, gamma 1]; ACTN1 [actinin, alpha 1]; ACTN2 [actinin, alpha
2];
ACTN4 [actinin, alpha 4]; ACTR2 [ARP2 actin-related protein 2 homolog
(yeast)];
ACVR1 [activin A receptor, type I]; ACVR1 B [activin A receptor, type IB];
ACVRL1 [activin A receptor type 11-1 ike 1 ]; ACY1 [aminoacylase 1 ]; ADA
[adenosine deaminase]; ADAM10 [ADAM metallopeptidase domain 10]; ADAM12
[ADAM metallopeptidase domain 12]; ADAM17 [ADAM metallopeptidase domain
17]; ADAM23 [ADAM metallopeptidase domain 23]; ADAM33 [ADAM
metallopeptidase domain 33]; ADAM8 [ADAM metallopeptidase domain 8];
ADAMS [ADAM metallopeptidase domain 9 (meltrin gamma)]; ADAMTS1 [ADAM
metallopeptidase with thrombospondin type 1 motif, 1]; ADAMTS12 [ADAM
metallopeptidase with thrombospondin type 1 motif, 12]; ADAMTS13 [ADAM
metallopeptidase with thrombospondin type 1 motif, 13]; ADAMTS15 [ADAM
metallopeptidase with thrombospondin type 1 motif, 15]; ADAMTSL1 [ADAMTS-
like 1]; ADAMTSL4 [ADAMTS-like 4]; ADAR [adenosine deaminase, RNA-
specific]; ADCY1 [adenylate cyclase 1 (brain)]; ADCY10 [adenylate cyclase 10
(soluble)]; ADCY3 [adenylate cyclase 3]; ADCY9 [adenylate cyclase 9];
ADCYAP1 [adenylate cyclase activating polypeptide 1 (pituitary)]; ADCYAP1 R1
[adenylate cyclase activating polypeptide 1 (pituitary) receptor type I]; ADD1
[adducin 1 (alpha)]; ADH5 [alcohol dehydrogenase 5 (class III), chi
polypeptide];
ADIPOQ [adiponectin, C1Q and collagen domain containing]; ADIPOR1
[adiponectin receptor 1]; ADK [adenosine kinase]; ADM [adrenomedullin];
ADORA1 [adenosine Al receptor]; ADORA2A [adenosine A2a receptor];
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ADORA2B [adenosine A2b receptor]; ADORA3 [adenosine A3 receptor];
ADRA1 B [adrenergic, alpha-1 B-, receptor]; ADRA2A [adrenergic, alpha-2A-,
receptor]; ADRA2B [adrenergic, alpha-2B-, receptor]; ADRB1 [adrenergic, beta-
1-, receptor]; ADRB2 [adrenergic, beta-2-, receptor, surface]; ADSL
[adenylosuccinate lyase]; ADSS [adenylosuccinate synthase]; AEBP1 [AE
binding protein 1]; AFP [alpha-fetoprotein]; AGER [advanced glycosylation end
product-specific receptor]; AGMAT [agmatine ureohydrolase (agmatinase)];
AGPS [alkylglycerone phosphate synthase]; AGRN [agrin]; AGRP [agouti related
protein homolog (mouse)]; AGT [angiotensinogen (serpin peptidase inhibitor,
Glade A, member 8)]; AGTR1 [angiotensin II receptor, type 1]; AGTR2
[angiotensin II receptor, type 2]; AHOY [adenosylhomocysteinase]; AHI1
[Abelson helper integration site 1]; AHR [aryl hydrocarbon receptor]; AHSP
[alpha hemoglobin stabilizing protein]; AICDA [activation-induced cytidine
deaminase]; AIDA [axin interactor, dorsalization associated]; AIMP1 [aminoacyl
tRNA synthetase complex-interacting multifunctional protein 1]; AIRE
[autoimmune regulator]; AK1 [adenylate kinase 1]; AK2 [adenylate kinase 2];
AKR1Al [aldo-keto reductase family 1, member Al (aldehyde reductase)];
AKR1 131 [aldo-keto reductase family 1, member 131 (aldose reductase)]; AKR1
C3
[aldo-keto reductase family 1, member C3 (3-alpha hydroxysteroid
dehydrogenase, type II)]; AKT1 [v-akt murine thymoma viral oncogene homolog
1]; AKT2 [v-akt murine thymoma viral oncogene homolog 2]; AKT3 [v-akt murine
thymoma viral oncogene homolog 3 (protein kinase B, gamma)]; ALB [albumin];
ALCAM [activated leukocyte cell adhesion molecule]; ALDHIAI [aldehyde
dehydrogenase 1 family, member A1]; ALDH2 [aldehyde dehydrogenase 2 family
(mitochondrial)]; ALDH3A1 [aldehyde dehydrogenase 3 family, memberA1 ];
ALDH7A1 [aldehyde dehydrogenase 7 family, member Al ]; ALDH9A1 [aldehyde
dehydrogenase 9 family, member A1]; ALG1 [asparagine-linked glycosylation 1,
beta- l,4-mannosyltransferase homolog (S. cerevisiae)]; ALG12 [asparagine-
linked glycosylation 12, alpha-1,6-mannosyltransferase homolog (S.
cerevisiae)];
ALK [anaplastic lymphoma receptor tyrosine kinase]; ALOX12 [arachidonate 12-
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lipoxygenase]; ALOX15 [arachidonate 15-lipoxygenase]; ALOX15B [arachidonate
15-lipoxygenase, type B]; ALOX5 [arachidonate 5-lipoxygenase]; ALOX5AP
[arachidonate 5-lipoxygenase-activating protein]; ALPI [alkaline phosphatase,
intestinal]; ALPL [alkaline phosphatase, liver/bone/kidney]; ALPP [alkaline
phosphatase, placental (Regan isozyme)]; AMACR [alpha-methylacyl-CoA
racemase]; AMBP [alpha-1-microglobulin/bikunin precursor]; AMPD3 [adenosine
monophosphate deaminase 3]; ANG [angiogenin, ribonuclease, RNase A family,
5]; ANGPT1 [angiopoietin 1]; ANGPT2 [angiopoietin 2]; ANK1 [ankyrin 1,
erythrocytic]; ANKH [ankylosis, progressive homolog (mouse)]; ANKRD1 [ankyrin
repeat domain 1 (cardiac muscle)]; ANPEP [alanyl (membrane) aminopeptidase];
ANTXR2 [anthrax toxin receptor 2]; ANXA1 [annexin Al ]; ANXA2 [annexin A2];
ANXA5 [annexin A5]; ANXA6 [annexin A6]; AOAH [acyloxyacyl hydrolase
(neutrophil)]; AOC2 [amine oxidase, copper containing 2 (retina-specific)];
AP2B1
[adaptor-related protein complex 2, beta 1 subunit]; AP3B1 [adaptor-related
protein complex 3, beta 1 subunit]; APC [adenomatous polyposis coli]; APCS
[amyloid P component, serum]; APEX1 [APEX nuclease (multifunctional DNA
repair enzyme) 1]; APLNR [apelin receptor]; APOA1 [apolipoprotein A-I]; APOA2
[apolipoprotein A-II]; APOA4 [apolipoprotein A-IV]; APOB [apolipoprotein B
(including Ag(x) antigen)]; APOBEC1 [apolipoprotein B mRNA editing enzyme,
catalytic polypeptide 1]; APOBEC3G [apolipoprotein B mRNA editing enzyme,
catalytic polypeptide-like 3G]; APOC3 [apolipoprotein C-III]; APOD
[apolipoprotein D]; APOE [apolipoprotein E]; APOH [apolipoprotein H (beta-2-
glycoprotein I)]; APP [amyloid beta (A4) precursor protein]; APRT [adenine
phosphoribosyltransferase]; APTX [aprataxin]; AQP1 [aquaporin 1 (Colton blood
group)]; AQP2 [aquaporin 2 (collecting duct)]; AQP3 [aquaporin 3 (Gill blood
group)]; AQP4 [aquaporin 4]; AQP5 [aquaporin 5]; AQP7 [aquaporin 7]; AQP8
[aquaporin 8]; AR [androgen receptor]; AREG [amphiregulin]; ARF6 [ADP-
ribosylation factor 6]; ARG1 [arginase, liver]; ARG2 [arginase, type II];
ARHGAP6
[Rho GTPase activating protein 6]; ARHGEF2 [Rho/Rac guanine nucleotide
exchange factor (GEF) 2]; ARHGEF6 [Rac/Cdc42 guanine nucleotide exchange
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factor (GEF) 6]; ARL13B [ADP-ribosylation factor-like 13B]; ARNT [aryl
hydrocarbon receptor nuclear translocator]; ARNTL [aryl hydrocarbon receptor
nuclear translocator-like]; ARRB1 [arrestin, beta 1]; ARRB2 [arrestin, beta
2];
ARSA [arylsulfatase A]; ARSB [arylsulfatase B]; ARSH [arylsulfatase family,
member H]; ART1 [ADP-ribosyltransferase 1]; ASAH1 [N-acylsphingosine
amidohydrolase (acid ceramidase) 1]; ASAP1 [ArfGAP with SH3 domain, ankyrin
repeat and PH domain 1]; ASGR2 [asialoglycoprotein receptor 2]; ASL
[argininosuccinate lyase]; ASNS [asparagine synthetase]; ASPA [aspartoacylase
(Canavan disease)]; ASPG [asparaginase homolog (S. cerevisiae)]; ASPH
[aspartate beta-hydroxylase]; ASRGL1 [asparaginase like 1]; ASS1
[argininosuccinate synthase 1]; ATF1 [activating transcription factor 1]; ATF2
[activating transcription factor 2]; ATF3 [activating transcription factor 3];
ATF4
[activating transcription factor 4 (tax-responsive enhancer element B67)];
ATG16L1 [ATG16 autophagy related 16-like 1 (S. cerevisiae)]; ATM [ataxia
telangiectasia mutated]; ATMIN [ATM interactor]; ATN1 [atrophin 1]; ATOH1
[atonal homolog 1 (Drosophila)]; ATP2A2 [ATPase, Ca++ transporting, cardiac
muscle, slow twitch 2]; ATP2A3 [ATPase, Ca++ transporting, ubiquitous];
ATP2C1 [ATPase, Ca++ transporting, type 2C, member 1]; ATP5E [ATP
synthase, H+ transporting, mitochondrial F1 complex, epsilon subunit]; ATP7B
[ATPase, Cu++ transporting, beta polypeptide]; ATP8B1 [ATPase, class I, type
8B, member 1]; ATPAF2 [ATP synthase mitochondrial F1 complex assembly
factor 2]; ATR [ataxia telangiectasia and Rad3 related]; ATRIP [ATR
interacting
protein]; ATRN [attractin]; AURKA [aurora kinase A]; AURKB [aurora kinase B];
AURKC [aurora kinase C]; AVP [arginine vasopressin]; AVPR2 [arginine
vasopressin receptor 2]; AXL [AXL receptor tyrosine kinase]; AZGP1 [alpha-2-
glycoprotein 1, zinc-binding]; B2M [beta-2-microglobulin]; B3GALTL [beta 1,3-
galactosyltransferase-like]; B3GAT1 [beta- 1,3-g I ucu ronyltransferase 1
(glucuronosyltransferase P)]; B4GALNT1 [beta-l,4-N-acetyl-galactosaminyl
transferase 1 ]; B4GALT1 [UDP-Gal:betaGlcNAc beta 1,4- galactosyltransferase,
polypeptide 1]; BACE1 [beta-site APP-cleaving enzyme 1]; BACE2 [beta-site
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APP-cleaving enzyme 2]; BACH1 [BTB and CNC homology 1, basic leucine
zipper transcription factor 1]; BAD [BCL2-associated agonist of cell death];
BAIAP2 [BAI1-associated protein 2]; BAK1 [BCL2-antagonist/killer 1]; BARX2
[BARX homeobox 2]; BAT1 [HLA-B associated transcript 1]; BAT2 [HLA-B
associated transcript 2]; BAX [BCL2-associated X protein]; BBC3 [BCL2 binding
component 3]; BCAR1 [breast cancer anti-estrogen resistance 1 ]; BCAT1
[branched chain aminotransferase 1, cytosolic]; BCAT2 [branched chain
aminotransferase 2, mitochondrial]; BCHE [butyrylcholinesterase]; BCL10 [B-
cell
CLL/lymphoma 10]; BCL11 B [B-cell CLL/lymphoma 11 B (zinc finger protein)];
BCL2 [B-cell CLL/lymphoma 2]; BCL2A1 [BCL2-related protein Al]; BCL2L1
[BCL2-like 1]; BCL2L1 1 [BCL2-like 11 (apoptosis facilitator)]; BCL3 [B-cell
CLL/lymphoma 3]; BCL6 [B-cell CLL/lymphoma 6]; BCR [breakpoint cluster
region]; BDKRB1 [bradykinin receptor B1]; BDKRB2 [bradykinin receptor B2];
BDNF [brain-derived neurotrophic factor]; BECN1 [beclin 1, autophagy related];
BEST1 [bestrophin 1]; BFAR [bifunctional apoptosis regulator]; BGLAP [bone
gamma-carboxyglutamate (gla) protein]; BHMT [betaine-homocysteine
methyltransferase]; BID [BH3 interacting domain death agonist]; BIK [BCL2-
interacting killer (apoptosis-inducing)]; BIRC2 [baculoviral IAP repeat-
containing
2]; BIRC3 [baculoviral IAP repeat-containing 3]; BIRC5 [baculoviral IAP repeat-
containing 5]; BLK [B lymphoid tyrosine kinase]; BLM [Bloom syndrome, RecQ
helicase-like]; BLNK [B-cell linker]; BLVRB [biliverdin reductase B (flavin
reductase (NADPH))]; BMI1 [BMI1 polycomb ring finger oncogene]; BMP1 [bone
morphogenetic protein 1]; BMP2 [bone morphogenetic protein 2]; BMP4 [bone
morphogenetic protein 4]; BMP6 [bone morphogenetic protein 6]; BMP7 [bone
morphogenetic protein 7]; BMPR1A [bone morphogenetic protein receptor, type
IA]; BMPR1 B [bone morphogenetic protein receptor, type IB]; BMPR2 [bone
morphogenetic protein receptor, type II (serine/threonine kinase)]; BPI
[bactericidal/permeability-increasing protein]; BRCA1 [breast cancer 1, early
onset]; BRCA2 [breast cancer 2, early onset]; BRCC3 [BRCA1/BRCA2-
containing complex, subunit 3]; BRD8 [bromodomain containing 8]; BRIP1
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[BRCA1 interacting protein C-terminal helicase 1]; BSG [basigin (Ok blood
group)]; BSN [bassoon (presynaptic cytomatrix protein)]; BSX [brain-specific
homeobox]; BTD [biotinidase]; BTK [Bruton agammaglobulinemia tyrosine
kinase]; BTLA [B and T lymphocyte associated]; BTNL2 [butyrophilin-like 2 (MHC
class II associated)]; BTRC [beta-transducin repeat containing]; C10orf67
[chromosome 10 open reading frame 67]; C11orf30 [chromosome 11 open
reading frame 30]; C11orf58 [chromosome 11 open reading frame 58]; C13orf23
[chromosome 13 open reading frame 23]; C13orf31 [chromosome 13 open
reading frame 31]; C15orf2 [chromosome 15 open reading frame 2]; C16orf75
[chromosome 16 open reading frame 75]; C19orf10 [chromosome 19 open
reading frame 10]; C1 QA [complement component 1, q subcomponent, A chain];
C1 QB [complement component 1, q subcomponent, B chain]; C1 QC
[complement component 1, q subcomponent, C chain]; C1 QTNF5 [C1 q and
tumor necrosis factor related protein 5]; C1 R [complement component 1, r
subcomponent]; C1S [complement component 1, s subcomponent]; C2
[complement component 2]; C20orf29 [chromosome 20 open reading frame 29];
C21orf33 [chromosome 21 open reading frame 33]; C3 [complement component
3]; C3AR1 [complement component 3a receptor 1]; C3orf27 [chromosome 3
open reading frame 27]; C4A [complement component 4A (Rodgers blood
group)]; C4B [complement component 4B (Chido blood group)]; C4BPA
[complement component 4 binding protein, alpha]; C4BPB [complement
component 4 binding protein, beta]; C5 [complement component 5]; C5AR1
[complement component 5a receptor 1]; C5orf56 [chromosome 5 open reading
frame 56]; C5orf62 [chromosome 5 open reading frame 62]; C6 [complement
component 6]; C6orf142 [chromosome 6 open reading frame 142]; C6orf25
[chromosome 6 open reading frame 25]; C7 [complement component 7]; C7orf72
[chromosome 7 open reading frame 72]; C8A [complement component 8, alpha
polypeptide]; C8B [complement component 8, beta polypeptide]; C8G
[complement component 8, gamma polypeptide]; C8orf38 [chromosome 8 open
reading frame 38]; C9 [complement component 9]; CA2 [carbonic anhydrase II];
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CA6 [carbonic anhydrase VI]; CA8 [carbonic anhydrase VIII]; CA9 [carbonic
anhydrase IX]; CABIN1 [calcineurin binding protein 1]; CACNA1C [calcium
channel, voltage-dependent, L type, alpha 1 C subunit]; CACNA1 S [calcium
channel, voltage-dependent, L type, alpha 1 S subunit]; CAD [carbamoyl-
phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase];
CALB1 [calbindin 1, 28kDa]; CALB2 [calbindin 2]; CALCA [calcitonin-related
polypeptide alpha]; CALCRL [calcitonin receptor-like]; CALD1 [caldesmon 1];
CALM1 [calmodulin 1 (phosphorylase kinase, delta)]; CALM2 [calmodulin 2
(phosphorylase kinase, delta)]; CALM3 [calmodulin 3 (phosphorylase kinase,
delta)]; CALR [calreticulin]; CAMK2G [calcium/calmodulin-dependent protein
kinase II gamma]; CAMP [cathelicidin antimicrobial peptide]; CANT1 [calcium
activated nucleotidase 1]; CANX [calnexin]; CAPN1 [calpain 1, (mu/I) large
subunit]; CARD10 [caspase recruitment domain family, member 10]; CARD16
[caspase recruitment domain family, member 16]; CARD8 [caspase recruitment
domain family, member 8]; CARDS [caspase recruitment domain family, member
9]; CASP1 [caspase 1, apoptosis-related cysteine peptidase (interleukin 1,
beta,
convertase)]; CASP10 [caspase 10, apoptosis-related cysteine peptidase];
CASP2 [caspase 2, apoptosis-related cysteine peptidase]; CASP3 [caspase 3,
apoptosis-related cysteine peptidase]; CASP5 [caspase 5, apoptosis-related
cysteine peptidase]; CASP6 [caspase 6, apoptosis-related cysteine peptidase];
CASP7 [caspase 7, apoptosis-related cysteine peptidase]; CASP8 [caspase 8,
apoptosis-related cysteine peptidase]; CASP8AP2 [caspase 8 associated protein
2]; CASP9 [caspase 9, apoptosis-related cysteine peptidase]; CASR [calcium-
sensing receptor]; CAST [calpastatin]; CAT [catalase]; CAV1 [caveolin 1,
caveolae protein, 22kDa]; CAV2 [caveolin 2]; CBL [Cas-Br-M (murine) ecotropic
retroviral transforming sequence]; CBS [cystathionine-beta-synthase]; CBX5
[chromobox homolog 5 (HP1 alpha homolog, Drosophila)]; CC2D2A [coiled-coil
and C2 domain containing 2A]; CCBP2 [chemokine binding protein 2];
CCDC144A [coiled-coil domain containing 144A]; CCDC144B [coiled-coil domain
containing 144B]; CCDC68 [coiled-coil domain containing 68]; CCK
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[cholecystokinin]; CCL1 [chemokine (C-C motif) ligand 1]; CCL11 [chemokine (C-
C motif) ligand 11]; CCL13 [chemokine (C-C motif) ligand 13]; CCL14
[chemokine (C-C motif) ligand 14]; CCL17 [chemokine (C-C motif) ligand 17];
CCL18 [chemokine (C-C motif) ligand 18 (pulmonary and activation-regulated)];
CCL19 [chemokine (C-C motif) ligand 19]; CCL2 [chemokine (C-C motif) ligand
2]; CCL20 [chemokine (C-C motif) ligand 20]; CCL21 [chemokine (C-C motif)
ligand 21]; CCL22 [chemokine (C-C motif) ligand 22]; CCL24 [chemokine (C-C
motif) ligand 24]; CCL25 [chemokine (C-C motif) ligand 25]; CCL26 [chemokine
(C-C motif) ligand 26]; CCL27 [chemokine (C-C motif) ligand 27]; CCL28
[chemokine (C-C motif) ligand 28]; CCL3 [chemokine (C-C motif) ligand 3]; CCL4
[chemokine (C-C motif) ligand 4]; CCL4L1 [chemokine (C-C motif) ligand 4-like
1]; CCL5 [chemokine (C-C motif) ligand 5]; CCL7 [chemokine (C-C motif) ligand
7]; CCL8 [chemokine (C-C motif) ligand 8]; CCNA1 [cyclin Al]; CCNA2 [cyclin
A2]; CCNB1 [cyclin B1]; CCNB2 [cyclin B2]; CCNC [cyclin C]; CCND1 [cyclin
D1]; CCND2 [cyclin D2]; CCND3 [cyclin D3]; CCNE1 [cyclin El]; CCNG1 [cyclin
G1]; CCNH [cyclin H]; CCNT1 [cyclin T1]; CCNT2 [cyclin T2]; CCNY [cyclin Y];
CCR1 [chemokine (C-C motif) receptor 1]; CCR2 [chemokine (C-C motif)
receptor 2]; CCR3 [chemokine (C-C motif) receptor 3]; CCR4 [chemokine (C-C
motif) receptor 4]; CCR5 [chemokine (C-C motif) receptor 5]; CCR6 [chemokine
(C-C motif) receptor 6]; CCR7 [chemokine (C-C motif) receptor 7]; CCR8
[chemokine (C-C motif) receptor 8]; CCR9 [chemokine (C-C motif) receptor 9];
CCRL1 [chemokine (C-C motif) receptor-like 1]; CD14 [CD14 molecule]; CD151
[CD151 molecule (Raph blood group)]; CD160 [CD160 molecule]; CD163
[CD163 molecule]; CD180 [CD180 molecule]; CD19 [CD19 molecule]; CD1A
[CD1 a molecule]; CD1 B [CD1 b molecule]; CD1 C [CD1 c molecule]; CD1 D [CD1 d
molecule]; CD2 [CD2 molecule]; CD200 [CD200 molecule]; CD207 [CD207
molecule, langerin]; CD209 [CD209 molecule]; CD22 [CD22 molecule]; CD226
[CD226 molecule]; CD24 [CD24 molecule]; CD244 [CD244 molecule, natural
killer cell receptor 2B4]; CD247 [CD247 molecule]; CD27 [CD27 molecule];
CD274 [CD274 molecule]; CD28 [CD28 molecule]; CD2AP [CD2-associated
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protein]; CD300LF [CD300 molecule-like family member f]; CD34 [CD34
molecule]; CD36 [CD36 molecule (thrombospondin receptor)]; CD37 [CD37
molecule]; CD38 [CD38 molecule]; CD3E [CD3e molecule, epsilon (CD3-TCR
complex)]; CD4 [CD4 molecule]; CD40 [CD40 molecule, TNF receptor
superfamily member 5]; CD40LG [CD40 ligand]; CD44 [CD44 molecule (Indian
blood group)]; CD46 [CD46 molecule, complement regulatory protein]; CD47
[CD47 molecule]; CD48 [CD48 molecule]; CD5 [CD5 molecule]; CD52 [CD52
molecule]; CD53 [CD53 molecule]; CD55 [CD55 molecule, decay accelerating
factor for complement (Cromer blood group)]; CD58 [CD58 molecule]; CD59
[CD59 molecule, complement regulatory protein]; CD63 [CD63 molecule]; CD68
[CD68 molecule]; CD69 [CD69 molecule]; CD7 [CD7 molecule]; CD70 [CD70
molecule]; CD72 [CD72 molecule]; CD74 [CD74 molecule, major
histocompatibility complex, class II invariant chain]; CD79A [CD79a molecule,
immunoglobulin-associated alpha]; CD79B [CD79b molecule, immunoglobulin-
associated beta]; CD80 [CD80 molecule]; CD81 [CD81 molecule]; CD82 [CD82
molecule]; CD83 [CD83 molecule]; CD86 [CD86 molecule]; CD8A [CD8a
molecule]; CD9 [CD9 molecule]; CD93 [CD93 molecule]; CD97 [CD97 molecule];
CDC20 [cell division cycle 20 homolog (S. cerevisiae)]; CDC25A [cell division
cycle 25 homolog A (S. pombe)]; CDC25B [cell division cycle 25 homolog B (S.
pombe)]; CDC25C [cell division cycle 25 homolog C (S. pombe)]; CDC42 [cell
division cycle 42 (GTP binding protein, 25kDa)]; CDC45 [CDC45 cell division
cycle 45 homolog (S. cerevisiae)]; CDC5L [CDC5 cell division cycle 5-like (S.
pombe)]; CDC6 [cell division cycle 6 homolog (S. cerevisiae)]; CDC7 [cell
division cycle 7 homolog (S. cerevisiae)]; CDH1 [cadherin 1, type 1, E-
cadherin
(epithelial)]; CDH2 [cadherin 2, type 1, N-cadherin (neuronal)]; CDH26
[cadherin
26]; CDH3 [cadherin 3, type 1, P-cadherin (placental)]; CDH5 [cadherin 5, type
2
(vascular endothelium)]; CDIPT [CDP-diacylglycerol--inositol 3-
phosphatidyltransferase (phosphatidylinositol synthase)]; CDK1 [cyclin-
dependent kinase 1]; CDK2 [cyclin-dependent kinase 2]; CDK4 [cyclin-dependent
kinase 4]; CDK5 [cyclin-dependent kinase 5]; CDK5R1 [cyclin-dependent kinase
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5, regulatory subunit 1 (p35)]; CDK7 [cyclin-dependent kinase 7]; CDK9 [cyclin-
dependent kinase 9]; CDKAL1 [CDK5 regulatory subunit associated protein 1-like
1]; CDKN1A [cyclin-dependent kinase inhibitor 1A (p21, Cip1)]; CDKN1B [cyclin-
dependent kinase inhibitor 1B (p27, Kip1)]; CDKN1C [cyclin-dependent kinase
inhibitor 1C (p57, Kip2)]; CDKN2A [cyclin-dependent kinase inhibitor 2A
(melanoma, p16, inhibits CDK4)]; CDKN2B [cyclin-dependent kinase inhibitor 2B
(p15, inhibits CDK4)]; CDKN3 [cyclin-dependent kinase inhibitor 3]; CDR2
[cerebellar degeneration-related protein 2, 62kDa]; CDT1 [chromatin licensing
and DNA replication factor 1]; CDX2 [caudal type homeobox 2]; CEACAM1
[carcinoembryonic antigen-related cell adhesion molecule 1 (biliary
glycoprotein)]; CEACAM3 [carcinoembryonic antigen-related cell adhesion
molecule 3]; CEACAM5 [carcinoembryonic antigen-related cell adhesion
molecule 5]; CEACAM6 [carcinoembryonic antigen-related cell adhesion
molecule 6 (non-specific cross reacting antigen)]; CEACAM7 [carcinoembryonic
antigen-related cell adhesion molecule 7]; CEBPB [CCAAT/enhancer binding
protein (C/EBP), beta]; CEL [carboxyl ester lipase (bile salt-stimulated
lipase)];
CENPJ [centromere protein J]; CENPV [centromere protein V]; CEP290
[centrosomal protein 290kDa]; CERK [ceramide kinase]; CETP [cholesteryl ester
transfer protein, plasma]; CFB [complement factor B]; CFD [complement factor D
(adipsin)]; CFDP1 [craniofacial development protein 1]; CFH [complement factor
H]; CFHR1 [complement factor H-related 1]; CFHR3 [complement factor H-
related 3]; CFI [complement factor I]; CFL1 [cofilin 1 (non-muscle)]; CFL2
[cofilin
2 (muscle)]; CFLAR [CASP8 and FADD-like apoptosis regulator]; CFP
[complement factor properdin]; CFTR [cystic fibrosis transmembrane
conductance regulator (ATP-binding cassette sub-family C, member 7)]; CGA
[glycoprotein hormones, alpha polypeptide]; CGB [chorionic gonadotropin, beta
polypeptide]; CGBS [chorionic gonadotropin, beta polypeptide 5]; CHAD
[chondroadherin]; CHAFIA [chromatin assembly factor 1, subunit A (p150)];
CHAF1 B [chromatin assembly factor 1, subunit B (p60)]; CHAT [choline
acetyltransferase]; CHD2 [chromodomain helicase DNA binding protein 2]; CHD7
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[chromodomain helicase DNA binding protein 7]; CHEK1 [CHK1 checkpoint
homolog (S. pombe)]; CHEK2 [CHK2 checkpoint homolog (S. pombe)]; CHGA
[chromogranin A (parathyroid secretory protein 1)]; CHGB [chromogranin B
(secretogranin 1)]; CHI3L1 [chitinase 3-like 1 (cartilage glycoprotein-39)];
CHIA
[chitinase, acidic]; CHIT1 [chitinase 1 (chitotriosidase)]; CHKA [choline
kinase
alpha]; CHML [choroideremia-like (Rab escort protein 2)]; CHRD [chordin];
CHRDL1 [chordin-like 1]; CHRM1 [cholinergic receptor, muscarinic 1]; CHRM2
[cholinergic receptor, muscarinic 2]; CHRM3 [cholinergic receptor, muscarinic
3];
CHRNA3 [cholinergic receptor, nicotinic, alpha 3]; CHRNA4 [cholinergic
receptor,
nicotinic, alpha 4]; CHRNA7 [cholinergic receptor, nicotinic, alpha 7]; CHUK
[conserved helix-loop-helix ubiquitous kinase]; CIB1 [calcium and integrin
binding
1 (calmyrin)]; CIITA [class II, major histocompatibility complex,
transactivator];
CILP [cartilage intermediate layer protein, nucleotide pyrophosphohydrolase];
CISH [cytokine inducible SH2-containing protein]; CKB [creatine kinase,
brain];
CKLF [chemokine-like factor]; CKM [creatine kinase, muscle]; CLC [Charcot-
Leyden crystal protein]; CLCA1 [chloride channel accessory 1]; CLCN1 [chloride
channel 1, skeletal muscle]; CLCN3 [chloride channel 3]; CLDN1 [claudin 1];
CLDN11 [claudin 11]; CLDN14 [claudin 14]; CLDN16 [claudin 16]; CLDN19
[claudin 19]; CLDN2 [claudin 2]; CLDN3 [claudin 3]; CLDN4 [claudin 4]; CLDN5
[claudin 5]; CLDN7 [claudin 7]; CLDN8 [claudin 8]; CLEC12A [C-type lectin
domain family 12, member A]; CLEC16A [C-type lectin domain family 16,
member A]; CLEC4A [C-type lectin domain family 4, member A]; CLEC4D [C-
type lectin domain family 4, member D]; CLEC4M [C-type lectin domain family 4,
member M]; CLEC7A [C-type lectin domain family 7, member A]; CLIP2 [CAP-
GLY domain containing linker protein 2]; CLK2 [CDC-like kinase 2]; CLSPN
[claspin homolog (Xenopus laevis)]; CLSTN2 [calsyntenin 2]; CLTCL1 [clathrin,
heavy chain-like 1]; CLU [clusterin]; CMA1 [chymase 1, mast cell]; CMKLR1
[chemokine-like receptor 1]; CNBP [CCHC-type zinc finger, nucleic acid binding
protein]; CNDP2 [CNDP dipeptidase 2 (metallopeptidase M20 family)]; CNN1
[calponin 1, basic, smooth muscle]; CNP [2',3'-cyclic nucleotide 3'
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phosphodiesterase]; CNR1 [cannabinoid receptor 1 (brain)]; CNR2 [cannabinoid
receptor 2 (macrophage)]; CNTF [ciliary neurotrophic factor]; CNTN2 [contactin
2
(axonal)]; COG1 [component of oligomeric golgi complex 1]; COG2 [component
of oligomeric golgi complex 2]; COIL [coilin]; COL11A1 [collagen, type XI,
alpha
1]; COL11A2 [collagen, type XI, alpha 2]; COL17A1 [collagen, type XVII, alpha
1]; COL18A1 [collagen, type XVI I I, alpha 1]; COL1A1 [collagen, type I, alpha
1];
COL1A2 [collagen, type I, alpha 2]; COL2A1 [collagen, type II, alpha 1];
COL3A1
[collagen, type III, alpha 1]; COL4A1 [collagen, type IV, alpha 1]; COL4A3
[collagen, type IV, alpha 3 (Goodpasture antigen)]; COL4A4 [collagen, type IV,
alpha 4]; COL4A5 [collagen, type IV, alpha 5]; COL4A6 [collagen, type IV,
alpha
6]; COL5A1 [collagen, type V, alpha 1 ]; COL5A2 [collagen, type V, alpha 2];
COL6A1 [collagen, type VI, alpha 1 ]; COL6A2 [collagen, type VI, alpha 2];
COL6A3 [collagen, type VI, alpha 3]; COL7A1 [collagen, type VII, alpha 1];
COL8A2 [collagen, type VIII, alpha 2]; COL9A1 [collagen, type IX, alpha 1];
COMT [catechol-O-methyltransferase]; COQ3 [coenzyme Q3 homolog,
methyltransferase (S. cerevisiae)]; COQ7 [coenzyme Q7 homolog, ubiquinone
(yeast)]; CORO1A [coronin, actin binding protein, 1A]; COX10 [COX10 homolog,
cytochrome c oxidase assembly protein, heme A: farnesyltransferase (yeast)];
COX15 [COX15 homolog, cytochrome c oxidase assembly protein (yeast)];
COXSA [cytochrome c oxidase subunit Va]; COXBA [cytochrome c oxidase
subunit VIIIA (ubiquitous)]; CP [ceruloplasmin (ferroxidase)]; CPA1
[carboxypeptidase Al (pancreatic)]; CPB2 [carboxypeptidase B2 (plasma)];
CPN1 [carboxypeptidase N, polypeptide 1]; CPOX [coproporphyrinogen oxidase];
CPS1 [carbamoyl-phosphate synthetase 1, mitochondrial]; CPT2 [carnitine
palmitoyltransferase 2]; CR1 [complement component (3b/4b) receptor 1 (Knops
blood group)]; CR2 [complement component (3d/Epstein Barr virus) receptor 2];
CRAT [carnitine O-acetyltransferase]; CRB1 [crumbs homolog 1 (Drosophila)];
CREB1 [cAMP responsive element binding protein 1]; CREBBP [CREB binding
protein]; CREM [cAMP responsive element modulator]; CRH [corticotropin
releasing hormone]; CRHR1 [corticotropin releasing hormone receptor 1];
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CRHR2 [corticotropin releasing hormone receptor 2]; CRK [v-crk sarcoma virus
CT10 oncogene homolog (avian)]; CRKL [v-crk sarcoma virus CT10 oncogene
homolog (avian)-like]; CRLF2 [cytokine receptor-like factor 2]; CRLF3
[cytokine
receptor-like factor 3]; CROT [carnitine 0-octanoyltransferase]; CRP [C-
reactive
protein, pentraxin-related]; CRX [cone-rod homeobox]; CRY2 [cryptochrome 2
(photolyase-like)]; CRYAA [crystallin, alpha A]; CRYAB [crystallin, alpha B];
CS
[citrate synthase]; CSF1 [colony stimulating factor 1 (macrophage)]; CSF1 R
[colony stimulating factor 1 receptor]; CSF2 [colony stimulating factor 2
(granulocyte-macrophage)]; CSF2RB [colony stimulating factor 2 receptor, beta,
low-affinity (granulocyte-macrophage)]; CSF3 [colony stimulating factor 3
(granulocyte)]; CSF3R [colony stimulating factor 3 receptor (granulocyte)];
CSK
[c-src tyrosine kinase]; CSMD3 [CUB and Sushi multiple domains 3]; CSN1S1
[casein alpha s1]; CSN2 [casein beta]; CSNK1A1 [casein kinase 1, alpha 1];
CSNK2A1 [casein kinase 2, alpha 1 polypeptide]; CSNK2B [casein kinase 2,
beta polypeptide]; CSPG4 [chondroitin sulfate proteoglycan 4]; CST3 [cystatin
C];
CST8 [cystatin 8 (cystatin-related epididymal specific)]; CSTA [cystatin A
(stefin
A)]; CSTB [cystatin B (stefin B)]; CTAGE1 [cutaneous T-cell lymphoma-
associated antigen 1]; CTF1 [cardiotrophin 1]; CTGF [connective tissue growth
factor]; CTH [cystathionase (cystathionine gamma-lyase)]; CTLA4 [cytotoxic T-
lymphocyte-associated protein 4]; CTNNA1 [catenin (cad herin-associated
protein), alpha 1, 102kDa]; CTNNA3 [catenin (cadherin-associated protein),
alpha 3]; CTNNAL1 [catenin (cadherin-associated protein), alpha-like 1];
CTNNB1 [catenin (cadherin-associated protein), beta 1, 88kDa]; CTNND1
[catenin (cadherin-associated protein), delta 1]; CTNS [cystinosis,
nephropathic];
CTRL [chymotrypsin-like]; CTSB [cathepsin B]; CTSC [cathepsin C]; CTSD
[cathepsin D]; CTSE [cathepsin E]; CTSG [cathepsin G]; CTSH [cathepsin H];
CTSK [cathepsin K]; CTSL1 [cathepsin L1]; CTTN [cortactin]; CUL1 [cullin 1];
CUL2 [cullin 2]; CUL4A [cullin 4A]; CUL5 [cullin 5]; CX3CL1 [chemokine (C-X3-C
motif) ligand 1]; CX3CR1 [chemokine (C-X3-C motif) receptor 1]; CXADR
[coxsackie virus and adenovirus receptor]; CXCL1 [chemokine (C-X-C motif)
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ligand 1 (melanoma growth stimulating activity, alpha)]; CXCL10 [chemokine (C-
X-C motif) ligand 10]; CXCL11 [chemokine (C-X-C motif) ligand 11]; CXCL12
[chemokine (C-X-C motif) ligand 12 (stromal cell-derived factor 1)]; CXCL13
[chemokine (C-X-C motif) ligand 13]; CXCL2 [chemokine (C-X-C motif) ligand 2];
CXCL5 [chemokine (C-X-C motif) ligand 5]; CXCL6 [chemokine (C-X-C motif)
ligand 6 (granulocyte chemotactic protein 2)]; CXCL9 [chemokine (C-X-C motif)
ligand 9]; CXCR1 [chemokine (C-X-C motif) receptor 1]; CXCR2 [chemokine (C-
X-C motif) receptor 2]; CXCR3 [chemokine (C-X-C motif) receptor 3]; CXCR4
[chemokine (C-X-C motif) receptor 4]; CXCR5 [chemokine (C-X-C motif) receptor
5]; CXCR6 [chemokine (C-X-C motif) receptor 6]; CXCR7 [chemokine (C-X-C
motif) receptor 7]; CXorf40A [chromosome X open reading frame 40A]; CYB5A
[cytochrome b5 type A (microsomal)]; CYB5R3 [cytochrome b5 reductase 3];
CYBA [cytochrome b-245, alpha polypeptide]; CYBB [cytochrome b-245, beta
polypeptide]; CYC1 [cytochrome c-1]; CYCS [cytochrome c, somatic]; CYFIP2
[cytoplasmic FMR1 interacting protein 2]; CYP11A1 [cytochrome P450, family 11,
subfamily A, polypeptide 1 ]; CYP11 B1 [cytochrome P450, family 11, subfamily
B,
polypeptide 1]; CYP1 1 B2 [cytochrome P450, family 11, subfamily B,
polypeptide
2]; CYP17A1 [cytochrome P450, family 17, subfamily A, polypeptide 1];
CYP19A1 [cytochrome P450, family 19, subfamily A, polypeptide 1]; CYP1A1
[cytochrome P450, family 1, subfamily A, polypeptide 1]; CYP1A2 [cytochrome
P450, family 1, subfamily A, polypeptide 2]; CYP1 B1 [cytochrome P450, family
1,
subfamily B, polypeptide 1]; CYP21A2 [cytochrome P450, family 21, subfamily A,
polypeptide 2]; CYP24A1 [cytochrome P450, family 24, subfamily A, polypeptide
1]; CYP27A1 [cytochrome P450, family 27, subfamily A, polypeptide 1];
CYP27B1 [cytochrome P450, family 27, subfamily B, polypeptide 1]; CYP2A6
[cytochrome P450, family 2, subfamily A, polypeptide 6]; CYP2B6 [cytochrome
P450, family 2, subfamily B, polypeptide 6]; CYP2C19 [cytochrome P450, family
2, subfamily C, polypeptide 19]; CYP2C8 [cytochrome P450, family 2, subfamily
C, polypeptide 8]; CYP2C9 [cytochrome P450, family 2, subfamily C, polypeptide
9]; CYP2D6 [cytochrome P450, family 2, subfamily D, polypeptide 6]; CYP2E1
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[cytochrome P450, family 2, subfamily E, polypeptide 1]; CYP2J2 [cytochrome
P450, family 2, subfamily J, polypeptide 2]; CYP2R1 [cytochrome P450, family
2,
subfamily R, polypeptide 1]; CYP3A4 [cytochrome P450, family 3, subfamily A,
polypeptide 4]; CYP3A5 [cytochrome P450, family 3, subfamily A, polypeptide
5];
CYP4F3 [cytochrome P450, family 4, subfamily F, polypeptide 3]; CYP51A1
[cytochrome P450, family 51, subfamily A, polypeptide 1]; CYP7A1 [cytochrome
P450, family 7, subfamily A, polypeptide 1]; CYR61 [cysteine-rich, angiogenic
inducer, 61]; CYSLTR1 [cysteinyl leukotriene receptor 1]; CYSLTR2 [cysteinyl
leukotriene receptor 2]; DAO [D-amino-acid oxidase]; DAOA [D-amino acid
oxidase activator]; DAP3 [death associated protein 3]; DAPK1 [death-associated
protein kinase 1]; DARC [Duffy blood group, chemokine receptor]; DAZ1 [deleted
in azoospermia 1]; DBH [dopamine beta-hydroxylase (dopamine beta-
monooxygenase)]; DCK [deoxycytidine kinase]; DCLRE1 C [DNA cross-link repair
1 C (PSO2 homolog, S. cerevisiae)]; DCN [decorin]; DCT [dopachrome
tautomerase (dopachrome delta-isomerase, tyrosine-related protein 2)]; DCTN2
[dynactin 2 (p50)]; DDB1 [damage-specific DNA binding protein 1, 127kDa];
DDB2 [damage-specific DNA binding protein 2, 48kDa]; DDC [dopa
decarboxylase (aromatic L-amino acid decarboxylase)]; DDIT3 [DNA-damage-
inducible transcript 3]; DDR1 [discoidin domain receptor tyrosine kinase 1];
DDX1
[DEAD (Asp-Glu-Ala-Asp) box polypeptide 1]; DDX41 [DEAD (Asp-Glu-Ala-Asp)
box polypeptide 41]; DDX42 [DEAD (Asp-Glu-Ala-Asp) box polypeptide 42];
DDX58 [DEAD (Asp-Glu-Ala-Asp) box polypeptide 58]; DEFA1 [defensin, alpha
1]; DEFAS [defensin, alpha 5, Paneth cell-specific]; DEFA6 [defensin, alpha 6,
Paneth cell-specific]; DEFB1 [defensin, beta 1]; DEFB103B [defensin, beta
103B]; DEFB104A [defensin, beta 104A]; DEFB4A [defensin, beta 4A]; DEK
[DEK oncogene]; DENND1 B [DENN/MADD domain containing 1 B]; DES
[desmin]; DGAT1 [diacylglycerol 0-acyltransferase homolog 1 (mouse)];
DGCR14 [DiGeorge syndrome critical region gene 14]; DGCR2 [DiGeorge
syndrome critical region gene 2]; DGCR6 [DiGeorge syndrome critical region
gene 6]; DGCR6L [DiGeorge syndrome critical region gene 6-like]; DGCR8
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[DiGeorge syndrome critical region gene 8]; DGUOK [deoxyguanosine kinase];
DHFR [dihydrofolate reductase]; DHODH [dihydroorotate dehydrogenase]; DHPS
[deoxyhypusine synthase]; DHRS7B [dehydrogenase/reductase (SDR family)
member 7B]; DHRS9 [dehydrogenase/reductase (SDR family) member 9];
DIAPH1 [diaphanous homolog 1 (Drosophila)]; DICER1 [dicer 1, ribonuclease
type III]; D102 [deiodinase, iodothyronine, type II]; DKC1 [dyskeratosis
congenita
1, dyskerin]; DKK1 [dickkopf homolog 1 (Xenopus laevis)]; DLAT
[dihydrolipoamide S-acetyltransferase]; DLG2 [discs, large homolog 2
(Drosophila)]; DLG5 [discs, large homolog 5 (Drosophila)]; DMBT1 [deleted in
malignant brain tumors 1]; DMC1 [DMC1 dosage suppressor of mckl homolog,
meiosis-specific homologous recombination (yeast)]; DMD [dystrophin]; DMP1
[dentin matrix acidic phosphoprotein 1]; DMPK [dystrophia myotonica-protein
kinase]; DMRT1 [doublesex and mab-3 related transcription factor 1]; DMXL2
[Dmx-like 2]; DNA2 [DNA replication helicase 2 homolog (yeast)]; DNAH1
[dynein, axonemal, heavy chain 1]; DNAH12 [dynein, axonemal, heavy chain 12];
DNAI1 [dynein, axonemal, intermediate chain 1]; DNAI2 [dynein, axonemal,
intermediate chain 2]; DNASE1 [deoxyribonuclease I]; DNM2 [dynamin 2]; DNM3
[dynamin 3]; DNMT1 [DNA (cytosine-5-)-methyltransferase 1]; DNMT3B [DNA
(cytosine-5-)-methyltransferase 3 beta]; DNTT [deoxynucleotidyltransferase,
terminal]; DOCK1 [dedicator of cytokinesis 1]; DOCK3 [dedicator of cytokinesis
3]; DOCK8 [dedicator of cytokinesis 8]; DOK1 [docking protein 1, 62kDa
(downstream of tyrosine kinase 1)]; DOLK [dolichol kinase]; DPAGT1 [dolichyl-
phosphate (UDP-N-acetylglucosamine) N-acetylglucosaminephosphotransferase
1 (GIcNAc-1-P transferase)]; DPEP1 [dipeptidase 1 (renal)]; DPH1 [DPH1
homolog (S. cerevisiae)]; DPM1 [dolichyl-phosphate mannosyltransferase
polypeptide 1, catalytic subunit]; DPP1 0 [dipeptidyl-peptidase 10]; DPP4
[dipeptidyl-peptidase 4]; DPYD [dihydropyrimidine dehydrogenase]; DRD2
[dopamine receptor D2]; DRD3 [dopamine receptor D3]; DRD4 [dopamine
receptor D4]; DSC2 [desmocollin 2]; DSG1 [desmoglein 1]; DSG2 [desmoglein
2]; DSG3 [desmoglein 3 (pemphigus vulgaris antigen)]; DSP [desmoplakin];
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DTNA [dystrobrevin, alpha]; DTYMK [deoxythymidylate kinase (thymidylate
kinase)]; DUOX1 [dual oxidase 1]; DUOX2 [dual oxidase 2]; DUSP1 [dual
specificity phosphatase 1]; DUSP14 [dual specificity phosphatase 14]; DUSP2
[dual specificity phosphatase 2]; DUSP5 [dual specificity phosphatase 5]; DUT
[deoxyuridine triphosphatase]; DVL1 [dishevelled, dsh homolog 1 (Drosophila)];
DYNC2H1 [dynein, cytoplasmic 2, heavy chain 1]; DYNLL1 [dynein, light chain,
LC8-type 1]; DYRK1A [dual-specificity tyrosine-(Y)-phosphorylation regulated
kinase 1A]; DYSF [dysferlin, limb girdle muscular dystrophy 2B (autosomal
recessive)]; E2F1 [E2F transcription factor 1]; EBF2 [early B-cell factor 2];
EBI3
[Epstein-Barr virus induced 3]; ECE1 [endothelin converting enzyme 1]; ECM1
[extracellular matrix protein 1]; EDA [ectodysplasin A]; EDAR [ectodysplasin A
receptor]; EDN1 [endothelin 1]; EDNRA [endothelin receptor type A]; EDNRB
[endothelin receptor type B]; EEF1A1 [eukaryotic translation elongation factor
1
alpha 1]; EEF1A2 [eukaryotic translation elongation factor 1 alpha 2]; EFEMP2
[EGF-containing fibulin-like extracellular matrix protein 2]; EFNA1 [ephrin-
A1];
EFNB2 [ephrin-B2]; EFS [embryonal Fyn-associated substrate]; EGF [epidermal
growth factor (beta-urogastrone)]; EGFR [epidermal growth factor receptor
(erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian)]; EGR1
[early
growth response 1]; EGR2 [early growth response 2]; EHF [ets homologous
factor]; EHMT2 [euchromatic histone-lysine N-methyltransferase 2]; EIF2AK2
[eukaryotic translation initiation factor 2-alpha kinase 2]; EIF2S1
[eukaryotic
translation initiation factor 2, subunit 1 alpha, 35kDa ]; EIF2S2 [eukaryotic
translation initiation factor 2, subunit 2 beta, 38kDa]; EIF3A [eukaryotic
translation initiation factor 3, subunit A]; EIF4B [eukaryotic translation
initiation
factor 4B]; EIF4E [eukaryotic translation initiation factor 4E]; EIF4EBP1
[eukaryotic translation initiation factor 4E binding protein 1]; EIF4G1
[eukaryotic
translation initiation factor 4 gamma, 1]; EIF6 [eukaryotic translation
initiation
factor 6]; ELAC2 [elaC homolog 2 (E. coli)]; ELANE [elastase, neutrophil
expressed]; ELAVL1 [ELAV (embryonic lethal, abnormal vision, Drosophila)-like
1 (Hu antigen R)]; ELF3 [E74-like factor 3 (ets domain transcription factor,
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epithelial-specific )]; ELF5 [E74-like factor 5 (ets domain transcription
factor)];
ELN [elastin]; ELOVL4 [elongation of very long chain fatty acids (FEN1/Elo2,
SUR4/Elo3, yeast)-like 4]; EMD [emerin]; EMILIN1 [elastin microfibril
interfacer
1]; EMR2 [egf-like module containing, mucin-like, hormone receptor-like 2];
EN2
[engrailed homeobox 2]; ENG [endoglin]; ENO1 [enolase 1, (alpha)]; ENO2
[enolase 2 (gamma, neuronal)]; ENO3 [enolase 3 (beta, muscle)]; ENPP2
[ectonucleotide pyrophosphatase/phosphodiesterase 2]; ENPP3 [ectonucleotide
pyrophosphatase/phosphodiesterase 3]; ENTPD1 [ectonucleoside triphosphate
diphosphohydrolase 1]; EP300 [E1A binding protein p300]; EPAS1 [endothelial
PAS domain protein 1]; EPB42 [erythrocyte membrane protein band 4.2];
EPCAM [epithelial cell adhesion molecule]; EPHA1 [EPH receptor Al ]; EPHA2
[EPH receptor A2]; EPHB2 [EPH receptor B2]; EPHB4 [EPH receptor B4];
EPHB6 [EPH receptor B6]; EPHX1 [epoxide hydrolase 1, microsomal
(xenobiotic)]; EPHX2 [epoxide hydrolase 2, cytoplasmic]; EPO [erythropoietin];
EPOR [erythropoietin receptor]; EPRS [glutamyl-prolyl-tRNA synthetase]; EPX
[eosinophil peroxidase]; ERBB2 [v-erb-b2 erythroblastic leukemia viral
oncogene
homolog 2, neuro/glioblastoma derived oncogene homolog (avian)]; ERBB2IP
[erbb2 interacting protein]; ERBB3 [v-erb-b2 erythroblastic leukemia viral
oncogene homolog 3 (avian)]; ERBB4 [v-erb-a erythroblastic leukemia viral
oncogene homolog 4 (avian)]; ERCC1 [excision repair cross-complementing
rodent repair deficiency, complementation group 1 (includes overlapping
antisense sequence)]; ERCC2 [excision repair cross-complementing rodent
repair deficiency, complementation group 2]; ERCC3 [excision repair cross-
complementing rodent repair deficiency, complementation group 3 (xeroderma
pigmentosum group B complementing)]; ERCC4 [excision repair cross-
complementing rodent repair deficiency, complementation group 4]; ERCC5
[excision repair cross-complementing rodent repair deficiency, complementation
group 5]; ERCC6 [excision repair cross-complementing rodent repair deficiency,
complementation group 6]; ERCC6L [excision repair cross-complementing rodent
repair deficiency, complementation group 6-like]; ERCC8 [excision repair cross-
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complementing rodent repair deficiency, complementation group 8]; ERO1 LB
[ERO1-like beta (S. cerevisiae)]; ERVK6 [endogenous retroviral sequence K, 6];
ERVWE1 [endogenous retroviral family W, env(C7), member 1]; ESD [esterase
D/formylglutathione hydrolase]; ESR1 [estrogen receptor 1]; ESR2 [estrogen
receptor 2 (ER beta)]; ESRRA [estrogen-related receptor alpha]; ESRRB
[estrogen-related receptor beta]; ETS1 [v-ets erythroblastosis virus E26
oncogene homolog 1 (avian)]; ETS2 [v-ets erythroblastosis virus E26 oncogene
homolog 2 (avian)]; EWSR1 [Ewing sarcoma breakpoint region 1]; EXO1
[exonuclease 1]; EYA1 [eyes absent homolog 1 (Drosophila)]; EZH2 [enhancer of
zeste homolog 2 (Drosophila)]; EZR [ezrin]; F10 [coagulation factor X]; F11
[coagulation factor XI]; F12 [coagulation factor XII (Hageman factor)]; F13A1
[coagulation factor XIII, Al polypeptide]; F1 3B [coagulation factor XIII, B
polypeptide]; F2 [coagulation factor II (thrombin)]; F2R [coagulation factor
II
(thrombin) receptor]; F2RL1 [coagulation factor II (thrombin) receptor-like
1];
F2RL3 [coagulation factor II (thrombin) receptor-like 3]; F3 [coagulation
factor III
(thromboplastin, tissue factor)]; F5 [coagulation factor V (proaccelerin,
labile
factor)]; F7 [coagulation factor VII (serum prothrombin conversion
accelerator)];
F8 [coagulation factor VIII, procoagulant component]; F9 [coagulation factor
IX];
FABP1 [fatty acid binding protein 1, liver]; FABP2 [fatty acid binding protein
2,
intestinal]; FABP4 [fatty acid binding protein 4, adipocyte]; FADD [Fas
(TNFRSF6)-associated via death domain]; FADS1 [fatty acid desaturase 1];
FADS2 [fatty acid desaturase 2]; FAF1 [Fas (TNFRSF6) associated factor 1];
FAH [fumarylacetoacetate hydrolase (fumarylacetoacetase)]; FAM189B [family
with sequence similarity 189, member B]; FAM92B [family with sequence
similarity 92, member B]; FANCA [Fanconi anemia, complementation group A];
FANCB [Fanconi anemia, complementation group B]; FANCC [Fanconi anemia,
complementation group C]; FANCD2 [Fanconi anemia, complementation group
D2]; FANCE [Fanconi anemia, complementation group E]; FANCF [Fanconi
anemia, complementation group F]; FANCG [Fanconi anemia, complementation
group G]; FANCI [Fanconi anemia, complementation group I]; FANCL [Fanconi
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anemia, complementation group L]; FANCM [Fanconi anemia, complementation
group M]; FANK1 [fibronectin type III and ankyrin repeat domains 1]; FAS [Fas
(TNF receptor superfamily, member 6)]; FASLG [Fas ligand (TNF superfamily,
member 6)]; FASN [fatty acid synthase]; FASTK [Fas-activated serine/threonine
kinase]; FBLN5 [fibulin 5]; FBN1 [fibrillin 1]; FBP1 [fructose-1,6-
bisphosphatase
1]; FBXO32 [F-box protein 32]; FBXW7 [F-box and WD repeat domain containing
7]; FCAR [Fc fragment of IgA, receptor for]; FCERIA [Fc fragment of IgE, high
affinity I, receptor for; alpha polypeptide]; FCER1 G [Fc fragment of IgE,
high
affinity I, receptor for; gamma polypeptide]; FCER2 [Fc fragment of IgE, low
affinity II, receptor for (CD23)]; FCGRIA [Fc fragment of IgG, high affinity
Ia,
receptor (CD64)]; FCGR2A [Fc fragment of IgG, low affinity Ila, receptor
(CD32)];
FCGR2B [Fc fragment of IgG, low affinity Ilb, receptor (CD32)]; FCGR3A [Fc
fragment of IgG, low affinity Ilia, receptor (CD16a)]; FCGR3B [Fc fragment of
IgG, low affinity Illb, receptor (CD16b)]; FCN2 [ficolin (collagen/fibrinogen
domain
containing lectin) 2 (hucolin)]; FCN3 [ficolin (collagen/fibrinogen domain
containing) 3 (Hakata antigen)]; FCRL3 [Fc receptor-like 3]; FCRL6 [Fc
receptor-
like 6]; FDFT1 [farnesyl-diphosphate farnesyltransferase 1]; FDPS [farnesyl
diphosphate synthase (farnesyl pyrophosphate synthetase,
dimethylallyltranstransferase, geranyltranstransferase)]; FDX1 [ferredoxin 1];
FEN1 [flap structure-specific endonuclease 1]; FERMTI [fermitin family homolog
1 (Drosophila)]; FERMT3 [fermitin family homolog 3 (Drosophila)]; FES [feline
sarcoma oncogene]; FFAR2 [free fatty acid receptor 2]; FGA [fibrinogen alpha
chain]; FGB [fibrinogen beta chain]; FGF1 [fibroblast growth factor 1
(acidic)];
FGF2 [fibroblast growth factor 2 (basic)]; FGF5 [fibroblast growth factor 5];
FGF7
[fibroblast growth factor 7 (keratinocyte growth factor)]; FGF8 [fibroblast
growth
factor 8 (androgen-induced)]; FGFBP2 [fibroblast growth factor binding protein
2];
FGFR1 [fibroblast growth factor receptor 1]; FGFR1 OP [FGFR1 oncogene
partner]; FGFR2 [fibroblast growth factor receptor 2]; FGFR3 [fibroblast
growth
factor receptor 3]; FGFR4 [fibroblast growth factor receptor 4]; FGG
[fibrinogen
gamma chain]; FGR [Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene
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homolog]; FHIT [fragile histidine triad gene]; FHL1 [four and a half LIM
domains
1]; FHL2 [four and a half LIM domains 2]; FIBP [fibroblast growth factor
(acidic)
intracellular binding protein]; FIGF [c-fos induced growth factor (vascular
endothelial growth factor D)]; FKBP1A [FK506 binding protein 1A, 12kDa];
FKBP4 [FK506 binding protein 4, 59kDa]; FKBP5 [FK506 binding protein 5];
FLCN [folliculin]; FLG [filaggrin]; FLG2 [filaggrin family member 2]; FLNA
[filamin
A, alpha]; FLNB [filamin B, beta]; FLT1 [fms-related tyrosine kinase 1
(vascular
endothelial growth factor/vascular permeability factor receptor)]; FLT3 [fms-
related tyrosine kinase 3]; FLT3LG [fms-related tyrosine kinase 3 ligand];
FLT4
[fms-related tyrosine kinase 4]; FMN1 [formin 1]; FMOD [fibromodulin]; FMR1
[fragile X mental retardation 1]; FN1 [fibronectin 1]; FOLH1 [folate hydrolase
(prostate-specific membrane antigen) 1]; FOLR1 [folate receptor 1 (adult)];
FOS
[FBJ murine osteosarcoma viral oncogene homolog]; FOXL2 [forkhead box L2];
FOXN1 [forkhead box N1]; FOXN2 [forkhead box N2]; FOXO3 [forkhead box
03]; FOXP3 [forkhead box P3]; FPGS [folylpolyglutamate synthase]; FPR1
[formyl peptide receptor 1]; FPR2 [formyl peptide receptor 2]; FRAS1 [Fraser
syndrome 1]; FREM2 [FRAS1 related extracellular matrix protein 2]; FSCN1
[fascin homolog 1, actin-bundling protein (Strongylocentrotus purpuratus)];
FSHB
[follicle stimulating hormone, beta polypeptide]; FSHR [follicle stimulating
hormone receptor]; FST [follistatin]; FTCD [formiminotransferase
cyclodeaminase]; FTH1 [ferritin, heavy polypeptide 1]; FTL [ferritin, light
polypeptide]; FURIN [furin (paired basic amino acid cleaving enzyme)]; FUT1
[fucosyltransferase 1 (galactoside 2-alpha-L-fucosyltransferase, H blood
group)];
FUT2 [fucosyltransferase 2 (secretor status included)]; FUT3
[fucosyltransferase
3 (galactoside 3(4)-L-fucosyltransferase, Lewis blood group)]; FUT4
[fucosyltransferase 4 (alpha (1,3) fucosyltransferase, myeloid-specific)];
FUT7
[fucosyltransferase 7 (alpha (1,3) fucosyltransferase)]; FUT8
[fucosyltransferase
8 (alpha (1,6) fucosyltransferase)]; FXN [frataxin]; FYN [FYN oncogene related
to
SRC, FGR, YES]; FZD4 [frizzled homolog 4 (Drosophila)]; G6PC3 [glucose 6
phosphatase, catalytic, 3]; G6PD [glucose-6-phosphate dehydrogenase]; GAA
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[glucosidase, alpha; acid]; GAB2 [GRB2-associated binding protein 2]; GABBR1
[gamma-aminobutyric acid (GABA) B receptor, 1]; GABRB3 [gamma-
aminobutyric acid (GABA) A receptor, beta 3]; GABRE [gamma-aminobutyric
acid (GABA) A receptor, epsilon]; GAD1 [glutamate decarboxylase 1 (brain,
67kDa)]; GAD2 [glutamate decarboxylase 2 (pancreatic islets and brain,
65kDa)];
GADD45A [growth arrest and DNA-damage-inducible, alpha]; GAL [galanin
prepropeptide]; GALC [galactosylceramidase]; GALK1 [galactokinase 1]; GALR1
[galanin receptor 1]; GAP43 [growth associated protein 43]; GAPDH
[glyceraldehyde-3-phosphate dehydrogenase]; GART
[phosphoribosylglycinamide formyltransferase, phosphoribosylglycinamide
synthetase, phosphoribosylaminoimidazole synthetase]; GAST [gastrin]; GATA1
[GATA binding protein 1 (globin transcription factor 1)]; GATA2 [GATA binding
protein 2]; GATA3 [GATA binding protein 3]; GATA4 [GATA binding protein 4];
GATA6 [GATA binding protein 6]; GBA [glucosidase, beta, acid]; GBA3
[glucosidase, beta, acid 3 (cytosolic)]; GBE1 [glucan (1 [4-alpha-), branching
enzyme 1]; GC [group-specific component (vitamin D binding protein)]; GCG
[glucagon]; GCH1 [GTP cyclohydrolase 1]; GCKR [glucokinase (hexokinase 4)
regulator]; GCLC [glutamate-cysteine ligase, catalytic subunit]; GCLM
[glutamate-cysteine ligase, modifier subunit]; GCNT2 [glucosaminyl (N-acetyl)
transferase 2, I-branching enzyme (I blood group)]; GDAP1 [ganglioside-induced
differentiation-associated protein 1]; GDF15 [growth differentiation factor
15];
GDNF [glial cell derived neurotrophic factor]; GFAP [glial fibrillary acidic
protein];
GGH [gamma-glutamyl hydrolase (conjugase, folylpolygammaglutamyl
hydrolase)]; GGT1 [gamma-glutamyltransferase 1]; GGT2 [gamma-
glutamyltransferase 2]; GH1 [growth hormone 1]; GHR [growth hormone
receptor]; GHRH [growth hormone releasing hormone]; GHRL [ghrelin/obestatin
prepropeptide]; GHSR [growth hormone secretagogue receptor]; GIF [gastric
intrinsic factor (vitamin B synthesis)]; GIP [gastric inhibitory polypeptide];
GJA1
[gap junction protein, alpha 1, 43kDa]; GJA4 [gap junction protein, alpha 4,
37kDa]; GJB2 [gap junction protein, beta 2, 26kDa]; GLA [galactosidase,
alpha];
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GLB1 [galactosidase, beta 1]; GLI2 [GLI family zinc finger 2]; GLMN [glomulin,
FKBP associated protein]; GLRX [glutaredoxin (thioltransferase)]; GLS
[glutaminase]; GLT25D1 [glycosyltransferase 25 domain containing 1]; GLUL
[glutamate-ammonia ligase (glutamine synthetase)]; GLYAT [glycine-N-
acyltransferase]; GM2A [GM2 ganglioside activator]; GMDS [GDP-mannose 4 [6-
dehydratase]; GNA12 [guanine nucleotide binding protein (G protein) alpha 12];
GNA13 [guanine nucleotide binding protein (G protein), alpha 13]; GNAI1
[guanine nucleotide binding protein (G protein), alpha inhibiting activity
polypeptide 1]; GNAO1 [guanine nucleotide binding protein (G protein), alpha
activating activity polypeptide 0]; GNAQ [guanine nucleotide binding protein
(G
protein), q polypeptide]; GNAS [GNAS complex locus]; GNAZ [guanine
nucleotide binding protein (G protein), alpha z polypeptide]; GNB1 [guanine
nucleotide binding protein (G protein), beta polypeptide 1]; GNB1L [guanine
nucleotide binding protein (G protein), beta polypeptide 1-like]; GNB2L1
[guanine
nucleotide binding protein (G protein), beta polypeptide 2-like 1]; GNB3
[guanine
nucleotide binding protein (G protein), beta polypeptide 3]; GNE [glucosamine
(UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase]; GNG2 [guanine
nucleotide binding protein (G protein), gamma 2]; GNLY [granulysin]; GNPAT
[glyceronephosphate 0-acyltransferase]; GNPDA2 [glucosamine-6-phosphate
deaminase 2]; GNRH1 [gonadotropin-releasing hormone 1 (luteinizing-releasing
hormone)]; GNRHR [gonadotropin-releasing hormone receptor]; GOLGA8B
[golgin A8 family, member B]; GOLGB1 [golgin B1]; GOT1 [glutamic-oxaloacetic
transaminase 1, soluble (aspartate aminotransferase 1)]; GOT2 [glutamic-
oxaloacetic transaminase 2, mitochondrial (aspartate aminotransferase 2)];
GP1 BA [glycoprotein lb (platelet), alpha polypeptide]; GP2 [glycoprotein 2
(zymogen granule membrane)]; GP6 [glycoprotein VI (platelet)]; GPBAR1 [G
protein-coupled bile acid receptor 1]; GPC5 [glypican 5]; GPI [glucose
phosphate
isomerase]; GPLD1 [glycosylphosphatidylinositol specific phospholipase D1];
GPN1 [GPN-loop GTPase 1]; GPR1 [G protein-coupled receptor 1]; GPR12 [G
protein-coupled receptor 12]; GPR123 [G protein-coupled receptor 123]; GPR143
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[G protein-coupled receptor 143]; GPR15 [G protein-coupled receptor 15];
GPR182 [G protein-coupled receptor 182]; GPR44 [G protein-coupled receptor
44]; GPR77 [G protein-coupled receptor 77]; GPRASP1 [G protein-coupled
receptor associated sorting protein 1 ]; GPRC6A [G protein-coupled receptor,
family C, group 6, member A]; GPT [glutamic-pyruvate transaminase (alanine
aminotransferase)]; GPX1 [glutathione peroxidase 1]; GPX2 [glutathione
peroxidase 2 (gastrointestinal)]; GPX3 [glutathione peroxidase 3 (plasma)];
GRAP2 [GRB2-related adaptor protein 2]; GRB2 [growth factor receptor-bound
protein 2]; GRIA2 [glutamate receptor, ionotropic, AMPA 2]; GRIN1 [glutamate
receptor, ionotropic, N-methyl D-aspartate 1]; GRIN2A [glutamate receptor,
ionotropic, N-methyl D-aspartate 2A]; GRIN2B [glutamate receptor, ionotropic,
N-
methyl D-aspartate 2B]; GRIN2C [glutamate receptor, ionotropic, N-methyl D-
aspartate 2C]; GRIN2D [glutamate receptor, ionotropic, N-methyl D-aspartate
2D]; GRIN3A [glutamate receptor, ionotropic, N-methyl-D-aspartate 3A]; GRIN3B
[glutamate receptor, ionotropic, N-methyl-D-aspartate 3B]; GRK5 [G protein-
coupled receptor kinase 5]; GRLF1 [glucocorticoid receptor DNA binding factor
1]; GRM1 [glutamate receptor, metabotropic 1]; GRP [gastrin-releasing
peptide];
GRPR [gastrin-releasing peptide receptor]; GSC [goosecoid homeobox]; GSC2
[goosecoid homeobox 2]; GSDMB [gasdermin B]; GSK3B [glycogen synthase
kinase 3 beta]; GSN [gelsolin]; GSR [glutathione reductase]; GSS [glutathione
synthetase]; GSTA1 [glutathione S-transferase alpha 1]; GSTA2 [glutathione S-
transferase alpha 2]; GSTM1 [glutathione S-transferase mu 1]; GSTM3
[glutathione S-transferase mu 3 (brain)]; GSTO2 [glutathione S-transferase
omega 2]; GSTP1 [glutathione S-transferase pi 1]; GSTT1 [glutathione S-
transferase theta 1]; GTF2A1 [general transcription factor I IA, 1, 19/37kDa];
GTF2F1 [general transcription factor IF, polypeptide 1, 74kDa]; GTF2H2
[general transcription factor IIH, polypeptide 2, 44kDa]; GTF2H4 [general
transcription factor IIH, polypeptide 4, 52kDa]; GTF2H5 [general transcription
factor IIH, polypeptide 5]; GTF2I [general transcription factor Ili]; GTF3A
[general
transcription factor IIIA]; GUCA2A [guanylate cyclase activator 2A
(guanylin)];
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GUCA2B [guanylate cyclase activator 2B (uroguanylin)]; GUCY2C [guanylate
cyclase 2C (heat stable enterotoxin receptor)]; GUK1 [guanylate kinase 1];
GULP1 [GULP, engulfment adaptor PTB domain containing 1]; GUSB
[glucuronidase, beta]; GYPA [glycophorin A (MNS blood group)]; GYPB
[glycophorin B (MNS blood group)]; GYPC [glycophorin C (Gerbich blood group)];
GYPE [glycophorin E (MNS blood group)]; GYS1 [glycogen synthase 1 (muscle)];
GZMA [granzyme A (granzyme 1, cytotoxic T-lymphocyte-associated serine
esterase 3)]; GZMB [granzyme B (granzyme 2, cytotoxic T-lymphocyte-
associated serine esterase 1)]; GZMK [granzyme K (granzyme 3; tryptase II)];
H1 FO [H1 histone family, member 0]; H2AFX [H2A histone family, member X];
HABP2 [hyaluronan binding protein 2]; HACL1 [2-hydroxyacyl-CoA lyase 1];
HADHA [hydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl-Coenzyme A
thiolase/enoyl-Coenzyme A hydratase (trifunctional protein), alpha subunit];
HAL
[histidine ammonia-lyase]; HAMP [hepcidin antimicrobial peptide]; HAPLNI
[hyaluronan and proteoglycan link protein 1]; HAVCR1 [hepatitis A virus
cellular
receptor 1 ]; HAVCR2 [hepatitis A virus cellular receptor 2]; HAX1 [HCLS1
associated protein X-1]; HBA1 [hemoglobin, alpha 1]; HBA2 [hemoglobin, alpha
2]; HBB [hemoglobin, beta]; HBE1 [hemoglobin, epsilon 1]; HBEGF [heparin-
binding EGF-like growth factor]; HBG2 [hemoglobin, gamma G]; HCCS
[holocytochrome c synthase (cytochrome c heme-lyase)]; HCK [hemopoietic cell
kinase]; HCRT [hypocretin (orexin) neuropeptide precursor]; HCRTR1
[hypocretin (orexin) receptor 1]; HCRTR2 [hypocretin (orexin) receptor 2];
HOST
[hematopoietic cell signal transducer]; HDAC1 [histone deacetylase 1]; HDAC2
[histone deacetylase 2]; HDAC6 [histone deacetylase 6]; HDAC9 [histone
deacetylase 9]; HDC [histidine decarboxylase]; HERC2 [hect domain and RLD 2];
HES1 [hairy and enhancer of split 1, (Drosophila)]; HES6 [hairy and enhancer
of
split 6 (Drosophila)]; HESX1 [HESX homeobox 1]; HEXA [hexosaminidase A
(alpha polypeptide)]; HEXB [hexosaminidase B (beta polypeptide)]; HFE
[hemochromatosis]; HGF [hepatocyte growth factor (hepapoietin A; scatter
factor)]; HGS [hepatocyte growth factor-regulated tyrosine kinase substrate];
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HGSNAT [heparan-alpha-glucosaminide N-acetyltransferase]; HIF1A [hypoxia
inducible factor 1, alpha subunit (basic helix-loop-helix transcription
factor)];
HINFP [histone H4 transcription factor]; HINT1 [histidine triad nucleotide
binding
protein 1]; HIPK2 [homeodomain interacting protein kinase 2]; HIRA [HIR
histone
cell cycle regulation defective homolog A (S. cerevisiae)]; HIST1 H1 B
[histone
cluster 1, H1b]; HIST1H3E [histone cluster 1, H3e]; HIST2H2AC [histone cluster
2, H2ac]; HIST2H3C [histone cluster 2, H3c]; HIST4H4 [histone cluster 4, H4];
HJURP [Holliday junction recognition protein]; HK2 [hexokinase 2]; HLA-A
[major
histocompatibility complex, class I, A]; HLA-B [major histocompatibility
complex,
class I, B]; HLA-C [major histocompatibility complex, class I, C]; HLA-DMA
[major
histocompatibility complex, class II, DM alpha]; HLA-DMB [major
histocompatibility complex, class II, DM beta]; HLA-DOA [major
histocompatibility
complex, class II, DO alpha]; HLA-DOB [major histocompatibility complex, class
II, DO beta]; HLA-DPA1 [major histocompatibility complex, class II, DP alpha
1];
HLA-DPB1 [major histocompatibility complex, class II, DP beta 1]; HLA-DQA1
[major histocompatibility complex, class II, DQ alpha 1]; HLA-DQA2 [major
histocompatibility complex, class II, DQ alpha 2]; HLA-DQB1 [major
histocompatibility complex, class II, DQ beta 1]; HLA-DRA [major
histocompatibility complex, class II, DR alpha]; HLA-DRB1 [major
histocompatibility complex, class II, DR beta 1]; HLA-DRB3 [major
histocompatibility complex, class II, DR beta 3]; HLA-DRB4 [major
histocompatibility complex, class II, DR beta 4]; HLA-DRB5 [major
histocompatibility complex, class II, DR beta 5]; HLA-E [major
histocompatibility
complex, class I, E]; HLA-F [major histocompatibility complex, class I, F];
HLA-G
[major histocompatibility complex, class I, G]; HLCS [holocarboxylase
synthetase
(biotin-(proprionyl-Coenzyme A-carboxylase (ATP-hydrolysing)) ligase)]; HLTF
[helicase-like transcription factor]; HLX [H2.0-like homeobox]; HMBS
[hydroxymethylbilane synthase]; HMGA1 [high mobility group AT-hook 1];
HMGB1 [high-mobility group box 1]; HMGCR [3-hydroxy-3-methylglutaryl-
Coenzyme A reductase]; HMOX1 [heme oxygenase (decycling) 1]; HMOX2
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[heme oxygenase (decycling) 2]; HNF1A [HNF1 homeobox A]; HNF4A
[hepatocyte nuclear factor 4, alpha]; HNMT [histamine N-m ethyltransferase];
HNRNPA1 [heterogeneous nuclear ribonucleoprotein Al]; HNRNPA2B1
[heterogeneous nuclear ribonucleoprotein A2/B1]; HNRNPH2 [heterogeneous
nuclear ribonucleoprotein H2 (H')]; HNRNPUL1 [heterogeneous nuclear
ribonucleoprotein U-like 1]; HOXA13 [homeobox Al 3]; HOXA4 [homeobox A4];
HOXA9 [homeobox A9]; HOXB4 [homeobox B4]; HP [haptoglobin]; HPGDS
[hematopoietic prostaglandin D synthase]; HPR [haptoglobin-related protein];
HPRT1 [hypoxanthine phosphoribosyltransferase 1]; HPS1 [Hermansky-Pudlak
syndrome 1]; HPS3 [Hermansky-Pudlak syndrome 3]; HPS4 [Hermansky-Pudlak
syndrome 4]; HPSE [heparanase]; HPX [hemopexin]; HRAS [v-Ha-ras Harvey rat
sarcoma viral oncogene homolog]; HRG [histidine-rich glycoprotein]; HRH1
[histamine receptor H1]; HRH2 [histamine receptor H2]; HRH3 [histamine
receptor H3]; HRH4 [histamine receptor H4]; HSD11 B1 [hydroxysteroid (11-beta)
dehydrogenase 1]; HSD11 B2 [hydroxysteroid (11-beta) dehydrogenase 2];
HSD17B1 [hydroxysteroid (17-beta) dehydrogenase 1 ]; HSD17B4
[hydroxysteroid (17-beta) dehydrogenase 4]; HSF1 [heat shock transcription
factor 1]; HSP90AA1 [heat shock protein 90kDa alpha (cytosolic), class A
member 1]; HSP90AB1 [heat shock protein 90kDa alpha (cytosolic), class B
member 1]; HSP90B1 [heat shock protein 90kDa beta (Grp94), member 1];
HSPA14 [heat shock 70kDa protein 14]; HSPA1 A [heat shock 70kDa protein 1 A];
HSPA1 B [heat shock 70kDa protein 1 B]; HSPA2 [heat shock 70kDa protein 2];
HSPA4 [heat shock 70kDa protein 4]; HSPA5 [heat shock 70kDa protein 5
(glucose-regulated protein, 78kDa)]; HSPA8 [heat shock 70kDa protein 8];
HSPB1 [heat shock 27kDa protein 1]; HSPB2 [heat shock 27kDa protein 2];
HSPD1 [heat shock 60kDa protein 1 (chaperonin)]; HSPE1 [heat shock 1 OkDa
protein 1 (chaperonin 10)]; HSPG2 [heparan sulfate proteoglycan 2]; HTN3
[histatin 3]; HTR1A [5-hydroxytryptamine (serotonin) receptor 1A]; HTR2A [5-
hydroxytryptamine (serotonin) receptor 2A]; HTR3A [5-hydroxytryptamine
(serotonin) receptor 3A]; HTRA1 [HtrA serine peptidase 1]; HTT [huntingtin];
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HUS1 [HUS1 checkpoint homolog (S. pombe)]; HUWE1 [HECT, UBA and WWE
domain containing 1]; HYAL1 [hyaluronoglucosaminidase 1]; HYLS1
[hydrolethalus syndrome 1]; IAPP [islet amyloid polypeptide]; IBSP [integrin-
binding sialoprotein]; ICAM1 [intercellular adhesion molecule 1]; ICAM2
[intercellular adhesion molecule 2]; ICAM3 [intercellular adhesion molecule
3];
ICAM4 [intercellular adhesion molecule 4 (Landsteiner-Wiener blood group)];
ICOS [inducible T-cell co-stimulator]; ICOSLG [inducible T-cell co-stimulator
ligand]; ID1 [inhibitor of DNA binding 1, dominant negative helix-loop-helix
protein]; ID2 [inhibitor of DNA binding 2, dominant negative helix-loop-helix
protein]; IDO1 [indoleamine 2 [3-dioxygenase 1]; IDS [iduronate 2-sulfatase];
IDUA [iduronidase, alpha-L-]; IF127 [interferon, alpha-inducible protein 27];
IF130
[interferon, gamma-inducible protein 30]; IFITM1 [interferon induced
transmembrane protein 1 (9-27)]; IFNA1 [interferon, alpha 1]; IFNA2
[interferon,
alpha 2]; IFNAR1 [interferon (alpha, beta and omega) receptor 1]; IFNAR2
[interferon (alpha, beta and omega) receptor 2]; IFNB1 [interferon, beta 1,
fibroblast]; IFNG [interferon, gamma]; IFNGR1 [interferon gamma receptor 1];
IFNGR2 [interferon gamma receptor 2 (interferon gamma transducer 1)]; IGF1
[insulin-like growth factor 1 (somatomedin C)]; IGF1 R [insulin-like growth
factor 1
receptor]; IGF2 [insulin-like growth factor 2 (somatomedin A)]; IGF2R [insulin-
like
growth factor 2 receptor]; IGFBP1 [insulin-like growth factor binding protein
1];
IGFBP2 [insulin-like growth factor binding protein 2, 36kDa]; IGFBP3 [insulin-
like
growth factor binding protein 3]; IGFBP4 [insulin-like growth factor binding
protein
4]; IGFBP5 [insulin-like growth factor binding protein 5]; IGHA1
[immunoglobulin
heavy constant alpha 1]; IGHE [immunoglobulin heavy constant epsilon]; IGHG1
[immunoglobulin heavy constant gamma 1 (G1 m marker)]; IGHG3
[immunoglobulin heavy constant gamma 3 (G3m marker)]; IGHG4
[immunoglobulin heavy constant gamma 4 (G4m marker)]; IGHM
[immunoglobulin heavy constant mu]; IGHMBP2 [immunoglobulin mu binding
protein 2]; IGKC [immunoglobulin kappa constant]; IGKV2D-29 [immunoglobulin
kappa variable 2D-29]; IGLL1 [immunoglobulin lambda-like polypeptide 1]; IGSF1
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[immunoglobulin superfamily, member 1]; IKBKAP [inhibitor of kappa light
polypeptide gene enhancer in B-cells, kinase complex-associated protein];
IKBKB [inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase
beta]; IKBKE [inhibitor of kappa light polypeptide gene enhancer in B-cells,
kinase epsilon]; IKBKG [inhibitor of kappa light polypeptide gene enhancer in
B-
cells, kinase gamma]; IKZF1 [IKAROS family zinc finger 1 (Ikaros)]; IKZF2
[IKAROS family zinc finger 2 (Helios)]; U0 [interleukin 10]; IL10RA
[interleukin
receptor, alpha]; IL1ORB [interleukin 10 receptor, beta]; IL11 [interleukin
11];
IL12A [interleukin 12A (natural killer cell stimulatory factor 1, cytotoxic
lymphocyte maturation factor 1, p35)]; IL12B [interleukin 12B (natural killer
cell
stimulatory factor 2, cytotoxic lymphocyte maturation factor 2, p40) ];
IL12RB1
[interleukin 12 receptor, beta 1]; IL12RB2 [interleukin 12 receptor, beta 2];
IL13
[interleukin 13]; IL13RA1 [interleukin 13 receptor, alpha 1]; IL13RA2
[interleukin
13 receptor, alpha 2]; IL15 [interleukin 15]; IL15RA [interleukin 15 receptor,
alpha]; U6 [interleukin 16 (lymphocyte chemoattractant factor)]; IL17A
[interleukin 17A]; IL17F [interleukin 17F]; IL17RA [interleukin 17 receptor
A];
IL17RB [interleukin 17 receptor B]; IL17RC [interleukin 17 receptor C]; U8
[interleukin 18 (interferon-gamma-inducing factor)]; IL18BP [interleukin 18
binding protein]; IL18R1 [interleukin 18 receptor 1]; IL18RAP [interleukin 18
receptor accessory protein]; IL19 [interleukin 19]; ILIA [interleukin 1,
alpha]; IL1 B
[interleukin 1, beta]; IL1 F9 [interleukin 1 family, member 9]; IL1 R1
[interleukin 1
receptor, type I]; IL1 RAP [interleukin 1 receptor accessory protein]; IL1 RL1
[interleukin 1 receptor-like 1 ]; IL1 RN [interleukin 1 receptor antagonist];
IL2
[interleukin 2]; IL20 [interleukin 20]; IL21 [interleukin 21]; IL21R
[interleukin 21
receptor]; IL22 [interleukin 22]; IL23A [interleukin 23, alpha subunit p19];
IL23R
[interleukin 23 receptor]; IL24 [interleukin 24]; IL25 [interleukin 25]; IL26
[interleukin 26]; IL27 [interleukin 27]; IL27RA [interleukin 27 receptor,
alpha]; IL29
[interleukin 29 (interferon, lambda 1)]; IL2RA [interleukin 2 receptor,
alpha];
IL2RB [interleukin 2 receptor, beta]; IL2RG [interleukin 2 receptor, gamma
(severe combined immunodeficiency)]; IL3 [interleukin 3 (colony-stimulating
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factor, multiple)]; IL31 [interleukin 31]; IL32 [interleukin 32]; IL33
[interleukin 33];
IL3RA [interleukin 3 receptor, alpha (low affinity)]; IL4 [interleukin 4];
IL4R
[interleukin 4 receptor]; IL5 [interleukin 5 (colony-stimulating factor,
eosinophil)];
IL5RA [interleukin 5 receptor, alpha]; IL6 [interleukin 6 (interferon, beta
2)]; IL6R
[interleukin 6 receptor]; IL6ST [interleukin 6 signal transducer (gp130,
oncostatin
M receptor)]; IL7 [interleukin 7]; IL7R [interleukin 7 receptor]; IL8
[interleukin 8];
IL9 [interleukin 9]; IL9R [interleukin 9 receptor]; ILK [integrin-linked
kinase]; IMP5
[intramembrane protease 5]; INCENP [inner centromere protein antigens
135/155kDa]; ING1 [inhibitor of growth family, member 1]; INHA [inhibin,
alpha];
INHBA [inhibin, beta A]; INPP4A [inositol polyphosphate-4-phosphatase, type I,
107kDa]; INPP5D [inositol polyphosphate-5-phosphatase, 145kDa]; INPP5E
[inositol polyphosphate-5-phosphatase, 72 kDa]; INPPL1 [inositol polyphosphate
phosphatase-like 1]; INS [insulin]; INSL3 [insulin-like 3 (Leydig cell)]; INSR
[insulin receptor]; IP013 [importin 13]; IP07 [importin 7]; IQGAP1 [IQ motif
containing GTPase activating protein 1]; IRAK1 [interleukin-1 receptor-
associated
kinase 1]; IRAK3 [interleukin-1 receptor-associated kinase 3]; IRAK4
[interleukin-
1 receptor-associated kinase 4]; IRF1 [interferon regulatory factor 1]; IRF2
[interferon regulatory factor 2]; IRF3 [interferon regulatory factor 3]; IRF4
[interferon regulatory factor 4]; IRF5 [interferon regulatory factor 5]; IRF7
[interferon regulatory factor 7]; IRF8 [interferon regulatory factor 8]; IRGM
[immunity-related GTPase family, M]; IRS1 [insulin receptor substrate 1]; IRS2
[insulin receptor substrate 2]; IRS4 [insulin receptor substrate 4]; ISG15
[ISG15
ubiquitin-like modifier]; ITCH [itchy E3 ubiquitin protein ligase homolog
(mouse)];
ITFG1 [integrin alpha FG-GAP repeat containing 1]; ITGA1 [integrin, alpha 1];
ITGA2 [integrin, alpha 2 (CD49B, alpha 2 subunit of VLA-2 receptor)]; ITGA2B
[integrin, alpha 2b (platelet glycoprotein IIb of IIb/Ills complex, antigen
CD41)];
ITGA3 [integrin, alpha 3 (antigen CD49C, alpha 3 subunit of VLA-3 receptor)];
ITGA4 [integrin, alpha 4 (antigen CD49D, alpha 4 subunit of VLA-4 receptor)];
ITGA5 [integrin, alpha 5 (fibronectin receptor, alpha polypeptide)]; ITGA6
[integrin, alpha 6]; ITGA8 [integrin, alpha 8]; ITGAE [integrin, alpha E
(antigen
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CD103, human mucosal lymphocyte antigen 1; alpha polypeptide)]; ITGAL
[integrin, alpha L (antigen CD11A (p180), lymphocyte function-associated
antigen 1; alpha polypeptide)]; ITGAM [integrin, alpha M (complement
component 3 receptor 3 subunit)]; ITGAV [integrin, alpha V (vitronectin
receptor,
alpha polypeptide, antigen CD51)]; ITGAX [integrin, alpha X (complement
component 3 receptor 4 subunit)]; ITGB1 [integrin, beta 1 (fibronectin
receptor,
beta polypeptide, antigen CD29 includes MDF2, MSK12)]; ITGB2 [integrin, beta
2 (complement component 3 receptor 3 and 4 subunit)]; ITGB3 [integrin, beta 3
(platelet glycoprotein Ilia, antigen CD61)]; ITGB3BP [integrin beta 3 binding
protein (beta3-endonexin)]; ITGB4 [integrin, beta 4]; ITGB6 [integrin, beta
6];
ITGB7 [integrin, beta 7]; ITIH4 [inter-alpha (globulin) inhibitor H4 (plasma
Kallikrein-sensitive glycoprotein)]; ITK [IL2-inducible T-cell kinase]; ITLN1
[intelectin 1 (galactofuranose binding)]; ITLN2 [intelectin 2]; ITPA [inosine
triphosphatase (nucleoside triphosphate pyrophosphatase)]; ITPR1 [inositol
1,4,5-triphosphate receptor, type 1]; ITPR3 [inositol 1,4,5-triphosphate
receptor,
type 3]; IVD [isovaleryl Coenzyme A dehydrogenase]; IVL [involucrin]; IVNS1ABP
[influenza virus NS1A binding protein]; JAG1 [jagged 1 (Alagille syndrome)];
JAK1 [Janus kinase 1]; JAK2 [Janus kinase 2]; JAK3 [Janus kinase 3]; JAKMIP1
[Janus kinase and microtubule interacting protein 1]; JMJD6 [jumonji domain
containing 6]; JPH4 [junctophilin 4]; JRKL [jerky homolog-like (mouse)]; JUN
[Jun
oncogene]; JUND [Jun D proto-oncogene]; JUP [junction plakoglobin]; KARS
[lysyl-tRNA synthetase]; KAT5 [K(lysine) acetyltransferase 5]; KCNA2
[potassium
voltage-gated channel, shaker-related subfamily, member 2]; KCNA5 [potassium
voltage-gated channel, shaker-related subfamily, member 5]; KCND1 [potassium
voltage-gated channel, Shal-related subfamily, member 1]; KCNH2 [potassium
voltage-gated channel, subfamily H (eag-related), member 2]; KCNIP4 [Kv
channel interacting protein 4]; KCNMA1 [potassium large conductance calcium-
activated channel, subfamily M, alpha member 1]; KCNMB1 [potassium large
conductance calcium-activated channel, subfamily M, beta member 1]; KCNN3
[potassium intermediate/small conductance calcium-activated channel, subfamily
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N, member 3]; KCNS3 [potassium voltage-gated channel, delayed-rectifier,
subfamily S, member 3]; KDR [kinase insert domain receptor (a type III
receptor
tyrosine kinase)]; KHDRBS1 [KH domain containing, RNA binding, signal
transduction associated 1]; KHDRBS3 [KH domain containing, RNA binding,
signal transduction associated 3]; KIAA0101 [KIAA0101]; KIP 6B [kinesin family
member 16B]; KIF20B [kinesin family member 20B]; KIF21 B [kinesin family
member 21 B]; KIF22 [kinesin family member 22]; KIF2B [kinesin family member
2B]; KIF2C [kinesin family member 2C]; KIR2DL1 [killer cell immunoglobulin-
like
receptor, two domains, long cytoplasmic tail, 1]; KIR2DL2 [killer cell
immunoglobulin-like receptor, two domains, long cytoplasmic tail, 2]; KIR2DL3
[killer cell immunoglobulin-like receptor, two domains, long cytoplasmic tail,
3];
KIR2DL5A [killer cell immunoglobulin-like receptor, two domains, long
cytoplasmic tail, 5A]; KIR2DS1 [killer cell immunoglobulin-like receptor, two
domains, short cytoplasmic tail, 1]; KIR2DS2 [killer cell immunoglobulin-like
receptor, two domains, short cytoplasmic tail, 2]; KIR2DS5 [killer cell
immunoglobulin-like receptor, two domains, short cytoplasmic tail, 5]; KIR3DL1
[killer cell immunoglobulin-like receptor, three domains, long cytoplasmic
tail, 1];
KIR3DS1 [killer cell immunoglobulin-like receptor, three domains, short
cytoplasmic tail, 1]; KISS1 [KiSS-1 metastasis-suppressor]; KISS1R [KISS1
receptor]; KIT [v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene
homolog];
KITLG [KIT ligand]; KLF2 [Kruppel-like factor 2 (lung)]; KLF4 [Kruppel-like
factor
4 (gut)]; KLK1 [kallikrein 1]; KLK11 [kallikrein-related peptidase 11]; KLK3
[kallikrein-related peptidase 3]; KLKB1 [kallikrein B, plasma (Fletcher
factor) 1 ];
KLRB1 [killer cell lectin-like receptor subfamily B, member 1]; KLRC1 [killer
cell
lectin-like receptor subfamily C, member 1]; KLRD1 [killer cell lectin-like
receptor
subfamily D, member 1]; KLRK1 [killer cell lectin-like receptor subfamily K,
member 1]; KNG1 [kininogen 1]; KPNA1 [karyopherin alpha 1 (importin alpha 5)];
KPNA2 [karyopherin alpha 2 (RAG cohort 1, importin alpha 1)]; KPNB1
[karyopherin (importin) beta 1]; KRAS [v-Ki-ras2 Kirsten rat sarcoma viral
oncogene homolog]; KRT1 [keratin 1 ]; KRT10 [keratin 10]; KRT13 [keratin 13];
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KRT14 [keratin 14]; KRT16 [keratin 16]; KRT18 [keratin 18]; KRT19 [keratin
19];
KRT20 [keratin 20]; KRT5 [keratin 5]; KRT7 [keratin 7]; KRT8 [keratin 8]; KRT9
[keratin 9]; KRTAP19-3 [keratin associated protein 19-3]; KRTAP2-1,keratin
associated protein 2-1]; L1 CAM [L1 cell adhesion molecule]; LACTB [lactamase,
beta]; LAG3 [lymphocyte-activation gene 3]; LALBA [lactalbumin, alpha-]; LAMA1
[laminin, alpha 1]; LAMA2 [laminin, alpha 2]; LAMA3 [laminin, alpha 3]; LAMA4
[laminin, alpha 4]; LAMB1 [laminin, beta 1]; LAMB2 [laminin, beta 2 (laminin
S)];
LAMB3 [laminin, beta 3]; LAMC1 [laminin, gamma 1 (formerly LAMB2)]; LAMC2
[laminin, gamma 2]; LAMP1 [lysosomal-associated membrane protein 1]; LAMP2
[lysosomal-associated membrane protein 2]; LAMP3 [lysosomal-associated
membrane protein 3]; LAP3 [leucine aminopeptidase 3]; LAPTM4A [lysosomal
protein transmembrane 4 alpha]; LAT [linker for activation of T cells]; LBP
[Iipopolysaccharid e binding protein]; LBR [lamin B receptor]; LBXCOR1
[Lbxcor1
homolog (mouse)]; LCAT [lecithin-cholesterol acyltransferase]; LCK [lymphocyte-
specific protein tyrosine kinase]; LCN1 [lipocalin 1 (tear prealbumin)]; LCN2
[lipocalin 2]; LCP1 [lymphocyte cytosolic protein 1 (L-plastin)]; LCT
[lactase];
LDLR [low density lipoprotein receptor]; LDLRAP1 [low density lipoprotein
receptor adaptor protein 1]; LECT2 [leukocyte cell-derived chemotaxin 2];
LELP1
[late cornified envelope-like proline-rich 1]; LEMD3 [LEM domain containing
3];
LEP [leptin]; LEPR [leptin receptor]; LGALS1 [lectin, galactoside-binding,
soluble,
1]; LGALS3 [lectin, galactoside-binding, soluble, 3]; LGALS3BP [lectin,
galactoside-binding, soluble, 3 binding protein]; LGALS4 [lectin, galactoside-
binding, soluble, 4]; LGALS9 [lectin, galactoside-binding, soluble, 9];
LGALS9B
[lectin, galactoside-binding, soluble, 9B]; LGR4 [leucine-rich repeat-
containing G
protein-coupled receptor 4]; LHCGR [luteinizing hormone/choriogonadotropin
receptor]; LIF [leukemia inhibitory factor (cholinergic differentiation
factor)]; LIFR
[leukemia inhibitory factor receptor alpha]; LIG1 [ligase I, DNA, ATP-
dependent];
LIG3 [ligase III, DNA, ATP-dependent]; LIG4 [ligase IV, DNA, ATP-dependent];
LILRA3 [leukocyte immunoglobulin-like receptor, subfamily A (without TM
domain), member 3]; LILRB4 [leukocyte immunoglobulin-like receptor, subfamily
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B (with TM and ITIM domains), member 4]; LIMS1 [LIM and senescent cell
antigen-like domains 1]; LIPA [lipase A, lysosomal acid, cholesterol
esterase];
LIPC [lipase, hepatic]; LIPE [lipase, hormone-sensitive]; LIPG [lipase,
endothelial]; LMAN1 [lectin, mannose-binding, 1]; LMLN [leishmanolysin-like
(metallopeptidase M8 family)]; LMNA [lamin A/C]; LMNB1 [lamin B1]; LMNB2
[lamin B2]; LOC646627 [phospholipase inhibitor]; LOX [lysyl oxidase]; LOXHD1
[lipoxygenase homology domains 1]; LOXL1 [lysyl oxidase-like 1]; LPA
[lipoprotein, Lp(a)]; LPAR3 [lysophosphatidic acid receptor 3]; LPCAT2
[lysophosphatidylcholine acyltransferase 2]; LPL [lipoprotein lipase]; LPO
[lactoperoxidase]; LPP [LIM domain containing preferred translocation partner
in
lipoma]; LRBA [LPS-responsive vesicle trafficking, beach and anchor
containing];
LRP1 [low density lipoprotein receptor-related protein 1]; LRP6 [low density
lipoprotein receptor-related protein 6]; LRPAP1 [low density lipoprotein
receptor-
related protein associated protein 1]; LRRC32 [leucine rich repeat containing
32];
LRRC37B [leucine rich repeat containing 37B]; LRRC8A [leucine rich repeat
containing 8 family, member A]; LRRK2 [leucine-rich repeat kinase 2]; LRTOMT
[leucine rich transmembrane and 0-methyltransferase domain containing]; LSM1
[LSM1 homolog, U6 small nuclear RNA associated (S. cerevisiae)]; LSM2 [LSM2
homolog, U6 small nuclear RNA associated (S. cerevisiae)]; LSP1 [lymphocyte-
specific protein 1 ]; LTA [lymphotoxin alpha (TNF superfamily, member 1)];
LTA4H [leukotriene A4 hydrolase]; LTB [lymphotoxin beta (TNF superfamily,
member 3)]; LTB4R [leukotriene B4 receptor]; LTB4R2 [leukotriene B4 receptor
2]; LTBR [lymphotoxin beta receptor (TNFR superfamily, member 3)]; LTC4S
[leukotriene C4 synthase]; LTF [lactotransferrin]; LY86 [lymphocyte antigen
86];
LY9 [lymphocyte antigen 9]; LYN [v-yes-1 Yamaguchi sarcoma viral related
oncogene homolog]; LYRM4 [LYR motif containing 4]; LYST [lysosomal
trafficking regulator]; LYZ [lysozyme (renal amyloidosis)]; LYZL6 [lysozyme-
like
6]; LZTR1 [leucine-zipper-like transcription regulator 1]; M6PR [mannose-6-
phosphate receptor (cation dependent)]; MADCAMI [mucosal vascular addressin
cell adhesion molecule 1 ]; MAF [v-maf musculoaponeurotic fibrosarcoma
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oncogene homolog (avian)]; MAG [myelin associated glycoprotein]; MAN2A1
[mannosidase, alpha, class 2A, member 1]; MAN2B1 [mannosidase, alpha, class
2B, member 1]; MANBA [mannosidase, beta A, lysosomal]; MANF
[mesencephalic astrocyte-derived neurotrophic factor]; MAOB [monoamine
oxidase B]; MAP2 [microtubule-associated protein 2]; MAP2K1 [mitogen-
activated protein kinase kinase 1]; MAP2K2 [mitogen-activated protein kinase
kinase 2]; MAP2K3 [mitogen-activated protein kinase kinase 3]; MAP2K4
[mitogen-activated protein kinase kinase 4]; MAP3K1 [mitogen-activated protein
kinase kinase kinase 1 ]; MAP3K11 [mitogen-activated protein kinase kinase
kinase 11]; MAP3K14 [mitogen-activated protein kinase kinase kinase 14];
MAP3K5 [mitogen-activated protein kinase kinase kinase 5]; MAP3K7 [mitogen-
activated protein kinase kinase kinase 7]; MAP3K9 [mitogen-activated protein
kinase kinase kinase 9]; MAPK1 [mitogen-activated protein kinase 1]; MAPK10
[mitogen-activated protein kinase 10]; MAPK1 1 [mitogen-activated protein
kinase
11]; MAPK12 [mitogen-activated protein kinase 12]; MAPK13 [mitogen-activated
protein kinase 13]; MAPK14 [mitogen-activated protein kinase 14]; MAPK3
[mitogen-activated protein kinase 3]; MAPK8 [mitogen-activated protein kinase
8]; MAPK9 [mitogen-activated protein kinase 9]; MAPKAP1 [mitogen-activated
protein kinase associated protein 1]; MAPKAPK2 [mitogen-activated protein
kinase-activated protein kinase 2]; MAPKAPK5 [mitogen-activated protein
kinase-activated protein kinase 5]; MAPT [microtubule-associated protein tau];
MARCKS [myristoylated alanine-rich protein kinase C substrate]; MASP2
[mannan-binding lectin serine peptidase 2]; MATN1 [matrilin 1, cartilage
matrix
protein]; MAVS [mitochondrial antiviral signaling protein]; MB [myoglobin];
MBD2
[methyl-CpG binding domain protein 2]; MBL2 [mannose-binding lectin (protein
C) 2, soluble (opsonic defect)]; MBP [myelin basic protein]; MBTPS2 [membrane-
bound transcription factor peptidase, site 2]; MC2R [melanocortin 2 receptor
(adrenocorticotropic hormone)]; MC3R [melanocortin 3 receptor]; MC4R
[melanocortin 4 receptor]; MCCC2 [m ethylcrotonoyl-Coenzyme A carboxylase 2
(beta)]; MCHR1 [melanin-concentrating hormone receptor 1]; MCL1 [myeloid cell
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leukemia sequence 1 (BCL2-related)]; MCM2 [minichromosome maintenance
complex component 2]; MCM4 [minichromosome maintenance complex
component 4]; MCOLN1 [mucolipin 1]; MCPH1 [microcephalin 1]; MDC1
[mediator of DNA-damage checkpoint 1]; MDH2 [malate dehydrogenase 2, NAD
(mitochondrial)]; MDM2 [Mdm2 p53 binding protein homolog (mouse)]; ME2
[malic enzyme 2, NAD(+)-dependent, mitochondrial]; MECOM [MDS1 and EVI1
complex locus]; MED1 [mediator complex subunit 1]; MED12 [mediator complex
subunit 12]; MED1 5 [mediator complex subunit 15]; MED28 [mediator complex
subunit 28]; MEFV [Mediterranean fever]; MEN1 [multiple endocrine neoplasia
I];
MEPE [matrix extracellular phosphoglycoprotein]; MERTK [c-mer proto-
oncogene tyrosine kinase]; MESP2 [mesoderm posterior 2 homolog (mouse)];
MET [met proto-oncogene (hepatocyte growth factor receptor)]; MGAM [maltase-
glucoamylase (alpha-glucosidase)]; MGAT1 [mannosyl (alpha-1,3-)-glycoprotein
beta- 1,2-N-acetylglucosaminyltransferase]; MGAT2 [mannosyl (alpha-1,6+
glycoprotein beta-1,2-N-acetylglucosaminyltransferase]; MGLL [monoglyceride
lipase]; MGMT [O-6-methylguanine-DNA methyltransferase]; MGST2
[microsomal glutathione S-transferase 2]; MICA [MHC class I polypeptide-
related
sequence A]; MICB [MHC class I polypeptide-related sequence B]; MIF
[macrophage migration inhibitory factor (glycosylation-inhibiting factor)];
MK167
[antigen identified by monoclonal antibody Ki-67]; MKS1 [Meckel syndrome, type
1]; MLH1 [mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli)]; MLL
[myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila)];
MLLT4 [myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog,
Drosophila); translocated to, 4]; MLN [motilin]; MLXIPL [MLX interacting
protein-
like]; MMAA [methylmalonic aciduria (cobalamin deficiency) cb1A type]; MMAB
[methylmalonic aciduria (cobalamin deficiency) cb1B type]; MMACHC
[methylmalonic aciduria (cobalamin deficiency) cblC type, with
homocystinuria];
MME [membrane metallo-endopeptidase]; MMP1 [matrix metallopeptidase 1
(interstitial collagenase)]; MMP10 [matrix metallopeptidase 10 (stromelysin
2)];
MMP12 [matrix metallopeptidase 12 (macrophage elastase)]; MMP13 [matrix
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metallopeptidase 13 (collagenase 3)]; MMP14 [matrix metallopeptidase 14
(membrane-inserted)]; MMP15 [matrix metallopeptidase 15 (membrane-
inserted)]; MMP17 [matrix metallopeptidase 17 (membrane-inserted)]; MMP2
[matrix metallopeptidase 2 (gelatinase A, 72kDa gelatinase, 72kDa type IV
collagenase)]; MMP20 [matrix metallopeptidase 20]; MMP21 [matrix
metallopeptidase 21]; MMP28 [matrix metallopeptidase 28]; MMP3 [matrix
metallopeptidase 3 (stromelysin 1, progelatinase)]; MMP7 [matrix
metallopeptidase 7 (matrilysin, uterine)]; MMP8 [matrix metallopeptidase 8
(neutrophil collagenase)]; MMP9 [matrix metallopeptidase 9 (gelatinase B,
92kDa
gelatinase, 92kDa type IV collagenase)]; MMRN1 [multimerin 1]; MNAT1
[menage a trois homolog 1, cyclin H assembly factor (Xenopus laevis)]; MOG
[myelin oligodendrocyte glycoprotein]; MOGS [mannosyl-oligosaccharide
glucosidase]; MPG [N-methylpurine-DNA glycosylase]; MPL [myeloproliferative
leukemia virus oncogene]; MPO [myeloperoxidase]; MPZ [myelin protein zero];
MR1 [major histocompatibility complex, class I-related]; MRC1 [mannose
receptor, C type 1]; MRC2 [mannose receptor, C type 2]; MRE1 1A [MRE1 1
meiotic recombination 11 homolog A (S. cerevisiae)]; MRGPRX1 [MAS-related
GPR, member Xl]; MRPL28 [mitochondrial ribosomal protein L28]; MRPL40
[mitochondrial ribosomal protein L40]; MRPS16 [mitochondrial ribosomal protein
S16]; MRPS22 [mitochondrial ribosomal protein S22]; MS4A1 [membrane-
spanning 4-domains, subfamily A, member 1]; MS4A2 [membrane-spanning 4-
domains, subfamily A, member 2 (Fc fragment of IgE, high affinity I, receptor
for;
beta polypeptide)]; MS4A3 [membrane-spanning 4-domains, subfamily A,
member 3 (hematopoietic cell-specific)]; MSH2 [mutS homolog 2, colon cancer,
nonpolyposis type 1 (E. coli)]; MSH5 [mutS homolog 5 (E. coli)]; MSH6 [mutS
homolog 6 (E. coli)]; MSLN [mesothelin]; MSN [moesin]; MSR1 [macrophage
scavenger receptor 1]; MST1 [macrophage stimulating 1 (hepatocyte growth
factor-like)]; MST1 R [macrophage stimulating 1 receptor (c-met-related
tyrosine
kinase)]; MSTN [myostatin]; MSX2 [msh homeobox 2]; MT2A [metallothionein
2A]; MTCH2 [mitochondrial carrier homolog 2 (C. elegans)]; MT-C02
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[mitochondrially encoded cytochrome c oxidase II]; MTCP1 [mature T-cell
proliferation 1]; MT-CYB [mitochondrially encoded cytochrome b]; MTHFD1
[m ethyl enetetrahydrofolate dehydrogenase (NADP+ dependent) 1,
methenyltetrahydrofolate cyclohydrolase, formyltetrahydrofolate synthetase];
MTHFR [5 [10-methyl enetetrahydrofolate reductase (NADPH) ]; MTMR14
[myotubularin related protein 14]; MTMR2 [myotubularin related protein 2]; MT-
ND1 [mitochondrially encoded NADH dehydrogenase 1]; MT-ND2
[mitochondrially encoded NADH dehydrogenase 2]; MTOR [mechanistic target of
rapamycin (serine/threonine kinase)]; MTR [5-methyltetrahydrofolate-
homocysteine methyltransferase]; MTRR [5-methyltetrahydrofolate-homocysteine
methyltransferase reductase]; MTTP [microsomal triglyceride transfer protein];
MTX1 [metaxin 1]; MUC1 [mucin 1, cell surface associated]; MUC12 [mucin 12,
cell surface associated]; MUC16 [mucin 16, cell surface associated]; MUC19
[mucin 19, oligomeric]; MUC2 [mucin 2, oligomeric mucus/gel-forming]; MUC3A
[mucin 3A, cell surface associated]; MUC3B [mucin 3B, cell surface
associated];
MUC4 [mucin 4, cell surface associated]; MUC5AC [mucin SAC, oligomeric
mucus/gel-forming]; MUCSB [mucin 5B, oligomeric mucus/gel-forming]; MUC6
[mucin 6, oligomeric mucus/gel-forming]; MUC7 [mucin 7, secreted]; MUS81
[MUS81 endonuclease homolog (S. cerevisiae)]; MUSK [muscle, skeletal,
receptor tyrosine kinase]; MUT [methylmalonyl Coenzyme A mutase]; MVK
[mevalonate kinase]; MVP [major vault protein]; MX1 [myxovirus (influenza
virus)
resistance 1, interferon-inducible protein p78 (mouse)]; MYB [v-myb
myeloblastosis viral oncogene homolog (avian)]; MYBPH [myosin binding protein
H]; MYC [v-myc myelocytomatosis viral oncogene homolog (avian)]; MYCN [v-
myc myelocytomatosis viral related oncogene, neuroblastoma derived (avian)];
MYD88 [myeloid differentiation primary response gene (88)]; MYH1 [myosin,
heavy chain 1, skeletal muscle, adult]; MYH10 [myosin, heavy chain 10, non-
muscle]; MYH11 [myosin, heavy chain 11, smooth muscle]; MYH14 [myosin,
heavy chain 14, non-muscle]; MYH2 [myosin, heavy chain 2, skeletal muscle,
adult]; MYH3 [myosin, heavy chain 3, skeletal muscle, embryonic]; MYH6
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[myosin, heavy chain 6, cardiac muscle, alpha]; MYH7 [myosin, heavy chain 7,
cardiac muscle, beta]; MYH8 [myosin, heavy chain 8, skeletal muscle,
perinatal];
MYH9 [myosin, heavy chain 9, non-muscle]; MYL2 [myosin, light chain 2,
regulatory, cardiac, slow]; MYL3 [myosin, light chain 3, alkali; ventricular,
skeletal, slow]; MYL7 [myosin, light chain 7, regulatory]; MYL9 [myosin, light
chain 9, regulatory]; MYLK [myosin light chain kinase ]; MYO15A [myosin XVA];
MYO1A [myosin IA]; MYO1 F [myosin IF]; MYO3A [myosin IIIA]; MYO5A [myosin
VA (heavy chain 12, myoxin)]; MYO6 [myosin VI]; MYO7A [myosin VIIA]; MYO9B
[myosin IXB]; MYOC [myocilin, trabecular meshwork inducible glucocorticoid
response]; MYOD1 [myogenic differentiation 1]; MYOM2 [myomesin (M-protein)
2, 165kDa]; MYST1 [MYST histone acetyltransferase 1]; MYST2 [MYST histone
acetyltransferase 2]; MYST3 [MYST histone acetyltransferase (monocytic
leukemia) 3]; MYST4 [MYST histone acetyltransferase (monocytic leukemia) 4];
NAGA [N-acetylgalactosaminidase, alpha-]; NAGLU [N-acetylglucosaminidase,
alpha-]; NAMPT [nicotinamide phosphoribosyltransferase]; NANOG [Nanog
homeobox]; NANOS1 [nanos homolog 1 (Drosophila)]; NAPA [N-ethylmaleimide-
sensitive factor attachment protein, alpha]; NAT1 [N-acetyltransferase 1
(arylamine N-acetyltransferase)]; NAT2 [N-acetyltransferase 2 (arylamine N-
acetyltransferase)]; NAT9 [N-acetyltransferase 9 (GCN5-related, putative)];
NBEA [neurobeachin]; NBN [nibrin]; NCAM1 [neural cell adhesion molecule 1];
NCF1 [neutrophil cytosolic factor 1]; NCF2 [neutrophil cytosolic factor 2];
NCF4
[neutrophil cytosolic factor 4, 40kDa]; NCK1 [NCK adaptor protein 1]; NCL
[nucleolin]; NCOA1 [nuclear receptor coactivator 1]; NCOA2 [nuclear receptor
coactivator 2]; NCOR1 [nuclear receptor co-repressor 1 ]; NCR3 [natural
cytotoxicity triggering receptor 3]; NDUFA13 [NADH dehydrogenase (ubiquinone)
1 alpha subcomplex, 13]; NDUFAB1 [NADH dehydrogenase (ubiquinone) 1,
alpha/beta subcomplex, 1, 8kDa]; NDUFAF2 [NADH dehydrogenase
(ubiquinone) 1 alpha subcomplex, assembly factor 2]; NEDD4 [neural precursor
cell expressed, developmentally down-regulated 4]; NEFL [neurofilament, light
polypeptide]; NEFM [neurofilament, medium polypeptide]; NEGR1 [neuronal
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growth regulator 1]; NEK6 [NIMA (never in mitosis gene a)-related kinase 6];
NELF [nasal embryonic LHRH factor]; NELL1 [NEL-like 1 (chicken)]; NES
[nestin]; NEW [sialidase 1 (lysosomal sialidase)]; NEUROD1 [neurogenic
differentiation 1]; NF1 [neurofibromin 1]; NF2 [neurofibromin 2 (merlin)];
NFAT5
[nuclear factor of activated T-cells 5, tonicity-responsive]; NFATC1 [nuclear
factor
of activated T-cells, cytoplasmic, calcineurin-dependent 1]; NFATC2 [nuclear
factor of activated T-cells, cytoplasmic, calcineurin-dependent 2]; NFATC4
[nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 4];
NFE2L2 [nuclear factor (erythroid-derived 2)-like 2]; NFKB1 [nuclear factor of
kappa light polypeptide gene enhancer in B-cells 1 ]; NFKB2 [nuclear factor of
kappa light polypeptide gene enhancer in B-cells 2 (p49/p100)]; NFKBIA
[nuclear
factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha];
NFKBIB [nuclear factor of kappa light polypeptide gene enhancer in B-cells
inhibitor, beta]; NFKBIL1 [nuclear factor of kappa light polypeptide gene
enhancer in B-cells inhibitor-like 1]; NFU1 [NFU1 iron-sulfur cluster scaffold
homolog (S. cerevisiae)]; NGF [nerve growth factor (beta polypeptide)]; NGFR
[nerve growth factor receptor (TNFR superfamily, member 16)]; NHEJ1
[nonhomologous end-joining factor 1]; NID1 [nidogen 1]; NKAP [NFkB activating
protein]; NKX2-1,NK2 homeobox 1]; NKX2-3 [NK2 transcription factor related,
locus 3 (Drosophila)]; NLRP3 [NLR family, pyrin domain containing 3]; NMB
[neuromedin B]; NME1 [non-metastatic cells 1, protein (NM23A) expressed in];
NME2 [non-metastatic cells 2, protein (NM23B) expressed in]; NMU [neuromedin
U]; NNAT [neuronatin]; NOD1 [nucleotide-binding oligomerization domain
containing 1]; NOD2 [nucleotide-binding oligomerization domain containing 2];
NONO [non-POU domain containing, octamer-binding]; NOS1 [nitric oxide
synthase 1 (neuronal)]; NOS2 [nitric oxide synthase 2, inducible]; NOS3
[nitric
oxide synthase 3 (endothelial cell)]; NOTCH1 [Notch homolog 1, translocation-
associated (Drosophila)]; NOTCH2 [Notch homolog 2 (Drosophila)]; NOTCH3
[Notch homolog 3 (Drosophila)]; NOTCH4 [Notch homolog 4 (Drosophila)]; NOX1
[NADPH oxidase 1]; NOX3 [NADPH oxidase 3]; NOX4 [NADPH oxidase 4];
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NOX5 [NADPH oxidase, EF-hand calcium binding domain 5]; NPAT [nuclear
protein, ataxia-telangiectasia locus]; NPC1 [Niemann-Pick disease, type Cl];
NPC1 L1 [NPC1 (Niemann-Pick disease, type C1, gene)-like 1]; NPC2 [Niemann-
Pick disease, type C2]; NPHP1 [nephronophthisis 1 (juvenile)]; NPHS1
[nephrosis 1, congenital, Finnish type (nephrin)]; NPHS2 [nephrosis 2,
idiopathic,
steroid-resistant (podocin)]; NPLOC4 [nuclear protein localization 4 homolog
(S.
cerevisiae)]; NPM1 [nucleophosmin (nucleolar phosphoprotein B23, numatrin)];
NPPA [natriuretic peptide precursor A]; NPPB [natriuretic peptide precursor
B];
NPPC [natriuretic peptide precursor C]; NPR1 [natriuretic peptide receptor
A/guanylate cyclase A (atrionatriuretic peptide receptor A)]; NPR3
[natriuretic
peptide receptor C/guanylate cyclase C (atrionatriuretic peptide receptor C)];
NPS [neuropeptide S]; NPSR1 [neuropeptide S receptor 1]; NPY [neuropeptide
Y]; NPY2R [neuropeptide Y receptor Y2]; NQO1 [NAD(P)H dehydrogenase,
quinone 1]; NROB1 [nuclear receptor subfamily 0, group B, member 1]; NR1 H2
[nuclear receptor subfamily 1, group H, member 2]; NR1 H3 [nuclear receptor
subfamily 1, group H, member 3]; NR1 H4 [nuclear receptor subfamily 1, group
H,
member 4]; NR112 [nuclear receptor subfamily 1, group I, member 2]; NR113
[nuclear receptor subfamily 1, group I, member 3]; NR2F2 [nuclear receptor
subfamily 2, group F, member 2]; NR3C1 [nuclear receptor subfamily 3, group C,
member 1 (glucocorticoid receptor)]; NR3C2 [nuclear receptor subfamily 3,
group
C, member 2]; NR4A1 [nuclear receptor subfamily 4, group A, member 1];
NR4A3 [nuclear receptor subfamily 4, group A, member 3]; NR5A1 [nuclear
receptor subfamily 5, group A, member 1]; NRF1 [nuclear respiratory factor 1];
NRG1 [neuregulin 1]; NRIP1 [nuclear receptor interacting protein 1]; NRIP2
[nuclear receptor interacting protein 2]; NRP1 [neuropilin 1]; NSD1 [nuclear
receptor binding SET domain protein 1]; NSDHL [NAD(P) dependent steroid
dehydrogenase-like]; NSF [N-ethylmaleimide-sensitive factor]; NT5E [5'-
nucleotidase, ecto (CD73)]; NTAN1 [N-terminal asparagine amidase]; NTF3
[neurotrophin 3]; NTF4 [neurotrophin 4]; NTN1 [netrin 1]; NTRK1 [neurotrophic
tyrosine kinase, receptor, type 1]; NTRK2 [neurotrophic tyrosine kinase,
receptor,
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type 2]; NTRK3 [neurotrophic tyrosine kinase, receptor, type 3]; NTS
[neurotensin]; NUCB2 [nucleobindin 2]; NUDT1 [nudix (nucleoside diphosphate
linked moiety X)-type motif 1]; NUDT2 [nudix (nucleoside diphosphate linked
moiety X)-type motif 2]; NUDT6 [nudix (nucleoside diphosphate linked moiety X)-
type motif 6]; NUFIP2 [nuclear fragile X mental retardation protein
interacting
protein 2]; NUP98 [nucleoporin 98kDa]; NXF1 [nuclear RNA export factor 1];
OCA2 [oculocutaneous albinism II]; OCLN [occludin]; ODC1 [ornithine
decarboxylase 1]; OFD1 [oral-facial-digital syndrome 1]; OGDH [oxoglutarate
(alpha-ketoglutarate) dehydrogenase (lipoamide)]; OGG1 [8-oxoguanine DNA
glycosylase]; OGT [0-linked N-acetylglucosamine (GIcNAc) transferase (UDP-N-
acetylglucosamine:polypeptide-N-acetylglucosaminyl transferase)]; OLR1
[oxidized low density lipoprotein (lectin-like) receptor 1]; OMP [olfactory
marker
protein]; ONECUT2 [one cut homeobox 2]; OPN3 [opsin 3]; OPRK1 [opioid
receptor, kappa 1]; OPRM1 [opioid receptor, mu 1]; OPTN [optineurin]; OR2B11
[olfactory receptor, family 2, subfamily B, member 11]; ORMDL3 [ORM1-like 3
(S. cerevisiae)]; OSBP [oxysterol binding protein]; OSGIN2 [oxidative stress
induced growth inhibitor family member 2]; OSM [oncostatin M]; OTC [ornithine
carbamoyltransferase]; OTOP2 [otopetrin 2]; OTOP3 [otopetrin 3]; OTUD1 [OTU
domain containing 1]; OXA1 L [oxidase (cytochrome c) assembly 1-like]; OXER1
[oxoeicosanoid (OXE) receptor 1]; OXT [oxytocin, prepropeptide]; OXTR
[oxytocin receptor]; P2RX7 [purinergic receptor P2X, ligand-gated ion channel,
7]; P2RY1 [purinergic receptor P2Y, G-protein coupled, 1]; P2RY12 [purinergic
receptor P2Y, G-protein coupled, 12]; P2RY14 [purinergic receptor P2Y, G-
protein coupled, 14]; P2RY2 [purinergic receptor P2Y, G-protein coupled, 2];
P4HA2 [prolyl 4-hydroxylase, alpha polypeptide II]; P4HB [prolyl 4-
hydroxylase,
beta polypeptide]; P4HTM [prolyl 4-hydroxylase, transmembrane (endoplasmic
reticulum)]; PABPC1 [poly(A) binding protein, cytoplasmic 1]; PACSIN3 [protein
kinase C and casein kinase substrate in neurons 3]; PAEP [progestagen-
associated endometrial protein]; PAFAH1B1 [platelet-activating factor
acetylhydrolase 1 b, regulatory subunit 1 (45kDa)]; PAH [phenylalanine
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hydroxylase]; PAK1 [p21 protein (Cdc42/Rac)-activated kinase 1]; PAK2 [p21
protein (Cdc42/Rac)-activated kinase 2]; PAK3 [p21 protein (Cdc42/Rac)-
activated kinase 3]; PAM [peptidylglycine alpha-amidating monooxygenase];
PAPPA [pregnancy-associated plasma protein A, pappalysin 1]; PARG [poly
(ADP-ribose) glycohydrolase]; PARK2 [Parkinson disease (autosomal recessive,
juvenile) 2, parkin]; PARP1 [poly (ADP-ribose) polymerase 1]; PAWR [PRKC,
apoptosis, WT1, regulator]; PAX2 [paired box 2]; PAX3 [paired box 3]; PAX5
[paired box 5]; PAX6 [paired box 6]; PAXIP1 [PAX interacting (with
transcription-
activation domain) protein 1]; PC [pyruvate carboxylase]; PCCA [propionyl
Coenzyme A carboxylase, alpha polypeptide]; PCCB [propionyl Coenzyme A
carboxylase, beta polypeptide]; PCDH1 [protocadherin 1]; PCK1
[phosphoenolpyruvate carboxykinase 1 (soluble)]; PCM1 [pericentriolar material
1]; PCNA [proliferating cell nuclear antigen ]; PCNT [pericentrin]; PCSK1
[proprotein convertase subtilisin/kexin type 1]; PCSK6 [proprotein convertase
subtilisin/kexin type 6]; PCSK7 [proprotein convertase subtilisin/kexin type
7];
PCYT1A [phosphate cytidylyltransferase 1, choline, alpha]; PCYT2 [phosphate
cytidylyltransferase 2, ethanolamine]; PDCD1 [programmed cell death 1];
PDCD1 LG2 [programmed cell death 1 ligand 2]; PDCD6 [programmed cell death
6]; PDE3B [phosphodiesterase 3B, cGMP-inhibited]; PDE4A [phosphodiesterase
4A, cAMP-specific (phosphodiesterase E2 dunce homolog, Drosophila)]; PDE4B
[phosphodiesterase 4B, cAMP-specific (phosphodiesterase E4 dunce homolog,
Drosophila)]; PDE4D [phosphodiesterase 4D, cAMP-specific (phosphodiesterase
E3 dunce homolog, Drosophila)]; PDE7A [phosphodiesterase 7A]; PDGFA
[platelet-derived growth factor alpha polypeptide]; PDGFB [platelet-derived
growth factor beta polypeptide (simian sarcoma viral (v-sis) oncogene
homolog)];
PDGFRA [platelet-derived growth factor receptor, alpha polypeptide]; PDGFRB
[platelet-derived growth factor receptor, beta polypeptide]; PDIA2 [protein
disulfide isomerase family A, member 2]; PDIA3 [protein disulfide isomerase
family A, member 3]; PDK1 [pyruvate dehydrogenase kinase, isozyme 1 ];
PDLIM1 [PDZ and LIM domain 1]; PDLIM5 [PDZ and LIM domain 5]; PDLIM7
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[PDZ and LIM domain 7 (enigma)]; PDP1 [pyruvate dehyrogenase phosphatase
catalytic subunit 1]; PDX1 [pancreatic and duodenal homeobox 1]; PDXK
[pyridoxal (pyridoxine, vitamin B6) kinase]; PDYN [prodynorphin]; PECAM1
[platelet/endothelial cell adhesion molecule]; PEMT [phosphatidylethanolamine
N-methyltransferase]; PENK [proenkephalin]; PEPD [peptidase D]; PER1 [period
homolog 1 (Drosophila)]; PEX1 [peroxisomal biogenesis factor 1]; PEX10
[peroxisomal biogenesis factor 10]; PEX12 [peroxisomal biogenesis factor 12];
PEX13 [peroxisomal biogenesis factor 13]; PEX14 [peroxisomal biogenesis
factor 14]; PEX16 [peroxisomal biogenesis factor 16]; PEX19 [peroxisomal
biogenesis factor 19]; PEX2 [peroxisomal biogenesis factor 2]; PEX26
[peroxisomal biogenesis factor 26]; PEX3 [peroxisomal biogenesis factor 3];
PEX5 [peroxisomal biogenesis factor 5]; PEX6 [peroxisomal biogenesis factor
6];
PEX7 [peroxisomal biogenesis factor 7]; PF4 [platelet factor 4]; PFAS
[phosphoribosylformylglycinamidine synthase]; PFDN4 [prefoldin subunit 4];
PFN1 [profilin 1]; PGC [progastricsin (pepsinogen C)]; PGD [phosphogluconate
dehydrogenase]; PGF [placental growth factor]; PGK1 [phosphoglycerate kinase
1]; PGM1 [phosphoglucomutase 1]; PGR [progesterone receptor]; PHB
[prohibitin]; PHEX [phosphate regulating endopeptidase homolog, X-linked];
PHF11 [PHD finger protein 11]; PHOX2B [paired-like homeobox 2b]; PHTF1
[putative homeodomain transcription factor 1]; PHYH [phytanoyl-CoA 2-
hydroxylase]; PHYHIP [phytanoyl-CoA 2-hydroxylase interacting protein]; P13
[peptidase inhibitor 3, skin-derived]; PIGA [phosphatidylinositol glycan
anchor
biosynthesis, class A]; PIGR [polymeric immunoglobulin receptor]; PIK3C2A
[phosphoinositide-3-kinase, class 2, alpha polypeptide]; PIK3C2B
[phosphoinositide-3-kinase, class 2, beta polypeptide]; PIK3C2G
[phosphoinositide-3-kinase, class 2, gamma polypeptide]; PIK3C3
[phosphoinositide-3-kinase, class 3]; PIK3CA [phosphoinositide-3-kinase,
catalytic, alpha polypeptide]; PIK3CB [phosphoinositide-3-kinase, catalytic,
beta
polypeptide]; PIK3CD [phosphoinositide-3-kinase, catalytic, delta
polypeptide];
PIK3CG [phosphoinositide-3-kinase, catalytic, gamma polypeptide]; PIK3R1
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[phosphoinositide-3-kinase, regulatory subunit 1 (alpha)]; PIK3R2
[phosphoinositide-3-kinase, regulatory subunit 2 (beta)]; PIK3R3
[phosphoinositide-3-kinase, regulatory subunit 3 (gamma)]; PIKFYVE
[phosphoinositide kinase, FYVE finger containing]; PIN1 [peptidylprolyl
cis/trans
isomerase, NIMA-interacting 1]; PINK1 [PTEN induced putative kinase 1]; PIP
[prolactin-induced protein]; PIP5KL1 [phosphatidylinositol-4-phosphate 5-
kinase-
like 1]; PITPNM1 [phosphatidylinositol transfer protein, membrane-associated
1];
PITRM1 [pitrilysin metallopeptidase 1]; PITX2 [paired-like homeodomain 2];
PKD2 [polycystic kidney disease 2 (autosomal dominant)]; PKLR [pyruvate
kinase, liver and RBC]; PKM2 [pyruvate kinase, muscle]; PKN1 [protein kinase
Ni]; PL-5283 [PL-5283 protein]; PLA2G1B [phospholipase A2, group IB
(pancreas)]; PLA2G2A [phospholipase A2, group IIA (platelets, synovial
fluid)];
PLA2G2D [phospholipase A2, group IID]; PLA2G4A [phospholipase A2, group
IVA (cytosolic, calcium-dependent)]; PLA2G6 [phospholipase A2, group VI
(cytosolic, calcium-independent)]; PLA2G7 [phospholipase A2, group VII
(platelet-activating factor acetylhydrolase, plasma)]; PLA2R1 [phospholipase
A2
receptor 1, 180kDa]; PLAT [plasminogen activator, tissue]; PLAU [plasminogen
activator, urokinase]; PLAUR [plasminogen activator, urokinase receptor];
PLCB1
[phospholipase C, beta 1 (phosphoinositide-specific)]; PLCB2 [phospholipase C,
beta 2]; PLCB4 [phospholipase C, beta 4]; PLCD1 [phospholipase C, delta 1];
PLCG1 [phospholipase C, gamma 1]; PLCG2 [phospholipase C, gamma 2
(phosphatidylinositol-specific)]; PLD1 [phospholipase D1, phosphatidylcholine-
specific]; PLEC [plectin]; PLEK [pleckstrin]; PLG [plasminogen]; PLIN1
[perilipin
1]; PLK1 [polo-like kinase 1 (Drosophila)]; PLK2 [polo-like kinase 2
(Drosophila)];
PLK3 [polo-like kinase 3 (Drosophila)]; PLP1 [proteolipid protein 1]; PLTP
[phospholipid transfer protein]; PMAIP1 [phorbol-1 2-myristate-1 3-acetate-
induced protein 1]; PMCH [pro-melanin-concentrating hormone]; PML
[promyelocytic leukemia]; PMP22 [peripheral myelin protein 22]; PMS2 [PMS2
postmeiotic segregation increased 2 (S. cerevisiae)]; PNLIP [pancreatic
lipase];
PNMA3 [paraneoplastic antigen MA3]; PNMT [phenylethanolamine N-
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methyltransferase]; PNP [purine nucleoside phosphorylase]; POLB [polymerase
(DNA directed), beta]; POLD3 [polymerase (DNA-directed), delta 3, accessory
subunit]; POLD4 [polymerase (DNA-directed), delta 4]; POLH [polymerase (DNA
directed), eta]; POLL [polymerase (DNA directed), lambda]; POLR2A
[polymerase (RNA) II (DNA directed) polypeptide A, 220kDa]; POLR2B
[polymerase (RNA) II (DNA directed) polypeptide B, 140kDa]; POLR2C
[polymerase (RNA) II (DNA directed) polypeptide C, 33kDa]; POLR2D
[polymerase (RNA) II (DNA directed) polypeptide D]; POLR2E [polymerase
(RNA) II (DNA directed) polypeptide E, 25kDa]; POLR2F [polymerase (RNA) II
(DNA directed) polypeptide F]; POLR2G [polymerase (RNA) II (DNA directed)
polypeptide G]; POLR2H [polymerase (RNA) II (DNA directed) polypeptide H];
POLR2I [polymerase (RNA) II (DNA directed) polypeptide I, 14.5kDa]; POLR2J
[polymerase (RNA) II (DNA directed) polypeptide J, 13.3kDa]; POLR2K
[polymerase (RNA) II (DNA directed) polypeptide K, 7.OkDa]; POLR2L
[polymerase (RNA) II (DNA directed) polypeptide L, 7.6kDa]; POMC
[proopiomelanocortin]; POMT1 [protein-O-mannosyltransferase 1]; PON1
[paraoxonase 1]; PON2 [paraoxonase 2]; PON3 [paraoxonase 3]; POSTN
[periostin, osteoblast specific factor]; POT1 [POT1 protection of telomeres 1
homolog (S. pombe)]; POU2AF1 [POU class 2 associating factor 1]; POU2F1
[POU class 2 homeobox 1]; POU2F2 [POU class 2 homeobox 2]; POU5F1 [POU
class 5 homeobox 1]; PPA1 [pyrophosphatase (inorganic) 1]; PPARA
[peroxisome proliferator-activated receptor alpha]; PPARD [peroxisome
proliferator-activated receptor delta]; PPARG [peroxisome proliferator-
activated
receptor gamma]; PPARGC1A [peroxisome proliferator-activated receptor
gamma, coactivator 1 alpha]; PPAT [phosphoribosyl pyrophosphate
amidotransferase]; PPBP [pro-platelet basic protein (chemokine (C-X-C motif)
ligand 7)]; PPFIA1 [protein tyrosine phosphatase, receptor type, f polypeptide
(PTPRF), interacting protein (liprin), alpha 1]; PPIA [peptidylprolyl
isomerase A
(cyclophilin A)]; PPIB [peptidylprolyl isomerase B (cyclophilin B)]; PPIG
[peptidylprolyl isomerase G (cyclophilin G)]; PPOX [protoporphyrinogen
oxidase];
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PPP1 CB [protein phosphatase 1, catalytic subunit, beta isozyme]; PPP1 R1 2A
[protein phosphatase 1, regulatory (inhibitor) subunit 12A]; PPP1R2 [protein
phosphatase 1, regulatory (inhibitor) subunit 2]; PPP2R1 B [protein
phosphatase
2, regulatory subunit A, beta]; PPP2R2B [protein phosphatase 2, regulatory
subunit B, beta]; PPP2R4 [protein phosphatase 2A activator, regulatory subunit
4]; PPP6C [protein phosphatase 6, catalytic subunit]; PPT1 [palmitoyl-protein
thioesterase 1]; PPY [pancreatic polypeptide]; PRDM1 [PR domain containing 1,
with ZNF domain]; PRDM2 [PR domain containing 2, with ZNF domain]; PRDX2
[peroxiredoxin 2]; PRDX3 [peroxiredoxin 3]; PRDX5 [peroxiredoxin 5]; PRF1
[perforin 1 (pore forming protein)]; PRG2 [proteoglycan 2, bone marrow
(natural
killer cell activator, eosinophil granule major basic protein)]; PRG4
[proteoglycan
4]; PRIM1 [primase, DNA, polypeptide 1 (49kDa)]; PRKAA1 [protein kinase,
AMP-activated, alpha 1 catalytic subunit]; PRKAA2 [protein kinase, AMP-
activated, alpha 2 catalytic subunit]; PRKAB1 [protein kinase, AMP-activated,
beta 1 non-catalytic subunit]; PRKACA [protein kinase, cAMP-dependent,
catalytic, alpha]; PRKACB [protein kinase, cAMP-dependent, catalytic, beta];
PRKACG [protein kinase, cAMP-dependent, catalytic, gamma]; PRKAR1A
[protein kinase, cAMP-dependent, regulatory, type I, alpha (tissue specific
extinguisher 1)]; PRKAR2A [protein kinase, cAMP-dependent, regulatory, type
II,
alpha]; PRKAR2B [protein kinase, cAMP-dependent, regulatory, type II, beta];
PRKCA [protein kinase C, alpha]; PRKCB [protein kinase C, beta]; PRKCD
[protein kinase C, delta]; PRKCE [protein kinase C, epsilon]; PRKCG [protein
kinase C, gamma]; PRKCH [protein kinase C, eta]; PRKCI [protein kinase C,
iota]; PRKCQ [protein kinase C, theta]; PRKCZ [protein kinase C, zeta]; PRKD1
[protein kinase D1]; PRKD3 [protein kinase D3]; PRKDC [protein kinase, DNA-
activated, catalytic polypeptide; also known as DNAPK]; PRKG1 [protein kinase,
cGMP-dependent, type I]; PRKRIR [protein-kinase, interferon-inducible double
stranded RNA dependent inhibitor, repressor of (P58 repressor)]; PRL
[prolactin];
PRLR [prolactin receptor]; PRNP [prion protein]; PROC [protein C (inactivator
of
coagulation factors Va and Villa)]; PRODH [proline dehydrogenase (oxidase) 1];
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PROK1 [prokineticin 1]; PROK2 [prokineticin 2]; PROM1 [prominin 1]; PROS1
[protein S (alpha)]; PRPH [peripherin]; PRSS1 [protease, serine, 1 (trypsin
1)];
PRSS2 [protease, serine, 2 (trypsin 2)]; PRSS21 [protease, serine, 21
(testisin)];
PRSS3 [protease, serine, 3]; PRTN3 [proteinase 3]; PSAP [prosaposin]; PSEN1
[presenilin 1]; PSEN2 [presenilin 2 (Alzheimer disease 4)]; PSMA1 [proteasome
(prosome, macropain) subunit, alpha type, 1]; PSMA2 [proteasome (prosome,
macropain) subunit, alpha type, 2]; PSMA3 [proteasome (prosome, macropain)
subunit, alpha type, 3]; PSMA5 [proteasome (prosome, macropain) subunit,
alpha type, 5]; PSMA6 [proteasome (prosome, macropain) subunit, alpha type,
6]; PSMA7 [proteasome (prosome, macropain) subunit, alpha type, 7]; PSMB10
[proteasome (prosome, macropain) subunit, beta type, 10]; PSMB2 [proteasome
(prosome, macropain) subunit, beta type, 2]; PSMB4 [proteasome (prosome,
macropain) subunit, beta type, 4]; PSMB5 [proteasome (prosome, macropain)
subunit, beta type, 5]; PSMB6 [proteasome (prosome, macropain) subunit, beta
type, 6]; PSMB8 [proteasome (prosome, macropain) subunit, beta type, 8 (large
multifunctional peptidase 7)]; PSMB9 [proteasome (prosome, macropain)
subunit, beta type, 9 (large multifunctional peptidase 2)]; PSMC3 [proteasome
(prosome, macropain) 26S subunit, ATPase, 3]; PSMC4 [proteasome (prosome,
macropain) 26S subunit, ATPase, 4]; PSMC6 [proteasome (prosome, macropain)
26S subunit, ATPase, 6]; PSMD4 [proteasome (prosome, macropain) 26S
subunit, non-ATPase, 4]; PSMD9 [proteasome (prosome, macropain) 26S
subunit, non-ATPase, 9]; PSME1 [proteasome (prosome, macropain) activator
subunit 1 (PA28 alpha)]; PSME3 [proteasome (prosome, macropain) activator
subunit 3 (PA28 gamma; Ki)]; PSMG2 [proteasome (prosome, macropain)
assembly chaperone 2]; PSORS1C1 [psoriasis susceptibility 1 candidate 1];
PSTPIP1 [proline-serine-threonine phosphatase interacting protein 1]; PTAFR
[platelet-activating factor receptor]; PTBP1 [polypyrimidine tract binding
protein
1]; PTCH1 [patched homolog 1 (Drosophila)]; PTEN [phosphatase and tensin
homolog]; PTGDR [prostaglandin D2 receptor (DP)]; PTGDS [prostaglandin D2
synthase 21 kDa (brain)]; PTGER1 [prostaglandin E receptor 1 (subtype EP1),
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42kDa]; PTGER2 [prostaglandin E receptor 2 (subtype EP2), 53kDa]; PTGER3
[prostaglandin E receptor 3 (subtype EP3)]; PTGER4 [prostaglandin E receptor 4
(subtype EP4)]; PTGES [prostaglandin E synthase]; PTGFR [prostaglandin F
receptor (FP)]; PTGIR [prostaglandin 12 (prostacyclin) receptor (IP)]; PTGS1
[prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and
cyclooxygenase)]; PTGS2 [prostaglandin-endoperoxide synthase 2
(prostaglandin G/H synthase and cyclooxygenase)]; PTH [parathyroid hormone];
PTHLH [parathyroid hormone-like hormone]; PTK2 [PTK2 protein tyrosine kinase
2]; PTK2B [PTK2B protein tyrosine kinase 2 beta]; PTK7 [PTK7 protein tyrosine
kinase 7]; PTMS [parathymosin]; PTN [pleiotrophin]; PTPN1 [protein tyrosine
phosphatase, non-receptor type 1]; PTPN11 [protein tyrosine phosphatase, non-
receptor type 11]; PTPN12 [protein tyrosine phosphatase, non-receptor type
12];
PTPN2 [protein tyrosine phosphatase, non-receptor type 2]; PTPN22 [protein
tyrosine phosphatase, non-receptor type 22 (lymphoid)]; PTPN6 [protein
tyrosine
phosphatase, non-receptor type 6]; PTPRC [protein tyrosine phosphatase,
receptor type, C]; PTPRD [protein tyrosine phosphatase, receptor type, D];
PTPRE [protein tyrosine phosphatase, receptor type, E]; PTPRJ [protein
tyrosine
phosphatase, receptor type, J]; PTPRN [protein tyrosine phosphatase, receptor
type, N]; PTPRT [protein tyrosine phosphatase, receptor type, T]; PTPRU
[protein tyrosine phosphatase, receptor type, U]; PTRF [polymerase I and
transcript release factor]; PTS [6-pyruvoyltetrahydropterin synthase]; PTTG1
[pituitary tumor-transforming 1]; PTX3 [pentraxin 3, long]; PUS10
[pseudouridylate synthase 10]; PXK [PX domain containing serine/threonine
kinase]; PXN [paxillin]; PYCR1 [pyrroline-5-carboxylate reductase 1]; PYCR2
[pyrroline-5-carboxylate reductase family, member 2]; PYGB [phosphorylase,
glycogen; brain]; PYGM [phosphorylase, glycogen, muscle]; PYY [peptide YY];
PZP [pregnancy-zone protein]; QDPR [quinoid dihydropteridine reductase];
RAB1 1A [RAB11A, member RAS oncogene family]; RAB1 1 FIP1 [RAB1 1 family
interacting protein 1 (class I)]; RAB27A [RAB27A, member RAS oncogene
family]; RAB37 [RAB37, member RAS oncogene family]; RAB39 [RAB39,
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member RAS oncogene family]; RAB7A [RAB7A, member RAS oncogene
family]; RAB9A [RAB9A, member RAS oncogene family]; RAC1 [ras-related C3
botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1)];
RAC2
[ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding
protein
Rac2)]; RAD17 [RAD17 homolog (S. pombe)]; RAD50 [RAD50 homolog (S.
cerevisiae)]; RAD51 [RAD51 homolog (RecA homolog, E. coli) (S. cerevisiae)];
RAD51 C [RAD51 homolog C (S. cerevisiae)]; RAD51 L1 [RAD51-like 1 (S.
cerevisiae)]; RAD51L3 [RAD51 -like 3 (S. cerevisiae)]; RAD54L [RAD54-like (S.
cerevisiae)]; RAD9A [RAD9 homolog A (S. pombe)]; RAF1 [v-raf-1 murine
leukemia viral oncogene homolog 1]; RAG1 [recombination activating gene 1];
RAG2 [recombination activating gene 2]; RAN [RAN, member RAS oncogene
family]; RANBP1 [RAN binding protein 1]; RAP1A [RAP1A, member of RAS
oncogene family]; RAPGEF4 [Rap guanine nucleotide exchange factor (GEF) 4];
RARA [retinoic acid receptor, alpha]; RARB [retinoic acid receptor, beta];
RARG
[retinoic acid receptor, gamma]; RARRES2 [retinoic acid receptor responder
(tazarotene induced) 2]; RARS [arginyl-tRNA synthetase]; RASA1 [RAS p21
protein activator (GTPase activating protein) 1]; RASGRP1 [RAS guanyl
releasing protein 1 (calcium and DAG-regulated)]; RASGRP2 [RAS guanyl
releasing protein 2 (calcium and DAG-regulated)]; RASGRP4 [RAS guanyl
releasing protein 4]; RASSF1 [Ras association (RaIGDS/AF-6) domain family
member 1]; RB1 [retinoblastoma 1]; RBBP4 [retinoblastoma binding protein 4];
RBBP8 [retinoblastoma binding protein 8]; RBL1 [retinoblastoma-like 1 (p107)];
RBL2 [retinoblastoma-like 2 (p130)]; RBP4 [retinol binding protein 4, plasma];
RBX1 [ring-box 1 ]; RCBTB1 [regulator of chromosome condensation (RCC1) and
BTB (POZ) domain containing protein 1]; RCN1 [reticulocalbin 1, EF-hand
calcium binding domain]; RCN2 [reticulocalbin 2, EF-hand calcium binding
domain]; RDX [radixin]; RECK [reversion-inducing-cysteine-rich protein with
kazal motifs]; RECQL [RecQ protein-like (DNA helicase Q1-like)]; RECQL4
[RecQ protein-like 4]; RECQL5 [RecQ protein-like 5]; REG1A [regenerating islet-
derived 1 alpha]; REG3A [regenerating islet-derived 3 alpha]; REG4
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[regenerating islet-derived family, member 4]; REL [v-rel
reticuloendotheliosis
viral oncogene homolog (avian)]; RELA [v-rel reticuloendotheliosis viral
oncogene homolog A (avian)]; RELB [v-rel reticuloendotheliosis viral oncogene
homolog B]; REN [renin]; RET [ret proto-oncogene]; RETN [resistin]; RETNLB
[resistin like beta]; RFC1 [replication factor C (activator 1) 1, 145kDa];
RFC2
[replication factor C (activator 1) 2, 40kDa]; RFC3 [replication factor C
(activator
1) 3, 38kDa]; RFX1 [regulatory factor X, 1 (influences HLA class II
expression)];
RFX5 [regulatory factor X, 5 (influences HLA class II expression)]; RFXANK
[regulatory factor X-associated ankyrin-containing protein]; RFXAP [regulatory
factor X-associated protein]; RGS1 8 [regulator of G-protein signaling 18];
RHAG
[Rh-associated glycoprotein]; RHD [Rh blood group, D antigen]; RHO
[rhodopsin]; RHOA [ras homolog gene family, member A]; RHOD [ras homolog
gene family, member D]; RIF1 [RAP1 interacting factor homolog (yeast)]; RIPK1
[receptor (TNFRSF)-interacting serine-threonine kinase 1]; RIPK2 [receptor-
interacting serine-threonine kinase 2]; RLBP1 [retinaldehyde binding protein
1];
RLN1 [relaxin 1]; RLN2 [relaxin 2]; RMI1 [RMI1, RecQ mediated genome
instability 1, homolog (S. cerevisiae)]; RNASE1 [ribonuclease, RNase A family,
1
(pancreatic)]; RNASE2 [ribonuclease, RNase A family, 2 (liver, eosinophil-
derived neurotoxin)]; RNASE3 [ribonuclease, RNase A family, 3 (eosinophil
cationic protein)]; RNASEH1 [ribonuclease H1]; RNASEH2A [ribonuclease H2,
subunit A]; RNASEL [ribonuclease L (2' [5'-oligoisoadenylate synthetase-
dependent)]; RNASEN [ribonuclease type III, nuclear]; RNF123 [ring finger
protein 123]; RNF13 [ring finger protein 13]; RNF135 [ring finger protein
135];
RNF138 [ring finger protein 138]; RNF4 [ring finger protein 4]; RNH1
[ribonuclease/angiogenin inhibitor 1]; RNPC3 [RNA-binding region (RNP1, RRM)
containing 3]; RNPEP [arginyl aminopeptidase (aminopeptidase B)]; ROCK1
[Rho-associated, coiled-coil containing protein kinase 1]; ROM1 [retinal outer
segment membrane protein 1]; ROR2 [receptor tyrosine kinase-like orphan
receptor 2]; RORA [RAR-related orphan receptor A]; RPA1 [replication protein
Al, 70kDa]; RPA2 [replication protein A2, 32kDa]; RPGRIP1L [RPGRIP1 -like];
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RPLP1 [ribosomal protein, large, P1]; RPS19 [ribosomal protein S19]; RPS6KA3
[ribosomal protein S6 kinase, 90kDa, polypeptide 3]; RPS6KB1 [ribosomal
protein S6 kinase, 70kDa, polypeptide 1]; RPSA [ribosomal protein SA]; RRBP1
[ribosome binding protein 1 homolog 180kDa (dog)]; RRM1 [ribonucleotide
reductase M1]; RRM2B [ribonucleotide reductase M2 B (TP53 inducible)];
RUNX1 [runt-related transcription factor 1]; RUNX3 [runt-related transcription
factor 3]; RXRA [retinoid X receptor, alpha]; RXRB [retinoid X receptor,
beta];
RYR1 [ryanodine receptor 1 (skeletal)]; RYR3 [ryanodine receptor 3]; S100A1
[S100 calcium binding protein Al]; S100A12 [S100 calcium binding protein A12];
S100A4 [S100 calcium binding protein A4]; S100A7 [S100 calcium binding
protein A7]; S100A8 [S100 calcium binding protein A8]; S100A9 [S100 calcium
binding protein A9]; S100B [S100 calcium binding protein B]; S100G [S100
calcium binding protein G]; S1 PR1 [sphingosine-l -phosphate receptor 1 ];
SAA1
[serum amyloid Al]; SAA4 [serum amyloid A4, constitutive]; SAFB [scaffold
attachment factor B]; SAG [S-antigen; retina and pineal gland (arrestin)];
SAGE1
[sarcoma antigen 1]; SARDH [sarcosine dehydrogenase]; SART3 [squamous cell
carcinoma antigen recognized by T cells 3]; SBDS [Shwachman-Bodian-
Diamond syndrome]; SBNO2 [strawberry notch homolog 2 (Drosophila)];
SCAMP3 [secretory carrier membrane protein 3]; SOAP [SREBF chaperone];
SCARB1 [scavenger receptor class B, member 1]; SCD [stearoyl-CoA
desaturase (delta-9-desaturase)]; SCG2 [secretogranin II]; SCG3 [secretogranin
III]; SCG5 [secretogranin V (7B2 protein)]; SCGB1A1 [secretoglobin, family 1A,
member 1 (uteroglobin) ]; SCGB3A2 [secretoglobin, family 3A, member 2];
SCN4A [sodium channel, voltage-gated, type IV, alpha subunit]; SCNN1A
[sodium channel, nonvoltage-gated 1 alpha]; SCNN1G [sodium channel,
nonvoltage-gated 1, gamma]; SCO1 [SCO cytochrome oxidase deficient
homolog 1 (yeast)]; SC02 [SCO cytochrome oxidase deficient homolog 2
(yeast)]; SCP2 [sterol carrier protein 2]; SCT [secretin]; SDC1 [syndecan 1];
SDC2 [syndecan 2]; SDC4 [syndecan 4]; SDHB [succinate dehydrogenase
complex, subunit B, iron sulfur (Ip)]; SDHD [succinate dehydrogenase complex,
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subunit D, integral membrane protein]; SEC14L2 [SEC14-like 2 (S. cerevisiae)];
SEC16A [SEC16 homolog A (S. cerevisiae)]; SEC23B [Sec23 homolog B (S.
cerevisiae)]; SELE [selectin E]; SELL [selectin L]; SELP [selectin P (granule
membrane protein 140kDa, antigen CD62)]; SELPLG [selectin P ligand]; SEPT5
[septin 5]; SEPP1 [selenoprotein P, plasma, 1]; SEPSECS [Sep (0-
phosphoserine) tRNA:Sec (selenocysteine) tRNA synthase]; SERBP1
[SERPINE1 mRNA binding protein 1]; SERPINA1 [serpin peptidase inhibitor,
Glade A (alpha-1 antiproteinase, antitrypsin), member 1]; SERPINA2 [serpin
peptidase inhibitor, Glade A (alpha-1 antiproteinase, antitrypsin), member 2];
SERPINA3 [serpin peptidase inhibitor, Glade A (alpha-1 antiproteinase,
antitrypsin), member 3]; SERPINA5 [serpin peptidase inhibitor, Glade A (alpha-
1
antiproteinase, antitrypsin), member 5]; SERPINA6 [serpin peptidase inhibitor,
Glade A (alpha-1 antiproteinase, antitrypsin), member 6]; SERPINA7 [serpin
peptidase inhibitor, Glade A (alpha-1 antiproteinase, antitrypsin), member 7];
SERPINBI [serpin peptidase inhibitor, Glade B (ovalbumin), member 1];
SERPINB2 [serpin peptidase inhibitor, Glade B (ovalbumin), member 2];
SERPINB3 [serpin peptidase inhibitor, Glade B (ovalbumin), member 3];
SERPINB4 [serpin peptidase inhibitor, Glade B (ovalbumin), member 4];
SERPINB5 [serpin peptidase inhibitor, Glade B (ovalbumin), member 5];
SERPINB6 [serpin peptidase inhibitor, Glade B (ovalbumin), member 6];
SERPINB9 [serpin peptidase inhibitor, Glade B (ovalbumin), member 9];
SERPINCI [serpin peptidase inhibitor, Glade C (antithrombin), member 1];
SERPINDI [serpin peptidase inhibitor, Glade D (heparin cofactor), member 1];
SERPINEI [serpin peptidase inhibitor, Glade E (nexin, plasminogen activator
inhibitor type 1), member 1 ]; SERPINE2 [serpin peptidase inhibitor, Glade E
(nexin, plasminogen activator inhibitor type 1), member 2]; SERPINF2 [serpin
peptidase inhibitor, Glade F (alpha-2 antiplasmin, pigment epithelium derived
factor), member 2]; SERPINGI [serpin peptidase inhibitor, Glade G (Cl
inhibitor),
member 1]; SERPINHI [serpin peptidase inhibitor, Glade H (heat shock protein
47), member 1, (collagen binding protein 1)]; SET [SET nuclear oncogene];
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SETDB2 [SET domain, bifurcated 2]; SETX [senataxin]; SFPQ [splicing factor
proline/glutamine-rich (polypyrimidine tract binding protein associated)];
SFRP1
[secreted frizzled-related protein 1]; SFRP2 [secreted frizzled-related
protein 2];
SFRP5 [secreted frizzled-related protein 5]; SFTPA1 [surfactant protein Al];
SFTPB [surfactant protein B]; SFTPC [surfactant protein C]; SFTPD [surfactant
protein D]; SGCA [sarcoglycan, alpha (50kDa dystrophin-associated
glycoprotein)]; SGCB [sarcoglycan, beta (43kDa dystrophin-associated
glycoprotein)]; SGK1 [serum/glucocorticoid regulated kinase 1]; SGSH [N-
sulfoglucosamine sulfohydrolase]; SGTA [small glutamine-rich tetratricopeptide
repeat (TPR)-containing, alpha]; SH2B1 [SH2B adaptor protein 1]; SH2B3 [SH2B
adaptor protein 3]; SH2D1A [SH2 domain containing 1A]; SH2D4B [SH2 domain
containing 4B]; SH3KBP1 [SH3-domain kinase binding protein 1]; SHBG [sex
hormone-binding globulin]; SHC1 [SHC (Src homology 2 domain containing)
transforming protein 1]; SHH [sonic hedgehog homolog (Drosophila)]; SHMT2
[serine hydroxymethyltransferase 2 (mitochondrial)]; SI [sucrase-isomaltase
(alpha-glucosidase)]; SIGIRR [single immunoglobulin and toll-interleukin 1
receptor (TIR) domain]; SIP1 [survival of motor neuron protein interacting
protein
1]; SIPA1 [signal-induced proliferation-associated 1]; SIRPA [signal-
regulatory
protein alpha]; SIRPB2 [signal-regulatory protein beta 2]; SIRT1 [sirtuin
(silent
mating type information regulation 2 homolog) 1 (S. cerevisiae)]; SKIV2L
[superkiller viralicidic activity 2-like (S. cerevisiae)]; SKP2 [S-phase
kinase-
associated protein 2 (p45)]; SLAMFI [signaling lymphocytic activation molecule
family member 1]; SLAMF6 [SLAM family member 6]; SLC11A1 [solute carrier
family 11 (proton-coupled divalent metal ion transporters), member 1]; SLC11A2
[solute carrier family 11 (proton-coupled divalent metal ion transporters),
member
2]; SLC1 2A1 [solute carrier family 12 (sodium/potassium/chloride
transporters),
member 1]; SLC12A2 [solute carrier family 12 (sodium/potassium/chloride
transporters), member 2]; SLC14A1 [solute carrier family 14 (urea
transporter),
member 1 (Kidd blood group)]; SLC15A1 [solute carrier family 15 (oligopeptide
transporter), member 1 ]; SLC16A1 [solute carrier family 16, member 1
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(monocarboxylic acid transporter 1)]; SLC17A5 [solute carrier family 17
(anion/sugar transporter), member 5]; SLC1 7A6 [solute carrier family 17
(sodium-
dependent inorganic phosphate cotransporter), member 6]; SLC17A7 [solute
carrier family 17 (sodium-dependent inorganic phosphate cotransporter),
member 7]; SLC19A1 [solute carrier family 19 (folate transporter), member 1];
SLC1A1 [solute carrier family 1 (neuronal/epithelial high affinity glutamate
transporter, system Xag), member 1]; SLC1A2 [solute carrier family 1 (glial
high
affinity glutamate transporter), member 2]; SLC1A4 [solute carrier family 1
(glutamate/neutral amino acid transporter), member 4]; SLC22A1 2 [solute
carrier
family 22 (organic anion/urate transporter), member 12]; SLC22A2 [solute
carrier
family 22 (organic cation transporter), member 2]; SLC22A23 [solute carrier
family 22, member 23]; SLC22A3 [solute carrier family 22 (extraneuronal
monoamine transporter), member 3]; SLC22A4 [solute carrier family 22 (organic
cation/ergothioneine transporter), member 4]; SLC22A5 [solute carrier family
22
(organic cation/carnitine transporter), member 5]; SLC22A6 [solute carrier
family
22 (organic anion transporter), member 6]; SLC24A2 [solute carrier family 24
(sodium/potassium/calcium exchanger), member 2]; SLC25A1 [solute carrier
family 25 (mitochondrial carrier; citrate transporter), member 1]; SLC25A20
[solute carrier family 25 (carnitine/acylcarnitine translocase), member 20];
SLC25A3 [solute carrier family 25 (mitochondrial carrier; phosphate carrier),
member 3]; SLC25A32 [solute carrier family 25, member 32]; SLC25A33 [solute
carrier family 25, member 33]; SLC25A4 [solute carrier family 25
(mitochondrial
carrier; adenine nucleotide translocator), member 4]; SLC26A4 [solute carrier
family 26, member 4]; SLC27A4 [solute carrier family 27 (fatty acid
transporter),
member 4]; SLC28A1 [solute carrier family 28 (sodium-coupled nucleoside
transporter), member 1]; SLC2A1 [solute carrier family 2 (facilitated glucose
transporter), member 1]; SLC2A13 [solute carrier family 2 (facilitated glucose
transporter), member 13]; SLC2A3 [solute carrier family 2 (facilitated glucose
transporter), member 3]; SLC2A4 [solute carrier family 2 (facilitated glucose
transporter), member 4]; SLC30A1 [solute carrier family 30 (zinc transporter),
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member 1]; SLC30A8 [solute carrier family 30 (zinc transporter), member 8];
SLC31A1 [solute carrier family 31 (copper transporters), member 1]; SLC35A1
[solute carrier family 35 (CMP-sialic acid transporter), member Al]; SLC35A2
[solute carrier family 35 (UDP-galactose transporter), member A2]; SLC35C1
[solute carrier family 35, member C1 ]; SLC35F2 [solute carrier family 35,
member F2]; SLC39A3 [solute carrier family 39 (zinc transporter), member 3];
SLC3A2 [solute carrier family 3 (activators of dibasic and neutral amino acid
transport), member 2]; SLC46A1 [solute carrier family 46 (folate transporter),
member 1]; SLC5A5 [solute carrier family 5 (sodium iodide symporter), member
5]; SLC6A1 1 [solute carrier family 6 (neurotransmitter transporter, GABA),
member 11]; SLC6A14 [solute carrier family 6 (amino acid transporter), member
14]; SLC6A19 [solute carrier family 6 (neutral amino acid transporter), member
19]; SLC6A3 [solute carrier family 6 (neurotransmitter transporter, dopamine),
member 3]; SLC6A4 [solute carrier family 6 (neurotransmitter transporter,
serotonin), member 4]; SLC6A8 [solute carrier family 6 (neurotransmitter
transporter, creatine), member 8]; SLC7A1 [solute carrier family 7 (cationic
amino
acid transporter, y+ system), member 1 ]; SLC7A2 [solute carrier family 7
(cationic amino acid transporter, y+ system), member 2]; SLC7A4 [solute
carrier
family 7 (cationic amino acid transporter, y+ system), member 4]; SLC7A5
[solute
carrier family 7 (cationic amino acid transporter, y+ system), member 5];
SLC8A1
[solute carrier family 8 (sodium/calcium exchanger), member 1]; SLC9A1 [solute
carrier family 9 (sodium/hydrogen exchanger), member 1]; SLC9A3R1 [solute
carrier family 9 (sodium/hydrogen exchanger), member 3 regulator 1]; SLCO1A2
[solute carrier organic anion transporter family, member 1A2]; SLCO1 B1
[solute
carrier organic anion transporter family, member 1 B1 ]; SLCO1 B3 [solute
carrier
organic anion transporter family, member 1 B3]; SLPI [secretory leukocyte
peptidase inhibitor]; SMAD1 [SMAD family member 1]; SMAD2 [SMAD family
member 2]; SMAD3 [SMAD family member 3]; SMAD4 [SMAD family member 4];
SMAD7 [SMAD family member 7]; SMARCA4 [SWI/SNF related, matrix
associated, actin dependent regulator of chromatin, subfamily a, member 4];
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SMARCAL1 [SWI/SNF related, matrix associated, actin dependent regulator of
chromatin, subfamily a-like 1]; SMARCB1 [SWI/SNF related, matrix associated,
actin dependent regulator of chromatin, subfamily b, member 1]; SMC1A
[structural maintenance of chromosomes 1A]; SMC3 [structural maintenance of
chromosomes 3]; SMG1 [SMG1 homolog, phosphatidylinositol 3-kinase-related
kinase (C. elegans)]; SMN1 [survival of motor neuron 1, telomeric]; SMPD1
[sphingomyelin phosphodiesterase 1, acid lysosomal]; SMPD2 [sphingomyelin
phosphodiesterase 2, neutral membrane (neutral sphingomyelinase)]; SMTN
[smoothelin]; SNAI2 [snail homolog 2 (Drosophila)]; SNAP25 [synaptosomal-
associated protein, 25kDa]; SNCA [synuclein, alpha (non A4 component of
amyloid precursor)]; SNCG [synuclein, gamma (breast cancer-specific protein
1)]; SNURF [SNRPN upstream reading frame]; SNW1 [SNW domain containing
1]; SNX9 [sorting nexin 9]; SOAT1 [sterol 0-acyltransferase 1]; SOCS1
[suppressor of cytokine signaling 1]; SOCS2 [suppressor of cytokine signaling
2];
SOCS3 [suppressor of cytokine signaling 3]; SOD1 [superoxide dismutase 1,
soluble]; SOD2 [superoxide dismutase 2, mitochondrial]; SORBS3 [sorbin and
SH3 domain containing 3]; SORD [sorbitol dehydrogenase]; SOX2 [SRY (sex
determining region Y)-box 2]; SP1 [Spl transcription factor]; SP1 10 [SP1 10
nuclear body protein]; SP3 [Sp3 transcription factor]; SPA17 [sperm
autoantigenic protein 17]; SPARC [secreted protein, acidic, cysteine-rich
(osteonectin)]; SPHK1 [sphingosine kinase 1]; SPI1 [spleen focus forming virus
(SFFV) proviral integration oncogene spit]; SPINK1 [serine peptidase
inhibitor,
Kazal type 1]; SPINK13 [serine peptidase inhibitor, Kazal type 13 (putative)];
SPINK5 [serine peptidase inhibitor, Kazal type 5]; SPN [sialophorin]; SPON1
[spondin 1, extracellular matrix protein]; SPP1 [secreted phosphoprotein 1];
SPRED1 [sprouty-related, EVH1 domain containing 1]; SPRR2A [small proline-
rich protein 2A]; SPRR2B [small proline-rich protein 2B]; SPTB [spectrin,
beta,
erythrocytic]; SRC [v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog
(avian)]; SRD5A1 [steroid-5-alpha-reductase, alpha polypeptide 1 (3-oxo-5
alpha-steroid delta 4-dehydrogenase alpha 1)]; SREBF1 [sterol regulatory
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element binding transcription factor 1]; SREBF2 [sterol regulatory element
binding transcription factor 2]; SRF [serum response factor (c-fos serum
response element-binding transcription factor)]; SRGN [serglycin]; SRP9
[signal
recognition particle 9kDa]; SRPX [sushi-repeat-containing protein, X-linked];
SRR
[serine racemase]; SRY [sex determining region Y]; SSB [Sjogren syndrome
antigen B (autoantigen La)]; SST [somatostatin]; SSTR2 [somatostatin receptor
2]; SSTR4 [somatostatin receptor 4]; ST8SIA4 [ST8 alpha-N-acetyl-neuraminide
alpha--2,8-sialyltransferase 4]; STAR [steroidogenic acute regulatory
protein];
STAT1 [signal transducer and activator of transcription 1, 91 kDa]; STAT2
[signal
transducer and activator of transcription 2, 113kDa]; STAT3 [signal transducer
and activator of transcription 3 (acute-phase response factor)]; STAT4 [signal
transducer and activator of transcription 4]; STAT5A [signal transducer and
activator of transcription 5A]; STAT5B [signal transducer and activator of
transcription 5B]; STAT6 [signal transducer and activator of transcription 6,
interleukin-4 induced]; STELLAR [germ and embryonic stem cell enriched protein
STELLA]; STIM1 [stromal interaction molecule 1]; STIP1 [stress-induced-
phosphoprotein 1]; STK1 1 [serine/threonine kinase 11]; STMN2 [stathmin-like
2];
STRAP [serine/threonine kinase receptor associated protein]; STRC
[stereocilin];
STS [steroid sulfatase (microsomal), isozyme S]; STX6 [syntaxin 6]; STX8
[syntaxin 8]; SULT1A1 [sulfotransferase family, cytosolic, 1A, phenol-
preferring,
member 1]; SULT1A3 [sulfotransferase family, cytosolic, 1A, phenol-preferring,
member 3]; SUMF1 [sulfatase modifying factor 1]; SUMO1 [SMT3 suppressor of
mif two 3 homolog 1 (S. cerevisiae)]; SUMO3 [SMT3 suppressor of mif two 3
homolog 3 (S. cerevisiae)]; SUOX [sulfite oxidase]; SUV39H1 [suppressor of
variegation 3-9 homolog 1 (Drosophila)]; SWAP70 [SWAP switching B-cell
complex 70kDa subunit]; SYCP3 [synaptonemal complex protein 3]; SYK [spleen
tyrosine kinase]; SYNM [synemin, intermediate filament protein]; SYNPO
[synaptopodin]; SYNPO2 [synaptopodin 2]; SYP [synaptophysin]; SYT3
[synaptotagmin III]; SYTL1 [synaptotagmin-like 1]; T [T, brachyury homolog
(mouse)]; TAC1 [tachykinin, precursor 1]; TAC4 [tachykinin 4 (hemokinin)];
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TACR1 [tachykinin receptor 1]; TACR2 [tachykinin receptor 2]; TACR3
[tachykinin receptor 3]; TAGLN [transgelin]; TALI [T-cell acute lymphocytic
leukemia 1]; TAOK3 [TAO kinase 3]; TAP1 [transporter 1, ATP-binding cassette,
sub-family B (MDR/TAP)]; TAP2 [transporter 2, ATP-binding cassette, sub-family
B (MDR/TAP)]; TARDBP [TAR DNA binding protein]; TARP [TCR gamma
alternate reading frame protein]; TAT [tyrosine aminotransferase]; TBK1 [TANK-
binding kinase 1]; TBP [TATA box binding protein]; TBX1 [T-box 1]; TBX2 [T-box
2]; TBX21 [T-box 21]; TBX3 [T-box 3]; TBX5 [T-box 5]; TBXA2R [thromboxane
A2 receptor]; TBXAS1 [thromboxane A synthase 1 (platelet)]; TCEA1
[transcription elongation factor A (SII), 1 ]; TCEAL1 [transcription
elongation factor
A (SII)-like 1]; TCF4 [transcription factor 4]; TCF7L2 [transcription factor 7-
like 2
(T-cell specific, HMG-box)]; TCL1A [T-cell leukemia/lymphoma 1A]; TCL1 B [T-
cell leukemia/lymphoma 1 B]; TCN1 [transcobalamin I (vitamin B12 binding
protein, R binder family)]; TCN2 [transcobalamin II; macrocytic anemia]; TDP1
[tyrosyl-DNA phosphodiesterase 1]; TEC [tec protein tyrosine kinase]; TECTA
[tectorin alpha]; TEK [TEK tyrosine kinase, endothelial]; TERF1 [telomeric
repeat
binding factor (NIMA-interacting) 1]; TERF2 [telomeric repeat binding factor
2];
TERT [telomerase reverse transcriptase]; TES [testis derived transcript (3 LIM
domains)]; TF [transferrin]; TFAM [transcription factor A, mitochondrial];
TFAP2A
[transcription factor AP-2 alpha (activating enhancer binding protein 2
alpha)];
TFF2 [trefoil factor 2]; TFF3 [trefoil factor 3 (intestinal)]; TFPI [tissue
factor
pathway inhibitor (lipoprotein-associated coagulation inhibitor)]; TFPT [TCF3
(E2A) fusion partner (in childhood Leukemia)]; TFR2 [transferrin receptor 2];
TFRC [transferrin receptor (p90, CD71)]; TG [thyroglobulin]; TGFA
[transforming
growth factor, alpha]; TGFB1 [transforming growth factor, beta 1]; TGFB2
[transforming growth factor, beta 2]; TGFB3 [transforming growth factor, beta
3];
TGFBR1 [transforming growth factor, beta receptor 1]; TGFBR2 [transforming
growth factor, beta receptor II (70/8OkDa)]; TGIF1 [TGFB-induced factor
homeobox 1]; TGM1 [transglutaminase 1 (K polypeptide epidermal type I,
protein-glutamine-gamma-glutamyltransferase)]; TGM2 [transglutaminase 2 (C
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polypeptide, protein-glutamine-gamma-glutamyltransferase)]; TGM3
[transglutaminase 3 (E polypeptide, protein-glutamine-gamma-
glutamyltransferase)]; TH [tyrosine hydroxylase]; THAP1 [THAP domain
containing, apoptosis associated protein 1]; THBD [thrombomodulin]; THBS1
[thrombospondin 1]; THBS3 [thrombospondin 3]; THPO [thrombopoietin]; THY1
[Thy-1 cell surface antigen]; TIA1 [TIA1 cytotoxic granule-associated RNA
binding protein]; TIE1 [tyrosine kinase with immunoglobulin-like and EGF-like
domains 1]; TIMD4 [T-cell immunoglobulin and mucin domain containing 4];
TIMELESS [timeless homolog (Drosophila)]; TIMP1 [TIMP metallopeptidase
inhibitor 1]; TIMP2 [TIMP metallopeptidase inhibitor 2]; TIMP3 [TIMP
metallopeptidase inhibitor 3]; TIRAP [toll-interleukin 1 receptor (TIR) domain
containing adaptor protein]; TJP1 [tight junction protein 1 (zona occludens
1)];
TK1 [thymidine kinase 1, soluble]; TK2 [thymidine kinase 2, mitochondrial];
TKT
[transketolase]; TLE4 [transducin-like enhancer of split 4 (E(spl) homolog,
Drosophila)]; TLR1 [toll-like receptor 1]; TLR10 [toll-like receptor 10]; TLR2
[toll-
like receptor 2]; TLR3 [toll-like receptor 3]; TLR4 [toll-like receptor 4];
TLR5 [toll-
like receptor 5]; TLR6 [toll-like receptor 6]; TLR7 [toll-like receptor 7];
TLR8 [toll-
like receptor 8]; TLR9 [toll-like receptor 9]; TLX1 [T-cell leukemia homeobox
1];
TM7SF4 [transmembrane 7 superfamily member 4]; TMED3 [transmembrane
emp24 protein transport domain containing 3]; TMEFF2 [transmembrane protein
with EGF-like and two follistatin-like domains 2]; TMEM132E [transmembrane
protein 132E]; TMEM18 [transmembrane protein 18]; TMEM19 [transmembrane
protein 19]; TMEM216 [transmembrane protein 216]; TMEM27 [transmembrane
protein 27]; TMEM67 [transmembrane protein 67]; TMPO [thymopoietin];
TMPRSS15 [transmembrane protease, serine 15]; TMSB4X [thymosin beta 4, X-
linked]; TNC [tenascin C]; TNF [tumor necrosis factor (TNF superfamily, member
2)]; TNFAIP1 [tumor necrosis factor, alpha-induced protein 1 (endothelial)];
TNFAIP3 [tumor necrosis factor, alpha-induced protein 3]; TNFAIP6 [tumor
necrosis factor, alpha-induced protein 6]; TNFRSF1 OA [tumor necrosis factor
receptor superfamily, member 1 Oa]; TNFRSF1 OB [tumor necrosis factor receptor
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superfamily, member 10b]; TNFRSF10C [tumor necrosis factor receptor
superfamily, member 10c, decoy without an intracellular domain]; TNFRSF1OD
[tumor necrosis factor receptor superfamily, member 10d, decoy with truncated
death domain]; TNFRSF1 1A [tumor necrosis factor receptor superfamily,
member 11 a, NFKB activator]; TNFRSF1 1 B [tumor necrosis factor receptor
superfamily, member 11 b]; TNFRSF1 3B [tumor necrosis factor receptor
superfamily, member 13B]; TNFRSF13C [tumor necrosis factor receptor
superfamily, member 13C]; TNFRSF14 [tumor necrosis factor receptor
superfamily, member 14 (herpesvirus entry mediator)]; TNFRSF17 [tumor
necrosis factor receptor superfamily, member 17]; TNFRSF1 8 [tumor necrosis
factor receptor superfamily, member 18]; TNFRSF1A [tumor necrosis factor
receptor superfamily, member 1A]; TNFRSF1 B [tumor necrosis factor receptor
superfamily, member 1 B]; TNFRSF21 [tumor necrosis factor receptor
superfamily, member 21]; TNFRSF25 [tumor necrosis factor receptor
superfamily, member 25]; TNFRSF4 [tumor necrosis factor receptor superfamily,
member 4]; TNFRSF6B [tumor necrosis factor receptor superfamily, member 6b,
decoy]; TNFRSF8 [tumor necrosis factor receptor superfamily, member 8];
TNFRSF9 [tumor necrosis factor receptor superfamily, member 9]; TNFSF10
[tumor necrosis factor (ligand) superfamily, member 10]; TNFSF1 1 [tumor
necrosis factor (ligand) superfamily, member 11]; TNFSF12 [tumor necrosis
factor (ligand) superfamily, member 12]; TNFSF13 [tumor necrosis factor
(ligand)
superfamily, member 13]; TNFSF13B [tumor necrosis factor (ligand) superfamily,
member 13b]; TNFSF14 [tumor necrosis factor (ligand) superfamily, member 14];
TNFSF15 [tumor necrosis factor (ligand) superfamily, member 15]; TNFSF18
[tumor necrosis factor (ligand) superfamily, member 18]; TNFSF4 [tumor
necrosis
factor (ligand) superfamily, member 4]; TNFSF8 [tumor necrosis factor (ligand)
superfamily, member 8]; TNFSF9 [tumor necrosis factor (ligand) superfamily,
member 9]; TNKS [tankyrase, TRF1 -interacting ankyrin-related ADP-ribose
polymerase]; TNNC1 [troponin C type 1 (slow)]; TNNI2 [troponin I type 2
(skeletal, fast)]; TNNI3 [troponin I type 3 (cardiac)]; TNNT3 [troponin T type
3
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(skeletal, fast)]; TNP01 [transportin 1]; TNS1 [tensin 1]; TNXB [tenascin XB];
TOM1 L2 [target of mybl -like 2 (chicken)]; TOP1 [topoisomerase (DNA) I];
TOP1 MT [topoisomerase (DNA) I, mitochondrial]; TOP2A [topoisomerase (DNA)
II alpha 170kDa]; TOP2B [topoisomerase (DNA) II beta 180kDa]; TOP3A
[topoisomerase (DNA) III alpha]; TOPBP1 [topoisomerase (DNA) II binding
protein 1]; TP53 [tumor protein p53]; TP53BP1 [tumor protein p53 binding
protein
1]; TP53RK [TP53 regulating kinase]; TP63 [tumor protein p63]; TP73 [tumor
protein p73]; TPD52 [tumor protein D52]; TPH1 [tryptophan hydroxylase 1]; TPI1
[triosephosphate isomerase 1]; TPM1 [tropomyosin 1 (alpha)]; TPM2
[tropomyosin 2 (beta)]; TPMT [thiopurine S-methyltransferase]; TPO [thyroid
peroxidase]; TPP1 [tripeptidyl peptidase I]; TPP2 [tripeptidyl peptidase II];
TPPP
[tubulin polymerization promoting protein]; TPPP3 [tubulin polymerization-
promoting protein family member 3]; TPSAB1 [tryptase alpha/beta 1]; TPSB2
[tryptase beta 2 (gene/pseudogene)]; TPSD1 [tryptase delta 1]; TPSG1 [tryptase
gamma 1]; TPT1 [tumor protein, translationally-controlled 1]; TRADD
[TNFRSFIA-associated via death domain]; TRAF1 [TNF receptor-associated
factor 1]; TRAF2 [TNF receptor-associated factor 2]; TRAF3IP2 [TRAF3
interacting protein 2]; TRAF6 [TNF receptor-associated factor 6]; TRAP [TRAF
interacting protein]; TRAPPC10 [trafficking protein particle complex 10]; TRDN
[triadin]; TREX1 [three prime repair exonuclease 1]; TRH [thyrotropin-
releasing
hormone]; TRIB1 [tribbles homolog 1 (Drosophila)]; TRIM21 [tripartite motif-
containing 21]; TRIM22 [tripartite motif-containing 22]; TRIM26 [tripartite
motif-
containing 26]; TRIM28 [tripartite motif-containing 28]; TRIM29 [tripartite
motif-
containing 29]; TRIM68 [tripartite motif-containing 68]; TRPA1 [transient
receptor
potential cation channel, subfamily A, member 1]; TRPC1 [transient receptor
potential cation channel, subfamily C, member 1]; TRPC3 [transient receptor
potential cation channel, subfamily C, member 3]; TRPC6 [transient receptor
potential cation channel, subfamily C, member 6]; TRPM1 [transient receptor
potential cation channel, subfamily M, member 1]; TRPM8 [transient receptor
potential cation channel, subfamily M, member 8]; TRPS1 [trichorhinophalangeal
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syndrome I]; TRPV1 [transient receptor potential cation channel, subfamily V,
member 1]; TRPV4 [transient receptor potential cation channel, subfamily V,
member 4]; TRPV5 [transient receptor potential cation channel, subfamily V,
member 5]; TRPV6 [transient receptor potential cation channel, subfamily V,
member 6]; TRRAP [transformation/transcription domain-associated protein];
TSC1 [tuberous sclerosis 1]; TSC2 [tuberous sclerosis 2]; TSC22D3 [TSC22
domain family, member 3]; TSG101 [tumor susceptibility gene 101]; TSHR
[thyroid stimulating hormone receptor]; TSLP [thymic stromal lymphopoietin];
TSPAN7 [tetraspanin 7]; TSPO [translocator protein (18kDa)]; TSSK2 [testis-
specific serine kinase 2]; TSTA3 [tissue specific transplantation antigen
P35B];
TTF2 [transcription termination factor, RNA polymerase II]; TTN [titin]; TTPA
[tocopherol (alpha) transfer protein]; TTR [transthyretin]; TUBA1 B [tubulin,
alpha
1b]; TUBA4A [tubulin, alpha 4a]; TUBB [tubulin, beta]; TUBB1 [tubulin, beta
1];
TUBG1 [tubulin, gamma 1]; TWIST1 [twist homolog 1 (Drosophila)]; TWSG1
[twisted gastrulation homolog 1 (Drosophila)]; TXK [TXK tyrosine kinase]; TXN
[thioredoxin]; TXN2 [thioredoxin 2]; TXNDC5 [thioredoxin domain containing 5
(endoplasmic reticulum)]; TXNDC9 [thioredoxin domain containing 9]; TXNIP
[thioredoxin interacting protein]; TXNRD1 [thioredoxin reductase 1]; TXNRD2
[thioredoxin reductase 2]; TYK2 [tyrosine kinase 2]; TYMP [thymidine
phosphorylase]; TYMS [thymidylate synthetase]; TYR [tyrosinase
(oculocutaneous albinism IA)]; TYRO3 [TYRO3 protein tyrosine kinase];
TYROBP [TYRO protein tyrosine kinase binding protein]; TYRP1 [tyrosinase-
related protein 1]; UBB [ubiquitin B]; UBC [ubiquitin C]; UBE2C [ubiquitin-
conjugating enzyme E2C]; UBE2N [ubiquitin-conjugating enzyme E2N (UBC13
homolog, yeast)]; UBE2U [ubiquitin-conjugating enzyme E2U (putative)]; UBE3A
[ubiquitin protein ligase E3A]; UBE4A [ubiquitination factor E4A (UFD2
homolog,
yeast)]; UCHL1 [ubiquitin carboxyl-terminal esterase L1 (ubiquitin
thiolesterase)];
UCN [urocortin]; UCN2 [urocortin 2]; UCP1 [uncoupling protein 1
(mitochondrial,
proton carrier)]; UCP2 [uncoupling protein 2 (mitochondrial, proton carrier)];
UCP3 [uncoupling protein 3 (mitochondrial, proton carrier)]; UFD1 L [ubiquitin
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fusion degradation 1 like (yeast)]; UGCG [UDP-glucose ceramide
glucosyltransferase]; UGP2 [UDP-glucose pyrophosphorylase 2]; UGT1A1 [UDP
glucuronosyltransferase 1 family, polypeptide Al]; UGT1A6 [UDP
glucuronosyltransferase 1 family, polypeptide A6]; UGT1A7 [UDP
glucuronosyltransferase 1 family, polypeptide A7]; UGT8 [UDP
glycosyltransferase 8]; UIMC1 [ubiquitin interaction motif containing 1];
ULBP1
[UL16 binding protein 1]; ULK2 [unc-51-like kinase 2 (C. elegans)]; UMOD
[uromodulin]; UMPS [uridine monophosphate synthetase]; UNC13D [unc-13
homolog D (C. elegans)]; UNC93B1 [unc-93 homolog 131 (C. elegans)]; UNG
[uracil-DNA glycosylase]; UQCRFS1 [ubiquinol-cytochrome c reductase, Rieske
iron-sulfur polypeptide 1]; UROD [uroporphyrinogen decarboxylase]; USF1
[upstream transcription factor 1]; USF2 [upstream transcription factor 2, c-
fos
interacting]; USP18 [ubiquitin specific peptidase 18]; USP34 [ubiquitin
specific
peptidase 34]; UTRN [utrophin]; UTS2 [urotensin 2]; VAMP8 [vesicle-associated
membrane protein 8 (endobrevin)]; VAPA [VAMP (vesicle-associated membrane
protein)-associated protein A, 33kDa]; VASP [vasodilator-stimulated
phosphoprotein]; VAV1 [vav 1 guanine nucleotide exchange factor]; VAV3 [vav 3
guanine nucleotide exchange factor]; VCAM1 [vascular cell adhesion molecule
1]; VCAN [versican]; VCL [vinculin]; VDAC1 [voltage-dependent anion channel
1]; VDR [vitamin D (1 [25- dihydroxyvitamin D3) receptor]; VEGFA [vascular
endothelial growth factor A]; VEGFC [vascular endothelial growth factor C];
VHL
[von Hippel-Lindau tumor suppressor]; VIL1 [villin 1]; VIM [vimentin]; VIP
[vasoactive intestinal peptide]; VIPR1 [vasoactive intestinal peptide receptor
1];
VIPR2 [vasoactive intestinal peptide receptor 2]; VLDLR [very low density
lipoprotein receptor]; VMAC [vimentin-type intermediate filament associated
coiled-coil protein]; VPREB1 [pre-B lymphocyte 1]; VPS39 [vacuolar protein
sorting 39 homolog (S. cerevisiae)]; VTN [vitronectin]; VWF [von Willebrand
factor]; WARS [tryptophanyl-tRNA synthetase]; WAS [Wiskott-Ald rich syndrome
(eczema-thrombocytopenia)]; WASF1 [WAS protein family, member 1]; WASF2
[WAS protein family, member 2]; WASL [Wiskott-Aldrich syndrome-like]; WDFY3
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[WD repeat and FYVE domain containing 3]; WDR36 [WD repeat domain 36];
WEE1 [WEE1 homolog (S. pombe)]; WIF1 [WNT inhibitory factor 1]; WIPF1
[WAS/WASL interacting protein family, member 1]; WNK1 [WNK lysine deficient
protein kinase 1]; WNT5A [wingless-type MMTV integration site family, member
5A]; WRN [Werner syndrome, RecQ helicase-like]; WT1 [Wilms tumor 1]; XBP1
[X-box binding protein 1]; XCL1 [chemokine (C motif) ligand 1]; XDH [xanthine
dehydrogenase]; XIAP [X-linked inhibitor of apoptosis]; XPA [xeroderma
pigmentosum, complementation group A]; XPC [xeroderma pigmentosum,
complementation group C]; XPO5 [exportin 5]; XRCC1 [X-ray repair
complementing defective repair in Chinese hamster cells 1]; XRCC2 [X-ray
repair
complementing defective repair in Chinese hamster cells 2]; XRCC3 [X-ray
repair
complementing defective repair in Chinese hamster cells 3]; XRCC4 [X-ray
repair
complementing defective repair in Chinese hamster cells 4]; XRCC5 [X-ray
repair
complementing defective repair in Chinese hamster cells 5 (double-strand-break
rejoining)]; XRCC6 [X-ray repair complementing defective repair in Chinese
hamster cells 6]; YAP1 [Yes-associated protein 1]; YARS [tyrosyl-tRNA
synthetase]; YBX1 [Y box binding protein 1]; YES1 [v-yes-1 Yamaguchi sarcoma
viral oncogene homolog 1]; YPEL1 [yippee-like 1 (Drosophila)]; YPEL2 [yippee-
like 2 (Drosophila)]; YWHAB [tyrosine 3-monooxygenase/tryptophan 5-
monooxygenase activation protein, beta polypeptide]; YWHAQ [tyrosine 3-
monooxygenase/tryptophan 5-monooxygenase activation protein, theta
polypeptide]; YWHAZ [tyrosine 3-monooxygenase/tryptophan 5-monooxygenase
activation protein, zeta polypeptide]; YY1 [YY1 transcription factor]; ZAP70
[zeta-
chain (TCR) associated protein kinase 70kDa]; ZBED1 [zinc finger, BED-type
containing 1]; ZC3H12A [zinc finger CCCH-type containing 12A]; ZC3H12D [zinc
finger CCCH-type containing 12D]; ZFR [zinc finger RNA binding protein];
ZNF148 [zinc finger protein 148]; ZNF267 [zinc finger protein 267]; ZNF287
[zinc
finger protein 287]; ZNF300 [zinc finger protein 300]; ZNF365 [zinc finger
protein
365]; ZNF521 [zinc finger protein 521]; ZNF74 [zinc finger protein 74]; and
ZPBP2 [zona pellucida binding protein 2].
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[0207] In certain embodiments, an animal created by a method of
the invention may be used to study the effects of mutations on the animal and
development and/or progression of an immunodeficiency using measures
commonly used in the study of immunodeficiencies.
[0208] It should be understood that the genetically modified
animals, e.g., knock-out and transgenic animals created by a method of the
invention may include genes altered singly or in combination, including
alteration
to any one or more of Rag 1, Rag2, FoxN1, and DNAPK. Accordingly, for
example, animals including a single, double or triple gene knock-out are
contemplated. Any of these may be used in various methods in which alteration
of one or more immunodeficiency genes may be useful. For example,
genetically modified animals as described herein may be used in studies of
hematopoietic cells, such as in the identification of progenitor cells
including
lymphoid progenitors and pluripotential stem cells; in the identification of
new
cytokines which play a role in the growth and differentiation of hematopoietic
cells; in the analysis of the effect of known cytokines; and in the analysis
of drugs
effects on hematopoietic cells. Such animals can also be used in studies on
pathogenetic mechanisms in disease caused by viral infections such as but not
limited to influenza, West Nile virus, herpesviruses, picornaviruses,
neurotropic
coronavirus, Varicella-zoster (chicken pox), respiratory syncytial virus,
cowpox,
hepatitis B, rabies, and Dengue virus, and lymphotropic viruses including
human
immunodeficiency virus (HIV), human T lymphotropic virus (HTLV-1), and
Epstein Barr virus (EBV), and also a virus that specifically infects rats but
models
the effects of a human-specific virus on its host, for example the rat-adapted
influenza virus (see, e.g., H. Lebrec and G.R. Burleson (1994) Toxicology. Jul
1;91(2):179-88).
[0209] In other embodiments, a genetically modified animal created
by a method of the invention may also be useful in studies of defense
mechanisms against microorganisms that cause disease in immunocompromised
patients, wherein the microorganism may be cytomegalovirus, Pneumocystic
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carinii or Candida species. Genetically modified animals, such as for example
knock-out rats can be subjects for pre-clinical evaluation of a specific "gene
therapy". For example, genes may be introduced into hematopoietic progenitor
cells, preferably into pluripotential stem cells with self-renewal capacity
from
patients with inherited genetic defects, or into pluripotential stem cells
with self-
renewal capacity from rat models of inherited genetic defects, and the cells
re-
introduced into the genetically modified rats for the purpose of determining
therapeutic usefulness of the modified cells. Genetically modified animals may
also be useful for studying the biological mechanisms underlying
immunodeficiency diseases and conditions caused by or linked to a mutation in
an immunodeficiency gene such as Rag 1, Rag2, FoxN1, or DNAPK.
[0210] Furthermore, a genetically modified animal created by a
method of the invention may be used to develop a diagnostic assay for an
immunodeficiency disorder including but not limited to a leukemia, in which
the
animal, either untreated or previously treated with a therapeutic agent, is
assessed for the presence of one or more biomarkers relative to a non-affected
control animal. Such a genetically modified animal may be used in a method of
screening a candidate therapy or therapeutic compound for treating an
immunodeficiency disorder such as a leukemia, using a genetically modified
animal in which one or more immunodeficiency genes including but not limited
to
Rag 1, Rag2, FoxN1, or DNAPK are knocked out, and the animal, either
untreated or previously treated with another therapeutic agent which may be a
drug, microbe, transplanted cells, or other agent, is then treated with the
candidate therapy or candidate therapeutic agent, a biological sample is
obtained
from the animal, and the biological sample evaluated relative to a sample from
a
non-affected wild-type control sample, or a sample from a genetically modified
animal not subjected to the candidate therapy or therapeutic agent.
[0211] In still further embodiments, a method for modeling an
autoimmune disease may involve the adoptive transfer of B cells reacting to an
antigen for an autoimmune disease, or T cells activated for an autoimmune
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disease. The appropriate non-human mammal with the antigen target of the
autoimmune disease can be immunized as follows.
[0212] Immune cells may be prepared from the immunized animal
and may be then transplanted to a genetically modified animal as described
herein such as a Rag 1, Rag2, FoxN1, or DNAPK knock-out rat, or a rat with any
combination of these genes knocked out. The development of autoimmune
phenotypes in the recipient knock-out animal may then evaluated as compared to
either a non-transplanted knock-out animal, or as compared to a knock-out
animal transplanted with non-pathologic immune cells that lack auto-
reactivity, or
as compared to a wild type animal transplanted with immune cells as described
above.
[0213] In some embodiments, a method for creating a combined
immunodeficiency syndrome model may include providing a genetically modified
animal such as a rat wherein Rag 1, Rag2, FoxN1, or DNAPK are knocked out as
described herein, and the knock-out animal may be further rendered deficient
for
natural killer (NK) cells by any one of several possible methods. Non-limiting
examples of methods of rendering the knock-out animal deficient for NK include
i) disruption of the Lyst gene; or ii) treatment of FoxN1 mutant animals with
a
compound that inhibits NK cell activity including but not limited to NSAIDs
(non-
steroidal anti-inflammatory drugs), statins, allosteric LFA-1 inhibitors,
vinblastine,
paclitaxel, docetaxel, cladribine, chlorambucil, bortezomib, or MG-132.
N. trinucleotide repeat disorders
[0214] Trinucleotide repeat expansion disorders are divided into two
categories determined by the type of repeat. The most common repeat is the
triplet CAG, which, when present in the coding region of a gene, codes for the
amino acid glutamine (Q). Therefore, these disorders are referred to as the
polyglutamine (polyQ) disorders and may include Huntington Disease (HD);
Spinobulbar Muscular Atrophy (SBMA); Spinocerebellar Ataxias (SCA types 1, 2,
3, 6, 7, and 17); and Dentatorubro-PalIidol uysian Atrophy (DRPLA). Other
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trinucleotide repeat expansion disorders either do not involve the CAG
triplet, or
the CAG triplet is not in the coding region of the gene and are referred to as
the
non-polyglutamine disorders. Non-polyglutamine disorders may include Fragile
X Syndrome (FRAXA); Fragile XE Mental Retardation (FRAXE); Friedreich
Ataxia (FRDA); Myotonic Dystrophy (DM); and Spinocerebellar Ataxias (SCA
types 8, and 12).
[0215] In one embodiment, a method of the invention may be used
to create a genetically modified animal or cell in which at least one
chromosomal
sequence associated with a trinucleotide repeat disorder has been edited.
Suitable chromosomal edits may include, but are not limited to, the type of
edits
detailed in section I(f) above.
[0216] In each of the above embodiments, one or more
chromosomal sequences associated with a trinucleotide repeat disorder may be
edited. A trinucleotide repeat disorder associated protein or control sequence
may typically be selected based on an experimental association of the protein
or
sequence to a trinucleotide repeat expansion disorder. Trinucleotide repeat
expansion proteins may include proteins associated with susceptibility for
developing a trinucleotide repeat expansion disorder, the presence of a
trinucleotide repeat expansion disorder, the severity of a trinucleotide
repeat
expansion disorder or any combination thereof. For example, the production
rate
or circulating concentration of a protein associated with a trinucleotide
repeat
expansion disorder may be elevated or depressed in a population having a
trinucleotide repeat expansion disorder relative to a population lacking the
trinucleotide repeat expansion disorder. Differences in protein levels may be
assessed using proteomic or genomic analysis techniques known in the art.
[0217] Non-limiting examples of proteins associated with
trinucleotide repeat expansion disorders include AR (androgen receptor), FMR1
(fragile X mental retardation 1), HTT (huntingtin), DMPK (dystrophia myotonica-
protein kinase), FXN (frataxin), ATXN2 (ataxin 2), ATN1 (atrophin 1), FEN1
(flap
structure-specific endonuclease 1), TNRC6A (trinucleotide repeat containing
6A),
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PABPN1 (poly(A) binding protein, nuclear 1), JPH3 (junctophilin 3), MED15
(mediator complex subunit 15), ATXN1 (ataxin 1), ATXN3 (ataxin 3), TBP (TATA
box binding protein), CACNA1A (calcium channel, voltage-dependent, P/Q type,
alpha 1A subunit), ATXN8OS (ATXN8 opposite strand (non-protein coding)),
PPP2R2B (protein phosphatase 2, regulatory subunit B, beta), ATXN7 (ataxin 7),
TNRC6B (trinucleotide repeat containing 6B), TNRC6C (trinucleotide repeat
containing 6C), CELF3 (CUGBP, Elav-like family member 3), MAB21 L1 (mab-21-
like 1 (C. elegans)), MSH2 (mutS homolog 2, colon cancer, nonpolyposis type 1
(E. coli)), TMEM185A (transmembrane protein 185A), SIX5 (SIX homeobox 5),
CNPY3 (canopy 3 homolog (zebrafish)), FRAXE (fragile site, folic acid type,
rare,
fra(X)(q28) E), GNB2 (guanine nucleotide binding protein (G protein), beta
polypeptide 2), RPL14 (ribosomal protein L14), ATXN8 (ataxin 8), INSR (insulin
receptor), TTR (transthyretin), EP400 (E1A binding protein p400), GIGYF2
(GRB1 0 interacting GYF protein 2), OGG1 (8-oxoguanine DNA glycosylase),
STC1 (stanniocalcin 1), CNDP1 (carnosine dipeptidase 1 (metallopeptidase M20
family)), C1 Oorf2 (chromosome 10 open reading frame 2), MAML3 mastermind-
like 3 (Drosophila), DKC1 (dyskeratosis congenita 1, dyskerin), PAXIP1 (PAX
interacting (with transcription-activation domain) protein 1), CASK
(calcium/calmodulin-dependent serine protein kinase (MAGUK family)), MAPT
(microtubule-associated protein tau), SP1 (Spl transcription factor), POLG
(polymerase (DNA directed), gamma), AFF2 (AF4/FMR2 family, member 2),
THBS1 (thrombospondin 1), TP53 (tumor protein p53), ESR1 (estrogen receptor
1), CGGBP1 (CGG triplet repeat binding protein 1), ABT1 (activator of basal
transcription 1), KLK3 (kallikrein-related peptidase 3), PRNP (prion protein),
JUN
(Jun oncogene), KCNN3 (potassium intermediate/small conductance calcium-
activated channel, subfamily N, member 3), BAX (BCL2-associated X protein),
FRAXA (fragile site, folic acid type, rare, fra(X)(q27.3) A (macroorchidism,
mental
retardation)), KBTBD10 (kelch repeat and BTB (POZ) domain containing 10),
MBNL1 (muscleblind-like (Drosophila)), RAD51 (RAD51 homolog (RecA
homolog, E. coli) (S. cerevisiae)), NCOA3 (nuclear receptor coactivator 3),
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ERDA1 (expanded repeat domain, CAG/CTG 1), TSC1 (tuberous sclerosis 1),
COMP (cartilage oligomeric matrix protein), GCLC (glutamate-cysteine ligase,
catalytic subunit), RRAD (Ras-related associated with diabetes), MSH3 (mutS
homolog 3 (E. coli)), DRD2 (dopamine receptor D2), CD44 (CD44 molecule
(Indian blood group)), CTCF (CCCTC-binding factor (zinc finger protein)),
CCND1 (cyclin D1), CLSPN (claspin homolog (Xenopus laevis)), MEF2A
(myocyte enhancer factor 2A), PTPRU (protein tyrosine phosphatase, receptor
type, U), GAPDH (glyceraldehyde-3-phosphate dehydrogenase), TRIM22
(tripartite motif-containing 22), WT1 (Wilms tumor 1), AHR (aryl hydrocarbon
receptor), GPX1 (glutathione peroxidase 1), TPMT (thiopurine S-
methyltransferase), NDP (Norrie disease (pseudoglioma)), ARX (aristaless
related homeobox), MUS81 (MUS81 endonuclease homolog (S. cerevisiae)),
TYR (tyrosinase (oculocutaneous albinism IA)), EGR1 (early growth response 1),
UNG (uracil-DNA glycosylase), NUMBL (numb homolog (Drosophila)-like),
FABP2 (fatty acid binding protein 2, intestinal), EN2 (engrailed homeobox 2),
CRYGC (crystallin, gamma C), SRP14 (signal recognition particle 14kDa
(homologous Alu RNA binding protein)), CRYGB (crystallin, gamma B), PDCD1
(programmed cell death 1), HOXA1 (homeobox Al), ATXN2L (ataxin 2-like),
PMS2 (PMS2 postmeiotic segregation increased 2 (S. cerevisiae)), GLA
(galactosidase, alpha), CBL (Cas-Br-M (murine) ecotropic retroviral
transforming
sequence), FTH1 (ferritin, heavy polypeptide 1), IL12RB2 (interleukin 12
receptor, beta 2), OTX2 (orthodenticle homeobox 2), HOXA5 (homeobox A5),
POLG2 (polymerase (DNA directed), gamma 2, accessory subunit), DLX2 (distal-
less homeobox 2), SIRPA (signal-regulatory protein alpha), OTX1 (orthodenticle
homeobox 1), AHRR (aryl-hydrocarbon receptor repressor), MANF
(mesencephalic astrocyte-derived neurotrophic factor), TMEM158
(transmembrane protein 158 (gene/pseudogene)), and ENSG00000078687.
[0218] Exemplary proteins associated with trinucleotide repeat
expansion disorders include HTT (Huntingtin), AR (androgen receptor), FXN
(frataxin), Atxn3 (ataxin), Atxnl (ataxin), Atxn2 (ataxin), Atxn7 (ataxin),
Atxn10
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(ataxin), DMPK (dystrophia myotonica-protein kinase), Atn1 (atrophin 1), CBP
(creb binding protein), VLDLR (very low density lipoprotein receptor), and any
combination thereof.
[0219] In certain embodiments, an animal created by a method of
the invention may be used to study the effects of mutations on the animal and
the
development and/or progression of a trinucleotide repeat disorder using
measures commonly used in the study of a trinucleotide repeat disorder.
0. neurotransmission disorders
[0220] Non-limiting examples of a neurotransmission disorder
include amylotropic lateral sclerosis (ALS), spinocerebellar ataxias (SCA)
including SCA2, Alzheimer's; autism, mental retardation, Rett's syndrome,
fragile
X syndrome, depression, schizophrenia, bi-polar disorders, disorders of
learning,
memory or behavior, anxiety, brain injury, seizure disorders, Huntington's
disease (chorea), mania, neuroleptic malignant syndrome, pain, Parkinsonism,
Parkinson's disease, tardive dyskinesia, myasthenia gravis, episodic ataxias,
hyperkalemic periodic paralysis, hypokalemic periodic paralysis, Lambert-Eaton
syndrome, paramyotonia congenita, Rasmussen's encephalitis, startle disease
(hyperexplexia, stiff baby syndrome), and the effects of poisoning such as
botulism, mushroom poisoning, organophosphates, snake venom such as from
Bungarus multicinctus (Taiwanese banded krait). In one embodiment, a method
of the invention may be used to create an animal or cell in which at least one
chromosomal sequence associated with a neurotransmission disorder has been
edited. Suitable chromosomal edits may include, but are not limited to, the
type
of edits detailed in section I(f) above.
[0221] In each of the above embodiments, one or more
chromosomal sequences associated with a neurotransmission disorder may be
edited. A neurotransmission disorder associated protein or control sequence
may
typically be selected based on an experimental association of the protein to a
neurotransmission disorder. Neurotransmission disorder-related proteins
include
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proteins associated with the susceptibility for developing a neurotransmission
disorder, the presence of a neurotransmission disorder, the severity of a
neurotransmission disorder or any combination thereof. For example, the
production rate or circulating concentration of a neurotransmission disorder-
related protein may be elevated or depressed in a population having a
neurotransmission disorder relative to a population lacking the
neurotransmission
disorder. Differences in protein levels may be assessed using proteomic or
genomic analysis techniques known in the art.
[0222] Non-limiting examples of neurotransmission disorder-related
proteins include SST (somatostatin), NOS1 (nitric oxide synthase 1
(neuronal)),
ADRA2A (adrenergic, alpha-2A-, receptor), ADRA2C (adrenergic, alpha-2C-,
receptor), TACR1 (tachykinin receptor 1), HTR2C (5-hydroxytryptamine
(serotonin) receptor 2C), SLC1A2 (solute carrier family 1 (glial high affinity
glutamate transporter), member 2), GRM5 (glutamate receptor, metabotropic 5),
GRM2 (glutamate receptor, metabotropic 2), GABRG3 (gamma-aminobutyric
acid (GABA) A receptor, gamma 3), CACNA1 B (calcium channel, voltage-
dependent, N type, alpha 1 B subunit), NOS2 (nitric oxide synthase 2,
inducible),
SLC6A5 (solute carrier family 6 (neurotransmitter transporter, glycine),
member
5), GABRG1 (gamma-aminobutyric acid (GABA) A receptor, gamma 1), NOS3
(nitric oxide synthase 3 (endothelial cell)), GRM3 (glutamate receptor,
metabotropic 3), HTR6 (5-hydroxytryptamine (serotonin) receptor 6), SLC1A3
(solute carrier family 1 (glial high affinity glutamate transporter), member
3),
GRM7 (glutamate receptor, metabotropic 7), HRH1 (histamine receptor H1),
SLC1A1 (solute carrier family 1 (neuronal/epithelial high affinity glutamate
transporter, system Xag), member 1), GRM4 (glutamate receptor, metabotropic
4), GLUD2 (glutamate dehydrogenase 2), ADRA2B (adrenergic, alpha-2B-,
receptor), SLC1A6 (solute carrier family 1 (high affinity aspartate/glutamate
transporter), member 6), GRM6 (glutamate receptor, metabotropic 6), SLC1A7
(solute carrier family 1 (glutamate transporter), member 7), SLC6A1 1 (solute
carrier family 6 (neurotransmitter transporter, GABA), member 11), CACNA1A
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(calcium channel, voltage-dependent, P/Q type, alpha 1A subunit), CACNA1 G
(calcium channel, voltage-dependent, T type, alpha 1 G subunit), GRM1
(glutamate receptor, metabotropic 1), CACNA1 H (calcium channel, voltage-
dependent, T type, alpha 1 H subunit), GRM8 (glutamate receptor, metabotropic
8), CHRNA3 (cholinergic receptor, nicotinic, alpha 3), P2RY2 (purinergic
receptor
P2Y, G-protein coupled, 2), TRPV6 (transient receptor potential cation
channel,
subfamily V, member 6), CACNA1 E (calcium channel, voltage-dependent, R
type, alpha 1 E subunit), ACCN1 (amiloride-sensitive cation channel 1,
neuronal),
CACNA1 I (calcium channel, voltage-dependent, T type, alpha 11 subunit),
GABARAP (GABA (A) receptor-associated protein), P2RY1 (purinergic receptor
P2Y, G-protein coupled, 1), P2RY6 (pyrimidinergic receptor P2Y, G-protein
coupled, 6), RPH3A (rabphilin 3A homolog (mouse)), HDC (histidine
decarboxylase), P2RY14 (purinergic receptor P2Y, G-protein coupled, 14),
P2RY4 (pyrimidinergic receptor P2Y, G-protein coupled, 4), P2RY10 (purinergic
receptor P2Y, G-protein coupled, 10), SLC28A3 (solute carrier family 28
(sodium-coupled nucleoside transporter), member 3), NOSTRIN (nitric oxide
synthase trafficker), P2RY13 (purinergic receptor P2Y, G-protein coupled, 13),
P2RY8 (purinergic receptor P2Y, G-protein coupled, 8), P2RY1 1 (purinergic
receptor P2Y, G-protein coupled, 11), SLC6A3 (solute carrier family 6
(neurotransmitter transporter, dopamine), member 3), HTR3A (5-
hydroxytryptamine (serotonin) receptor 3A), DRD2 (dopamine receptor D2),
HTR2A (5-hydroxytryptamine (serotonin) receptor 2A), TH (tyrosine
hydroxylase), CNR1 (cannabinoid receptor 1 (brain)), VIP (vasoactive
intestinal
peptide), NPY (neuropeptide Y), GAL (galanin prepropeptide), TAC1 (tachykinin,
precursor 1), SYP (synaptophysin), SLC6A4 (solute carrier family 6
(neurotransmitter transporter, serotonin), member 4), DBH (dopamine beta-
hydroxylase (dopamine beta-monooxygenase)), DRD3 (dopamine receptor D3),
NR3C1 (nuclear receptor subfamily 3, group C, member 1 (glucocorticoid
receptor)), HTR1 B (5-hydroxytryptamine (serotonin) receptor 1 B), GABBR1
(gamma-aminobutyric acid (GABA) B receptor, 1), CALCA (calcitonin-related
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polypeptide alpha), CRH (corticotropin releasing hormone), HTR1A (5-
hydroxytryptamine (serotonin) receptor 1A), TACR2 (tachykinin receptor 2),
COMT (catechol-O-methyltransferase), GRIN2B (glutamate receptor, ionotropic,
N-methyl D-aspartate 2B), GRIN2A (glutamate receptor, ionotropic, N-methyl D-
aspartate 2A), PRL (prolactin), ACHE (acetylcholinesterase (Yt blood group)),
ADRB2 (adrenergic, beta-2-, receptor, surface), ACE (angiotensin I converting
enzyme (peptidyl-dipeptidase A) 1), SNAP25 (synaptosomal-associated protein,
25kDa), GABRA5 (gamma-aminobutyric acid (GABA) A receptor, alpha 5),
MECP2 (methyl CpG binding protein 2 (Rett syndrome)), BCHE
(butyrylcholinesterase), ADRB1 (adrenergic, beta-1 -,receptor), GABRAI
(gamma-aminobutyric acid (GABA) A receptor, alpha 1), GCH1 (GTP
cyclohydrolase 1), DDC (dopa decarboxylase (aromatic L-amino acid
decarboxylase)), MAOB (monoamine oxidase B), DRD5 (dopamine receptor D5),
GABRE (gamma-aminobutyric acid (GABA) A receptor, epsilon), SLC6A2 (solute
carrier family 6 (neurotransmitter transporter, noradrenalin), member 2),
GABRR2 (gamma-aminobutyric acid (GABA) receptor, rho 2), SV2A (synaptic
vesicle glycoprotein 2A), GABRRI (gamma-aminobutyric acid (GABA) receptor,
rho 1), GHRH (growth hormone releasing hormone), CCK (cholecystokinin),
PDYN (prodynorphin), SLC6A9 (solute carrier family 6 (neurotransmitter
transporter, glycine), member 9), KCND1 (potassium voltage-gated channel,
Shal-related subfamily, member 1), SRR (serine racemase), DYT10 (dystonia
10), MAPT (microtubule-associated protein tau), APP (amyloid beta (A4)
precursor protein), CTSB (cathepsin B), ADA (adenosine deaminase), AKT1 (v-
akt murine thymoma viral oncogene homolog 1), GRIN1 (glutamate receptor,
ionotropic, N-methyl D-aspartate 1), BDNF (brain-derived neurotrophic factor),
HMOX1 (heme oxygenase (decycling) 1), OPRM1 (opioid receptor, mu 1),
GRIN2C (glutamate receptor, ionotropic, N-methyl D-aspartate 2C), GRIA1
(glutamate receptor, ionotropic, AMPA 1), GABRA6 (gamma-aminobutyric acid
(GABA) A receptor, alpha 6), FOS (FBJ murine osteosarcoma viral oncogene
homolog), GABRG2 (gamma-aminobutyric acid (GABA) A receptor, gamma 2),
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GABRB3 (gamma-aminobutyric acid (GABA) A receptor, beta 3), OPRK1 (opioid
receptor, kappa 1), GABRB2 (gamma-aminobutyric acid (GABA) A receptor, beta
2), GABRD (gamma-aminobutyric acid (GABA) A receptor, delta), ALDH5A1
(aldehyde dehydrogenase 5 family, member Al), GAD1 (glutamate
decarboxylase 1 (brain, 67kDa)), NSF (N-ethylmaleimide-sensitive factor),
GRIN2D (glutamate receptor, ionotropic, N-methyl D-aspartate 2D), ADORA1
(adenosine Al receptor), GABRA2 (gamma-aminobutyric acid (GABA) A
receptor, alpha 2), GLRA1 (glycine receptor, alpha 1), CHRM3 (cholinergic
receptor, muscarinic 3), CHAT (choline acetyltransferase), KNG1 (kininogen 1),
HMOX2 (heme oxygenase (decycling) 2), DRD4 (dopamine receptor D4), MAOA
(monoamine oxidase A), CHRM2 (cholinergic receptor, muscarinic 2), ADORA2A
(adenosine A2a receptor), STXBP1 (syntaxin binding protein 1), GABRA3
(gamma-aminobutyric acid (GABA) A receptor, alpha 3), TPH1 (tryptophan
hydroxylase 1), HCRTR1 (hypocretin (orexin) receptor 1), HCRTR2 (hypocretin
(orexin) receptor 2), CHRM1 (cholinergic receptor, muscarinic 1), FOLH1
(folate
hydrolase (prostate-specific membrane antigen) 1), AANAT (arylalkylamine N-
acetyltransferase), INS (insulin), NR3C2 (nuclear receptor subfamily 3, group
C,
member 2), FAAH (fatty acid amide hydrolase), GALR2 (galanin receptor 2),
ADCYAP1 (adenylate cyclase activating polypeptide 1 (pituitary)), PPP1 R1 B
(protein phosphatase 1, regulatory (inhibitor) subunit 1 B), HOMER1 (homer
homolog 1 (Drosophila)), ADCY10 (adenylate cyclase 10 (soluble)), PSEN2
(presenilin 2 (Alzheimer disease 4)), UBE3A (ubiquitin protein ligase E3A),
SOD1
(superoxide dismutase 1, soluble), LYN (v-yes-1 Yamaguchi sarcoma viral
related oncogene homolog), TSC2 (tuberous sclerosis 2), PRKCA (protein kinase
C, alpha), PPARG (peroxisome proliferator-activated receptor gamma), ESR1
(estrogen receptor 1), NTRK1 (neurotrophic tyrosine kinase, receptor, type 1),
EGFR (epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-
b)
oncogene homolog, avian)), S100B (S100 calcium binding protein B), NTRK3
(neurotrophic tyrosine kinase, receptor, type 3), PLCG2 (phospholipase C,
gamma 2 (phosphatidylinositol-specific)), NTRK2 (neurotrophic tyrosine kinase,
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receptor, type 2), DNMT1 (DNA (cytosine-5-)-m ethyltransferase 1), EGF
(epidermal growth factor (beta-urogastrone)), GRIA3 (glutamate receptor,
ionotrophic, AMPA 3), NCAM1 (neural cell adhesion molecule 1), CDKN1A
(cyclin-dependent kinase inhibitor 1A (p21, Cip1)), BCL2L1 (BCL2-like 1), TP53
(tumor protein p53), CASP9 (caspase 9, apoptosis-related cysteine peptidase),
CCKBR (cholecystokinin B receptor), PARK2 (Parkinson's disease (autosomal
recessive, juvenile) 2, parkin), ADRA1 B (adrenergic, alpha-1 B-, receptor),
CASP3 (caspase 3, apoptosis-related cysteine peptidase), PRNP (prion protein),
CRHR1 (corticotropin releasing hormone receptor 1), L1 CAM (L1 cell adhesion
molecule), NGFR (nerve growth factor receptor (TNFR superfamily, member
16)), CREB1 (cAMP responsive element binding protein 1), PLCG1
(phospholipase C, gamma 1), CAV1 (caveolin 1, caveolae protein, 22kDa),
ABCC8 (ATP-binding cassette, sub-family C (CFTR/MRP), member 8), ACTN2
(actinin, alpha 2), GRIA2 (glutamate receptor, ionotropic, AMPA 2), HPRT1
(hypoxanthine phosphoribosyltransferase 1), SYN1 (synapsin I), CSNK2A1
(casein kinase 2, alpha 1 polypeptide), GRIK1 (glutamate receptor, ionotropic,
kainate 1), ABCB1 (ATP-binding cassette, sub-family B (MDR/TAP), member 1),
AVPR2 (arginine vasopressin receptor 2), HTR4 (5-hydroxytryptamine
(serotonin) receptor 4), C3 (complement component 3), AGT (angiotensinogen
(serpin peptidase inhibitor, Glade A, member 8)), AGTR1 (angiotensin II
receptor,
type 1), CDK5 (cyclin-dependent kinase 5), LRP1 (low density lipoprotein
receptor-related protein 1), ARRB2 (arrestin, beta 2), PLD2 (phospholipase
D2),
OPRD1 (opioid receptor, delta 1), GNB3 (guanine nucleotide binding protein (G
protein), beta polypeptide 3), PIK3CG (phosphoinositide-3-kinase, catalytic,
gamma polypeptide), APAF1 (apoptotic peptidase activating factor 1), SSTR2
(somatostatin receptor 2), IL2 (interleukin 2), ADORA3 (adenosine A3
receptor),
ADRA1A (adrenergic, alpha-1A-, receptor), HTR7 (5-hydroxytryptamine
(serotonin) receptor 7 (adenylate cyclase-coupled)), ADRBK2 (adrenergic, beta,
receptor kinase 2), ALOX5 (arachidonate 5-lipoxygenase), NPR1 (natriuretic
peptide receptor A/guanylate cyclase A (atrionatriuretic peptide receptor A)),
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AVPR1A (arginine vasopressin receptor 1A), CHRNB1 (cholinergic receptor,
nicotinic, beta 1 (muscle)), SET (SET nuclear oncogene), PAH (phenylalanine
hydroxylase), POMC (proopiomelanocortin), LEPR (leptin receptor), SDC2
(syndecan 2), VIPR1 (vasoactive intestinal peptide receptor 1), DBI (diazepam
binding inhibitor (GABA receptor modulator, acyl-Coenzyme A binding protein)),
NPY1 R (neuropeptide Y receptor Y1), NPR2 (natriuretic peptide receptor
B/guanylate cyclase B (atrionatriuretic peptide receptor B)), CNR2
(cannabinoid
receptor 2 (macrophage)), LEP (leptin), CCKAR (cholecystokinin A receptor),
GLRB (glycine receptor, beta), KCNQ2 (potassium voltage-gated channel, KQT-
like subfamily, member 2), CHRNA2 (cholinergic receptor, nicotinic, alpha 2
(neuronal)), BDKRB2 (bradykinin receptor B2), CHRNA1 (cholinergic receptor,
nicotinic, alpha 1 (muscle)), CHRND (cholinergic receptor, nicotinic, delta),
CHRNA7 (cholinergic receptor, nicotinic, alpha 7), PLD1 (phospholipase D1,
phosphatidylcholine-specific), NRXN1 (neurexin 1), NRP1 (neuropilin 1), DLG3
(discs, large homolog 3 (Drosophila)), GNAQ (guanine nucleotide binding
protein
(G protein), q polypeptide), DRD1 (dopamine receptor D1), PRKG1 (protein
kinase, cGMP-dependent, type I), CNTNAP2 (contactin associated protein-like
2), EDN3 (endothelin 3), ABAT (4-aminobutyrate aminotransferase), TDO2
(tryptophan 2,3-dioxygenase), NEUROD1 (neurogenic differentiation 1), CHRNE
(cholinergic receptor, nicotinic, epsilon), CHRNB2 (cholinergic receptor,
nicotinic,
beta 2 (neuronal)), CHRNB3 (cholinergic receptor, nicotinic, beta 3), HTR1 D
(5-
hydroxytryptamine (serotonin) receptor 1 D), ADRA1 D (adrenergic, alpha-1 D-,
receptor), HTR2B (5-hydroxytryptamine (serotonin) receptor 2B), GRIK3
(glutamate receptor, ionotropic, kainate 3), NPY2R (neuropeptide Y receptor
Y2),
GRIK5 (glutamate receptor, ionotropic, kainate 5), GRIA4 (glutamate receptor,
ionotrophic, AMPA 4), EDN1 (endothelin 1), PRLR (prolactin receptor), GABRB1
(gamma-aminobutyric acid (GABA) A receptor, beta 1), GARS (glycyl-tRNA
synthetase), GRIK2 (glutamate receptor, ionotropic, kainate 2), ALOX12
(arachidonate 12-lipoxygenase), GAD2 (glutamate decarboxylase 2 (pancreatic
islets and brain, 65kDa)), LHCGR (luteinizing hormone/choriogonadotropin
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receptor), SHMT1 (serine hydroxymethyltransferase 1 (soluble)), PDXK
(pyridoxal (pyridoxine, vitamin B6) kinase), LIF (leukemia inhibitory factor
(cholinergic differentiation factor)), PLCD1 (phospholipase C, delta 1), NTF3
(neurotrophin 3), NFE2L2 (nuclear factor (erythroid-derived 2)-like 2), PLCB4
(phospholipase C, beta 4), GNRHR (gonadotropin-releasing hormone receptor),
NLGN1 (neuroligin 1), PPP2R4 (protein phosphatase 2A activator, regulatory
subunit 4), SSTR3 (somatostatin receptor 3), CRHR2 (corticotropin releasing
hormone receptor 2), NGF (nerve growth factor (beta polypeptide)), NRCAM
(neuronal cell adhesion molecule), NRXN3 (neurexin 3), GNRH1 (gonadotropin-
releasing hormone 1 (luteinizing-releasing hormone)), TRHR (thyrotropin-
releasing hormone receptor), ARRB1 (arrestin, beta 1), INPP1 (inositol
polyphosphate-1-phosphatase), PTN (pleiotrophin), PSMD10 (proteasome
(prosome, macropain) 26S subunit, non-ATPase, 10), DLG1 (discs, large
homolog 1 (Drosophila)), PSMB8 (proteasome (prosome, macropain) subunit,
beta type, 8 (large multifunctional peptidase 7)), CYCS (cytochrome c,
somatic),
ADORA2B (adenosine A2b receptor), ADRB3 (adrenergic, beta-3-, receptor),
CHGA (chromogranin A (parathyroid secretory protein 1)), ADM
(adrenomedullin), GABRP (gamma-aminobutyric acid (GABA) A receptor, pi),
GLRA2 (glycine receptor, alpha 2), PRKG2 (protein kinase, cGMP-dependent,
type II), GLS (glutaminase), TACR3 (tachykinin receptor 3), ALDH7A1 (aldehyde
dehydrogenase 7 family, member Al), GABBR2 (gamma-aminobutyric acid
(GABA) B receptor, 2), GDNF (glial cell derived neurotrophic factor), CNTFR
(ciliary neurotrophic factor receptor), CNTN2 (contactin 2 (axonal)), TOR1A
(torsin family 1, member A (torsin A)), CNTN1 (contactin 1), CAMK1
(calcium/calmodulin-dependent protein kinase I), NPPB (natriuretic peptide
precursor B), OXTR (oxytocin receptor), OSM (oncostatin M), VIPR2 (vasoactive
intestinal peptide receptor 2), CHRNB4 (cholinergic receptor, nicotinic, beta
4),
CHRNA5 (cholinergic receptor, nicotinic, alpha 5), AVP (arginine vasopressin),
RELN (reelin), GRLF1 (glucocorticoid receptor DNA binding factor 1), NPR3
(natriuretic peptide receptor C/guanylate cyclase C (atrionatriuretic peptide
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receptor C)), GRIK4 (glutamate receptor, ionotropic, kainate 4), KISS1 (KiSS-1
metastasis-suppressor), HTR5A (5-hydroxytryptamine (serotonin) receptor 5A),
ADCYAP1 R1 (adenylate cyclase activating polypeptide 1 (pituitary) receptor
type
I), GABRA4 (gamma-aminobutyric acid (GABA) A receptor, alpha 4), GLRA3
(glycine receptor, alpha 3), INHBA (inhibin, beta A), DLG2 (discs, large
homolog
2 (Drosophila)), PPYR1 (pancreatic polypeptide receptor 1), SSTR4
(somatostatin receptor 4), NPPA (natriuretic peptide precursor A), SNAP23
(synaptosomal-associated protein, 23kDa), AKAP9 (A kinase (PRKA) anchor
protein (yotiao) 9), NRXN2 (neurexin 2), FHL2 (four and a half LIM domains 2),
TJP1 (tight junction protein 1 (zona occludens 1)), NRG1 (neuregulin 1), CAMK4
(calcium/calmodulin-dependent protein kinase IV), CAV3 (caveolin 3), VAMP2
(vesicle-associated membrane protein 2 (synaptobrevin 2)), GALR1 (galanin
receptor 1), GHRHR (growth hormone releasing hormone receptor), HTR1 E (5-
hydroxytryptamine (serotonin) receptor 1 E), PENK (proenkephalin), HTT
(huntingtin), HOXA1 (homeobox Al), NPY5R (neuropeptide Y receptor Y5),
UNC1 19 (unc-119 homolog (C. elegans)), TAT (tyrosine aminotransferase),
CNTF (ciliary neurotrophic factor), SHMT2 (serine hydroxymethyltransferase 2
(mitochondrial)), ENTPD1 (ectonucleoside triphosphate diphosphohydrolase 1),
GRIP1 (glutamate receptor interacting protein 1), GRP (gastrin-releasing
peptide), NCAM2 (neural cell adhesion molecule 2), SSTR1 (somatostatin
receptor 1), CLTB (clathrin, light chain (Lcb)), DAO (D-amino-acid oxidase),
QDPR (quinoid dihydropteridine reductase), PYY (peptide YY), PNMT
(phenylethanolamine N-methyltransferase), NTSR1 (neurotensin receptor 1 (high
affinity)), NTS (neurotensin), HCRT (hypocretin (orexin) neuropeptide
precursor),
SNAP29 (synaptosomal-associated protein, 29kDa), SNAP91 (synaptosomal-
associated protein, 91 kDa homolog (mouse)), MADD (MAP-kinase activating
death domain), IDO1 (indoleamine 2,3-dioxygenase 1), TPH2 (tryptophan
hydroxylase 2), TAC3 (tachykinin 3), GRIN3A (glutamate receptor, ionotropic, N-
methyl -D-aspartate 3A), REN (renin), GALR3 (galanin receptor 3), MAGI2
(membrane associated guanylate kinase, WW and PDZ domain containing 2),
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KCNJ9 (potassium inwardly-rectifying channel, subfamily J, member 9), BDKRB1
(bradykinin receptor B1), CHRNA6 (cholinergic receptor, nicotinic, alpha 6),
CHRM5 (cholinergic receptor, muscarinic 5), CHRNG (cholinergic receptor,
nicotinic, gamma), SLC6A1 (solute carrier family 6 (neurotransmitter
transporter,
GABA), member 1), ENTPD2 (ectonucleoside triphosphate diphosphohydrolase
2), CALCB (calcitonin-related polypeptide beta), SHBG (sex hormone-binding
globulin), SERPINA6 (serpin peptidase inhibitor, Glade A (alpha-1
antiproteinase,
antitrypsin), member 6), NRG2 (neuregulin 2), PNOC (prepronociceptin), NAPA
(N-ethylmaleimide-sensitive factor attachment protein, alpha), PICK1 (protein
interacting with PRKCA 1), PLCD4 (phospholipase C, delta 4), GCDH (glutaryl-
Coenzyme A dehydrogenase), NLGN2 (neuroligin 2), NBEA (neurobeachin),
ATP1 OA (ATPase, class V, type 1 OA), RAPGEF4 (Rap guanine nucleotide
exchange factor (GEF) 4), UCN (urocortin), PCSK6 (proprotein convertase
subtilisin/kexin type 6), HTR1 F (5-hydroxytryptamine (serotonin) receptor 1
F),
SGCB (sarcoglycan, beta (43kDa dystrophin-associated glycoprotein)), GABRQ
(gamma-aminobutyric acid (GABA) receptor, theta), GHRL (ghrelin/obestatin
prepropeptide), NCALD (neurocalcin delta), NEUROD2 (neurogenic
differentiation 2), DPEP1 (dipeptidase 1 (renal)), SLC1A4 (solute carrier
family 1
(glutamate/neutral amino acid transporter), member 4), DNM3 (dynamin 3),
SLC6A12 (solute carrier family 6 (neurotransmitter transporter, betaine/GABA),
member 12), SLC6A6 (solute carrier family 6 (neurotransmitter transporter,
taurine), member 6), YME1 L1 (YME1-like 1 (S. cerevisiae)), VSNL1 (visinin-
like
1), SLC17A7 (solute carrier family 17 (sodium-dependent inorganic phosphate
cotransporter), member 7), HOMER2 (homer homolog 2 (Drosophila)), SYT7
(synaptotagmin VII), TFIP11 (tuftelin interacting protein 11), GMFB (glia
maturation factor, beta), PREB (prolactin regulatory element binding), NTSR2
(neurotensin receptor 2), NTF4 (neurotrophin 4), PPP1 R9B (protein phosphatase
1, regulatory (inhibitor) subunit 9B), DISC1 (disrupted in schizophrenia 1),
NRG3
(neuregulin 3), OXT (oxytocin, prepropeptide), TRH (thyrotropin-releasing
hormone), NISCH (nischarin), CRHBP (corticotropin releasing hormone binding
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protein), SLC6A1 3 (solute carrier family 6 (neurotransmitter transporter,
GABA),
member 13), NPPC (natriuretic peptide precursor C), CNTN3 (contactin 3
(plasmacytoma associated)), KAT5 (K (lysine) acetyltransferase 5), CNTN6
(contactin 6), KIAA0101 (KIAA0101), PANX1 (pannexin 1), CTSL1 (cathepsin
L1), EARS2 (glutamyl-tRNA synthetase 2, mitochondrial (putative)), CRIPT
(cysteine-rich PDZ-binding protein), CORT (cortistatin), DLGAP4 (discs, large
(Drosophila) homolog-associated protein 4), ASTN2 (astrotactin 2), HTR3B (5-
hydroxytryptamine (serotonin) receptor 3B), PMCH (pro-melanin-concentrating
hormone), TSPO (translocator protein (18kDa)), GDF2 (growth differentiation
factor 2), CNTNAP1 (contactin associated protein 1), GNRH2 (gonadotropin-
releasing hormone 2), AUTS2 (autism susceptibility candidate 2), SV2C
(synaptic
vesicle glycoprotein 2C), CARTPT (CART prepropeptide), NSUN4 (NOP2/Sun
domain family, member 4), CNTN5 (contactin 5), NEUROD4 (neurogenic
differentiation 4), NEUROG1 (neurogenin 1), SLTM (SAFB-like, transcription
modulator), GNRHR2 (gonadotropin-releasing hormone (type 2) receptor 2),
ASTN1 (astrotactin 1), SLC22A18 (solute carrier family 22, member 18),
SLC17A6 (solute carrier family 17 (sodium-dependent inorganic phosphate
cotransporter), member 6), GABRR3 (gamma-aminobutyric acid (GABA)
receptor, rho 3), DAOA (D-amino acid oxidase activator), ENSG00000123384,
nd NOS2P1 (nitric oxide synthase 2 pseudogene 1).
[0223] Exemplary neurotransmission-related proteins include 5-HTT
(5-hydroxyltryptamine transporter), SLC6A4 (Solute carrier family 6, member
4),
COMT (Catechol-O-methyltransferase), DRD1A (Dopamine receptor D1A),
SLC6A3 (Solute carrier family 6, member 3), DAO1 (D-amino-acid oxidase),
DTNBP1 (Dystrobrevin binding protein 1), and any combination thereof.
[0224] In certain embodiments, an animal created by a method of
the invention may be used to study the effects of mutations on the animal and
on
the development and/or progression of a neurotransmission disorder using
measures commoningly used in the study of a neurotransmission disorder.
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ii. pharmacological models
[0225] A method of the invention may be used to create an animal
or cell that may be used as a pharmacological model. Such a pharmacological
model may be a model for pharmacokinetics or a model for pharmacodynamics.
For instance, in one embodiment, a method of the invention may be used to
create an animal or cell that comprises a chromosomal edit in one or more
nucleic acid sequences associated with the metabolism of a pharmaceutically
active compound. Such an animal or cell may be used to study the effect of the
nucleic acid sequence on the pharmaceutical compound.
[0226] Alternatively, a method of the invention may be used to
create an animal or cell that comprises a chromosomal edit in a disease
associated sequence. Such an animal or cell may be used for assessing the
effect(s) of a therapeutic agent in the development or progression of the
disease.
For example, the effect(s) of a therapeutic agent may be measured in a
"humanized" animal, such that the information gained therefrom may be used to
predict the effect of the agent in a human. In general, the method comprises
contacting a genetically modified animal comprising at least one edited
chromosomal sequence encoding a protein associated with the disease with the
therapeutic agent, and comparing results of a selected parameter to results
obtained from contacting a wild-type animal with the same agent. Non-limiting
examples of suitable diseases include those listed in section II(a)i.
[0227] Also provided are methods to assess the effect(s) of an
agent in an isolated cell comprising at least one edited chromosomal sequence
encoding a protein associated with a disease, as well as methods of using
lysates of such cells (or cells derived from a genetically modified animal
disclosed herein) to assess the effect(s) of an agent. For example, the role
of a
particular protein associated with a disease in the metabolism of a particular
agent may be determined using such methods. Similarly, substrate specificity
and pharmacokinetic parameters may be readily determined using such
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methods. Those of skill in the art are familiar with suitable tests and/or
procedures.
[0228] In one embodiment, a method of the invention may be used
to create an animal or cell in which at least one chromosomal sequence
associated with toxicology has been edited. Suitable chromosomal edits may
include, but are not limited to, the type of edits detailed in section I(f)
above. Any
chromosomal sequence or protein involved in absorption, distribution,
metabolism, and excretion (ADME) and toxicology may be utilized for purposes
of the present invention. The ADME and toxicology-related proteins are
typically
selected based on an experimental association of the protein to an ADME and
toxicology-related disorder. For example, the production rate or circulating
concentration of an ADME and toxicology-related protein may be elevated or
depressed in a population having an ADME and toxicology disorder relative to a
population lacking the ADME and toxicology disorder. Differences in protein
levels may be assessed using proteomic or genomic analysis techniques known
in the art.
[0229] Exemplary non-limiting examples of the chromosomal
sequence or protein involved in ADME and toxicology may be chosen from Oct 1,
Oct 2, Hfe2, Ppar(alpha) MDR1 a (ABC Transporter ABCB1 a), MDR1 b
(ABCB1b), BCRP (ABCC1), MRP1 (ABCG2), MRP2 (ABCC2, cMOAT), and
combinations thereof
[0230] A further aspect of the present disclosure encompasses a
method for assessing the effect(s) of an agent. Suitable agents include
without
limit pharmaceutically active ingredients, drugs, food additives, pesticides,
herbicides, toxins, industrial chemicals, household chemicals, and other
environmental chemicals. For example, the effect(s) of an agent may be
measured in a "humanized" genetically modified animal, such that the
information
gained therefrom may be used to predict the effect of the agent in a human. In
general, the method comprises contacting a genetically modified animal
comprising at least one inactivated chromosomal sequence involved in ADME
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and toxicology and at least one chromosomally integrated sequence encoding an
orthologous human protein involved in ADME and toxicology with the agent, and
comparing results of a selected parameter to results obtained from contacting
a
wild-type animal with the same agent. Selected parameters include but are not
limited to (a) rate of elimination of the agent or its metabolite(s); (b)
circulatory
levels of the agent or its metabolite(s); (c)bioavailability of the agent or
its
metabolite(s); (d) rate of metabolism of the agent or its metabolite(s); (e)
rate of
clearance of the agent or its metabolite(s); (f) toxicity of the agent or its
metabolite(s); (g) efficacy of the agent or its metabolite(s); (h) disposition
of the
agent or its metabolite(s); and (i) extrahepatic contribution to metabolic
rate and
clearance of the agent or its metabolite(s).
[0231] Also provided are methods to assess the effect(s) of an
agent in an isolated cell comprising at least one edited chromosomal sequence
involved in ADME and toxicology, as well as methods of using lysates of such
cells (or cells derived from a genetically modified animal disclosed herein)
to
assess the effect(s) of an agent. For example, the role of a particular
protein
involved in ADME and toxicology in the metabolism of a particular agent may be
determined using such methods. Similarly, substrate specificity and
pharmacokinetic parameters may be readily determined using such methods.
Those of skill in the art are familiar with suitable tests and/or procedures.
[0232] Among the proteins of interest that are involved in drug
ADME and toxicology are the ABC transporters, also known as efflux transport
proteins. Thus, for example, the genetically modified animals as described
herein containing an edited chromosomal sequences encoding an ABC
transporter can be useful for screening biologically active agents including
drugs
and for investigating their distribution, efficacy, metabolism and/or
toxicity. These
screening methods are of particular use for assessing with improved
predictability the behavior of a drug in a genetically modified animal as
described
herein, e.g. in a genetically modified rat, as a model for humans.
Accordingly, the
present disclosure also features a method of assessing the ADME profile of a
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drug in a genetically modified animal, as part of a drug screening or
evaluation
process. A candidate therapeutic agent, i.e, a candidate drug can be
administered to a genetically modified animal that harbors a targeted gene
knock-out and/or an expressed transgene, which was achieved through use of
ZFNs. The knock-out or knock-in gene is associated with at least one aspect of
the drug ADME profile or toxicology, and/or metabolism, and may be derived
from a mouse, rat, or human genome.
[0233] For example, a method of screening for the target of a test
compound can make use of a genetically modified animal in which any one or
more of an ABC transporter such as Mdrl a, Mdrl b, PXR, BCRP, MRP1, or
MRP2 are knocked out, thus inhibiting or eliminating transmembrane transport
mediated by the knocked out protein(s). Such an animal can be exposed to a
test compound suspected of inhibiting transporter activity of the knocked-out
protein(s). Inhibition of transport by the compound in the genetically
modified
animal can be determined using any of a number of routine laboratory tests and
techniques, and the inhibition of transport may be compared to that observed
in a
wild-type animal treated with the same test compound. A difference in the
effect
of the test compound in the two animals can be indicative of the target of the
test
compound. Further, inhibition of one or more ABC transporter proteins such as
Mdrl a, Mdrl b, PXR, BCRP, MRP1, or MRP2, may improve certain ADME
characteristics of a candidate therapeutic agent. For example, the absorption
or
efficacy of a candidate therapeutic compound may be improved by knock-ing out
expression of one or more ABC transporter proteins such as Mdrl a, Mdrl b,
PXR, BCRP, MRP1, or MRP2, in a particular tissue. It will thus be understood
that genetically modified animals and cells as described herein, for example
genetically modified animals and cells including a genetic modification of one
or
more ABC transporter proteins, can be used advantageously in many methods
that evaluate the ADME and toxicology characteristics of a candidate
therapeutic
compound, to identify targets of a test compound, or to identify ways in which
the
ADME characteristics and toxicology of a candidate compound may be improved.
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[0234] The overwhelming need to accurately predict how drugs and
environmental chemicals may affect large populations can be readily
appreciated. The genetically modified animals, embryos, cells and cell lines
described herein can be used to analyze how various compounds may interact
with biological systems. Genetically modified cells and cell lines can be
used,
for example, to control many of the known complexities in biological systems
to
improve the predictive ability of cell-based assay systems, such as those used
to
evaluate new molecular entities and possible drug-drug interactions. More
specifically, it is recognized that biological systems typically include
multiple
components that respond to exposure to new, potentially harmful compounds.
[0235] The "ADMET system" has been described as including five
components. The first component are those biological systems that when
disrupted signal the drug metabolism system to turn on, and may include stress
response and DNA repair pathways. Once the drug metabolism system is
activated "xenosensors" surveil for exogenous molecules that need removal.
Detection of an exogenous molecule by the xenosensors then activates a
cascade of gene inductions that up-regulate the enzymes responsible for
metabolizing exogenous molecules into forms for easier removal. The enzymes
of the third ADMET component include Phase I enzymes that include at least
three classes of oxidases, of which the best known class is the cytochrome
P450
s class. Cytochrome 450 enzymes typically add reactive hydroxyl moieties to
potential toxins to inactivate and render the toxins more polar (soluble). The
fourth component of the ADMET system includes at least seven classes of
enzymes that further alter the products of Phase I enzymatic modification.
Typically, these enzymes are conjugating enzymes that add hydrophilic moieties
to make the now oxidized xenobiotics even more water soluble ADMET, and
readily collected and excreted through urine or bile. The last component is
the
transporter system involving transporter proteins, such as the ABC
transporters,
that function as molecular pumps to facilitate the movement of the xenobiotics
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from one tissue to another. The transporter proteins are responsible for
moving
drugs into a cell, out of a cell, or through a cell.
[0236] Each component of the ADMET system has its own set of
substrate structural specificities, which must be taken into account by any
assay.
Making predictability an even larger challenge is that, for critical members
of
each of the five component classes, a constellation of genetic polymorphisms
exists in the population and these can dramatically affect activity towards
specific
xenobiotic chemical structures. The growing field of pharmacogenomics
addresses the challenges created by such genetic variation. In addition,
gender
differences in how the different components of the xenobiotic system respond
are
also known to play a role in variations in drug metabolism.
[0237] Thus, genetically modified animals, cells and particularly cell
lines as described herein will be useful as the basis for cell-based assays
with
improved predictive ability with respect to a drug's clinical outcome or a
chemical's toxicological problems. Panels of cell lines are expressly
contemplated for such a purpose. For example, cell-based assays can be
created that are representative of the target tissue where metabolism or
toxicity
of a drug compound is likely to occur. Presently, standard assays are usually
run
in transformed cell lines that are derived from the target tissue and have
some
concordant functional properties. To create even better cell-based assays that
are even more representative of the natural state, genetically modified and
differentiated pluripotent cells could be used to replace the immortalized
cell
components. In other words, genetically modified cell lines can be used in
more
highly predictive cell-based assays suitable for high-throughput, high-content
compound screening.
[0238] Accordingly, the present disclosure contemplates ZFN-
mediated genetic modifications of genes relevant to each part of the
xenobiotic
metabolism machinery. Such modifications include knock-outs, knock-ins of
reporter tags, the introduction of specific mutations known to affect
activity, or
combinations of these. For example, the genetically modified cells and cell
lines
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can be used to create tissue-specific, gender-specific, and/or population-
reflective transporter panels; cell-based xenosenor assay panels that are
tissue-
specific and functionally reflective of the population; and induction assays
that
measure the genetic activation of different drug metabolism components and
overt toxicological responses such as genotoxicity, cardiotoxicity, and
apoptosis.
[0239] According to the present disclosure, tissue-specific lines can
be established that have been modified to isolate specific transporter
activities
and predict the reaction of populations to individual chemical entities. For
example, ZFNs can be used to create transporter gene knock-outs in enterocyte
cell lines, such as to introduce important, common polymorphisms into
enterocyte cell lines, and in cell lines representative of liver, blood-brain-
barrier
(brain micro-vasculature endothelial cells), kidney and any relevant tissue-
specific cell lines. Panels of cell lines can include enterocytes (Caco2 or
BBe1)
with knock-outs of individual transporter proteins (e.g. MDR-1, MRP1, 2, 3, 4,
6,
BCRP), knock-out combinations to isolate effects of individual transporters
(e.g.
BCRP and MRP2, MDR-1 and MRP2, MRP-3 and MRP1), and a transporter null
line (i.e. all 7 transporters knocked out). Panels of enterocytes may include
knock-outs of OATP-2B1, PEPT-1, and OCT-N2. Panels of enterocytes may be
created which include prevalent polymorphisms in the major transporter genes
that affect drug transport and are of concern to pharmaceutical researchers.
[0240] The three xenosensors in humans (PXR, AhR and CAR) are
known to have overlapping specificities in response to xenobiotics. Knowing
which xenosensors are activated and to what extent by any particular chemical
compound is also an important consideration for understanding drug responses,
and drug-drug interactions. Creating panels of cells that report induction by
the
xenosensors can delineate the specificities. Further modifying the cells to
address functionally important polymorphisms in the xenosensors would permit
population predictions. ZFNs can be used to create knock-out cell lines
analogous to transporter knockout cell lines as described above, and to create
reporter cell lines that express different fluorescent proteins upon induction
of
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different xenosensors. For example, cell lines can be created in which green
FP
is expressed if PXR is induced, red FP if CAR activity is induced, blue FP if
AhR
is induced. All lines may be constructed in the relevant tissue-type cell
lines, i.e.
intestine, liver, kidney, brain, and heart. Panels of cells can be created
that
represent the tissues most involved with drug toxicity and metabolism, and in
which each xenosensor (CAR, PXR, AhR) is knocked out. Cell lines can also be
produced that produce fluorescent proteins upon the activation of each of the
three xenosensors.
[0241] Also contemplated are induction assays of ADME
biotransformation and toxicological response genes. While the activities of
each
of the many Phase I and Phase II enzymes can be done today in simple
biochemical assays, available assays cannot measure, in high-throughput
fashion, the induction of any particular enzyme by an exogenously added
xenobiotic. ZFNs can be used to create genetically modified cell lines as
described herein that can provide the basis for assays that can measure the
up/down regulation of key Phase I and Phase II enzymes, along with genes
involved in a toxicological response. For example, ZFNs can be used to build
lines that have a reporter gene (e.g. encoding fluorescent protein or
luciferase)
inserted proximal to the promoter of the gene being measured. These gene
targets can be any of the critical Phase I, Phase II, transporter, genotox, or
apoptosis/necrosis pathway components. Tissue-specific panels of cells can
also
be created, which report on the activation of genes encoding either the Phase
I
or Phase II enzymes, the transporters, or toxicity response pathways (e.g.,
genotoxicity or apoptosis).
N. developmental models
[0242] A method of the invention may be used to create an animal
or cell that may be used as a developmental model. Such a model may be used
to study embryogenesis, organ development, organ system development, or the
like. For instance, in one embodiment, a method of the invention may be used
to
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create an animal or cell that comprises a chromosomal edit in one or more
nucleic acid sequences associated with the development of an organ or organ
system. Non-limiting examples of organs include the brain, eyes, nose, ears,
throat, mouth (including teeth, tongue, lips, gums), spinal cord, bones,
heart,
blood vessels, lungs, liver, pancreas, gall bladder, spleen, esophagus,
stomach,
small intestines, large intestines, appendix, rectum, bladder, organs of the
reproductive system, organs of the immune system (including thyroid, lymph
nodes, lymph vessels), and organs of the endocrine system. Non-limiting
examples of organ systems include the nervous system, the circulatory system,
the digestive system, the respiratory system, the skeletal system, the
lymphatic
system, the reproductive system, the muscular system, the integumentary
system, the excretory system, and the endocrine system.
[0243] In one embodiment, a method of the invention may be used
to create an animal or cell in which at least one chromosomal sequence
associated with neurodevelopment has been edited. Suitable chromosomal edits
may include, but are not limited to, the type of edits detailed in section
I(f) above.
A chromosomal sequence associated with neurodevelopment may be a protein
coding sequence or a control sequence. In certain embodiments, a
neurodevelopmental sequence may be associated with a neurodevelopmental
disorder, with biochemical pathways associated with a neurodevelopmental
disorder, or associated with a disorder such as phenylketonuria that is
closely
associated with neurodevelopmental disorders.
[0244] Non-limiting examples of neurodevelopmental-associated
sequences include A2BP1 [ataxin 2-binding protein 1], AADAT [aminoadipate
aminotransferase], AANAT [arylalkylamine N-acetyltransferase], ABAT [4-
aminobutyrate aminotransferase], ABCA1 [ATP-binding cassette, sub-family A
(ABC1), member 1 ], ABCA13 [ATP-binding cassette, sub-family A (ABC1),
member 13], ABCA2 [ATP-binding cassette, sub-family A (ABC1), member 2],
ABCB1 [ATP-binding cassette, sub-family B (MDR/TAP), member 1], ABCB11
[ATP-binding cassette, sub-family B (MDR/TAP), member 11], ABCB4 [ATP-
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binding cassette, sub-family B (MDR/TAP), member 4], ABCB6 [ATP-binding
cassette, sub-family B (MDR/TAP), member 6], ABCB7 [ATP-binding cassette,
sub-family B (MDR/TAP), member 7], ABCC1 [ATP-binding cassette, sub-family
C (CFTR/MRP), member 1], ABCC2 [ATP-binding cassette, sub-family C
(CFTR/MRP), member 2], ABCC3 [ATP-binding cassette, sub-family C
(CFTR/MRP), member 3], ABCC4 [ATP-binding cassette, sub-family C
(CFTR/MRP), member 4], ABCD1 [ATP-binding cassette, sub-family D (ALD),
member 1], ABCD3 [ATP-binding cassette, sub-family D (ALD), member 3],
ABCG1 [ATP-binding cassette, sub-family G (WHITE), member 1], ABCG2 [ATP-
binding cassette, sub-family G (WHITE), member 2], ABCG4 [ATP-binding
cassette, sub-family G (WHITE), member 4], ABHD1 1 [abhydrolase domain
containing 11], ABI1 [abl-interactor 1], ABL1 [c-abl oncogene 1, receptor
tyrosine
kinase], ABL2 [v-abl Abelson murine leukemia viral oncogene homolog 2 (arg,
Abelson-related gene)], ABLIM1 [actin binding LIM protein 1], ABLIM2 [actin
binding LIM protein family, member 2], ABLIM3 [actin binding LIM protein
family,
member 3], ABO [ABO blood group (transferase A, alpha 1-3-N-
acetylgalactosaminyltransferase; transferase B, alpha 1-3-
galactosyltransferase)], ACAA1 [acetyl-Coenzyme A acyltransferase 1 ], ACACA
[acetyl-Coenzyme A carboxylase alpha], ACACB [acetyl-Coenzyme A
carboxylase beta], ACADL [acyl-Coenzyme A dehydrogenase, long chain],
ACADM [acyl-Coenzyme A dehydrogenase, C-4 to C-12 straight chain], ACADS
[acyl-Coenzyme A dehydrogenase, C-2 to C-3 short chain], ACADSB [acyl-
Coenzyme A dehydrogenase, short/branched chain], ACAN [aggrecan], ACAT2
[acetyl-Coenzyme A acetyltransferase 2], ACCN1 [amiloride-sensitive cation
channel 1, neuronal], ACE [angiotensin I converting enzyme (peptidyl-
dipeptidase A) 1], ACE2 [angiotensin I converting enzyme (peptidyl-dipeptidase
A) 2], ACHE [acetylcholinesterase (Yt blood group)], ACLY [ATP citrate lyase],
ACO1 [aconitase 1, soluble], ACTA1 [actin, alpha 1, skeletal muscle], ACTB
[actin, beta], ACTC1 [actin, alpha, cardiac muscle 1], ACTG1 [actin, gamma 1],
ACTL6A [actin-like 6A], ACTL6B [actin-like 6B], ACTN1 [actinin, alpha 1],
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ACTR1A [ARP1 actin-related protein 1 homolog A, centractin alpha (yeast)],
ACTR2 [ARP2 actin-related protein 2 homolog (yeast)], ACTR3 [ARP3 actin-
related protein 3 homolog (yeast)], ACTR3B [ARP3 actin-related protein 3
homolog B (yeast)], ACVR1 [activin A receptor, type I], ACVR2A [activin A
receptor, type IIA], ADA [adenosine deaminase], ADAM10 [ADAM
metallopeptidase domain 10], ADAM1 1 [ADAM metallopeptidase domain 11],
ADAM12 [ADAM metallopeptidase domain 12], ADAM15 [ADAM
metallopeptidase domain 15], ADAM17 [ADAM metallopeptidase domain 17],
ADAM18 [ADAM metallopeptidase domain 18], ADAM19 [ADAM
metallopeptidase domain 19 (meltrin beta)], ADAM2 [ADAM metallopeptidase
domain 2], ADAM20 [ADAM metallopeptidase domain 20], ADAM21 [ADAM
metallopeptidase domain 21], ADAM22 [ADAM metallopeptidase domain 22],
ADAM23 [ADAM metallopeptidase domain 23], ADAM28 [ADAM
metallopeptidase domain 28], ADAM29 [ADAM metallopeptidase domain 29],
ADAM30 [ADAM metallopeptidase domain 30], ADAM8 [ADAM metallopeptidase
domain 8], ADAMS [ADAM metallopeptidase domain 9 (meltrin gamma)],
ADAMTS1 [ADAM metallopeptidase with thrombospondin type 1 motif, 1],
ADAMTS13 [ADAM metallopeptidase with thrombospondin type 1 motif, 13],
ADAMTS4 [ADAM metallopeptidase with thrombospondin type 1 motif, 4],
ADAMTS5 [ADAM metallopeptidase with thrombospondin type 1 motif, 5],
ADAP2 [ArfGAP with dual PH domains 2], ADAR [adenosine deaminase, RNA-
specific], ADARB1 [adenosine deaminase, RNA-specific, B1 (RED1 homolog
rat)], ADCY1 [adenylate cyclase 1 (brain)], ADCY10 [adenylate cyclase 10
(soluble)], ADCYAP1 [adenylate cyclase activating polypeptide 1 (pituitary)],
ADD1 [adducin 1 (alpha)], ADD2 [adducin 2 (beta)], ADH1A [alcohol
dehydrogenase 1A (class I), alpha polypeptide], ADIPOQ [adiponectin, C1Q and
collagen domain containing], ADK [adenosine kinase], ADM [adrenomedullin],
ADNP [activity-dependent neuroprotector homeobox], ADORA1 [adenosine Al
receptor], ADORA2A [adenosine A2a receptor], ADORA2B [adenosine A2b
receptor], ADORA3 [adenosine A3 receptor], ADRA1 B [adrenergic, alpha-1 B-,
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receptor], ADRA2A [adrenergic, alpha-2A-, receptor], ADRA2B [adrenergic,
alpha-2B-, receptor], ADRA2C [adrenergic, alpha-2C-, receptor], ADRB1
[adrenergic, beta-l-, receptor], ADRB2 [adrenergic, beta-2-, receptor,
surface],
ADRB3 [adrenergic, beta-3-, receptor], ADRBK2 [adrenergic, beta, receptor
kinase 2], ADSL [adenylosuccinate lyase], AFF2 [AF4/FMR2 family, member 2],
AFM [afamin], AFP [alpha-fetoprotein], AGAP1 [ArfGAP with GTPase domain,
ankyrin repeat and PH domain 1], AGER [advanced glycosylation end product-
specific receptor], AGFG1 [ArfGAP with FG repeats 1], AGPS [alkylglycerone
phosphate synthase], AGRN [agrin], AGRP [agouti related protein homolog
(mouse)], AGT [angiotensinogen (serpin peptidase inhibitor, Glade A, member
8)], AGTR1 [angiotensin II receptor, type 1], AGTR2 [angiotensin II receptor,
type
2], AHOY [adenosylhomocysteinase], AHI1 [Abelson helper integration site 1],
AHR [aryl hydrocarbon receptor], AHSG [alpha-2-HS-glycoprotein], AICDA
[activation-induced cytidine deaminase], AIFM1 [apoptosis-inducing factor,
mitochondrion-associated, 1], AIRE [autoimmune regulator], AKAP1 2 [A kinase
(PRKA) anchor protein 12], AKAP9 [A kinase (PRKA) anchor protein (yotiao) 9],
AKR1A1 [aldo-keto reductase family 1, member Al (aldehyde reductase)],
AKR1 131 [aldo-keto reductase family 1, member 131 (aldose reductase)], AKR1
C3
[aldo-keto reductase family 1, member C3 (3-alpha hydroxysteroid
dehydrogenase, type II)], AKT1 [v-akt murine thymoma viral oncogene homolog
1], AKT2 [v-akt murine thymoma viral oncogene homolog 2], AKT3 [v-akt murine
thymoma viral oncogene homolog 3 (protein kinase B, gamma)], ALAD
[aminolevulinate, delta-, dehydratase], ALB [albumin], ALB [albumin], ALCAM
[activated leukocyte cell adhesion molecule], ALDHIAI [aldehyde
dehydrogenase 1 family, member Al ], ALDH3A1 [aldehyde dehydrogenase 3
family, memberA1], ALDH5A1 [aldehyde dehydrogenase 5 family, member A1],
ALDH7A1 [aldehyde dehydrogenase 7 family, member Al ], ALDH9A1 [aldehyde
dehydrogenase 9 family, member Al ], ALDOA [aldolase A, fructose-
bisphosphate], ALDOB [aldolase B, fructose-bisphosphate], ALDOC [aldolase C,
fructose-bisphosphate], ALK [anaplastic lymphoma receptor tyrosine kinase],
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ALOX12 [arachidonate 12-lipoxygenase], ALOX5 [arachidonate 5-lipoxygenase],
ALOX5AP [arachidonate 5-lipoxygenase-activating protein ], ALPI [alkaline
phosphatase, intestinal], ALPL [alkaline phosphatase, liver/bone/kidney], ALPP
[alkaline phosphatase, placental (Regan isozyme)], ALS2 [amyotrophic lateral
sclerosis 2 (juvenile)], AMACR [alpha-methylacyl-CoA racemase], AMBP [alpha-
1-microglobulin/bikunin precursor], AMPH [amphiphysin], ANG [angiogenin,
ribonuclease, RNase A family, 5], ANGPT1 [angiopoietin 1], ANGPT2
[angiopoietin 2], ANGPTL3 [angiopoietin-like 3], ANK1 [ankyrin 1,
erythrocytic],
ANK3 [ankyrin 3, node of Ranvier (ankyrin G)], ANKRD1 [ankyrin repeat domain
1 (cardiac muscle)], ANP32E [acidic (leucine-rich) nuclear phosphoprotein 32
family, member E], ANPEP [alanyl (membrane) aminopeptidase], ANXA1
[annexin Al ], ANXA2 [annexin A2], ANXA5 [annexin A5], AP1 S1 [adaptor-related
protein complex 1, sigma 1 subunit], AP1S2 [adaptor-related protein complex 1,
sigma 2 subunit], AP2A1 [adaptor-related protein complex 2, alpha 1 subunit],
AP2B1 [adaptor-related protein complex 2, beta 1 subunit], APAF1 [apoptotic
peptidase activating factor 1], APBA1 [amyloid beta (A4) precursor protein-
binding, family A, member 1], APBA2 [amyloid beta (A4) precursor protein-
binding, family A, member 2], APBB1 [amyloid beta (A4) precursor protein-
binding, family B, member 1 (Fe65)], APBB2 [amyloid beta (A4) precursor
protein-binding, family B, member 2], APC [adenomatous polyposis coli], APCS
[amyloid P component, serum], APEX1 [APEX nuclease (multifunctional DNA
repair enzyme) 1], APH1 B [anterior pharynx defective 1 homolog B (C.
elegans)],
APLP1 [amyloid beta (A4) precursor-like protein 1], APOA1 [apolipoprotein A-
I],
APOA5 [apolipoprotein A-V], APOB [apolipoprotein B (including Ag(x) antigen)],
APOC2 [apolipoprotein C-II], APOD [apolipoprotein D], APOE [apolipoprotein E],
APOM [apolipoprotein M], APP [amyloid beta (A4) precursor protein], APPL1
[adaptor protein, phosphotyrosine interaction, PH domain and leucine zipper
containing 1], APRT [adenine phosphoribosyltransferase], APTX [aprataxin],
AQP1 [aquaporin 1 (Colton blood group)], AQP2 [aquaporin 2 (collecting duct)],
AQP3 [aquaporin 3 (Gill blood group)], AQP4 [aquaporin 4], AR [androgen
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receptor], ARC [activity-regulated cytoskeleton-associated protein], AREG
[amphiregulin], ARFGEF2 [ADP-ribosylation factor guanine nucleotide-exchange
factor 2 (brefeldin A-inhibited)], ARG1 [arginase, liver], ARHGAP1 [Rho GTPase
activating protein 1], ARHGAP32 [Rho GTPase activating protein 32], ARHGAP4
[Rho GTPase activating protein 4], ARHGAP5 [Rho GTPase activating protein 5],
ARHGDIA [Rho GDP dissociation inhibitor (GDI) alpha], ARHGEF1 [Rho guanine
nucleotide exchange factor (GEF) 1], ARHGEF10 [Rho guanine nucleotide
exchange factor (GEF) 10], ARHGEF11 [Rho guanine nucleotide exchange
factor (GEF) 11 ], ARHGEF1 2 [Rho guanine nucleotide exchange factor (GEF)
12], ARHGEF15 [Rho guanine nucleotide exchange factor (GEF) 15],
ARHGEF16 [Rho guanine nucleotide exchange factor (GEF) 16], ARHGEF2
[Rho/Rac guanine nucleotide exchange factor (GEF) 2], ARHGEF3 [Rho guanine
nucleotide exchange factor (GEF) 3], ARHGEF4 [Rho guanine nucleotide
exchange factor (GEF) 4], ARHGEF5 [Rho guanine nucleotide exchange factor
(GEF) 5], ARHGEF6 [Rac/Cdc42 guanine nucleotide exchange factor (GEF) 6],
ARHGEF7 [Rho guanine nucleotide exchange factor (GEF) 7], ARHGEF9
[Cdc42 guanine nucleotide exchange factor (GEF) 9], ARID1A [AT rich
interactive domain 1A (SWI-like)], ARID1 B [AT rich interactive domain 1 B
(SWI1-
like)], ARL13B [ADP-ribosylation factor-like 13B], ARPC1A [actin related
protein
2/3 complex, subunit 1A, 41 kDa], ARPC1 B [actin related protein 2/3 complex,
subunit 1 B, 41 kDa], ARPC2 [actin related protein 2/3 complex, subunit 2,
34kDa],
ARPC3 [actin related protein 2/3 complex, subunit 3, 21 kDa], ARPC4 [actin
related protein 2/3 complex, subunit 4, 20kDa], ARPC5 [actin related protein
2/3
complex, subunit 5, 16kDa], ARPC5L [actin related protein 2/3 complex, subunit
5-like], ARPP19 [cAMP-regulated phosphoprotein, 19kDa], ARR3 [arrestin 3,
retinal (X-arrestin)], ARRB2 [arrestin, beta 2], ARSA [arylsulfatase A], ARTN
[artemin], ARX [aristaless related homeobox], ASCL1 [achaete-scute complex
homolog 1 (Drosophila)], ASMT [acetylserotonin 0-methyltransferase], ASPA
[aspartoacylase (Canavan disease)], ASPG [asparaginase homolog (S.
cerevisiae)], ASPH [aspartate beta-hydroxylase], ASPM [asp (abnormal spindle)
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homolog, microcephaly associated (Drosophila)], ASRGL1 [asparaginase like 1],
ASS1 [argininosuccinate synthase 1], ASTN1 [astrotactin 1], ATAD5 [ATPase
family, AAA domain containing 5], ATF2 [activating transcription factor 2],
ATF4
[activating transcription factor 4 (tax-responsive enhancer element B67)],
ATF6
[activating transcription factor 6], ATM [ataxia telangiectasia mutated],
ATOH1
[atonal homolog 1 (Drosophila)], ATOX1 [ATX1 antioxidant protein 1 homolog
(yeast)], ATP10A [ATPase, class V, type 10A], ATP2A2 [ATPase, Ca++
transporting, cardiac muscle, slow twitch 2], ATP2B2 [ATPase, Ca++
transporting, plasma membrane 2], ATP2B4 [ATPase, Ca++ transporting, plasma
membrane 4], ATP5O [ATP synthase, H+ transporting, mitochondrial F1
complex, 0 subunit], ATP6AP1 [ATPase, H+ transporting, lysosomal accessory
protein 1], ATP6VOC [ATPase, H+ transporting, lysosomal 16kDa, VO subunit c],
ATP7A [ATPase, Cu++ transporting, alpha polypeptide], ATP8A1 [ATPase,
aminophospholipid transporter (APLT), class I, type 8A, member 1], ATR [ataxia
telangiectasia and Rad3 related], ATRN [attractin], ATRX [alpha
thalassemia/mental retardation syndrome X-linked (RAD54 homolog, S.
cerevisiae)], ATXN1 [ataxin 1], ATXN2 [ataxin 2], ATXN3 [ataxin 3], AURKA
[aurora kinase A], AUTS2 [autism susceptibility candidate 2], AVP [arginine
vasopressin], AVPR1A [arginine vasopressin receptor 1A], AXIN2 [axin 2], AXL
[AXL receptor tyrosine kinase], AZU1 [azurocidin 1], B2M [beta-2-
microglobulin],
B3GNT2 [UDP-GIcNAc:betaGal beta-1 [3-N-acetylglucosaminyltransferase 2],
B9D1 [B9 protein domain 1 ], BACE1 [beta-site APP-cleaving enzyme 1 ], BACE2
[beta-site APP-cleaving enzyme 2], BACH1 [BTB and CNC homology 1, basic
leucine zipper transcription factor 1 ], BAD [BCL2-associated agonist of cell
death], BAGE2 [B melanoma antigen family, member 2], BAIAP2 [BAI1-
associated protein 2], BAIAP2L1 [BAI1-associated protein 2-like 1], BAK1 [BCL2-
antagonist/killer 1], BARD1 [BRCA1 associated RING domain 1], BARHLI [BarH-
like homeobox 1], BARHL2 [BarH-like homeobox 2], BASP1 [brain abundant,
membrane attached signal protein 1], BAX [BCL2-associated X protein], BAZ1A
[bromodomain adjacent to zinc finger domain, 1A], BAZ1 B [bromodomain
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adjacent to zinc finger domain, 1 B], BBS9 [Bardet-Biedl syndrome 9], BCAR1
[breast cancer anti-estrogen resistance 1], BCHE [butyrylcholinesterase],
BCL10
[B-cell CLL/lymphoma 10], BCL2 [B-cell CLL/lymphoma 2], BCL2A1 [BCL2-
related protein Al], BCL2L1 [BCL2-like 1], BCL2L1 1 [BCL2-like 11 (apoptosis
facilitator)], BCL3 [B-cell CLL/lymphoma 3], BCL6 [B-cell CLL/lymphoma 6],
BCL7A [B-cell CLL/lymphoma 7A], BCL7B [B-cell CLL/lymphoma 7B], BCL7C [B-
cell CLL/lymphoma 7C], BCR [breakpoint cluster region], BDKRB1 [bradykinin
receptor B1], BDNF [brain-derived neurotrophic factor], BECN1 [beclin 1,
autophagy related], BEST1 [bestrophin 1], BEX1 [brain expressed, X-linked 1],
BEX2 [brain expressed X-linked 2], BGLAP [bone gamma-carboxyglutamate
(gla) protein], BGN [biglycan], BID [BH3 interacting domain death agonist],
BIN1
[bridging integrator 1], BIRC2 [baculoviral IAP repeat-containing 2], BIRC3
[baculoviral IAP repeat-containing 3], BIRC5 [baculoviral IAP repeat-
containing
5], BIRC7 [baculoviral IAP repeat-containing 7], BLK [B lymphoid tyrosine
kinase], BLVRB [biliverdin reductase B (flavin reductase (NADPH))], BMI1 [BMI1
polycomb ring finger oncogene], BMP1 [bone morphogenetic protein 1], BMP10
[bone morphogenetic protein 10], BMP15 [bone morphogenetic protein 15],
BMP2 [bone morphogenetic protein 2], BMP3 [bone morphogenetic protein 3],
BMP4 [bone morphogenetic protein 4], BMP5 [bone morphogenetic protein 5],
BMP6 [bone morphogenetic protein 6], BMP7 [bone morphogenetic protein 7],
BMP8A [bone morphogenetic protein 8a], BMP8B [bone morphogenetic protein
8b], BMPR1A [bone morphogenetic protein receptor, type IA], BMPR1 B [bone
morphogenetic protein receptor, type IB], BMPR2 [bone morphogenetic protein
receptor, type II (serine/threonine kinase)], BOC [Boc homolog (mouse)], BOK
[BCL2-related ovarian killer], BPI [bactericidal/permeability-increasing
protein],
BRAF [v-raf murine sarcoma viral oncogene homolog 131], BRCA1 [breast cancer
1, early onset], BRCA2 [breast cancer 2, early onset], BRWD1 [bromodomain
and WD repeat domain containing 1], BSND [Bartter syndrome, infantile, with
sensorineural deafness (Barttin)], BST2 [bone marrow stromal cell antigen 2],
BTBD10 [BTB (POZ) domain containing 10], BTC [betacellulin], BTD
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[biotinidase], BTG3 [BTG family, member 3], BTK [Bruton agammaglobulinemia
tyrosine kinase], BTN1A1 [butyrophilin, subfamily 1, member Al], BUB1B
[budding uninhibited by benzimidazoles 1 homolog beta (yeast)], C15orf2
[chromosome 15 open reading frame 2], C16orf75 [chromosome 16 open
reading frame 75], C17orf42 [chromosome 17 open reading frame 42], C1orf187
[chromosome 1 open reading frame 187], C1 R [complement component 1, r
subcomponent], C1 S [complement component 1, s subcomponent], C21 orf2
[chromosome 21 open reading frame 2], C21orf33 [chromosome 21 open
reading frame 33], C21orf45 [chromosome 21 open reading frame 45], C21orf62
[chromosome 21 open reading frame 62], C21orf74 [chromosome 21 open
reading frame 74], C3 [complement component 3], C3orf58 [chromosome 3 open
reading frame 58], C4A [complement component 4A (Rodgers blood group)],
C4B [complement component 4B (Chido blood group)], C5AR1 [complement
component 5a receptor 1], C6orf106 [chromosome 6 open reading frame 106],
C6orf25 [chromosome 6 open reading frame 25], CA1 [carbonic anhydrase I],
CA2 [carbonic anhydrase II], CA3 [carbonic anhydrase III, muscle specific],
CA6
[carbonic anhydrase VI], CA9 [carbonic anhydrase IX], CABIN1 [calcineurin
binding protein 1], CABLES1 [CdkS and AN enzyme substrate 1], CACNA1 B
[calcium channel, voltage-dependent, N type, alpha 1B subunit], CACNA1C
[calcium channel, voltage-dependent, L type, alpha 1 C subunit], CACNA1 G
[calcium channel, voltage-dependent, T type, alpha 1 G subunit], CACNA1 H
[calcium channel, voltage-dependent, T type, alpha 1 H subunit], CACNA2D1
[calcium channel, voltage-dependent, alpha 2/delta subunit 1], CADM1 [cell
adhesion molecule 1], CADPS2 [Ca++-dependent secretion activator 2], CALB2
[calbindin 2], CALCA [calcitonin-related polypeptide alpha], CALCR [calcitonin
receptor], CALM3 [calmodulin 3 (phosphorylase kinase, delta)], CALR
[calreticulin], CAMK1 [calcium/calmodulin-dependent protein kinase I], CAMK2A
[calcium/calmodulin-dependent protein kinase II alpha], CAMK2B
[calcium/calmodulin-dependent protein kinase II beta], CAMK2G
[calcium/calmodulin-dependent protein kinase II gamma], CAMK4
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[calcium/calmodulin-dependent protein kinase IV], CAMKK2 [calcium/calmodulin-
dependent protein kinase kinase 2, beta], CAMP [cathelicidin antimicrobial
peptide], CANT1 [calcium activated nucleotidase 1], CANX [calnexin], CAPN1
[calpain 1, (mu/1) large subunit], CAPN2 [calpain 2, (m/II) large subunit],
CAPN5
[calpain 5], CAPZA1 [capping protein (actin filament) muscle Z-line, alpha 1],
CARD16 [caspase recruitment domain family, member 16], CARM1 [coactivator-
associated arginine methyltransferase 1], CARTPT [CART prepropeptide], CASK
[calcium/calmodulin-dependent serine protein kinase (MAGUK family)], CASP1
[caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta,
convertase)], CASP10 [caspase 10, apoptosis-related cysteine peptidase],
CASP2 [caspase 2, apoptosis-related cysteine peptidase], CASP3 [caspase 3,
apoptosis-related cysteine peptidase], CASP6 [caspase 6, apoptosis-related
cysteine peptidase], CASP7 [caspase 7, apoptosis-related cysteine peptidase],
CASP8 [caspase 8, apoptosis-related cysteine peptidase], CASP8AP2 [caspase
8 associated protein 2], CASP9 [caspase 9, apoptosis-related cysteine
peptidase], CASR [calcium-sensing receptor], CAST [calpastatin], CAT
[catalase], CAV1 [caveolin 1, caveolae protein, 22kDa], CAV2 [caveolin 2],
CAV3
[caveolin 3], CBL [Cas-Br-M (murine) ecotropic retroviral transforming
sequence],
CBLB [Cas-Br-M (murine) ecotropic retroviral transforming sequence b], CBR1
[carbonyl reductase 1], CBR3 [carbonyl reductase 3], CBS [cystathionine-beta-
synthase], CBX1 [chromobox homolog 1 (HP1 beta homolog Drosophila )], CBX5
[chromobox homolog 5 (HP1 alpha homolog, Drosophila)], CC2D2A [coiled-coil
and C2 domain containing 2A], CCBE1 [collagen and calcium binding EGF
domains 1], CCBL1 [cysteine conjugate-beta lyase, cytoplasmic], CCDC50
[coiled-coil domain containing 50], CCK [cholecystokinin], CCKAR
[cholecystokinin A receptor], CCL1 [chemokine (C-C motif) ligand 1], CCL1 1
[chemokine (C-C motif) ligand 11], CCL13 [chemokine (C-C motif) ligand 13],
CCL17 [chemokine (C-C motif) ligand 17], CCL19 [chemokine (C-C motif) ligand
19], CCL2 [chemokine (C-C motif) ligand 2], CCL20 [chemokine (C-C motif)
ligand 20], CCL21 [chemokine (C-C motif) ligand 21], CCL22 [chemokine (C-C
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motif) ligand 22], CCL26 [chemokine (C-C motif) ligand 26], CCL27 [chemokine
(C-C motif) ligand 27], CCL3 [chemokine (C-C motif) ligand 3], CCL4 [chemokine
(C-C motif) ligand 4], CCL5 [chemokine (C-C motif) ligand 5], CCL7 [chemokine
(C-C motif) ligand 7], CCL8 [chemokine (C-C motif) ligand 8], CCNA1 [cyclin
Al],
CCNA2 [cyclin A2], CCNB1 [cyclin B1], CCND1 [cyclin D1], CCND2 [cyclin D2],
CCND3 [cyclin D3], CCNG1 [cyclin G1], CCNH [cyclin H], CCNT1 [cyclin T1],
CCR1 [chemokine (C-C motif) receptor 1], CCR3 [chemokine (C-C motif)
receptor 3], CCR4 [chemokine (C-C motif) receptor 4], CCR5 [chemokine (C-C
motif) receptor 5], CCR6 [chemokine (C-C motif) receptor 6], CCR7 [chemokine
(C-C motif) receptor 7], COTS [chaperonin containing TCP1, subunit 5
(epsilon)],
CD14 [CD14 molecule], CD19 [CD19 molecule], CD1 A [CD1 a molecule], CD1 B
[CD1 b molecule], CD1D [CD1 d molecule], CD2 [CD2 molecule], CD209 [CD209
molecule], CD22 [CD22 molecule], CD244 [CD244 molecule, natural killer cell
receptor 2B4], CD247 [CD247 molecule], CD27 [CD27 molecule], CD274
[CD274 molecule], CD28 [CD28 molecule], CD2AP [CD2-associated protein],
CD33 [CD33 molecule], CD34 [CD34 molecule], CD36 [CD36 molecule
(thrombospondin receptor)], CD3E [CD3e molecule, epsilon (CD3-TCR
complex)], CD3G [CD3g molecule, gamma (CD3-TCR complex)], CD4 [CD4
molecule], CD40 [CD40 molecule, TNF receptor superfamily member 5],
CD40LG [CD40 ligand], CD44 [CD44 molecule (Indian blood group)], CD46
[CD46 molecule, complement regulatory protein], CD47 [CD47 molecule], CD5
[CD5 molecule], CD55 [CD55 molecule, decay accelerating factor for
complement (Cromer blood group)], CD58 [CD58 molecule], CD59 [CD59
molecule, complement regulatory protein], CD63 [CD63 molecule], CD69 [CD69
molecule], CD7 [CD7 molecule], CD72 [CD72 molecule], CD74 [CD74 molecule,
major histocompatibility complex, class II invariant chain], CD79A [CD79a
molecule, immunoglobulin-associated alpha], CD79B [CD79b molecule,
immunoglobulin-associated beta], CD80 [CD80 molecule], CD81 [CD81
molecule], CD86 [CD86 molecule], CD8A [CD8a molecule], CD9 [CD9 molecule],
CD99 [CD99 molecule], CDA [cytidine deaminase], CDC25A [cell division cycle
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25 homolog A (S. pombe)], CDC25C [cell division cycle 25 homolog C (S.
pombe)], CDC37 [cell division cycle 37 homolog (S. cerevisiae)], CDC42 [cell
division cycle 42 (GTP binding protein, 25kDa)], CDC5L [CDC5 cell division
cycle
5-like (S. pombe)], CDH1 [cadherin 1, type 1, E-cadherin (epithelial)], CDH10
[cadherin 10, type 2 (T2-cadherin)], CDH12 [cadherin 12, type 2 (N-cadherin
2)],
CDH15 [cadherin 15, type 1, M-cadherin (myotubule)], CDH2 [cadherin 2, type 1,
N-cadherin (neuronal)], CDH4 [cadherin 4, type 1, R-cadherin (retinal)], CDH5
[cadherin 5, type 2 (vascular endothelium)], CDH9 [cadherin 9, type 2 (T1-
cadherin)], CDIPT [CDP-diacylglycerol--inositol 3-phosphatidyltransferase
(phosphatidylinositol synthase)], CDK1 [cyclin-dependent kinase 1], CDK14
[cyclin-dependent kinase 14], CDK2 [cyclin-dependent kinase 2], CDK4 [cyclin-
dependent kinase 4], CDK5 [cyclin-dependent kinase 5], CDK5R1 [cyclin-
dependent kinase 5, regulatory subunit 1 (p35)], CDK5RAP2 [CDK5 regulatory
subunit associated protein 2], CDK6 [cyclin-dependent kinase 6], CDK7 [cyclin-
dependent kinase 7], CDK9 [cyclin-dependent kinase 9], CDKL5 [cyclin-
dependent kinase-like 5], CDKN1A [cyclin-dependent kinase inhibitor 1A (p21,
Cip1)], CDKN1B [cyclin-dependent kinase inhibitor 1B (p27, Kip1)], CDKN1C
[cyclin-dependent kinase inhibitor 1C (p57, Kip2)], CDKN2A [cyclin-dependent
kinase inhibitor 2A (melanoma, p16, inhibits CDK4)], CDKN2B [cyclin-dependent
kinase inhibitor 2B (p15, inhibits CDK4)], CDKN2C [cyclin-dependent kinase
inhibitor 2C (p18, inhibits CDK4)], CDKN2D [cyclin-dependent kinase inhibitor
2D
(p19, inhibits CDK4)], CDNF [cerebral dopamine neurotrophic factor], CDO1
[cysteine dioxygenase, type I], CDR2 [cerebellar degeneration-related protein
2,
62kDa], CDT1 [chromatin licensing and DNA replication factor 1], CDX1 [caudal
type homeobox 1], CDX2 [caudal type homeobox 2], CEACAM1
[carcinoembryonic antigen-related cell adhesion molecule 1 (biliary
glycoprotein)], CEACAM3 [carcinoembryonic antigen-related cell adhesion
molecule 3], CEACAMS [carcinoembryonic antigen-related cell adhesion
molecule 5], CEACAM7 [carcinoembryonic antigen-related cell adhesion
molecule 7], CEBPB [CCAAT/enhancer binding protein (C/EBP), beta], CEBPD
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[CCAAT/enhancer binding protein (C/EBP), delta], CECR2 [cat eye syndrome
chromosome region, candidate 2], CEL [carboxyl ester lipase (bile salt-
stimulated
lipase)], CENPC1 [centromere protein C 1], CENPJ [centromere protein J],
CEP290 [centrosomal protein 290kDa], CER1 [cerberus 1, cysteine knot
superfamily, homolog (Xenopus laevis)], CETP [cholesteryl ester transfer
protein,
plasma], CFC1 [cripto, FRL-1, cryptic family 1], CFH [complement factor H],
CFHR1 [complement factor H-related 1], CFHR3 [complement factor H-related
3], CFHR4 [complement factor H-related 4], CFI [complement factor I], CFL1
[cofilin 1 (non-muscle)], CFL2 [cofilin 2 (muscle)], CFLAR [CASP8 and FADD-
like
apoptosis regulator], CFTR [cystic fibrosis transmembrane conductance
regulator
(ATP-binding cassette sub-family C, member 7)], CGA [glycoprotein hormones,
alpha polypeptide], CGB [chorionic gonadotropin, beta polypeptide], CGB5
[chorionic gonadotropin, beta polypeptide 5], CGGBP1 [CGG triplet repeat
binding protein 1], CHAFIA [chromatin assembly factor 1, subunit A (p150)],
CHAF1 B [chromatin assembly factor 1, subunit B (p60)], CHAT [choline
acetyltransferase], CHEK1 [CHK1 checkpoint homolog (S. pombe)], CHEK2
[CHK2 checkpoint homolog (S. pombe)], CHGA [chromogranin A (parathyroid
secretory protein 1)], CHKA [choline kinase alpha], CHL1 [cell adhesion
molecule
with homology to L1 CAM (close homolog of L1)], CHN1 [chimerin (chimaerin) 1
],
CHP [calcium binding protein P22], CHP2 [calcineurin B homologous protein 2],
CHRD [chordin], CHRM1 [cholinergic receptor, muscarinic 1], CHRM2
[cholinergic receptor, muscarinic 2], CHRM3 [cholinergic receptor, muscarinic
3],
CHRM5 [cholinergic receptor, muscarinic 5], CHRNA3 [cholinergic receptor,
nicotinic, alpha 3], CHRNA4 [cholinergic receptor, nicotinic, alpha 4], CHRNA7
[cholinergic receptor, nicotinic, alpha 7], CHRNB2 [cholinergic receptor,
nicotinic,
beta 2 (neuronal)], CHST1 [carbohydrate (keratan sulfate Gal-6)
sulfotransferase
1], CHST10 [carbohydrate sulfotransferase 10], CHST3 [carbohydrate
(chondroitin 6) sulfotransferase 3], CHUK [conserved helix-loop-helix
ubiquitous
kinase], CHURC1 [churchill domain containing 1], CIB1 [calcium and integrin
binding 1 (calmyrin)], CIITA [class II, major histocompatibility complex,
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transactivator], CIRBP [cold inducible RNA binding protein], CISD1 [CDGSH iron
sulfur domain 1], CISH [cytokine inducible SH2-containing protein], CIT
[citron
(rho-interacting, serine/threonine kinase 21)], CLASP2 [cytoplasmic linker
associated protein 2], CLCF1 [cardiotrophin-like cytokine factor 1], CLCN2
[chloride channel 2], CLDN1 [claudin 1], CLDN14 [claudin 14], CLDN16 [claudin
16], CLDN3 [claudin 3], CLDN4 [claudin 4], CLDN5 [claudin 5], CLDN8 [claudin
8], CLEC1 2A [C-type lectin domain family 12, member A], CLEC1 6A [C-type
lectin domain family 16, member A], CLEC5A [C-type lectin domain family 5,
member A], CLEC7A [C-type lectin domain family 7, member A], CLIP2 [CAP-
GLY domain containing linker protein 2], CLSTN1 [calsyntenin 1], CLTC
[clathrin,
heavy chain (Hc)], CLU [clusterin], CMIP [c-Maf-inducing protein], CNBP [CCHC-
type zinc finger, nucleic acid binding protein], CNGA3 [cyclic nucleotide
gated
channel alpha 3], CNGB3 [cyclic nucleotide gated channel beta 3], CNN1
[calponin 1, basic, smooth muscle], CNN2 [calponin 2], CNN3 [calponin 3,
acidic], CNOT8 [CCR4-NOT transcription complex, subunit 8], CNP [2' [3'-cyclic
nucleotide 3' phosphodiesterase], CNR1 [cannabinoid receptor 1 (brain)], CNR2
[cannabinoid receptor 2 (macrophage)], CNTF [ciliary neurotrophic factor],
CNTFR [ciliary neurotrophic factor receptor], CNTFR [ciliary neurotrophic
factor
receptor], CNTFR [ciliary neurotrophic factor receptor], CNTLN [centlein,
centrosomal protein], CNTN1 [contactin 1], CNTN2 [contactin 2 (axonal)], CNTN4
[contactin 4], CNTNAP1 [contactin associated protein 1], CNTNAP2 [contactin
associated protein-like 2], COBL [cordon-bleu homolog (mouse)], COG2
[component of oligomeric golgi complex 2], COL18A1 [collagen, type XVIII,
alpha
1], COL1A1 [collagen, type I, alpha 1], COL1 A2 [collagen, type I, alpha 2],
COL2A1 [collagen, type II, alpha 1], COL3A1 [collagen, type III, alpha 1],
COL4A3 [collagen, type IV, alpha 3 (Goodpasture antigen)], COL4A3BP
[collagen, type IV, alpha 3 (Goodpasture antigen) binding protein], COL5A1
[collagen, type V, alpha 1 ], COL5A2 [collagen, type V, alpha 2], COL6A1
[collagen, type VI, alpha 1], COL6A2 [collagen, type VI, alpha 2], COL6A3
[collagen, type VI, alpha 3], COMT [catechol-O-methyltransferase], COPG2
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[coatomer protein complex, subunit gamma 2], COPS4 [COP9 constitutive
photomorphogenic homolog subunit 4 (Arabidopsis)], CORO1A [coronin, actin
binding protein, 1A], COXSA [cytochrome c oxidase subunit Va], COX7B
[cytochrome c oxidase subunit VIIb], CP [ceruloplasmin (ferroxidase)], CPA1
[carboxypeptidase Al (pancreatic)], CPA2 [carboxypeptidase A2 (pancreatic)],
CPA5 [carboxypeptidase A5], CPB2 [carboxypeptidase B2 (plasma)], CPOX
[coproporphyrinogen oxidase], CPS1 [carbamoyl-phosphate synthetase 1,
mitochondrial], CPT1A [carnitine palm itoyltransferase 1A (liver)], CR1
[complement component (3b/4b) receptor 1 (Knops blood group)], CR2
[complement component (3d/Epstein Barr virus) receptor 2], CRABP1 [cellular
retinoic acid binding protein 1], CRABP2 [cellular retinoic acid binding
protein 2],
CRAT [carnitine 0-acetyltransferase], CRB1 [crumbs homolog 1 (Drosophila)],
CREB1 [cAMP responsive element binding protein 1], CREBBP [CREB binding
protein], CRELD1 [cysteine-rich with EGF-like domains 1], CRH [corticotropin
releasing hormone], CRIP1 [cysteine-rich protein 1 (intestinal)], CRK [v-crk
sarcoma virus CT10 oncogene homolog (avian)], CRKL [v-crk sarcoma virus
CT10 oncogene homolog (avian)-like], CRLF1 [cytokine receptor-like factor 1],
CRLF2 [cytokine receptor-like factor 2], CRLF3 [cytokine receptor-like factor
3],
CRMP1 [collapsin response mediator protein 1], CRP [C-reactive protein,
pentraxin-related], CRTC1 [CREB regulated transcription coactivator 1], CRX
[cone-rod homeobox], CRYAA [crystallin, alpha A], CRYAB [crystallin, alpha B],
CS [citrate synthase], CSAD [cysteine sulfinic acid decarboxylase], CSF1
[colony
stimulating factor 1 (macrophage)], CSF1 R [colony stimulating factor 1
receptor],
CSF2 [colony stimulating factor 2 (granulocyte-macrophage)], CSF2RA [colony
stimulating factor 2 receptor, alpha, low-affinity (granulocyte-macrophage)],
CSF3 [colony stimulating factor 3 (granulocyte)], CSF3R [colony stimulating
factor 3 receptor (granulocyte)], CSH2 [chorionic somatomammotropin hormone
2], CSK [c-src tyrosine kinase], CSMD1 [CUB and Sushi multiple domains 1],
CSMD3 [CUB and Sushi multiple domains 3], CSNK1 D [casein kinase 1, delta],
CSNK1 E [casein kinase 1, epsilon], CSNK2A1 [casein kinase 2, alpha 1
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polypeptide], CSPG4 [chondroitin sulfate proteoglycan 4], CSPG5 [chondroitin
sulfate proteoglycan 5 (neuroglycan C)], CST3 [cystatin C], CST7 [cystatin F
(leukocystatin)], CSTB [cystatin B (stefin B)], CTAG1 B [cancer/testis antigen
1 B],
CTBP1 [C-terminal binding protein 1], CTCF [CCCTC-binding factor (zinc finger
protein)], CTDSP1 [CTD (carboxy-terminal domain, RNA polymerase II,
polypeptide A) small phosphatase 1], CTF1 [cardiotrophin 1], CTGF [connective
tissue growth factor], CTLA4 [cytotoxic T-lymphocyte-associated protein 4],
CTNNA1 [catenin (cadherin-associated protein), alpha 1, 102kDa], CTNNAL1
[catenin (cadherin-associated protein), alpha-like 1], CTNNB1 [catenin
(cadherin-
associated protein), beta 1, 88kDa], CTNND1 [catenin (cadherin-associated
protein), delta 1], CTNND2 [catenin (cadherin-associated protein), delta 2
(neural
plakophilin-related arm-repeat protein)], CTNS [cystinosis, nephropathic],
CTRL
[chymotrypsin-like], CTSB [cathepsin B], CTSC [cathepsin C], CTSD [cathepsin
D], CTSG [cathepsin G], CTSH [cathepsin H], CTSL1 [cathepsin L1], CTSS
[cathepsin S], CTTN [cortactin], CTTNBP2 [cortactin binding protein 2], CUL4B
[cullin 4B], CUL5 [cullin 5], CUX2 [cut-like homeobox 2], CX3CL1 [chemokine (C-
X3-C motif) ligand 1], CX3CR1 [chemokine (C-X3-C motif) receptor 1], CXADR
[coxsackie virus and adenovirus receptor], CXCL1 [chemokine (C-X-C motif)
ligand 1 (melanoma growth stimulating activity, alpha)], CXCL10 [chemokine (C-
X-C motif) ligand 10], CXCL12 [chemokine (C-X-C motif) ligand 12 (stromal cell-
derived factor 1)], CXCL16 [chemokine (C-X-C motif) ligand 16], CXCL2
[chemokine (C-X-C motif) ligand 2], CXCL5 [chemokine (C-X-C motif) ligand 5],
CXCR1 [chemokine (C-X-C motif) receptor 1], CXCR2 [chemokine (C-X-C motif)
receptor 2], CXCR3 [chemokine (C-X-C motif) receptor 3], CXCR4 [chemokine
(C-X-C motif) receptor 4], CXCR5 [chemokine (C-X-C motif) receptor 5], CYB5A
[cytochrome b5 type A (microsomal)], CYBA [cytochrome b-245, alpha
polypeptide], CYBB [cytochrome b-245, beta polypeptide], CYCS [cytochrome c,
somatic], CYFIP1 [cytoplasmic FMR1 interacting protein 1], CYLD
[cylindromatosis (turban tumor syndrome)], CYP11A1 [cytochrome P450, family
11, subfamily A, polypeptide 1 ], CYP11 B1 [cytochrome P450, family 11,
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subfamily B, polypeptide 1], CYP11B2 [cytochrome P450, family 11, subfamily B,
polypeptide 2], CYP17A1 [cytochrome P450, family 17, subfamily A, polypeptide
1], CYP19A1 [cytochrome P450, family 19, subfamily A, polypeptide 1], CYP1A1
[cytochrome P450, family 1, subfamily A, polypeptide 1], CYP1A2 [cytochrome
P450, family 1, subfamily A, polypeptide 2], CYP1 B1 [cytochrome P450, family
1,
subfamily B, polypeptide 1], CYP21A2 [cytochrome P450, family 21, subfamily A,
polypeptide 2], CYP2A6 [cytochrome P450, family 2, subfamily A, polypeptide
6],
CYP2B6 [cytochrome P450, family 2, subfamily B, polypeptide 6], CYP2C9
[cytochrome P450, family 2, subfamily C, polypeptide 9], CYP2D6 [cytochrome
P450, family 2, subfamily D, polypeptide 6], CYP2E1 [cytochrome P450, family
2,
subfamily E, polypeptide 1], CYP3A4 [cytochrome P450, family 3, subfamily A,
polypeptide 4], CYP7A1 [cytochrome P450, family 7, subfamily A, polypeptide
1],
CYR61 [cysteine-rich, angiogenic inducer, 61], CYSLTR1 [cysteinyl leukotriene
receptor 1], CYSLTR2 [cysteinyl leukotriene receptor 2], DAB1 [disabled
homolog 1 (Drosophila)], DAGLA [diacylglycerol lipase, alpha], DAGLB
[diacylglycerol lipase, beta], DAO [D-amino-acid oxidase], DAOA [D-amino acid
oxidase activator], DAPK1 [death-associated protein kinase 1], DAPK3 [death-
associated protein kinase 3], DAXX [death-domain associated protein], DBH
[dopamine beta-hydroxylase (dopamine beta-monooxygenase)], DBI [diazepam
binding inhibitor (GABA receptor modulator, acyl-Coenzyme A binding protein)],
DBN1 [drebrin 1], DCAF6 [DDB1 and CUL4 associated factor 6], DCC [deleted in
colorectal carcinoma], DCDC2 [doublecortin domain containing 2], DCK
[deoxycytidine kinase], DCLK1 [doublecortin-like kinase 1], DCN [decorin],
DCTN1 [dynactin 1 (p150, glued homolog, Drosophila)], DCTN2 [dynactin 2
(p50)], DCTN4 [dynactin 4 (p62)], DCUN1D1 [DCN1, defective in cullin
neddylation 1, domain containing 1 (S. cerevisiae)], DCX [doublecortin], DDB1
[damage-specific DNA binding protein 1, 127kDa], DDC [dopa decarboxylase
(aromatic L-amino acid decarboxylase)], DDIT3 [DNA-damage-inducible
transcript 3], DDIT4 [DNA-damage-inducible transcript 4], DDIT4L [DNA-
damage-inducible transcript 4-like], DDR1 [discoidin domain receptor tyrosine
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kinase 1 ], DDX10 [DEAD (Asp-Glu-Ala-Asp) box polypeptide 10], DDX17 [DEAD
(Asp-Glu-Ala-Asp) box polypeptide 17], DEFB4A [defensin, beta 4A], DEK [DEK
oncogene], DES [desmin], DEXI [Dexi homolog (mouse)], DFFA [DNA
fragmentation factor, 45kDa, alpha polypeptide], DFNB31 [deafness, autosomal
recessive 31], DGCR6 [DiGeorge syndrome critical region gene 6], DGUOK
[deoxyguanosine kinase], DHCR7 [7-dehydrocholesterol reductase], DHFR
[dihydrofolate reductase], DIAPH1 [diaphanous homolog 1 (Drosophila)],
DICER1 [dicer 1, ribonuclease type III], DIO1 [deiodinase, iodothyronine, type
I],
D102 [deiodinase, iodothyronine, type II], DIP2A [DIP2 disco-interacting
protein 2
homolog A (Drosophila)], DIRAS3 [DIRAS family, GTP-binding RAS-like 3],
DISC1 [disrupted in schizophrenia 1], DISC2 [disrupted in schizophrenia 2 (non-
protein coding)], DKC1 [dyskeratosis congenita 1, dyskerin], DLG1 [discs,
large
homolog 1 (Drosophila)], DLG2 [discs, large homolog 2 (Drosophila)], DLG3
[discs, large homolog 3 (Drosophila)], DLG4 [discs, large homolog 4
(Drosophila)], DLGAP1 [discs, large (Drosophila) homolog-associated protein
1],
DLGAP2 [discs, large (Drosophila) homolog-associated protein 2], DLK1 [delta-
like 1 homolog (Drosophila)], DLL1 [delta-like 1 (Drosophila)], DLX1 [distal-
less
homeobox 1], DLX2 [distal-less homeobox 2], DLX3 [distal-less homeobox 3],
DLX4 [distal-less homeobox 4], DLX5 [distal-less homeobox 5], DLX6 [distal-
less
homeobox 6], DMBT1 [deleted in malignant brain tumors 1], DMC1 [DMC1
dosage suppressor of mckl homolog, meiosis-specific homologous
recombination (yeast)], DMD [dystrophin], DMPK [dystrophia myotonica-protein
kinase], DNAI2 [dynein, axonemal, intermediate chain 2], DNAJC28 [DnaJ
(Hsp40) homolog, subfamily C, member 28], DNAJC30 [DnaJ (Hsp40) homolog,
subfamily C, member 30], DNASE1 [deoxyribonuclease I], DNER [delta/notch-
like EGF repeat containing], DNLZ [DNL-type zinc finger], DNM1 [dynamin 1],
DNM3 [dynamin 3], DNMT1 [DNA (cytosine-5-)-methyltransferase 1], DNMT3A
[DNA (cytosine-5-)-methyltransferase 3 alpha], DNMT3B [DNA (cytosine-5-)-
methyltransferase 3 beta], DNTT [deoxynucleotidyltransferase, terminal], DOC2A
[double C2-like domains, alpha], DOCK1 [dedicator of cytokinesis 1], DOCK3
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[dedicator of cytokinesis 3], DOCK4 [dedicator of cytokinesis 4], DOCK7
[dedicator of cytokinesis 7], DOK7 [docking protein 7], DONSON [downstream
neighbor of SON], DOPEY1 [dopey family member 1], DOPEY2 [dopey family
member 2], DPF1 [D4, zinc and double PHD fingers family 1], DPF3 [D4, zinc
and double PHD fingers, family 3], DPH1 [DPH1 homolog (S. cerevisiae)],
DPP1 0 [dipeptidyl-peptidase 10], DPP4 [dipeptidyl-peptidase 4], DPRXP4
[divergent-paired related homeobox pseudogene 4], DPT [dermatopontin], DPYD
[dihydropyrimidine dehydrogenase], DPYSL2 [dihydropyrimidinase-like 2],
DPYSL3 [dihydropyrimidinase-like 3], DPYSL4 [dihydropyrimidinase-like 4],
DPYSL5 [dihydropyrimidinase-like 5], DRD1 [dopamine receptor D1], DRD2
[dopamine receptor D2], DRD3 [dopamine receptor D3], DRD4 [dopamine
receptor D4], DRD5 [dopamine receptor D5], DRG1 [developmentally regulated
GTP binding protein 1], DRGX [dorsal root ganglia homeobox], DSC2
[desmocollin 2], DSCAM [Down syndrome cell adhesion molecule], DSCAML1
[Down syndrome cell adhesion molecule like 1], DSCR3 [Down syndrome critical
region gene 3], DSCR4 [Down syndrome critical region gene 4], DSCR6 [Down
syndrome critical region gene 6], DSERG1 [Down syndrome encephalopathy
related protein 1], DSG1 [desmoglein 1], DSG2 [desmoglein 2], DSP
[desmoplakin], DST [dystonin], DSTN [destrin (actin depolymerizing factor)],
DTNBP1 [dystrobrevin binding protein 1], DULLARD [dullard homolog (Xenopus
laevis)], DUSP1 [dual specificity phosphatase 1 ], DUSP13 [dual specificity
phosphatase 13], DUSP6 [dual specificity phosphatase 6], DUT [deoxyuridine
triphosphatase], DVL1 [dishevelled, dsh homolog 1 (Drosophila)], DYRK1A [dual-
specificity tyrosine-(Y)-phosphorylation regulated kinase 1A], DYRK3 [dual-
specificity tyrosine-(Y)-phosphorylation regulated kinase 3], DYSF [dysferlin,
limb
girdle muscular dystrophy 2B (autosomal recessive)], DYX1 C1 [dyslexia
susceptibility 1 candidate 1], E2F1 [E2F transcription factor 1], EARS2
[glutamyl-
tRNA synthetase 2, mitochondrial (putative)], EBF4 [early B-cell factor 4],
ECE1
[endothelin converting enzyme 1], ECHS1 [enoyl Coenzyme A hydratase, short
chain, 1, mitochondrial], EDN1 [endothelin 1], EDN2 [endothelin 2], EDN3
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[endothelin 3], EDNRA [endothelin receptor type A], EDNRB [endothelin receptor
type B], EEF1A1 [eukaryotic translation elongation factor 1 alpha 1], EEF2
[eukaryotic translation elongation factor 2], EEF2K [eukaryotic elongation
factor-2
kinase], EFHA1 [EF-hand domain family, member Al], EFNA1 [ephrin-Al],
EFNA2 [ephrin-A2], EFNA3 [ephrin-A3], EFNA4 [ephrin-A4], EFNA5 [ephrin-A5],
EFNB2 [ephrin-B2], EFNB3 [ephrin-B3], EFS [embryonal Fyn-associated
substrate], EGF [epidermal growth factor (beta-urogastrone)], EGFR [epidermal
growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene
homolog,
avian)], EGLN1 [egl nine homolog 1 (C. elegans)], EGR1 [early growth response
1], EGR2 [early growth response 2], EGR3 [early growth response 3], EHHADH
[enoyl-Coenzyme A, hydratase/3-hydroxyacyl Coenzyme A dehydrogenase],
EHMT2 [euchromatic histone-lysine N-methyltransferase 2], EID1 [EP300
interacting inhibitor of differentiation 1], EIFIAY [eukaryotic translation
initiation
factor 1A, Y-linked], EIF2AK2 [eukaryotic translation initiation factor 2-
alpha
kinase 2], EIF2AK3 [eukaryotic translation initiation factor 2-alpha kinase
3],
EIF2B2 [eukaryotic translation initiation factor 2B, subunit 2 beta, 39kDa],
EIF2B5 [eukaryotic translation initiation factor 2B, subunit 5 epsilon,
82kDa],
EIF2S1 [eukaryotic translation initiation factor 2, subunit 1 alpha, 35kDa],
EIF2S2
[eukaryotic translation initiation factor 2, subunit 2 beta, 38kDa], EIF3M
[eukaryotic translation initiation factor 3, subunit M], EIF4E [eukaryotic
translation
initiation factor 4E], EIF4EBP1 [eukaryotic translation initiation factor 4E
binding
protein 1], EIF4G1 [eukaryotic translation initiation factor 4 gamma, 1],
EIF4H
[eukaryotic translation initiation factor 4H], ELANE [elastase, neutrophil
expressed], ELAVL1 [ELAV (embryonic lethal, abnormal vision, Drosophila)-like
1 (Hu antigen R)], ELAVL3 [ELAV (embryonic lethal, abnormal vision,
Drosophila)-like 3 (Hu antigen C)], ELAVL4 [ELAV (embryonic lethal, abnormal
vision, Drosophila)-like 4 (Hu antigen D)], ELF5 [E74-like factor 5 (ets
domain
transcription factor)], ELK1 [ELK1, member of ETS oncogene family], ELMO1
[engulfment and cell motility 1], ELN [elastin], ELP4 [elongation protein 4
homolog (S. cerevisiae)], EMP2 [epithelial membrane protein 2], EMP3
[epithelial
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membrane protein 3], EMX1 [empty spiracles homeobox 1], EMX2 [empty
spiracles homeobox 2], EN1 [engrailed homeobox 1], EN2 [engrailed homeobox
2], ENAH [enabled homolog (Drosophila)], ENDOG [endonuclease G], ENG
[endoglin], ENO1 [enolase 1, (alpha)], ENO2 [enolase 2 (gamma, neuronal)],
ENPEP [glutamyl aminopeptidase (aminopeptidase A)], ENPP1 [ectonucleotide
pyrophosphatase/phosphodiesterase 1], ENPP2 [ectonucleotide
pyrophosphatase/phosphodiesterase 2], ENSA [endosulfine alpha],
ENSG00000174496 [], ENSG00000183653 [], ENSG00000215557 [], ENTPD1
[ectonucleoside triphosphate diphosphohydrolase 1], EP300 [E1A binding protein
p300], EPCAM [epithelial cell adhesion molecule], EPHA1 [EPH receptor Al],
EPHA1 0 [EPH receptor Al 0], EPHA2 [EPH receptor A2], EPHA3 [EPH receptor
A3], EPHA4 [EPH receptor A4], EPHA5 [EPH receptor A5], EPHA6 [EPH
receptor A6], EPHA7 [EPH receptor A7], EPHA8 [EPH receptor A8], EPHB1
[EPH receptor B1], EPHB2 [EPH receptor B2 ], EPHB3 [EPH receptor B3],
EPHB4 [EPH receptor B4], EPHB6 [EPH receptor B6], EPHX2 [epoxide
hydrolase 2, cytoplasmic], EPM2A [epilepsy, progressive myoclonus type 2A,
Lafora disease (laforin)], EPO [erythropoietin], EPOR [erythropoietin
receptor],
EPRS [glutamyl-prolyl-tRNA synthetase], EPS15 [epidermal growth factor
receptor pathway substrate 15], ERBB2 [v-erb-b2 erythroblastic leukemia viral
oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian)],
ERBB3 [v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian)],
ERBB4 [v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian)],
ERC2 [ELKS/RAB6-interacting/CAST family member 2], ERCC2 [excision repair
cross-complementing rodent repair deficiency, complementation group 2],
ERCC3 [excision repair cross-complementing rodent repair deficiency,
complementation group 3 (xeroderma pigmentosum group B complementing)],
ERCC5 [excision repair cross-complementing rodent repair deficiency,
complementation group 5], ERCC6 [excision repair cross-complementing rodent
repair deficiency, complementation group 6], ERCC8 [excision repair cross-
complementing rodent repair deficiency, complementation group 8], EREG
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[epiregulin], ERG [v-ets erythroblastosis virus E26 oncogene homolog (avian)],
ERVWE1 [endogenous retroviral family W, env(C7), member 1], ESD [esterase
D/formylglutathione hydrolase], ESR1 [estrogen receptor 1], ESR2 [estrogen
receptor 2 (ER beta)], ESRRA [estrogen-related receptor alpha], ESRRB
[estrogen-related receptor beta], ETS1 [v-ets erythroblastosis virus E26
oncogene homolog 1 (avian)], ETS2 [v-ets erythroblastosis virus E26 oncogene
homolog 2 (avian)], ETV1 [ets variant 1 ], ETV4 [ets variant 4], ETV5 [ets
variant
5], ETV6 [ets variant 6], EVL [EnahNasp-like], EXOC4 [exocyst complex
component 4], EXOC8 [exocyst complex component 8], EXT1 [exostoses
(multiple) 1], EXT2 [exostoses (multiple) 2], EZH2 [enhancer of zeste homolog
2
(Drosophila)], EZR [ezrin], F12 [coagulation factor XII (Hageman factor)], F2
[coagulation factor II (thrombin)], F2R [coagulation factor II (thrombin)
receptor],
F2RL1 [coagulation factor II (thrombin) receptor-like 1], F3 [coagulation
factor III
(thromboplastin, tissue factor)], F7 [coagulation factor VII (serum
prothrombin
conversion accelerator)], F8 [coagulation factor VIII, procoagulant
component],
F9 [coagulation factor IX], FAAH [fatty acid amide hydrolase], FABP3 [fatty
acid
binding protein 3, muscle and heart (mammary-derived growth inhibitor)], FABP4
[fatty acid binding protein 4, adipocyte], FABP5 [fatty acid binding protein 5
(psoriasis-associated)], FABP7 [fatty acid binding protein 7, brain], FADD
[Fas
(TNFRSF6)-associated via death domain], FADS2 [fatty acid desaturase 2],
FAM120C [family with sequence similarity 120C], FAM165B [family with
sequence similarity 165, member B], FAM3C [family with sequence similarity 3,
member C], FAM53A [family with sequence similarity 53, member A], FARP2
[FERM, RhoGEF and pleckstrin domain protein 2], FARSA [phenylalanyl-tRNA
synthetase, alpha subunit], FAS [Fas (TNF receptor superfamily, member 6)],
FASLG [Fas ligand (TNF superfamily, member 6)], FASN [fatty acid synthase],
FASTK [Fas-activated serine/threonine kinase], FBLN1 [fibulin 1], FBN1
[fibrillin
1], FBP1 [fructose-1 [6-bisphosphatase 1], FBXO45 [F-box protein 45], FBXW5
[F-box and WD repeat domain containing 5], FBXW7 [F-box and WD repeat
domain containing 7], FCER2 [Fc fragment of IgE, low affinity II, receptor for
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(CD23)], FCGR1A [Fc fragment of IgG, high affinity Ia, receptor (CD64)],
FCGR2A [Fc fragment of IgG, low affinity Ila, receptor (CD32)], FCGR2B [Fc
fragment of IgG, low affinity Ilb, receptor (CD32)], FCGR3A [Fc fragment of
IgG,
low affinity Ilia, receptor (CD16a)], FCRL3 [Fc receptor-like 3], FDFT1
[farnesyl-
diphosphate farnesyltransferase 1 ], FDX1 [ferredoxin 1 ], FDXR [ferredoxin
reductase], FECH [ferrochelatase (protoporphyria)], FEM1A [fem-1 homolog a
(C. elegans)], FER [fer (fps/fes related) tyrosine kinase], FES [feline
sarcoma
oncogene], FEZ1 [fasciculation and elongation protein zeta 1 (zygin I)], FEZ2
[fasciculation and elongation protein zeta 2 (zygin II)], FEZF1 [FEZ family
zinc
finger 1 ], FEZF2 [FEZ family zinc finger 2], FGF1 [fibroblast growth factor 1
(acidic)], FGF19 [fibroblast growth factor 19], FGF2 [fibroblast growth factor
2
(basic)], FGF20 [fibroblast growth factor 20], FGF3 [fibroblast growth factor
3
(murine mammary tumor virus integration site (v-int-2) oncogene homolog)],
FGF4 [fibroblast growth factor 4], FGF5 [fibroblast growth factor 5], FGF7
[fibroblast growth factor 7 (keratinocyte growth factor)], FGF8 [fibroblast
growth
factor 8 (androgen-induced)], FGF9 [fibroblast growth factor 9 (glia-
activating
factor)], FGFBP1 [fibroblast growth factor binding protein 1], FGFR1
[fibroblast
growth factor receptor 1 ], FGFR2 [fibroblast growth factor receptor 2], FGFR3
[fibroblast growth factor receptor 3], FGFR4 [fibroblast growth factor
receptor 4],
FHIT [fragile histidine triad gene], FHL1 [four and a half LIM domains 1],
FHL2
[four and a half LIM domains 2], FIBP [fibroblast growth factor (acidic)
intracellular binding protein ], FIGF [c-fos induced growth factor (vascular
endothelial growth factor D)], FIGNL1 [fidgetin-like 1], FKBP15 [FK506 binding
protein 15, 133kDa], FKBP1 B [FK506 binding protein 1 B, 12.6 kDa], FKBP5
[FK506 binding protein 5], FKBP6 [FK506 binding protein 6, 36kDa], FKBP8
[FK506 binding protein 8, 38kDa], FKTN [fukutin], FLCN [folliculin], FLG
[filaggrin], FL11 [Friend leukemia virus integration 1], FLNA [filamin A,
alpha],
FLNB [filamin B, beta], FLNC [filamin C, gamma], FLT1 [fms-related tyrosine
kinase 1 (vascular endothelial growth factor/vascular permeability factor
receptor)], FLT3 [fms-related tyrosine kinase 3], FMN1 [formin 1], FMNL2
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[formin-like 2], FMR1 [fragile X mental retardation 1], FN1 [fibronectin 1],
FOLH1
[folate hydrolase (prostate-specific membrane antigen) 1], FOLR1 [folate
receptor 1 (adult)], FOS [FBJ murine osteosarcoma viral oncogene homolog],
FOSB [FBJ murine osteosarcoma viral oncogene homolog B], FOXC2 [forkhead
box C2 (MFH-1, mesenchyme forkhead 1)], FOXG1 [forkhead box G1], FOXL2
[forkhead box L2], FOXM1 [forkhead box M1], FOXO1 [forkhead box 01],
FOXO3 [forkhead box 03], FOXP2 [forkhead box P2], FOXP3 [forkhead box P3],
FPR1 [formyl peptide receptor 1], FPR2 [formyl peptide receptor 2], FRMD7
[FERM domain containing 7], FRS2 [fibroblast growth factor receptor substrate
2], FRS3 [fibroblast growth factor receptor substrate 3], FRYL [FRY-like],
FSCN1
[fascin homolog 1, actin-bundling protein (Strongylocentrotus purpuratus)],
FSHB
[follicle stimulating hormone, beta polypeptide], FSHR [follicle stimulating
hormone receptor], FST [follistatin], FSTL1 [follistatin-like 1], FSTL3
[follistatin-
like 3 (secreted glycoprotein)], FTCD [formiminotransferase cyclodeaminase],
FTH1 [ferritin, heavy polypeptide 1], FTL [ferritin, light polypeptide], FTMT
[ferritin
mitochondrial], FTSJ1 [FtsJ homolog 1 (E. coli)], FUCA1 [fucosidase, alpha-L-
1,
tissue], FURIN [furin (paired basic amino acid cleaving enzyme)], FUT1
[fucosyltransferase 1 (galactoside 2-alpha-L-fucosyltransferase, H blood
group)],
FUT4 [fucosyltransferase 4 (alpha (1 [3) fucosyltransferase, myeloid-
specific)],
FXN [frataxin], FXR1 [fragile X mental retardation, autosomal homolog 1], FXR2
[fragile X mental retardation, autosomal homolog 2], FXYD1 [FXYD domain
containing ion transport regulator 1], FYB [FYN binding protein (FYB-1
20/130)],
FYN [FYN oncogene related to SRC, FGR, YES], FZD1 [frizzled homolog 1
(Drosophila)], FZD10 [frizzled homolog 10 (Drosophila)], FZD2 [frizzled
homolog
2 (Drosophila)], FZD3 [frizzled homolog 3 (Drosophila)], FZD4 [frizzled
homolog
4 (Drosophila)], FZD5 [frizzled homolog 5 (Drosophila)], FZD6 [frizzled
homolog
6 (Drosophila)], FZD7 [frizzled homolog 7 (Drosophila)], FZD8 [frizzled
homolog
8 (Drosophila)], FZD9 [frizzled homolog 9 (Drosophila)], FZR1 [fizzy/cell
division
cycle 20 related 1 (Drosophila)], G6PD [glucose-6-phosphate dehydrogenase],
GAA [glucosidase, alpha; acid], GAB1 [GRB2-associated binding protein 1],
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GABARAP [GABA(A) receptor-associated protein], GABBR1 [gamma-
aminobutyric acid (GABA) B receptor, 1], GABBR2 [gamma-aminobutyric acid
(GABA) B receptor, 2], GABPA [GA binding protein transcription factor, alpha
subunit 60kDa], GABRA1 [gamma-aminobutyric acid (GABA) A receptor, alpha
1], GABRA2 [gamma-aminobutyric acid (GABA) A receptor, alpha 2], GABRA3
[gamma-aminobutyric acid (GABA) A receptor, alpha 3], GABRA4 [gamma-
aminobutyric acid (GABA) A receptor, alpha 4], GABRA5 [gamma-aminobutyric
acid (GABA) A receptor, alpha 5], GABRA6 [gamma-aminobutyric acid (GABA) A
receptor, alpha 6], GABRB1 [gamma-aminobutyric acid (GABA) A receptor, beta
1], GABRB2 [gamma-aminobutyric acid (GABA) A receptor, beta 2], GABRB3
[gamma-aminobutyric acid (GABA) A receptor, beta 3], GABRD [gamma-
aminobutyric acid (GABA) A receptor, delta], GABRE [gamma-aminobutyric acid
(GABA) A receptor, epsilon], GABRG1 [gamma-aminobutyric acid (GABA) A
receptor, gamma 1], GABRG2 [gamma-aminobutyric acid (GABA) A receptor,
gamma 2], GABRG3 [gamma-aminobutyric acid (GABA) A receptor, gamma 3],
GABRP [gamma-aminobutyric acid (GABA) A receptor, pi], GAD1 [glutamate
decarboxylase 1 (brain, 67kDa)], GAD2 [glutamate decarboxylase 2 (pancreatic
islets and brain, 65kDa)], GAL [galanin prepropeptide], GALE [UDP-galactose-4-
epimerase], GALK1 [galactokinase 1 ], GALT [galactose-1 -phosphate
uridylyltransferase], GAP43 [growth associated protein 43], GAPDH
[glyceraldehyde-3-phosphate dehydrogenase], GARS [glycyl-tRNA synthetase],
GART [phosphoribosylglycinamide formyltransferase, phosphoribosylglycinamide
synthetase, phosphoribosylaminoimidazole synthetase], GAS1 [growth arrest-
specific 1], GAS6 [growth arrest-specific 6], GAST [gastrin], GATA1 [GATA
binding protein 1 (globin transcription factor 1)], GATA2 [GATA binding
protein 2],
GATA3 [GATA binding protein 3], GATA4 [GATA binding protein 4], GATA6
[GATA binding protein 6], GBA [glucosidase, beta, acid], GBE1 [glucan (1 [4-
alpha-), branching enzyme 1], GBX2 [gastrulation brain homeobox 2], GC [group-
specific component (vitamin D binding protein)], GCG [glucagon], GCH1 [GTP
cyclohydrolase 1], GCNT1 [glucosaminyl (N-acetyl) transferase 1, core 2],
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GDAP1 [ganglioside-induced differentiation-associated protein 1], GDF1 [growth
differentiation factor 1], GDF11 [growth differentiation factor 11], GDF15
[growth
differentiation factor 15], GDF7 [growth differentiation factor 7], GDI1 [GDP
dissociation inhibitor 1], GDI2 [GDP dissociation inhibitor 2], GDNF [glial
cell
derived neurotrophic factor], GDPD5 [glycerophosphodiester phosphodiesterase
domain containing 5], GEM [GTP binding protein overexpressed in skeletal
muscle], GFAP [glial fibrillary acidic protein], GFER [growth factor,
augmenter of
liver regeneration], GFI1 B [growth factor independent 1 B transcription
repressor],
GFRA1 [GDNF family receptor alpha 1], GFRA2 [GDNF family receptor alpha 2],
GFRA3 [GDNF family receptor alpha 3], GFRA4 [GDNF family receptor alpha 4],
GGCX [gamma-glutamyl carboxylase], GGNBP2 [gametogenetin binding protein
2], GGT1 [gamma-glutamyltransferase 1], GGT2 [gamma-glutamyltransferase 2],
GH1 [growth hormone 1], GHR [growth hormone receptor], GHRH [growth
hormone releasing hormone], GHRHR [growth hormone releasing hormone
receptor], GHRL [ghrelin/obestatin prepropeptide], GHSR [growth hormone
secretagogue receptor], GIPR [gastric inhibitory polypeptide receptor], GIT1
[G
protein-coupled receptor kinase interacting ArfGAP 1 ], GJA1 [gap junction
protein, alpha 1, 43kDa], GJA4 [gap junction protein, alpha 4, 37kDa], GJA5
[gap
junction protein, alpha 5, 40kDa], GJB1 [gap junction protein, beta 1, 32kDa],
GJB2 [gap junction protein, beta 2, 26kDa], GJB6 [gap junction protein, beta
6,
30kDa], GLA [galactosidase, alpha], GLB1 [galactosidase, beta 1], GLDC
[glycine dehydrogenase (decarboxylating)], GLI1 [GLI family zinc finger 1 ],
GLI2
[GLI family zinc finger 2], GLI3 [GLI family zinc finger 3], GLIS1 [GLIS
family zinc
finger 1 ], GLIS2 [GLIS family zinc finger 2], GLO1 [glyoxalase I], GLRA2
[glycine
receptor, alpha 2], GLRB [glycine receptor, beta], GLS [glutaminase], GLUD1
[glutamate dehydrogenase 1], GLUD2 [glutamate dehydrogenase 2], GLUL
[glutamate-ammonia ligase (glutamine synthetase)], GLYAT [glycine-N-
acyltransferase], GMFB [glia maturation factor, beta], GMNN [geminin, DNA
replication inhibitor], GMPS [guanine monphosphate synthetase], GNA1 1
[guanine nucleotide binding protein (G protein), alpha 11 (Gq class)], GNA12
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[guanine nucleotide binding protein (G protein) alpha 12], GNA13 [guanine
nucleotide binding protein (G protein), alpha 13], GNA14 [guanine nucleotide
binding protein (G protein), alpha 14], GNA15 [guanine nucleotide binding
protein
(G protein), alpha 15 (Gq class)], GNAI1 [guanine nucleotide binding protein
(G
protein), alpha inhibiting activity polypeptide 1], GNAI2 [guanine nucleotide
binding protein (G protein), alpha inhibiting activity polypeptide 2], GNAI3
[guanine nucleotide binding protein (G protein), alpha inhibiting activity
polypeptide 3], GNAL [guanine nucleotide binding protein (G protein), alpha
activating activity polypeptide, olfactory type], GNAO1 [guanine nucleotide
binding protein (G protein), alpha activating activity polypeptide 0], GNAQ
[guanine nucleotide binding protein (G protein), q polypeptide], GNAS [GNAS
complex locus], GNAT1 [guanine nucleotide binding protein (G protein), alpha
transducing activity polypeptide 1], GNAT2 [guanine nucleotide binding protein
(G protein), alpha transducing activity polypeptide 2], GNAZ [guanine
nucleotide
binding protein (G protein), alpha z polypeptide], GNB1 [guanine nucleotide
binding protein (G protein), beta polypeptide 1], GNB1L [guanine nucleotide
binding protein (G protein), beta polypeptide 1-like], GNB2 [guanine
nucleotide
binding protein (G protein), beta polypeptide 2], GNB2L1 [guanine nucleotide
binding protein (G protein), beta polypeptide 2-like 1], GNB3 [guanine
nucleotide
binding protein (G protein), beta polypeptide 3], GNB4 [guanine nucleotide
binding protein (G protein), beta polypeptide 4], GNB5 [guanine nucleotide
binding protein (G protein), beta 5], GNG10 [guanine nucleotide binding
protein
(G protein), gamma 10], GNG11 [guanine nucleotide binding protein (G protein),
gamma 11], GNG12 [guanine nucleotide binding protein (G protein), gamma 12],
GNG13 [guanine nucleotide binding protein (G protein), gamma 13], GNG2
[guanine nucleotide binding protein (G protein), gamma 2], GNG3 [guanine
nucleotide binding protein (G protein), gamma 3], GNG4 [guanine nucleotide
binding protein (G protein), gamma 4], GNG5 [guanine nucleotide binding
protein
(G protein), gamma 5], GNG7 [guanine nucleotide binding protein (G protein),
gamma 7], GNLY [granulysin], GNRH1 [gonadotropin-releasing hormone 1
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(luteinizing-releasing hormone)], GNRHR [gonadotropin-releasing hormone
receptor], GOLGA2 [golgin A2], GOLGA4 [golgin A4], GOT2 [glutamic-
oxaloacetic transaminase 2, mitochondrial (aspartate aminotransferase 2)],
GP1 BA [glycoprotein lb (platelet), alpha polypeptide], GP5 [glycoprotein V
(platelet)], GP6 [glycoprotein VI (platelet)], GP9 [glycoprotein IX
(platelet)], GPC1
[glypican 1], GPC3 [glypican 3], GPD1 [glycerol-3-phosphate dehydrogenase 1
(soluble)], GPHN [gephyrin], GPI [glucose phosphate isomerase], GPM6A
[glycoprotein M6A], GPM6B [glycoprotein M6B], GPR161 [G protein-coupled
receptor 161 ], GPR182 [G protein-coupled receptor 182], GPR56 [G protein-
coupled receptor 56], GPRC6A [G protein-coupled receptor, family C, group 6,
member A], GPRIN1 [G protein regulated inducer of neurite outgrowth 1], GPT
[glutamic-pyruvate transaminase (alanine aminotransferase)], GPT2 [glutamic
pyruvate transaminase (alanine aminotransferase) 2], GPX1 [glutathione
peroxidase 1], GPX3 [glutathione peroxidase 3 (plasma)], GPX4 [glutathione
peroxidase 4 (phospholipid hydroperoxidase)], GRAP [GRB2-related adaptor
protein], GRB10 [growth factor receptor-bound protein 10], GRB2 [growth factor
receptor-bound protein 2], GRB7 [growth factor receptor-bound protein 7],
GREM1 [gremlin 1, cysteine knot superfamily, homolog (Xenopus laevis)], GRIA1
[glutamate receptor, ionotropic, AMPA 1], GRIA2 [glutamate receptor,
ionotropic,
AMPA 2], GRIA3 [glutamate receptor, ionotrophic, AMPA 3], GRID2 [glutamate
receptor, ionotropic, delta 2], GRID2IP [glutamate receptor, ionotropic, delta
2
(Grid2) interacting protein], GRIK1 [glutamate receptor, ionotropic, kainate
1],
GRIK2 [glutamate receptor, ionotropic, kainate 2], GRIN1 [glutamate receptor,
ionotropic, N-methyl D-aspartate 1], GRIN2A [glutamate receptor, ionotropic, N-
methyl D-aspartate 2A], GRIP1 [glutamate receptor interacting protein 1],
GRLF1
[glucocorticoid receptor DNA binding factor 1], GRM1 [glutamate receptor,
metabotropic 1], GRM2 [glutamate receptor, metabotropic 2], GRM5 [glutamate
receptor, metabotropic 5], GRM7 [glutamate receptor, metabotropic 7], GRM8
[glutamate receptor, metabotropic 8], GRN [granulin], GRP [gastrin-releasing
peptide], GRPR [gastrin-releasing peptide receptor], GSK3B [glycogen synthase
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kinase 3 beta], GSN [gelsolin], GSR [glutathione reductase], GSS [glutathione
synthetase], GSTA1 [glutathione S-transferase alpha 1], GSTM1 [glutathione S-
transferase mu 1], GSTP1 [glutathione S-transferase pi 1], GSTT1 [glutathione
S-transferase theta 1], GSTZ1 [glutathione transferase zeta 1], GTF2B [general
transcription factor IIB], GTF2E2 [general transcription factor IIE,
polypeptide 2,
beta 34kDa], GTF2H1 [general transcription factor IIH, polypeptide 1, 62kDa],
GTF2H2 [general transcription factor IIH, polypeptide 2, 44kDa], GTF2H3
[general transcription factor IIH, polypeptide 3, 34kDa], GTF2H4 [general
transcription factor IIH, polypeptide 4, 52kDa], GTF2I [general transcription
factor
Ili], GTF2IRD1 [GTF2I repeat domain containing 1], GTF2IRD2 [GTF2I repeat
domain containing 2], GUCA2A [guanylate cyclase activator 2A (guanylin)],
GUCY1A3 [guanylate cyclase 1, soluble, alpha 3], GUSB [glucuronidase, beta],
GYPA [glycophorin A (MNS blood group)], GYPC [glycophorin C (Gerbich blood
group)], GZF1 [GDNF-inducible zinc finger protein 1], GZMA [granzyme A
(granzyme 1, cytotoxic T-lymphocyte-associated serine esterase 3)], GZMB
[granzyme B (granzyme 2, cytotoxic T-lymphocyte-associated serine esterase
1)], H19 [H19, imprinted maternally expressed transcript (non-protein
coding)],
H1 FO [H1 histone family, member 0], H2AFX [H2A histone family, member X],
H2AFY [H2A histone family, member Y], H6PD [hexose-6-phosphate
dehydrogenase (glucose 1-dehydrogenase)], HADHA [hydroxyacyl-Coenzyme A
dehydrogenase/3-ketoacyl-Coenzyme A thiolase/enoyl-Coenzyme A hydratase
(trifunctional protein), alpha subunit], HAMP [hepcidin antimicrobial
peptide],
HAND1 [heart and neural crest derivatives expressed 1], HAND2 [heart and
neural crest derivatives expressed 2], HAP1 [huntingtin-associated protein 1],
HAPLNI [hyaluronan and proteoglycan link protein 1], HARS [histidyl-tRNA
synthetase], HAS1 [hyaluronan synthase 1], HAS2 [hyaluronan synthase 2],
HAS3 [hyaluronan synthase 3], HAX1 [HCLS1 associated protein X-1], HBA2
[hemoglobin, alpha 2], HBB [hemoglobin, beta], HBEGF [heparin-binding EGF-
like growth factor], HBG1 [hemoglobin, gamma A], HBG2 [hemoglobin, gamma
G], HCCS [holocytochrome c synthase (cytochrome c heme-lyase)], HCK
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