SH2D3C

Summary

SH2D3C (SH2 domain containing 3C, HGNC:16884) is a protein-coding gene on chromosome 9q34.11, encoding SH2 domain-containing protein 3C (Q8N5H7). Acts as an adapter protein that mediates cell signaling pathways involved in cellular functions such as cell adhesion and migration, tissue organization, and the regulation of the immune response.

This gene encodes an adaptor protein and member of a cytoplasmic protein family involved in cell migration. The encoded protein contains a putative Src homology 2 (SH2) domain and guanine nucleotide exchange factor-like domain which allows this signaling protein to form a complex with scaffolding protein Crk-associated substrate. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 10044 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 123 total — 1 pathogenic
• MANE Select transcript: NM_170600

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16884
Approved symbol	SH2D3C
Name	SH2 domain containing 3C
Location	9q34.11
Locus type	gene with protein product
Status	Approved
Aliases	NSP3
Ensembl gene	ENSG00000095370
Ensembl biotype	protein_coding
OMIM	604722
Entrez	10044

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 10 protein_coding, 5 protein_coding_CDS_not_defined

ENST00000314830, ENST00000373276, ENST00000373277, ENST00000414380, ENST00000420366, ENST00000429553, ENST00000440630, ENST00000464239, ENST00000468969, ENST00000471939, ENST00000484160, ENST00000488685, ENST00000629203, ENST00000902454, ENST00000902455

RefSeq mRNA: 7 — MANE Select: NM_170600 NM_001142531, NM_001142532, NM_001142533, NM_001142534, NM_001252334, NM_005489, NM_170600

CCDS: CCDS48026, CCDS48027, CCDS48028, CCDS59145, CCDS6877, CCDS6878

Canonical transcript exons

ENST00000314830 — 12 exons

Exon	Start	End
ENSE00001253130	127773990	127774467
ENSE00001253273	127778591	127778666
ENSE00001924997	127738317	127738921
ENSE00003360528	127739682	127739888
ENSE00003368357	127740258	127740369
ENSE00003415216	127741788	127741959
ENSE00003465568	127749211	127749665
ENSE00003555058	127751172	127751300
ENSE00003574172	127744564	127745099
ENSE00003635009	127761611	127761650
ENSE00003652044	127742849	127742964
ENSE00003665962	127747147	127747271

Expression profiles

Bgee: expression breadth ubiquitous, 209 present calls, max score 96.03.

FANTOM5 (CAGE): breadth broad, TPM avg 7.8076 / max 361.4076, expressed in 835 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
102567	2.7072	533
102570	1.7305	233
102562	0.9565	238
102571	0.9438	223
102573	0.2287	113
102569	0.2224	58
102568	0.2105	109
102572	0.1876	89
102564	0.1606	79
102566	0.1254	86

Top tissues by expression

243 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	96.03	gold quality
right lung	UBERON:0002167	95.57	gold quality
blood	UBERON:0000178	93.86	gold quality
apex of heart	UBERON:0002098	93.58	gold quality
upper lobe of left lung	UBERON:0008952	93.50	gold quality
upper lobe of lung	UBERON:0008948	93.33	gold quality
spleen	UBERON:0002106	92.37	gold quality
leukocyte	CL:0000738	92.32	gold quality
monocyte	CL:0000576	92.08	gold quality
lower lobe of lung	UBERON:0008949	90.54	gold quality
heart left ventricle	UBERON:0002084	89.86	gold quality
lung	UBERON:0002048	89.75	gold quality
cardiac ventricle	UBERON:0002082	89.64	gold quality
lymph node	UBERON:0000029	89.23	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.16	gold quality
right lobe of thyroid gland	UBERON:0001119	88.99	gold quality
omental fat pad	UBERON:0010414	88.34	gold quality
peritoneum	UBERON:0002358	88.26	gold quality
adipose tissue of abdominal region	UBERON:0007808	88.07	gold quality
subcutaneous adipose tissue	UBERON:0002190	87.41	gold quality
vermiform appendix	UBERON:0001154	86.63	gold quality
left lobe of thyroid gland	UBERON:0001120	86.45	gold quality
thyroid gland	UBERON:0002046	85.69	gold quality
heart	UBERON:0000948	85.62	gold quality
adipose tissue	UBERON:0001013	84.94	gold quality
thymus	UBERON:0002370	84.80	gold quality
left uterine tube	UBERON:0001303	84.24	gold quality
body of uterus	UBERON:0009853	83.93	gold quality
prefrontal cortex	UBERON:0000451	83.83	gold quality
caecum	UBERON:0001153	83.82	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.20

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

29 targeting SH2D3C, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-6815-3P	99.13	68.98	1530
HSA-MIR-219A-1-3P	98.91	67.87	639
HSA-MIR-4725-5P	98.67	65.42	628
HSA-MIR-504-5P	98.67	65.40	631
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-210-5P	98.57	64.37	832
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-4708-5P	97.77	67.82	831
HSA-MIR-8089	97.74	66.21	1698
HSA-MIR-4667-5P	97.61	66.67	1683
HSA-MIR-7855-5P	97.39	67.18	925
HSA-MIR-1913	97.07	66.20	1417
HSA-MIR-3126-5P	96.87	65.83	912
HSA-MIR-6875-5P	96.87	65.49	958
HSA-MIR-3907	96.76	65.04	662

Literature-anchored findings (GeneRIF, showing 4)

• This protein positively regulates T cell receptor-mediated interleukin-2 production by Jurkat cells. (PMID:12486027)
• SH2D3C (SHEP1) is less highly expressed than BCAR3 and NSP1 in breast cancer cells, and the expression patterns suggest differential roles for the three genes during breast cancer progression. (PMID:17270363)
• NSP3 overexpression did not induce anti-estrogen resistance in breast tumor cell lines. (PMID:17427198)
• The structure of the NSP3-p130Cas complex reveals that this closed conformation is instrumental for interaction of NSP proteins with a focal adhesion-targeting domain present in Cas proteins. (PMID:22081014)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sh2d3ca	ENSDARG00000028099
danio_rerio	sh2d3cb	ENSDARG00000104555
mus_musculus	Sh2d3c	ENSMUSG00000059013
rattus_norvegicus	Sh2d3c	ENSRNOG00000054560
drosophila_melanogaster	CG9098	FBGN0031762

Paralogs (2): SH2D3A (ENSG00000125731), BCAR3 (ENSG00000137936)

Protein

Protein identifiers

SH2 domain-containing protein 3C — Q8N5H7 (reviewed: Q8N5H7)

Alternative names: Cas/HEF1-associated signal transducer, Novel SH2-containing protein 3, SH2 domain-containing Eph receptor-binding protein 1

All UniProt accessions (3): Q8N5H7, H0Y5X5, Q5JU32

UniProt curated annotations — full annotation on UniProt →

Function. Acts as an adapter protein that mediates cell signaling pathways involved in cellular functions such as cell adhesion and migration, tissue organization, and the regulation of the immune response. Plays a role in integrin-mediated cell adhesion through BCAR1-CRK-RAPGEF1 signaling and activation of the small GTPase RAP1. Promotes cell migration and invasion through the extracellular matrix. Required for marginal zone B-cell development and thymus-independent type 2 immune responses. Mediates migration and adhesion of B cells in the splenic marginal zone via promoting hyperphosphorylation of NEDD9/CASL. Plays a role in CXCL13-induced chemotaxis of B-cells. Plays a role in the migration of olfactory sensory neurons (OSNs) into the forebrain and the innervation of the olfactory bulb by the OSN axons during development. Required for the efficient tyrosine phosphorylation of BCAR1 in OSN axons. Important regulator of chemokine-induced, integrin-mediated T lymphocyte adhesion and migration, acting upstream of RAP1. Required for tissue-specific adhesion of T lymphocytes to peripheral tissues. Required for basal and CXCL2 stimulated serine-threonine phosphorylation of NEDD9. May be involved in the regulation of T-cell receptor-mediated IL2 production through the activation of the JNK pathway in T-cells. May be involved in the BCAR1/CAS-mediated JNK activation pathway.

Subunit / interactions. Component of a complex comprised of SH2D3C, BCAR1/CAS, and CRK. Within the complex, interacts with CRK and (via C-terminus) with BCAR1/CAS (via C-terminus). Interacts with NEDD9/HEF1. Interacts with EPHB2. Interacts with NEDD9/HEF1. Interacts with BCAR1/CAS. Interacts with PTK2B. Interacts (via C-terminus) with BCAR1/CAS (via C-terminus). Interacts with IGF1.

Subcellular location. Cytoplasm. Cell membrane. Cell projection. Axon. Ruffle membrane Cell membrane.

Tissue specificity. Ubiquitously expressed.

Post-translational modifications. Phosphorylated by MAPK/ERK upon T-cell receptor stimulation in T-cells.

Domain organisation. The C-terminal Cdc25-homology/Ras-GEF domain adopts a closed conformation rendering it incapable of carrying out canonical exchange factor function, this closed conformation is required for interaction with BCAR1.

Isoforms (6)

UniProt ID	Names	Canonical?
Q8N5H7-1	1, Chat-H	yes
Q8N5H7-2	2
Q8N5H7-3	3
Q8N5H7-4	4
Q8N5H7-5	5
Q8N5H7-6	6

RefSeq proteins (7): NP_001136003, NP_001136004, NP_001136005, NP_001136006, NP_001239263, NP_005480, NP_733745* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000980	SH2	Domain
IPR001895	RASGEF_cat_dom	Domain
IPR023578	Ras_GEF_dom_sf	Homologous_superfamily
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR036964	RASGEF_cat_dom_sf	Homologous_superfamily
IPR044102	SH2_SHEP1/BCAR3/NSP1	Domain
IPR051853	SH2-Ras-GEF_adapter	Family

Pfam: PF00017, PF00617

UniProt features (50 total): helix 21, modified residue 6, splice variant 5, compositionally biased region 4, sequence conflict 3, strand 3, region of interest 3, domain 2, chain 1, sequence variant 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3T6G	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N5H7-F1	67.31	0.46

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (6): 22, 278, 283, 359, 440, 793

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 169 (showing top): AREB6_03, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOCC_RUFFLE, GGGTGGRR_PAX4_03, GOBP_JNK_CASCADE, ELK1_01, MA_MYELOID_DIFFERENTIATION_UP, GOCC_NEURON_PROJECTION, GATA4_Q3, RGAGGAARY_PU1_Q6, DANG_BOUND_BY_MYC, GOBP_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOCC_CELL_PROJECTION_MEMBRANE, ATGTACA_MIR493

GO Biological Process (2): JNK cascade (GO:0007254), small GTPase-mediated signal transduction (GO:0007264)

GO Molecular Function (3): phosphotyrosine residue binding (GO:0001784), guanyl-nucleotide exchange factor activity (GO:0005085), protein binding (GO:0005515)

GO Cellular Component (7): cytosol (GO:0005829), axon (GO:0030424), ruffle membrane (GO:0032587), cytoplasm (GO:0005737), plasma membrane (GO:0005886), membrane (GO:0016020), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
MAPK cascade	1
intracellular signaling cassette	1
protein phosphorylated amino acid binding	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
binding	1
cytoplasm	1
neuron projection	1
ruffle	1
cell projection membrane	1
leading edge membrane	1
intracellular anatomical structure	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1974 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SH2D3C	PRSS57	Q6UWY2	998
SH2D3C	EIF4G1	Q04637	984
SH2D3C	SH2D3A	Q9BRG2	931
SH2D3C	SPECC1	Q5M775	927
SH2D3C	IRF3	Q14653	890
SH2D3C	G3BP1	Q13283	868
SH2D3C	ZC3H7B	Q9UGR2	825
SH2D3C	ISG15	P05161	795
SH2D3C	MYOM2	P54296	785
SH2D3C	PPP1CA	P08129	722
SH2D3C	ASZ1	Q8WWH4	697
SH2D3C	G3BP2	Q9UN86	696
SH2D3C	SRC	P12931	694
SH2D3C	YBX1	P16990	692
SH2D3C	ACE2	Q9BYF1	665

IntAct

143 interactions, top by confidence:

A	B	Type	Score
SH2D3C	EFS	psi-mi:“MI:0915”(physical association)	0.550
EGFR	SH2D3C	psi-mi:“MI:0915”(physical association)	0.550
SH2D3C	EGFR	psi-mi:“MI:0915”(physical association)	0.550
BCAR1	SH2D3C	psi-mi:“MI:0915”(physical association)	0.500
CAV1	SH2D3C	psi-mi:“MI:0407”(direct interaction)	0.440
SH2D3C	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
SH2D3C	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.440
SH2D3C	ARHGEF12	psi-mi:“MI:0407”(direct interaction)	0.440
SH2D3C	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
SH2D3C	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
SH2D3C	SNX27	psi-mi:“MI:0407”(direct interaction)	0.440
SH2D3C	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
SH2D3C	SYNJ2BP	psi-mi:“MI:0407”(direct interaction)	0.440
SH2D3C	TAMALIN	psi-mi:“MI:0407”(direct interaction)	0.440
SH2D3C	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.440
SH2D3C	GRID2IP	psi-mi:“MI:0407”(direct interaction)	0.440
NHERF2	SH2D3C	psi-mi:“MI:0407”(direct interaction)	0.440
SH2D3C	DLG1	psi-mi:“MI:0407”(direct interaction)	0.440
SH2D3C	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
SH2D3C	NHERF4	psi-mi:“MI:0407”(direct interaction)	0.440
SH2D3C	ARHGEF11	psi-mi:“MI:0407”(direct interaction)	0.440
SH2D3C	PDZRN3	psi-mi:“MI:0407”(direct interaction)	0.440
SH2D3C	SNTB1	psi-mi:“MI:0407”(direct interaction)	0.440
SH2D3C	PDZD2	psi-mi:“MI:0407”(direct interaction)	0.440
SH2D3C	SNTA1	psi-mi:“MI:0407”(direct interaction)	0.440
SH2D3C	APBA3	psi-mi:“MI:0407”(direct interaction)	0.440
SH2D3C	PICK1	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (173): SH2D3C (Two-hybrid), EFS (Two-hybrid), SH2D3C (PCA), SH2D3C (Two-hybrid), PRPSAP1 (Affinity Capture-MS), AKAP12 (Affinity Capture-MS), PRPS1 (Affinity Capture-MS), PRPS2 (Affinity Capture-MS), PRPSAP2 (Affinity Capture-MS), HSPB1 (Affinity Capture-MS), YWHAG (Affinity Capture-MS), IGF2BP3 (Affinity Capture-MS), OSBPL8 (Affinity Capture-MS), YWHAZ (Affinity Capture-MS), AP3S1 (Affinity Capture-MS)

ESM2 similar proteins: A2AKB4, A2APT9, O54824, P49796, Q0V8R5, Q14005, Q32LQ1, Q3B7M3, Q3TYG6, Q494U1, Q4FZU8, Q4V7B1, Q5BJM5, Q5JV73, Q5RA50, Q5SYB0, Q5T7N3, Q68FE6, Q6P1H6, Q6P9J5, Q6PCP7, Q6PG95, Q6ZPF3, Q6ZUX3, Q7TNY7, Q7TP65, Q80TI1, Q80UZ0, Q80XI1, Q80YE4, Q86V42, Q86XL3, Q8BLK9, Q8C886, Q8IVF5, Q8K124, Q8K3I4, Q8K451, Q8N5H7, Q8N878

Diamond homologs: D3ZAZ5, O14796, O70142, O70143, O75791, O75815, O88900, P00519, P00520, P00521, P00522, P00530, P00541, P00542, P00543, P07332, P10447, P14238, P16591, P16879, P29350, P29351, P29353, P29355, P42684, P46109, P47941, P53356, P62993, P62994, P70451, P81718, P87379, P98077, P98083, Q07883, Q08012, Q0IIE2, Q13588, Q4JIM5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 89 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	5	49.2×	4e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	46.9×	4e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	46.9×	4e-06
Assembly and cell surface presentation of NMDA receptors	10	43.8×	5e-12
Dopamine Neurotransmitter Release Cycle	5	42.8×	4e-06
Long-term potentiation	5	41.0×	5e-06
Neurexins and neuroligins	10	34.0×	4e-11
Protein-protein interactions at synapses	6	27.5×	4e-06

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	75.2×	7e-16
receptor clustering	7	51.4×	2e-08
protein localization to synapse	5	45.1×	7e-06
regulation of postsynaptic membrane neurotransmitter receptor levels	7	40.8×	8e-08
cell-cell adhesion	11	13.1×	1e-07
protein-containing complex assembly	8	10.7×	7e-05
establishment of localization in cell	5	9.4×	5e-03
chemical synaptic transmission	7	6.4×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

123 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	95
Likely benign	10
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1457478	NC_000009.11:g.(?130216807)(130953136_?)del	Pathogenic

SpliceAI

2273 predictions. Top by Δscore:

Variant	Effect	Δscore
9:127738920:CC:C	acceptor_gain	1.0000
9:127738921:CC:C	acceptor_gain	1.0000
9:127739677:CTCA:C	donor_loss	1.0000
9:127739679:CACCC:C	donor_loss	1.0000
9:127739680:A:AC	donor_gain	1.0000
9:127739680:AC:A	donor_gain	1.0000
9:127739680:ACC:A	donor_gain	1.0000
9:127739681:C:CG	donor_gain	1.0000
9:127739681:CC:C	donor_gain	1.0000
9:127739681:CCC:C	donor_gain	1.0000
9:127739681:CCCT:C	donor_gain	1.0000
9:127739681:CCCTG:C	donor_gain	1.0000
9:127739884:GCCTT:G	acceptor_gain	1.0000
9:127739885:CCTTC:C	acceptor_gain	1.0000
9:127739886:CTT:C	acceptor_gain	1.0000
9:127739887:TT:T	acceptor_gain	1.0000
9:127739889:C:CC	acceptor_gain	1.0000
9:127740253:AGTAC:A	donor_loss	1.0000
9:127740254:GTAC:G	donor_loss	1.0000
9:127740255:TA:T	donor_loss	1.0000
9:127740256:ACCT:A	donor_loss	1.0000
9:127740257:C:CT	donor_loss	1.0000
9:127741784:GTACC:G	donor_loss	1.0000
9:127741786:A:C	donor_loss	1.0000
9:127741787:C:CA	donor_loss	1.0000
9:127741958:ACC:A	acceptor_loss	1.0000
9:127741959:CCTG:C	acceptor_loss	1.0000
9:127741960:C:CA	acceptor_loss	1.0000
9:127741960:C:CC	acceptor_gain	1.0000
9:127741961:T:A	acceptor_loss	1.0000

AlphaMissense

5596 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:127749379:G:C	P324R	1.000
9:127749379:G:T	P324Q	1.000
9:127749388:C:G	R321P	1.000
9:127749389:G:C	R321G	1.000
9:127749389:G:T	R321S	1.000
9:127749463:A:G	L296P	1.000
9:127749463:A:T	L296H	1.000
9:127749480:A:C	F290L	1.000
9:127749480:A:T	F290L	1.000
9:127749482:A:G	F290L	1.000
9:127749503:A:C	Y283D	1.000
9:127749550:A:C	I267S	1.000
9:127749550:A:G	I267T	1.000
9:127749550:A:T	I267N	1.000
9:127749555:G:C	F265L	1.000
9:127749555:G:T	F265L	1.000
9:127749556:A:G	F265S	1.000
9:127749557:A:G	F265L	1.000
9:127749558:G:C	H264Q	1.000
9:127749558:G:T	H264Q	1.000
9:127749560:G:C	H264D	1.000
9:127749586:G:C	T255R	1.000
9:127749586:G:T	T255K	1.000
9:127749589:A:C	L254R	1.000
9:127749589:A:G	L254P	1.000
9:127749589:A:T	L254H	1.000
9:127749592:A:T	V253E	1.000
9:127749619:T:A	D244V	1.000
9:127749622:C:G	R243P	1.000
9:127749623:G:C	R243G	1.000

dbSNP variants (sampled 300 via entrez): RS1000112329 (9:127753032 T>C), RS1000138694 (9:127777958 A>C), RS1000254093 (9:127746424 C>T), RS1000365933 (9:127775538 A>G), RS1000371394 (9:127762320 C>T), RS1000467063 (9:127740838 G>A), RS1000552604 (9:127752671 C>A,T), RS1000586807 (9:127747798 G>A), RS1000629491 (9:127740678 A>T), RS1000740740 (9:127776551 T>C), RS1000786694 (9:127744238 T>C), RS1000798803 (9:127775259 T>G), RS1000811771 (9:127751116 G>A), RS1000814113 (9:127771285 T>C), RS1000848262 (9:127771011 A>G,T)

Disease associations

OMIM: gene MIM:604722 | disease phenotypes: MIM:615042

GenCC curated gene-disease

Mondo (1): congenital muscular dystrophy with intellectual disability and severe epilepsy (MONDO:0014023)

Orphanet (1): Congenital muscular dystrophy with intellectual disability and severe epilepsy (Orphanet:329178)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST004608_155	Granulocyte percentage of myeloid white cells	8.000000e-11
GCST004609_8	Monocyte percentage of white cells	8.000000e-11
GCST90002380_63	Basophil percentage of white cells	3.000000e-10
GCST90002393_315	Monocyte count	1.000000e-15
GCST90002394_331	Monocyte percentage of white cells	3.000000e-14
GCST90002399_83	Neutrophil percentage of white cells	2.000000e-12

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0007992	basophil percentage of leukocytes
EFO:0005091	monocyte count
EFO:0007990	neutrophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

36 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	2
Estradiol	increases expression, affects expression, increases reaction, affects binding	2
Valproic Acid	increases expression, increases methylation	2
GSK-J4	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
bisphenol A	increases expression	1
butyraldehyde	increases expression	1
tobacco tar	decreases expression, decreases reaction	1
diallyl disulfide	decreases expression, decreases reaction	1
ferrous chloride	increases expression	1
allyl sulfide	decreases expression, decreases reaction	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
pentanal	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
(+)-JQ1 compound	decreases expression	1
Bortezomib	decreases expression	1
Decitabine	affects expression	1
Acetaminophen	decreases expression	1
Air Pollutants, Occupational	decreases expression	1
Aldehydes	increases expression	1
Arsenic	affects expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects expression	1
Doxorubicin	decreases expression	1
Formaldehyde	decreases expression	1
Lead	increases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression, affects cotreatment	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.