SEMA4C

Summary

SEMA4C (semaphorin 4C, HGNC:10731) is a protein-coding gene on chromosome 2q11.2, encoding Semaphorin-4C (Q9C0C4). Cell surface receptor for PLXNB2 that plays an important role in cell-cell signaling.

Predicted to enable chemorepellent activity; neuropilin binding activity; and semaphorin receptor binding activity. Involved in muscle cell differentiation and positive regulation of stress-activated MAPK cascade. Located in extracellular space.

Source: NCBI Gene 54910 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 141 total
• MANE Select transcript: NM_017789

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10731
Approved symbol	SEMA4C
Name	semaphorin 4C
Location	2q11.2
Locus type	gene with protein product
Status	Approved
Aliases	Semacl1, Semaf
Ensembl gene	ENSG00000168758
Ensembl biotype	protein_coding
OMIM	604462
Entrez	54910

Gene structure

Transcript identifiers

Ensembl transcripts: 46 — 43 protein_coding, 3 retained_intron

ENST00000305476, ENST00000442264, ENST00000449330, ENST00000467747, ENST00000474420, ENST00000482925, ENST00000897274, ENST00000897275, ENST00000897276, ENST00000897277, ENST00000897278, ENST00000897279, ENST00000897280, ENST00000897281, ENST00000897282, ENST00000897283, ENST00000897284, ENST00000897285, ENST00000897286, ENST00000897287, ENST00000897288, ENST00000897289, ENST00000897290, ENST00000897291, ENST00000897292, ENST00000897293, ENST00000897294, ENST00000897295, ENST00000897296, ENST00000897297, ENST00000914305, ENST00000914306, ENST00000914307, ENST00000914308, ENST00000914309, ENST00000914310, ENST00000914311, ENST00000914312, ENST00000914313, ENST00000914314, ENST00000914315, ENST00000914316, ENST00000914317, ENST00000914318, ENST00000914319, ENST00000914320

RefSeq mRNA: 1 — MANE Select: NM_017789 NM_017789

CCDS: CCDS2029

Canonical transcript exons

ENST00000305476 — 15 exons

Exon	Start	End
ENSE00001153920	96866283	96866431
ENSE00001373665	96867778	96867923
ENSE00001387737	96869876	96870080
ENSE00001812554	96859718	96861455
ENSE00003478571	96861579	96861649
ENSE00003479221	96863682	96863794
ENSE00003509054	96865867	96865929
ENSE00003512135	96861737	96861894
ENSE00003572655	96864964	96865115
ENSE00003593205	96865666	96865764
ENSE00003598851	96865441	96865537
ENSE00003600052	96864238	96864382
ENSE00003618961	96864705	96864880
ENSE00003673579	96865204	96865320
ENSE00003679744	96863926	96864148

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 98.78.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.0216 / max 160.0953, expressed in 1639 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
29780	6.1283	1314
29779	3.0620	1248
29777	1.6648	918
29778	1.4925	974
29784	0.5154	247
29783	0.4032	182
29776	0.3693	176
29782	0.2791	151
29781	0.0518	25
29785	0.0363	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory bulb	UBERON:0002264	98.78	gold quality
trigeminal ganglion	UBERON:0001675	98.76	gold quality
cervix squamous epithelium	UBERON:0006922	98.38	gold quality
dorsal root ganglion	UBERON:0000044	97.91	gold quality
cerebellar vermis	UBERON:0004720	97.74	gold quality
tibial nerve	UBERON:0001323	97.67	gold quality
inferior vagus X ganglion	UBERON:0005363	97.48	gold quality
sural nerve	UBERON:0015488	97.43	gold quality
inferior olivary complex	UBERON:0002127	97.31	gold quality
endothelial cell	CL:0000115	96.74	gold quality
pericardium	UBERON:0002407	96.41	gold quality
medulla oblongata	UBERON:0001896	96.39	gold quality
left uterine tube	UBERON:0001303	96.07	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	96.07	gold quality
visceral pleura	UBERON:0002401	95.97	gold quality
saphenous vein	UBERON:0007318	95.84	gold quality
nipple	UBERON:0002030	95.80	gold quality
placenta	UBERON:0001987	95.76	gold quality
ventral tegmental area	UBERON:0002691	95.76	gold quality
vena cava	UBERON:0004087	95.62	gold quality
cardia of stomach	UBERON:0001162	95.56	gold quality
body of uterus	UBERON:0009853	95.51	gold quality
trachea	UBERON:0003126	95.42	gold quality
superior vestibular nucleus	UBERON:0007227	95.41	gold quality
pylorus	UBERON:0001166	95.34	gold quality
parietal pleura	UBERON:0002400	95.25	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.24	gold quality
hair follicle	UBERON:0002073	95.23	gold quality
subthalamic nucleus	UBERON:0001906	95.15	gold quality
germinal epithelium of ovary	UBERON:0001304	95.08	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.49

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

103 targeting SEMA4C, 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-8485	100.00	77.57	4731
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-LET-7D-5P	99.96	71.76	1632

Literature-anchored findings (GeneRIF, showing 15)

• High Sema4C is associated with epithelial-mesenchymal transition and renal fibrosis. (PMID:20959347)
• There is a high expression of Sema4C in esophageal cancer, gastric cancer and rectal cancer, and expression is strongly correlated with lymphatic metastasis. (PMID:22944267)
• Data suggest that Erbin can interact with Sema4C, and co-expression of Erbin blocks the process of Sema4C-induced epithelial-mesenchymal transition. (PMID:24142719)
• Suggest that up-regulation of miR-125b or targeting Sema4C could serve as novel approaches to reverse chemotherapy resistance in breast cancers. (PMID:25605244)
• Data show that G-protein-coupled receptor kinase-interacting protein 1 (GIT1) and semaphorin 4C (SEMA4C) were found to have putative microRNA miR-138 binding sites in their 3’ untranslated region (3’UTRs). (PMID:26283050)
• Tumor-associated LECs produce sSEMA4C to promote lymphatic metastasis of tumors. (PMID:27401250)
• data indicate that Sema4C/PlexinB2 signaling is essential for the growth of breast carcinoma cells, featuring a novel potential therapeutic target. In addition, elevated Sema4C expression enables indolent luminal-type tumors to become resistant to estrogen deprivation, invasive and metastatic in vivo (PMID:29555978)
• SEMA4C expression in breast cancer cells promotes cancer cell proliferation, macrophage recruitment, and angiogenesis. (PMID:31308149)
• SEMA4C is a novel target to limit osteosarcoma growth, progression, and metastasis. (PMID:31582836)
• Sema4C mediates EMT inducing chemotherapeutic resistance of miR-31-3p in cervical cancer cells. (PMID:31776419)
• Downregulation of SEMA4C Inhibit Epithelial-Mesenchymal Transition (EMT) and the Invasion and Metastasis of Cervical Cancer Cells via Inhibiting Transforming Growth Factor-beta 1 (TGF-beta1)-Induced Hela cells p38 Mitogen-Activated Protein Kinase (MAPK) Activation. (PMID:31951596)
• Sema4D and 4C can contribute to tumor progression in human patients or experimental models, while the role of Sema4A has not yet been fully understood (PMID:32244055)
• High SEMA4C expression promotes the epithelial-mesenchymal transition and predicts poor prognosis in colorectal carcinoma. (PMID:33177246)
• Serum semaphorin4C as an auxiliary diagnostic biomarker for breast cancer. (PMID:34459126)
• Effect of microrna-138 on epithelial-Mesenchymal transition and invasion of breast cancer cells by targeting semaphorin 4C. (PMID:34747314)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	sema4c	ENSDARG00000079611
mus_musculus	Sema4c	ENSMUSG00000026121
rattus_norvegicus	Sema4c	ENSRNOG00000016254

Paralogs (19): SEMA3F (ENSG00000001617), SEMA3G (ENSG00000010319), SEMA3B (ENSG00000012171), SEMA3A (ENSG00000075213), SEMA3C (ENSG00000075223), SEMA5B (ENSG00000082684), SEMA6A (ENSG00000092421), SEMA4G (ENSG00000095539), SEMA5A (ENSG00000112902), SEMA4F (ENSG00000135622), SEMA6D (ENSG00000137872), SEMA7A (ENSG00000138623), SEMA6C (ENSG00000143434), SEMA3D (ENSG00000153993), SEMA6B (ENSG00000167680), SEMA3E (ENSG00000170381), SEMA4B (ENSG00000185033), SEMA4D (ENSG00000187764), SEMA4A (ENSG00000196189)

Protein

Protein identifiers

Semaphorin-4C — Q9C0C4 (reviewed: Q9C0C4)

All UniProt accessions (3): Q9C0C4, C9J4M7, C9JV89

UniProt curated annotations — full annotation on UniProt →

Function. Cell surface receptor for PLXNB2 that plays an important role in cell-cell signaling. PLXNB2 binding promotes downstream activation of RHOA and phosphorylation of ERBB2 at ‘Tyr-1248’. Required for normal brain development, axon guidance and cell migration. Probable signaling receptor which may play a role in myogenic differentiation through activation of the stress-activated MAPK cascade.

Subunit / interactions. Interacts (via the PDZ-binding motif) with GIPC (via the PDZ domain). Interacts with NCDN. Interacts (via the PDZ-binding motif) with DLG4. Interacts with PLXNB2.

Subcellular location. Postsynaptic density membrane. Cytoplasmic vesicle. Secretory vesicle. Synaptic vesicle membrane.

Similarity. Belongs to the semaphorin family.

RefSeq proteins (1): NP_060259* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001627	Semap_dom	Domain
IPR002165	Plexin_repeat	Repeat
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR016201	PSI	Domain
IPR027231	Semaphorin	Family
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR036352	Semap_dom_sf	Homologous_superfamily

Pfam: PF01403, PF01437

UniProt features (29 total): glycosylation site 6, disulfide bond 6, region of interest 3, domain 3, topological domain 2, strand 2, signal peptide 1, chain 1, short sequence motif 1, compositionally biased region 1, modified residue 1, sequence conflict 1, transmembrane region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6N5Z	X-RAY DIFFRACTION	2.45

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9C0C4-F1	82.30	0.65

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 (1): 742

Disulfide bonds (6): 99–110, 128–137, 261–370, 285–330, 500–517, 509–526

Glycosylation sites (6): 106, 121, 310, 419, 522, 564

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 334 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, ATF_B, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_HINDBRAIN_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_METENCEPHALON_DEVELOPMENT, GOBP_REGULATION_OF_STRESS_ACTIVATED_PROTEIN_KINASE_SIGNALING_CASCADE, GOBP_SYNAPSE_ASSEMBLY, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, CREBP1_Q2, GOBP_NEURAL_TUBE_DEVELOPMENT

GO Biological Process (13): neural crest cell migration (GO:0001755), neural tube closure (GO:0001843), axon guidance (GO:0007411), cell migration in hindbrain (GO:0021535), cerebellum development (GO:0021549), positive regulation of cell migration (GO:0030335), positive regulation of stress-activated MAPK cascade (GO:0032874), muscle cell differentiation (GO:0042692), negative chemotaxis (GO:0050919), semaphorin-plexin signaling pathway (GO:0071526), regulation of postsynapse assembly (GO:0150052), nervous system development (GO:0007399), cell differentiation (GO:0030154)

GO Molecular Function (4): semaphorin receptor binding (GO:0030215), neuropilin binding (GO:0038191), chemorepellent activity (GO:0045499), protein binding (GO:0005515)

GO Cellular Component (10): obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), postsynaptic density (GO:0014069), synaptic vesicle membrane (GO:0030672), postsynaptic density membrane (GO:0098839), glutamatergic synapse (GO:0098978), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), synapse (GO:0045202), postsynaptic membrane (GO:0045211)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell migration	2
signaling receptor binding	2
neural crest cell development	1
mesenchymal cell migration	1
primary neural tube formation	1
tube closure	1
axonogenesis	1
neuron projection guidance	1
hindbrain development	1
metencephalon development	1
anatomical structure development	1
regulation of cell migration	1
positive regulation of cell motility	1
regulation of stress-activated MAPK cascade	1
positive regulation of MAPK cascade	1
stress-activated MAPK cascade	1
positive regulation of stress-activated protein kinase signaling cascade	1
cell differentiation	1
muscle structure development	1
chemotaxis	1
cell surface receptor signaling pathway	1
regulation of synapse assembly	1
postsynapse assembly	1
regulation of postsynapse organization	1
system development	1
cellular developmental process	1
receptor ligand activity	1
negative chemotaxis	1
binding	1
membrane	1
cell periphery	1
asymmetric synapse	1
postsynaptic specialization	1
synaptic vesicle	1
exocytic vesicle membrane	1
postsynaptic density	1
postsynaptic membrane	1
postsynaptic specialization membrane	1
synapse	1
cellular anatomical structure	1

Protein interactions and networks

STRING

700 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SEMA4C	PLXNB2	O15031	957
SEMA4C	CHST10	O43529	791
SEMA4C	CNGA3	Q16281	745
SEMA4C	PLXND1	Q9Y4D7	676
SEMA4C	MERTK	Q12866	639
SEMA4C	PLXNC1	O60486	522
SEMA4C	LNX1	Q8TBB1	485
SEMA4C	PDZRN3	Q9UPQ7	477
SEMA4C	SNRNP200	O75643	474
SEMA4C	VAPA	Q9P0L0	471
SEMA4C	SEMA4D	Q92854	438
SEMA4C	GRK4	P32298	418
SEMA4C	PLXNB1	O43157	412
SEMA4C	GRK5	P34947	406
SEMA4C	SNAI1	O95863	404

IntAct

217 interactions, top by confidence:

A	B	Type	Score
SEMA4C	KRT31	psi-mi:“MI:0915”(physical association)	0.720
SEMA4C	PNMA1	psi-mi:“MI:0915”(physical association)	0.720
PNMA1	SEMA4C	psi-mi:“MI:0915”(physical association)	0.720
KRT31	SEMA4C	psi-mi:“MI:0915”(physical association)	0.720
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
SEMA4C	PLXNB2	psi-mi:“MI:0407”(direct interaction)	0.590
KRT40	SEMA4C	psi-mi:“MI:0915”(physical association)	0.560
SEMA4C	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.560
RCHY1	SEMA4C	psi-mi:“MI:0915”(physical association)	0.560
SEMA4C	KRT40	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLA	SEMA4C	psi-mi:“MI:0915”(physical association)	0.560
SEMA4C	RCHY1	psi-mi:“MI:0915”(physical association)	0.560
USHBP1	SEMA4C	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLC	SEMA4C	psi-mi:“MI:0915”(physical association)	0.560
HSF2BP	SEMA4C	psi-mi:“MI:0915”(physical association)	0.560
KRT27	SEMA4C	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	SEMA4C	psi-mi:“MI:0915”(physical association)	0.560
KRTAP6-3	SEMA4C	psi-mi:“MI:0915”(physical association)	0.560
KRT34	SEMA4C	psi-mi:“MI:0915”(physical association)	0.560
KRT16	SEMA4C	psi-mi:“MI:0915”(physical association)	0.560
SEMA4C	PEX1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (208): SEMA4C (Two-hybrid), SEMA4C (Two-hybrid), SEMA4C (Two-hybrid), KRT40 (Two-hybrid), NOTCH2NL (Two-hybrid), SEMA4C (Affinity Capture-MS), SEMA4C (Affinity Capture-MS), SEMA4C (Affinity Capture-MS), SEMA4C (Affinity Capture-MS), SEMA4C (Affinity Capture-MS), SEMA4C (Affinity Capture-MS), SEMA4C (Affinity Capture-MS), SEMA4C (Affinity Capture-MS), SEMA4C (Proximity Label-MS), SEMA4C (Affinity Capture-MS)

ESM2 similar proteins: A2BD09, B0BNI5, B5MFE9, D3Z7H8, O70624, O75326, O88632, P09531, P42917, P82350, Q0P3W2, Q0V9V5, Q0VCP3, Q13275, Q16586, Q25C36, Q28686, Q29RB4, Q2HJE5, Q2KHV9, Q2PT31, Q3UH93, Q4LFA9, Q594P2, Q64255, Q66H86, Q68BL7, Q6UWY5, Q6ZMI3, Q80WF4, Q80WL1, Q863A3, Q866N2, Q8BH02, Q8BHP7, Q8BK62, Q8BMF8, Q8IUL8, Q8IYS2, Q91X21

Diamond homologs: A7MB70, D3ZTD8, O08665, O09126, O15041, O35464, O42236, O42237, O88632, O95025, O95754, P70275, Q13214, Q13275, Q13591, Q14563, Q17330, Q24322, Q24323, Q26473, Q26972, Q4LFA9, Q5EA85, Q5R7F5, Q5RE75, Q60519, Q62177, Q62178, Q62179, Q62181, Q62217, Q63548, Q64151, Q76KF0, Q8BH34, Q8NFY4, Q90607, Q90663, Q90665, Q92854

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 151 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	6	33.3×	8e-06
Assembly and cell surface presentation of NMDA receptors	6	14.8×	5e-04
Neurexins and neuroligins	7	13.4×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	42.1×	2e-11
protein localization to synapse	5	27.8×	1e-04
receptor clustering	6	27.1×	2e-05
regulation of postsynaptic membrane neurotransmitter receptor levels	5	18.0×	1e-03
morphogenesis of an epithelium	5	12.5×	5e-03
bicellular tight junction assembly	5	12.0×	5e-03
cell-cell adhesion	11	8.1×	3e-05
chemical synaptic transmission	9	5.0×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	119
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2338 predictions. Top by Δscore:

Variant	Effect	Δscore
2:96861452:CTGA:C	acceptor_gain	1.0000
2:96861453:TGA:T	acceptor_gain	1.0000
2:96861453:TGAC:T	acceptor_loss	1.0000
2:96861454:GA:G	acceptor_gain	1.0000
2:96861456:C:CC	acceptor_gain	1.0000
2:96861461:G:GC	acceptor_gain	1.0000
2:96861574:CTCA:C	donor_loss	1.0000
2:96861575:TCA:T	donor_loss	1.0000
2:96861576:CA:C	donor_loss	1.0000
2:96861577:ACCT:A	donor_loss	1.0000
2:96861578:C:CG	donor_loss	1.0000
2:96861578:CCTTT:C	donor_gain	1.0000
2:96861586:A:AC	donor_gain	1.0000
2:96861587:C:CC	donor_gain	1.0000
2:96861647:GATC:G	acceptor_loss	1.0000
2:96861648:ATC:A	acceptor_loss	1.0000
2:96861649:TCT:T	acceptor_loss	1.0000
2:96861650:C:CC	acceptor_gain	1.0000
2:96861650:C:T	acceptor_loss	1.0000
2:96861731:ACT:A	donor_loss	1.0000
2:96861732:CTC:C	donor_loss	1.0000
2:96861733:TCA:T	donor_loss	1.0000
2:96861734:CACCC:C	donor_loss	1.0000
2:96861735:A:AC	donor_gain	1.0000
2:96861735:AC:A	donor_gain	1.0000
2:96861736:C:A	donor_loss	1.0000
2:96861736:C:CC	donor_gain	1.0000
2:96861736:CC:C	donor_gain	1.0000
2:96863677:ACTAC:A	donor_gain	1.0000
2:96863678:CT:C	donor_gain	1.0000

AlphaMissense

5344 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:96864842:C:A	W275C	0.999
2:96864842:C:G	W275C	0.999
2:96864844:A:G	W275R	0.999
2:96864844:A:T	W275R	0.999
2:96865750:G:C	N112K	0.999
2:96865750:G:T	N112K	0.999
2:96861364:C:A	W588C	0.998
2:96861364:C:G	W588C	0.998
2:96865757:C:G	C110S	0.998
2:96865758:A:T	C110S	0.998
2:96865892:C:G	C99S	0.998
2:96865893:A:T	C99S	0.998
2:96864827:C:A	K280N	0.997
2:96864827:C:G	K280N	0.997
2:96864968:C:G	C261S	0.997
2:96864969:A:T	C261S	0.997
2:96865687:G:C	F133L	0.997
2:96865687:G:T	F133L	0.997
2:96865689:A:G	F133L	0.997
2:96865756:G:C	C110W	0.997
2:96861255:A:C	Y625D	0.996
2:96864077:G:C	F393L	0.996
2:96864077:G:T	F393L	0.996
2:96864079:A:G	F393L	0.996
2:96864974:C:G	R259P	0.996
2:96865106:A:C	F215C	0.996
2:96865682:G:T	P135H	0.996
2:96865702:A:C	C128W	0.996
2:96865703:C:T	C128Y	0.996
2:96865704:A:G	C128R	0.996

dbSNP variants (sampled 300 via entrez): RS1000187051 (2:96860101 G>A), RS1000467649 (2:96861346 G>A,T), RS1000633827 (2:96868084 C>G), RS1000674321 (2:96867259 C>T), RS1000676799 (2:96867050 G>C), RS1000796267 (2:96862118 G>A), RS1001288707 (2:96866533 C>G,T), RS1001746850 (2:96860383 C>A,T), RS1001845927 (2:96872238 G>A), RS1002130002 (2:96867618 A>AGAG), RS1002312404 (2:96867431 TA>T), RS1002480877 (2:96861415 T>C), RS1002582669 (2:96870399 C>G,T), RS1003185059 (2:96869056 G>A,C), RS1003237346 (2:96868810 G>A,T)

Disease associations

OMIM: gene MIM:604462 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006585_353	Blood protein levels	4.000000e-15

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases methylation	5
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment, decreases expression	2
Arsenic	increases abundance, increases expression, affects methylation, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
FR900359	affects phosphorylation	1
beta-lapachone	decreases expression	1
arsenite	increases methylation	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
butyraldehyde	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
nickel sulfate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, affects response to substance, increases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
ICG 001	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Vorinostat	decreases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Cisplatin	increases expression	1
Diazinon	increases methylation	1
Dinitrochlorobenzene	increases expression	1
Doxorubicin	decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment, decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Ozone	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	increases expression	1

Clinical trials (associated diseases)

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