SDC3

Summary

SDC3 (syndecan 3, HGNC:10660) is a protein-coding gene on chromosome 1p35.2, encoding Syndecan-3 (O75056). Cell surface proteoglycan that may bear heparan sulfate.

The protein encoded by this gene belongs to the syndecan proteoglycan family. It may play a role in the organization of cell shape by affecting the actin cytoskeleton, possibly by transferring signals from the cell surface in a sugar-dependent mechanism. Allelic variants of this gene have been associated with obesity.

Source: NCBI Gene 9672 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 99 total
• Phenotypes (HPO): 6
• MANE Select transcript: NM_014654

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10660
Approved symbol	SDC3
Name	syndecan 3
Location	1p35.2
Locus type	gene with protein product
Status	Approved
Aliases	N-syndecan, SYND3
Ensembl gene	ENSG00000162512
Ensembl biotype	protein_coding
OMIM	186357
Entrez	9672

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000336798, ENST00000339394, ENST00000471567, ENST00000487984, ENST00000937355

RefSeq mRNA: 1 — MANE Select: NM_014654 NM_014654

CCDS: CCDS30661

Canonical transcript exons

ENST00000339394 — 5 exons

Exon	Start	End
ENSE00001065952	30874297	30874588
ENSE00001399392	30876552	30877165
ENSE00001461463	30908449	30908758
ENSE00001952023	30869466	30873377
ENSE00003606923	30878623	30878740

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 97.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.7844 / max 364.0717, expressed in 1681 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
11443	29.6022	1681
11431	0.1225	42
11432	0.0418	11
11442	0.0179	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland cortex	UBERON:0035827	97.51	gold quality
left adrenal gland cortex	UBERON:0035825	97.49	gold quality
adrenal cortex	UBERON:0001235	97.38	gold quality
right adrenal gland	UBERON:0001233	97.34	gold quality
left adrenal gland	UBERON:0001234	97.28	gold quality
nucleus accumbens	UBERON:0001882	97.21	gold quality
cortical plate	UBERON:0005343	96.70	gold quality
amygdala	UBERON:0001876	96.69	gold quality
adrenal gland	UBERON:0002369	96.50	gold quality
caudate nucleus	UBERON:0001873	95.53	gold quality
anterior cingulate cortex	UBERON:0009835	95.40	gold quality
hypothalamus	UBERON:0001898	95.39	gold quality
cingulate cortex	UBERON:0003027	95.36	gold quality
putamen	UBERON:0001874	95.23	gold quality
right frontal lobe	UBERON:0002810	95.16	gold quality
left uterine tube	UBERON:0001303	94.72	gold quality
ganglionic eminence	UBERON:0004023	94.69	gold quality
prefrontal cortex	UBERON:0000451	94.54	gold quality
lateral globus pallidus	UBERON:0002476	94.52	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.09	gold quality
temporal lobe	UBERON:0001871	93.85	gold quality
ventral tegmental area	UBERON:0002691	93.78	gold quality
decidua	UBERON:0002450	93.74	gold quality
sural nerve	UBERON:0015488	93.61	gold quality
ventricular zone	UBERON:0003053	93.42	gold quality
spleen	UBERON:0002106	93.38	gold quality
tibial nerve	UBERON:0001323	93.32	gold quality
neocortex	UBERON:0001950	93.31	gold quality
telencephalon	UBERON:0001893	93.29	gold quality
frontal cortex	UBERON:0001870	93.19	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	22.47
E-ANND-3	yes	7.26
E-ENAD-17	no	174.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): RUNX2

miRNA regulators (miRDB)

267 targeting SDC3, 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-6867-5P	100.00	82.21	3464
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-6721-5P	99.93	68.92	2981

Literature-anchored findings (GeneRIF, showing 26)

• Augmented synthesis and differential localization of heparan sulfate proteoglycans in Duchenne muscular dystrophy. (PMID:11968010)
• Selective induction of CXCL8 binding site on endothelial syndecan-3 in rheumatoid arthritis(RA) synovium. This site may be involved in leukocyte trafficking into RA synovial tissue. (PMID:16052590)
• The high expression of syndecan 3 and its localization to the smooth muscle bundles during normal labour, together with the significant reduction in prolonged labour, may indicate a role for this protein in the co-ordination of myometrial contractility. (PMID:16674815)
• There are ethnic differences in the SDC3 polymorphisms, and the polymorphisms are strongly associated with obesity. (PMID:17018662)
• Midkine, pleiotrophin (PTN), and their receptors syndecan-3 and receptor protein tyrosine phosphatase beta/zeta, were highly expressed in the striatum during developmen (PMID:17368428)
• Syndecan-3 was identified as a major HIV-1 attachment receptor on DCs. (PMID:18040049)
• syndecan TMD homodimerization and heterodimerization can be mediated by GxxxG motifs and modulated by sequence context (PMID:18093920)
• pleiotrophin (PTN) and syndecan-2 and -3 as direct binding partners of Y-P30. (PMID:18599487)
• found in 57.9% of pancreatic ductal carcinoma specimens (PMID:18716876)
• These findings indicate that SDC3 polymorphisms could contribute to the link between female hyperandrogenism and obesity and suggest a novel potential role for SDC3 as a modulator of gonadal steroid function. (PMID:19820907)
• Data report that the bFGF, FGFR1/2 and syndecan 1-4 expressions are altered in bladder tumours. (PMID:19822079)
• Syndecan-3 may directly transduce Glial cell line-derived neurotrophic factor (GDNF) family ligands (GFL) signals or serve as a coreceptor, presenting GFLs to the signaling receptor RET. (PMID:21200028)
• SDC3 is a target gene of the BACH1 transcription factor according to ChIP-seq analysis in HEK 293 cells. (PMID:21555518)
• Syndecan-3 expression was not associated with disease progression and outcome in specific subtypes of mammary carcinoma. (PMID:23351331)
• frequently expressed in pancreatic cancer and associated with perineural invasion (PMID:24659893)
• Data indicate that the extracellular and cytoplasmic domains of syndecans 1/2/3/4 are intrinsically disordered regions. (PMID:24956062)
• Syndecan-3 and TFPI colocalize on the surface of endothelial-, smooth muscle-, and cancer cells (PMID:25617766)
• High PTN and N-syndecan expression was closely associated with metastasis and poor prognosis, suggesting that they may promote tumor progression and perineural invasion in the orthotopic mouse model of pancreatic cancer. (PMID:28638231)
• Data show that soluble syndecan-3 occurred naturally in the sera of patients with rheumatoid arthritis. (PMID:31300004)
• Contribution of syndecans to cellular uptake and fibrillation of alpha-synuclein and tau. (PMID:31719623)
• Hypoxia Promotes Syndecan-3 Expression in the Tumor Microenvironment. (PMID:33117401)
• LncRNA TRPM2-AS promotes ovarian cancer progression and cisplatin resistance by sponging miR-138-5p to release SDC3 mRNA. (PMID:33621194)
• The Interplay of Apoes with Syndecans in Influencing Key Cellular Events of Amyloid Pathology. (PMID:34209175)
• Syndecan Family Gene and Protein Expression and Their Prognostic Values for Prostate Cancer. (PMID:34445387)
• The Cell Surface Heparan Sulfate Proteoglycan Syndecan-3 Promotes Ovarian Cancer Pathogenesis. (PMID:35628603)
• A genome-wide association study identifies a novel association between SDC3 and apparent treatment-resistant hypertension. (PMID:36447229)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
		ENSDARG00000100562
mus_musculus	Sdc3	ENSMUSG00000025743
rattus_norvegicus	Sdc3	ENSRNOG00000011927
drosophila_melanogaster	Sdc	FBGN0010415
caenorhabditis_elegans		WBGENE00004749

Paralogs (3): SDC1 (ENSG00000115884), SDC4 (ENSG00000124145), SDC2 (ENSG00000169439)

Protein

Protein identifiers

Syndecan-3 — O75056 (reviewed: O75056)

All UniProt accessions (2): A0A9K3Y886, O75056

UniProt curated annotations — full annotation on UniProt →

Function. Cell surface proteoglycan that may bear heparan sulfate. May have a role in the organization of cell shape by affecting the actin cytoskeleton, possibly by transferring signals from the cell surface in a sugar-dependent mechanism.

Subunit / interactions. Interacts with TIAM1. Interacts with PTN (via heparan sulfate chains); this interaction mediates the neurite outgrowth-promoting signal from PTN to the cytoskeleton of growing neurites; this interaction mediates osteoblast recruitment. Interacts with MDK; this interaction induces SDC3 clustering; this interaction induces neuronal cell adhesion and neurite outgrowth.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in the nervous system, the adrenal gland, and the spleen.

Post-translational modifications. O-glycosylated within the Thr/Ser-rich region which could interact with lectin domains on other molecules.

Similarity. Belongs to the syndecan proteoglycan family.

RefSeq proteins (1): NP_055469* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001050	Syndecan	Family
IPR003585	Neurexin-like	Domain
IPR027789	Syndecan/Neurexin_dom	Domain
IPR030479	Syndecan_CS	Conserved_site

Pfam: PF01034

UniProt features (40 total): glycosylation site 15, compositionally biased region 7, region of interest 6, modified residue 4, sequence variant 3, topological domain 2, chain 1, site 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75056-F1	53.00	0.04

Functional residue map

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

Catalytic / active sites (1): 383–384 (cleavage of ectodomain)

Post-translational modifications (4): 409, 419, 431, 441

Glycosylation sites (15): 80, 82, 84, 91, 108, 109, 110, 160, 161, 162, 169, 170, 171, 314, 367

Function

Pathways and Gene Ontology

Reactome pathways

40 pathways

ID	Pathway
R-HSA-1971475	Glycosaminoglycan-protein linkage region biosynthesis
R-HSA-2022928	HS-GAG biosynthesis
R-HSA-2024096	HS-GAG degradation
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-3000170	Syndecan interactions
R-HSA-3560783	Defective B4GALT7 causes EDS, progeroid type
R-HSA-3560801	Defective B3GAT3 causes JDSSDHD
R-HSA-3656237	Defective EXT2 causes exostoses 2
R-HSA-3656253	Defective EXT1 causes exostoses 1, TRPS2 and CHDS
R-HSA-4420332	Defective B3GALT6 causes EDSP2 and SEMDJL1
R-HSA-9694614	Attachment and Entry
R-HSA-975634	Retinoid metabolism and transport
R-HSA-9769735	Initiation of coagulation cascade
R-HSA-9769739	Regulation of clotting cascade
R-HSA-9820960	Respiratory syncytial virus (RSV) attachment and entry
R-HSA-9833110	RSV-host interactions
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-9918485	Dengue Virus Attachment and Entry
R-HSA-109582	Hemostasis
R-HSA-1430728	Metabolism
R-HSA-1474244	Extracellular matrix organization
R-HSA-1630316	Glycosaminoglycan metabolism
R-HSA-1638091	Heparan sulfate/heparin (HS-GAG) metabolism
R-HSA-1643685	Disease
R-HSA-1793185	Chondroitin sulfate/dermatan sulfate metabolism
R-HSA-196854	Metabolism of vitamins and cofactors
R-HSA-2187338	Visual phototransduction
R-HSA-3000171	Non-integrin membrane-ECM interactions
R-HSA-3560782	Diseases associated with glycosaminoglycan metabolism
R-HSA-3781865	Diseases of glycosylation

MSigDB gene sets: 301 (showing top): MORF_RAGE, MODULE_255, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, MODULE_317, GOCC_CELL_SURFACE, JOHANSSON_GLIOMAGENESIS_BY_PDGFB_UP, WEI_MYCN_TARGETS_WITH_E_BOX, BASSO_HAIRY_CELL_LEUKEMIA_UP, ONDER_CDH1_TARGETS_2_UP, MORF_PML, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, REACTOME_CELL_SURFACE_INTERACTIONS_AT_THE_VASCULAR_WALL, KEGG_CELL_ADHESION_MOLECULES_CAMS, REACTOME_METABOLISM_OF_CARBOHYDRATES_AND_CARBOHYDRATE_DERIVATIVES, GOCC_LYSOSOMAL_LUMEN

GO Biological Process (1): cell migration (GO:0016477)

GO Molecular Function (2): identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (7): Golgi lumen (GO:0005796), plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020), extracellular matrix (GO:0031012), lysosomal lumen (GO:0043202), microspike (GO:0044393)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Diseases associated with glycosaminoglycan metabolism	5
Heparan sulfate/heparin (HS-GAG) metabolism	2
Coagulation pathway	2
Respiratory Syncytial Virus Infection Pathway	2
Dengue Virus Infection	2
Glycosaminoglycan metabolism	1
Hemostasis	1
Non-integrin membrane-ECM interactions	1
Early SARS-CoV-2 Infection Events	1
Visual phototransduction	1
Metabolism of fat-soluble vitamins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cell motility	1
protein binding	1
binding	1
Golgi apparatus	1
intracellular organelle lumen	1
membrane	1
cell periphery	1
external encapsulating structure	1
lysosome	1
vacuolar lumen	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

996 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SDC3	PTN	P21246	993
SDC3	GDNF	P39905	891
SDC3	SRC	P12931	872
SDC3	CTTN	Q14247	871
SDC3	ITIH4	Q14624	841
SDC3	NRTN	Q99748	824
SDC3	ARTN	Q5T4W7	818
SDC3	HCLS1	P14317	807
SDC3	LAPTM5	Q13571	778
SDC3	GALNT13	Q8IUC8	770
SDC3	FN1	P02751	695
SDC3	ASIP	P42127	681
SDC3	MDK	P21741	674
SDC3	GPC1	P35052	656
SDC3	GALNT1	Q10472	648

IntAct

147 interactions, top by confidence:

A	B	Type	Score
SDC3	SDC3	psi-mi:“MI:0407”(direct interaction)	0.540
EFNB2	FAM171A2	psi-mi:“MI:0914”(association)	0.530
HADHA	AGRN	psi-mi:“MI:0914”(association)	0.530
SDC3	SDC4	psi-mi:“MI:0407”(direct interaction)	0.440
SDC2	SDC3	psi-mi:“MI:0407”(direct interaction)	0.440
SDC1	SDC3	psi-mi:“MI:0407”(direct interaction)	0.440
SDC4	SDC3	psi-mi:“MI:0407”(direct interaction)	0.440
SDC3	SDC2	psi-mi:“MI:0407”(direct interaction)	0.440
TIAM1	SDC3	psi-mi:“MI:0407”(direct interaction)	0.440
SDC3	HTRA1	psi-mi:“MI:0407”(direct interaction)	0.440
SDC3	PARD3B	psi-mi:“MI:0407”(direct interaction)	0.440
HTRA3	SDC3	psi-mi:“MI:0407”(direct interaction)	0.440
SDC3	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
DLG3	SDC3	psi-mi:“MI:0407”(direct interaction)	0.440
TIAM2	SDC3	psi-mi:“MI:0407”(direct interaction)	0.440
SDC3	FRMPD3	psi-mi:“MI:0407”(direct interaction)	0.440
APBA3	SDC3	psi-mi:“MI:0407”(direct interaction)	0.440
SDC3	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
SDC3	PDZRN4	psi-mi:“MI:0407”(direct interaction)	0.440
PICK1	SDC3	psi-mi:“MI:0407”(direct interaction)	0.440
SDC3	IL16	psi-mi:“MI:0407”(direct interaction)	0.440
SDC3	TJP1	psi-mi:“MI:0407”(direct interaction)	0.440
SDC3	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
SDC3	CARD11	psi-mi:“MI:0407”(direct interaction)	0.440
SDC3	WHRN	psi-mi:“MI:0407”(direct interaction)	0.440
SDC3	HTRA4	psi-mi:“MI:0407”(direct interaction)	0.440
SDC3	NHERF4	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (43): SDC3 (Two-hybrid), KRTAP10-3 (Two-hybrid), KRTAP10-3 (Two-hybrid), KRTAP5-9 (Two-hybrid), SDC3 (Affinity Capture-MS), SDC3 (Affinity Capture-RNA), KRTAP5-9 (Two-hybrid), KRTAP4-2 (Two-hybrid), KRTAP2-4 (Two-hybrid), KRTAP10-3 (Two-hybrid), ITGB4 (Two-hybrid), SDC3 (Affinity Capture-Western), SDC3 (Two-hybrid), SDC3 (Two-hybrid), SDC3 (Two-hybrid)

ESM2 similar proteins: A6QLF8, B1ARY8, E9Q7X6, J3KML8, O14594, O35188, O55145, O60279, O60667, O75056, O95196, P07141, P09603, P18827, P33671, P39061, P47951, P55066, P55067, P55068, P78423, Q08DZ5, Q28062, Q28645, Q2TA21, Q52S86, Q58Y74, Q5FWE3, Q5IS41, Q5R770, Q5SWP3, Q5U2P6, Q61361, Q64519, Q6PE13, Q6UXF1, Q71M36, Q80XH2, Q8BHE4, Q8BT18

Diamond homologs: O35988, O75056, P18827, P18828, P26260, P26261, P31431, P33671, P34740, P34741, P34900, P34901, P43407, P47951, P49414, P49415, P49416, Q08DZ5, Q1AGV6, Q1AGV7, Q58DD4, Q5RAT9, Q64519, Q6GR51, Q8HZJ6, P50605

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SDC3	“up-regulates activity”	NOTCH1	binding
SDC3	“up-regulates activity”	NOTCH	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 97 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	42.0×	8e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	40.0×	8e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	40.0×	8e-06
Long-term potentiation	5	35.0×	1e-05
Assembly and cell surface presentation of NMDA receptors	9	33.6×	7e-10
Neurexins and neuroligins	10	29.0×	4e-10
Protein-protein interactions at synapses	6	23.4×	1e-05
Non-integrin membrane-ECM interactions	7	15.9×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	68.7×	2e-15
receptor clustering	8	53.7×	4e-10
protein localization to synapse	6	49.4×	3e-07
regulation of postsynaptic membrane neurotransmitter receptor levels	8	42.6×	2e-09
protein-containing complex assembly	9	11.0×	9e-06
cell-cell adhesion	10	10.9×	3e-06
regulation of small GTPase mediated signal transduction	6	9.3×	2e-03
chemical synaptic transmission	7	5.8×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	74
Likely benign	5
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

1177 predictions. Top by Δscore:

Variant	Effect	Δscore
1:30873373:CACAG:C	acceptor_gain	1.0000
1:30873375:CAG:C	acceptor_gain	1.0000
1:30873378:C:CC	acceptor_gain	1.0000
1:30874308:T:TA	donor_gain	1.0000
1:30874584:GGGGT:G	acceptor_gain	1.0000
1:30874585:GGGT:G	acceptor_gain	1.0000
1:30874586:GGT:G	acceptor_gain	1.0000
1:30874587:GT:G	acceptor_gain	1.0000
1:30874589:C:CC	acceptor_gain	1.0000
1:30874590:T:A	acceptor_loss	1.0000
1:30877174:G:GC	acceptor_gain	1.0000
1:30878621:A:AC	donor_gain	1.0000
1:30878621:ACAG:A	donor_gain	1.0000
1:30878621:ACAGC:A	donor_gain	1.0000
1:30878622:C:CT	donor_gain	1.0000
1:30878622:CA:C	donor_gain	1.0000
1:30878622:CAG:C	donor_gain	1.0000
1:30878622:CAGC:C	donor_gain	1.0000
1:30878622:CAGCC:C	donor_gain	1.0000
1:30873376:AG:A	acceptor_gain	0.9900
1:30873377:GC:G	acceptor_loss	0.9900
1:30873378:CT:C	acceptor_loss	0.9900
1:30873379:T:C	acceptor_loss	0.9900
1:30873380:G:GC	acceptor_gain	0.9900
1:30874296:CCTA:C	donor_gain	0.9900
1:30874299:A:AC	donor_gain	0.9900
1:30874300:C:CC	donor_gain	0.9900
1:30874312:T:TA	donor_gain	0.9900
1:30877163:AGT:A	acceptor_gain	0.9900
1:30877164:GT:G	acceptor_gain	0.9900

AlphaMissense

2783 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:30873341:G:T	A400D	1.000
1:30873353:C:T	G396D	1.000
1:30873365:C:T	G392D	1.000
1:30873220:G:C	F440L	0.999
1:30873220:G:T	F440L	0.999
1:30873221:A:C	F440C	0.999
1:30873222:A:G	F440L	0.999
1:30873308:A:G	M411T	0.999
1:30873320:A:G	L407P	0.999
1:30873323:A:G	L406P	0.999
1:30873329:A:T	V404D	0.999
1:30873350:G:T	A397D	0.999
1:30873354:C:G	G396R	0.999
1:30873362:C:T	G393E	0.999
1:30873363:C:G	G393R	0.999
1:30873363:C:T	G393R	0.999
1:30873366:C:G	G392R	0.999
1:30873371:A:T	I390N	0.999
1:30873221:A:G	F440S	0.998
1:30873285:A:G	Y419H	0.998
1:30873286:G:C	S418R	0.998
1:30873286:G:T	S418R	0.998
1:30873288:T:G	S418R	0.998
1:30873291:C:A	G417C	0.998
1:30873291:C:G	G417R	0.998
1:30873296:T:G	D415A	0.998
1:30873297:C:G	D415H	0.998
1:30873298:C:A	K414N	0.998
1:30873298:C:G	K414N	0.998
1:30873301:T:A	K413N	0.998

dbSNP variants (sampled 300 via entrez): RS1000100437 (1:30880579 G>A,C,T), RS1000194733 (1:30905288 T>A,G), RS1000259642 (1:30899607 T>C), RS1000318857 (1:30888192 A>G), RS1000366556 (1:30893264 C>G,T), RS1000492360 (1:30884282 C>CA,CG), RS1000512180 (1:30878364 A>G), RS1000566863 (1:30884100 C>A,T), RS1000613380 (1:30885771 G>A,C), RS1000626057 (1:30873664 T>C), RS1000756364 (1:30899846 G>A), RS1000960188 (1:30900583 C>A,T), RS1001085275 (1:30905885 C>T), RS1001089955 (1:30869866 A>G), RS1001148248 (1:30883544 A>G)

Disease associations

OMIM: gene MIM:186357 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

6 total (6 of 6 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0001513	Obesity
HP:0010982	Polygenic inheritance
HP:0012340	Decreased resting energy expenditure
HP:0031819	Increased waist to hip ratio

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003771_22	Loneliness	2.000000e-06
GCST012051_3	Systolic blood pressure	7.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007865	loneliness measurement
EFO:0006335	systolic blood pressure

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases methylation	3
Air Pollutants	decreases expression, increases abundance, increases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
Estradiol	affects cotreatment, increases expression	2
Lead	affects methylation, affects expression	2
Aflatoxin B1	decreases methylation, increases expression	2
Cadmium Chloride	decreases expression	2
Particulate Matter	increases expression, decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
uranyl acetate	affects expression	1
bisphenol A	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sodium arsenite	increases abundance, increases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	increases expression	1
pentanal	increases expression	1
monomethylarsonous acid	decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	decreases expression	1
perfluorobutanesulfonic acid	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Ethanol	increases expression	1
Arsenic	increases abundance, increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Selenium	increases expression	1
Silicon Dioxide	decreases expression	1

Clinical trials (associated diseases)

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