VSIG1

Summary

VSIG1 (V-set and immunoglobulin domain containing 1, HGNC:28675) is a protein-coding gene on chromosome Xq22.3, encoding V-set and immunoglobulin domain-containing protein 1 (Q86XK7).

This gene encodes a member of the junctional adhesion molecule (JAM) family. The encoded protein contains multiple glycosylation sites at the N-terminal region, and multiple phosphorylation sites and glutamic acid/proline (EP) repeats at the C-terminal region. The gene is expressed in normal stomach and testis, as well as in gastric, esophageal and ovarian cancers. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 340547 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 70 total
• MANE Select transcript: NM_182607

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28675
Approved symbol	VSIG1
Name	V-set and immunoglobulin domain containing 1
Location	Xq22.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC44287, GPA34
Ensembl gene	ENSG00000101842
Ensembl biotype	protein_coding
OMIM	300620
Entrez	340547

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000217957, ENST00000415430, ENST00000458383, ENST00000479635, ENST00000485533

RefSeq mRNA: 2 — MANE Select: NM_182607 NM_001170553, NM_182607

CCDS: CCDS14535, CCDS55474

Canonical transcript exons

ENST00000217957 — 7 exons

Exon	Start	End
ENSE00000866544	108058038	108058201
ENSE00001661051	108076077	108076218
ENSE00001698717	108045065	108045179
ENSE00001765589	108073250	108073369
ENSE00001770932	108077048	108079184
ENSE00003519067	108066936	108067134
ENSE00003621426	108072677	108072832

Expression profiles

Bgee: expression breadth ubiquitous, 147 present calls, max score 93.65.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.8197 / max 503.0153, expressed in 24 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
197198	0.5703	20
197195	0.0869	8
197199	0.0608	10
197197	0.0475	8
197196	0.0327	8
197194	0.0215	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pylorus	UBERON:0001166	93.65	gold quality
adult organism	UBERON:0007023	92.99	gold quality
right testis	UBERON:0004534	90.16	gold quality
left testis	UBERON:0004533	88.46	gold quality
epithelial cell of pancreas	CL:0000083	87.04	gold quality
testis	UBERON:0000473	86.77	gold quality
stomach	UBERON:0000945	86.59	gold quality
body of stomach	UBERON:0001161	85.82	gold quality
cardia of stomach	UBERON:0001162	82.78	gold quality
pancreatic ductal cell	CL:0002079	82.68	silver quality
gall bladder	UBERON:0002110	82.38	gold quality
mucosa of stomach	UBERON:0001199	78.04	gold quality
fundus of stomach	UBERON:0001160	76.74	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	74.70	gold quality
granulocyte	CL:0000094	67.48	gold quality
blood	UBERON:0000178	65.55	gold quality
adenohypophysis	UBERON:0002196	64.76	gold quality
pituitary gland	UBERON:0000007	64.43	gold quality
vermiform appendix	UBERON:0001154	63.91	gold quality
lymph node	UBERON:0000029	63.33	gold quality
islet of Langerhans	UBERON:0000006	61.91	gold quality
duodenum	UBERON:0002114	59.05	gold quality
caecum	UBERON:0001153	58.76	gold quality
tibialis anterior	UBERON:0001385	58.44	silver quality
ileal mucosa	UBERON:0000331	57.81	gold quality
bone marrow cell	CL:0002092	57.31	silver quality
urinary bladder	UBERON:0001255	56.79	gold quality
deltoid	UBERON:0001476	56.31	gold quality
colonic epithelium	UBERON:0000397	55.95	silver quality
prefrontal cortex	UBERON:0000451	55.59	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.41
E-GEOD-124858	no	1.71

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

115 targeting VSIG1, 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-6748-5P	100.00	65.81	1057
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482

Literature-anchored findings (GeneRIF, showing 5)

• expressed, both at the mRNA and protein level, in gastric, esophageal, and ovarian cancers, while expression in normal tissues was restricted to testis and stomach (PMID:16405301)
• VSIG1 expression was significantly reduced at both the mRNA and protein levels in gastric cancer tissues. loss of VSIG1 expression was significantly correlated with poor overall survival and disease-free survival in gastric cancer patients. (PMID:22095633)
• Study showed that VSIG1 is expressed tissue specifically in both non-cancerous and cancerous tissues, and that VSIG1 has suppressive functions in proliferation, migration, and invasion in cancer cells. (PMID:28603843)
• Interaction between cadherins, vimentin, and V-set and immunoglobulin domain containing 1 in gastric-type hepatocellular carcinoma. (PMID:34170400)
• V-set and immunoglobulin domain containing 1 (VSIG1) as an emerging target for epithelial-mesenchymal transition of gastric cancer. (PMID:36171238)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Vsig1	ENSMUSG00000031430
rattus_norvegicus	Vsig1	ENSRNOG00000054219

Paralogs (14): VSIG2 (ENSG00000019102), VSIR (ENSG00000107738), GPA33 (ENSG00000143167), IGSF11 (ENSG00000144847), ESAM (ENSG00000149564), CXADR (ENSG00000154639), JAM2 (ENSG00000154721), F11R (ENSG00000158769), MXRA8 (ENSG00000162576), JAM3 (ENSG00000166086), CLMP (ENSG00000166250), MUC15 (ENSG00000169550), VSTM2B (ENSG00000187135), VSIG8 (ENSG00000243284)

Protein

Protein identifiers

V-set and immunoglobulin domain-containing protein 1 — Q86XK7 (reviewed: Q86XK7)

Alternative names: Cell surface A33 antigen, Glycoprotein A34

All UniProt accessions (2): Q86XK7, C9JY48

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Tissue specificity. Detected only in stomach mucosa and testis, and to a much lesser level in pancreas (at protein level). Detected in gastric cancers (31%), esophageal carcinomas (50%) and ovarian cancers (23%).

Post-translational modifications. Highly N-glycosylated. Appears not to contain significant amounts of O-linked carbohydrates or sialic acid in its sugar moieties.

Isoforms (2)

UniProt ID	Names	Canonical?
Q86XK7-1	1	yes
Q86XK7-2	2

RefSeq proteins (2): NP_001164024, NP_872413* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000920	Myelin_P0-rel	Family
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR029861	VSIG1	Family
IPR036179	Ig-like_dom_sf	Homologous_superfamily

Pfam: PF07686, PF13927

UniProt features (21 total): glycosylation site 5, compositionally biased region 4, disulfide bond 2, topological domain 2, domain 2, signal peptide 1, chain 1, splice variant 1, sequence variant 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86XK7-F1	75.44	0.44

Functional residue map

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

Disulfide bonds (2): 43–116, 161–211

Glycosylation sites (5): 32, 38, 133, 200, 219

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 96 (showing top): GOBP_DIGESTION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_EPITHELIAL_CELL_DEVELOPMENT, HNF1_Q6, EFC_Q6, LEE_NAIVE_T_LYMPHOCYTE, GOBP_MAINTENANCE_OF_GASTROINTESTINAL_EPITHELIUM, GOBP_DIGESTIVE_SYSTEM_PROCESS, HNF1_C, GOBP_MULTICELLULAR_ORGANISMAL_LEVEL_HOMEOSTASIS, POU3F2_02, GOBP_EPITHELIAL_CELL_MORPHOGENESIS, HNF1_01, GOBP_EPITHELIAL_STRUCTURE_MAINTENANCE, SOX5_01

GO Biological Process (2): epithelial cell morphogenesis (GO:0003382), maintenance of gastrointestinal epithelium (GO:0030277)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): basolateral plasma membrane (GO:0016323), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell morphogenesis	1
epithelial cell development	1
epithelial structure maintenance	1
digestive system process	1
binding	1
basal plasma membrane	1
plasma membrane region	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

492 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VSIG1	CTSE	P14091	515
VSIG1	CST9L	Q9H4G1	488
VSIG1	ANXA10	Q9UJ72	479
VSIG1	CLDN18	P56856	461
VSIG1	IGSF11	Q5DX21	454
VSIG1	IZUMO1	Q8IYV9	438
VSIG1	CACNG4	Q9UBN1	434
VSIG1	GJB5	O95377	434
VSIG1	GKN1	Q9NS71	416
VSIG1	TEX13B	Q9BXU2	394
VSIG1	LGALS4	P56470	388
VSIG1	SLC4A5	Q9BY07	384
VSIG1	VPS35	Q96QK1	383
VSIG1	MAPK15	Q8TD08	374
VSIG1	FATE1	Q969F0	372

IntAct

19 interactions, top by confidence:

A	B	Type	Score
VSIG1	TTI1	psi-mi:“MI:0914”(association)	0.640
EMP3	VSIG1	psi-mi:“MI:0915”(physical association)	0.560
UPK1B	VSIG1	psi-mi:“MI:0915”(physical association)	0.560
VSIG1	NINJ2	psi-mi:“MI:0915”(physical association)	0.560
HGFAC	VSIG1	psi-mi:“MI:0915”(physical association)	0.560
VSIG1	TNPO2	psi-mi:“MI:0914”(association)	0.530
VSIG1	H1-5	psi-mi:“MI:0915”(physical association)	0.400
VSIG1	H1-2	psi-mi:“MI:0915”(physical association)	0.400
VSIG1	H1-1	psi-mi:“MI:0915”(physical association)	0.400
VSIG1	RIMOC1	psi-mi:“MI:0914”(association)	0.350
EMP3	VSIG1	psi-mi:“MI:0915”(physical association)	0.000
UPK1B	VSIG1	psi-mi:“MI:0915”(physical association)	0.000
HGFAC	VSIG1	psi-mi:“MI:0915”(physical association)	0.000
NINJ2	VSIG1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (115): UBE4A (Affinity Capture-MS), CDS1 (Affinity Capture-MS), ATP2A3 (Affinity Capture-MS), IP6K1 (Affinity Capture-MS), RRP1 (Affinity Capture-MS), SLC25A17 (Affinity Capture-MS), DEPDC1 (Affinity Capture-MS), CYP20A1 (Affinity Capture-MS), EXOG (Affinity Capture-MS), TTI1 (Affinity Capture-MS), FANCL (Affinity Capture-MS), TMEM160 (Affinity Capture-MS), DAGLB (Affinity Capture-MS), NF1 (Affinity Capture-MS), C4A (Affinity Capture-MS)

ESM2 similar proteins: A0JM41, A2VD98, A6QQC6, A8MVW5, B0CLX4, B6ZK76, B6ZK77, O60487, O70255, O88324, O88775, O95976, P01832, P03228, P06907, P08920, P08921, P09619, P0C6B7, P0C6N0, P0CW72, P10522, P20938, P21995, P25189, P27573, P37301, P37998, P59823, P59824, P86176, Q01151, Q4VAH7, Q5EAB0, Q5R804, Q640U3, Q6PCB8, Q6WEB5, Q80UL9, Q86XK7

Diamond homologs: A0JM41, A2VD98, A5D7C3, O60487, O60939, O70255, O95297, P06907, P10522, P20938, P25189, P27573, P37301, P54900, Q29RR6, Q32PI9, Q3TEW6, Q3V3F6, Q4KLY3, Q5EAB0, Q5R804, Q6AYT8, Q6UWV2, Q6WEB5, Q7M729, Q7M730, Q86XK7, Q8AVM3, Q8IWT1, Q9D2J4, Q9PWR4, Q08E08, P78310, P97792, Q5R764, Q864L3, Q8WMV3, Q9R066, A2AJ76, D3YXG0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	25
Likely benign	11
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1067 predictions. Top by Δscore:

Variant	Effect	Δscore
X:108058037:GGT:G	acceptor_gain	1.0000
X:108058197:TTTCT:T	donor_gain	1.0000
X:108058198:TTCT:T	donor_gain	1.0000
X:108058199:TCT:T	donor_gain	1.0000
X:108058199:TCTGT:T	donor_loss	1.0000
X:108058200:CT:C	donor_gain	1.0000
X:108058200:CTGT:C	donor_loss	1.0000
X:108058201:TG:T	donor_loss	1.0000
X:108058202:G:GG	donor_gain	1.0000
X:108058203:T:G	donor_loss	1.0000
X:108058207:G:GT	donor_gain	1.0000
X:108066935:GATTT:G	acceptor_gain	1.0000
X:108072675:A:AG	acceptor_gain	1.0000
X:108072675:A:T	acceptor_loss	1.0000
X:108072675:AGT:A	acceptor_gain	1.0000
X:108072676:G:GG	acceptor_gain	1.0000
X:108072676:GT:G	acceptor_gain	1.0000
X:108072676:GTG:G	acceptor_gain	1.0000
X:108072676:GTGA:G	acceptor_gain	1.0000
X:108072800:G:T	donor_gain	1.0000
X:108072828:CTTCA:C	donor_gain	1.0000
X:108072829:TTCA:T	donor_gain	1.0000
X:108072833:G:GG	donor_gain	1.0000
X:108073249:GACCC:G	acceptor_gain	1.0000
X:108073366:TCACG:T	donor_loss	1.0000
X:108073367:CACG:C	donor_loss	1.0000
X:108073369:CG:C	donor_loss	1.0000
X:108073370:G:GG	donor_gain	1.0000
X:108073370:GTGAG:G	donor_loss	1.0000
X:108073371:T:TC	donor_loss	1.0000

AlphaMissense

2528 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:108058165:G:C	W59C	0.999
X:108058165:G:T	W59C	0.999
X:108067062:T:G	Y114D	0.999
X:108067068:T:A	C116S	0.999
X:108067069:G:A	C116Y	0.999
X:108067069:G:C	C116S	0.999
X:108072745:T:C	C161R	0.999
X:108072747:T:G	C161W	0.999
X:108072786:G:C	W174C	0.999
X:108072786:G:T	W174C	0.999
X:108073312:T:A	C211S	0.999
X:108073312:T:C	C211R	0.999
X:108073313:G:C	C211S	0.999
X:108073326:C:A	N215K	0.999
X:108073326:C:G	N215K	0.999
X:108058115:T:C	C43R	0.998
X:108058116:G:A	C43Y	0.998
X:108058117:C:G	C43W	0.998
X:108058163:T:A	W59R	0.998
X:108058163:T:C	W59R	0.998
X:108067068:T:C	C116R	0.998
X:108067070:C:G	C116W	0.998
X:108072697:T:A	C145S	0.998
X:108072698:G:C	C145S	0.998
X:108072745:T:A	C161S	0.998
X:108072746:G:A	C161Y	0.998
X:108072746:G:C	C161S	0.998
X:108073261:G:T	G194W	0.998
X:108073314:T:G	C211W	0.998
X:108066988:G:C	R89P	0.997

dbSNP variants (sampled 300 via entrez): RS1000006215 (X:108063458 T>C), RS1000202294 (X:108046025 A>G), RS1000251717 (X:108028199 G>A), RS1000260646 (X:108036822 G>A), RS1000269279 (X:108034321 C>G,T), RS1000376902 (X:108056132 T>C), RS1000478373 (X:108023682 A>C), RS1000522224 (X:108057620 T>C), RS1000578919 (X:108034898 G>A), RS1000584395 (X:108068449 T>A), RS1000629304 (X:108046051 G>A,T), RS1000658865 (X:108046394 A>G), RS1000679342 (X:108020699 T>C), RS1000716255 (X:108065444 C>A,T), RS1000743274 (X:108045592 T>G)

Disease associations

OMIM: gene MIM:300620 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	2
Copper	affects cotreatment, decreases expression, affects binding	2
aristolochic acid I	decreases expression	1
methyleugenol	increases expression	1
propionaldehyde	decreases expression	1
bisphenol A	increases methylation, affects cotreatment	1
trichostatin A	decreases expression	1
butyraldehyde	decreases expression	1
CGP 52608	affects binding, increases reaction	1
nutlin 3	affects cotreatment, increases expression	1
abrine	increases expression	1
bisphenol S	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Camptothecin	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
N-Nitrosopyrrolidine	increases expression	1
Silicon Dioxide	decreases expression	1
Smoke	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	decreases expression	1
Aflatoxin B1	increases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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