VSIG8

Summary

VSIG8 (V-set and immunoglobulin domain containing 8, HGNC:32063) is a protein-coding gene on chromosome 1q23.2, encoding V-set and immunoglobulin domain-containing protein 8 (P0DPA2).

Enables RNA binding activity. Predicted to be located in membrane.

Source: NCBI Gene 391123 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 51 total
• Druggable target: yes
• MANE Select transcript: NM_001013661

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32063
Approved symbol	VSIG8
Name	V-set and immunoglobulin domain containing 8
Location	1q23.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000243284
Ensembl biotype	protein_coding
OMIM	621098
Entrez	391123

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000368100

RefSeq mRNA: 1 — MANE Select: NM_001013661 NM_001013661

CCDS: CCDS30913

Canonical transcript exons

ENST00000368100 — 7 exons

Exon	Start	End
ENSE00001364882	159855883	159856081
ENSE00001367592	159857745	159857966
ENSE00001370997	159856524	159856643
ENSE00001446320	159854316	159855026
ENSE00001446321	159862473	159862657
ENSE00003600996	159858734	159858912
ENSE00003602666	159858090	159858291

Expression profiles

Bgee: expression breadth broad, 64 present calls, max score 77.36.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1336 / max 122.1031, expressed in 20 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15423	0.1336	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of leg	UBERON:0001511	77.36	gold quality
zone of skin	UBERON:0000014	76.43	gold quality
skin of abdomen	UBERON:0001416	75.29	gold quality
adult mammalian kidney	UBERON:0000082	64.73	gold quality
right uterine tube	UBERON:0001302	64.27	gold quality
lower esophagus mucosa	UBERON:0035834	63.81	gold quality
esophagus mucosa	UBERON:0002469	62.54	gold quality
cerebellum	UBERON:0002037	59.09	gold quality
cerebellar cortex	UBERON:0002129	58.87	gold quality
cerebellar hemisphere	UBERON:0002245	58.56	gold quality
right hemisphere of cerebellum	UBERON:0014890	58.36	gold quality
tonsil	UBERON:0002372	56.78	gold quality
kidney	UBERON:0002113	56.40	gold quality
blood	UBERON:0000178	52.53	gold quality
vagina	UBERON:0000996	51.15	gold quality
esophagus	UBERON:0001043	49.07	gold quality
cortex of kidney	UBERON:0001225	47.46	gold quality
ectocervix	UBERON:0012249	45.58	gold quality
minor salivary gland	UBERON:0001830	44.71	gold quality
metanephros cortex	UBERON:0010533	44.14	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	43.69	gold quality
ventricular zone	UBERON:0003053	43.67	gold quality
saliva-secreting gland	UBERON:0001044	43.32	gold quality
uterine cervix	UBERON:0000002	41.61	gold quality
colonic epithelium	UBERON:0000397	41.15	gold quality
placenta	UBERON:0001987	40.41	silver quality
apex of heart	UBERON:0002098	40.33	silver quality
stromal cell of endometrium	CL:0002255	39.65	gold quality
primary visual cortex	UBERON:0002436	39.19	gold quality
multicellular organism	UBERON:0000468	38.94	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.95

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

12 targeting VSIG8, 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-5193	100.00	67.26	1744
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-2355-5P	98.83	65.51	1589
HSA-MIR-6882-3P	98.23	67.01	1119

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	vsig8a	ENSDARG00000054050
mus_musculus	Vsig8	ENSMUSG00000049598
rattus_norvegicus	Vsig8	ENSRNOG00000008668

Paralogs (14): VSIG2 (ENSG00000019102), VSIG1 (ENSG00000101842), VSIR (ENSG00000107738), GPA33 (ENSG00000143167), IGSF11 (ENSG00000144847), ESAM (ENSG00000149564), CXADR (ENSG00000154639), JAM2 (ENSG00000154721), F11R (ENSG00000158769), MXRA8 (ENSG00000162576), JAM3 (ENSG00000166086), CLMP (ENSG00000166250), MUC15 (ENSG00000169550), VSTM2B (ENSG00000187135)

Protein

Protein identifiers

V-set and immunoglobulin domain-containing protein 8 — P0DPA2 (reviewed: P0DPA2)

All UniProt accessions (1): P0DPA2

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

RefSeq proteins (1): NP_001013683* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR052871	V-set/Ig_domain	Family

Pfam: PF07686, PF13927

UniProt features (9 total): topological domain 2, domain 2, disulfide bond 2, signal peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0DPA2-F1	69.97	0.43

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): 44–126, 167–239

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 14 (showing top): MARSON_BOUND_BY_FOXP3_UNSTIMULATED, GSE13762_CTRL_VS_125_VITAMIND_DAY5_DC_DN, CAGTGTT_MIR141_MIR200A, DESCARTES_MAIN_FETAL_CILIATED_EPITHELIAL_CELLS, HARALAMBIEVA_PBMC_M_M_R_II_AGE_11_22YO_VACCINATED_VS_UNVACCINATED_7YR_DN, GSE9946_MATURE_STIMULATORY_VS_PROSTAGLANDINE2_TREATED_MATURE_DC_DN, ZHANG_FH_DEFICIENT_RCC_C2_VS_OTHERS_UP, chr1q23, GSE3039_CD4_TCELL_VS_ALPHAALPHA_CD8_TCELL_UP, GSE5589_LPS_VS_LPS_AND_IL6_STIM_IL6_KO_MACROPHAGE_45MIN_DN, GSE5589_LPS_AND_IL10_VS_LPS_AND_IL6_STIM_IL10_KO_MACROPHAGE_45MIN_UP, GSE5589_WT_VS_IL10_KO_LPS_STIM_MACROPHAGE_45MIN_DN, GSE6259_FLT3L_INDUCED_DEC205_POS_DC_VS_CD8_TCELL_UP, GSE43863_TH1_VS_LY6C_INT_CXCR5POS_MEMORY_CD4_TCELL_DN

GO Biological Process (0):

GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nucleic acid binding	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

894 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VSIG8	PRR9	Q5T870	480
VSIG8	LRRC15	Q8TF66	466
VSIG8	B4GALT4	O60513	458
VSIG8	HOXC13	P31276	431
VSIG8	SPC24	Q8NBT2	424
VSIG8	C10orf105	Q8TEF2	419
VSIG8	GPRC5A	Q8NFJ5	407
VSIG8	FGFBP1	Q14512	406
VSIG8	RIPOR3	Q96MK2	377
VSIG8	SUSD1	Q6UWL2	371
VSIG8	PLEKHG7	Q6ZR37	370
VSIG8	DSG4	Q86SJ6	369
VSIG8	ZSCAN30	Q86W11	358
VSIG8	FOXN1	O15353	355
VSIG8	KRT84	Q9NSB2	355

IntAct

146 interactions, top by confidence:

A	B	Type	Score
SMARCD1	ARID1A	psi-mi:“MI:0914”(association)	0.790
KIF3A	KIF3C	psi-mi:“MI:0914”(association)	0.730
ANXA9	PPL	psi-mi:“MI:0914”(association)	0.660
RAB11B	SH3BP5	psi-mi:“MI:0914”(association)	0.640
CDK4	HSP90AA1	psi-mi:“MI:0914”(association)	0.640
CAPZA2	CNOT1	psi-mi:“MI:0914”(association)	0.640
IRAK4	VSIG8	psi-mi:“MI:0915”(physical association)	0.590
PMM1	PMM2	psi-mi:“MI:0914”(association)	0.530
CABCOCO1	NME2P1	psi-mi:“MI:0914”(association)	0.530
SLC5A5	SLC19A2	psi-mi:“MI:0914”(association)	0.530
GDF5	SERPINB7	psi-mi:“MI:0914”(association)	0.530
TKTL1	DNAJB5	psi-mi:“MI:0914”(association)	0.530
CPLX3	CIAO1	psi-mi:“MI:0914”(association)	0.530
LACC1	DUSP14	psi-mi:“MI:0914”(association)	0.530
MRPL38	DUSP14	psi-mi:“MI:0914”(association)	0.530
OR51E2	DUSP14	psi-mi:“MI:0914”(association)	0.530
FBXL4	DUSP14	psi-mi:“MI:0914”(association)	0.530
VSIG8	RPN2	psi-mi:“MI:0914”(association)	0.530
RAB40AL	VSIG8	psi-mi:“MI:0914”(association)	0.530
SEMG2	VSIG8	psi-mi:“MI:0914”(association)	0.530
DOLPP1	VSIG8	psi-mi:“MI:0914”(association)	0.530
APIP	VSIG8	psi-mi:“MI:0914”(association)	0.530
POLR3H	POLR3A	psi-mi:“MI:0914”(association)	0.530

ESM2 similar proteins: A0A8M2B818, A3KPA0, B0JYH6, O55005, O89026, O94898, P0DPA2, P16170, P17790, P36335, P40190, P57087, P57097, P60755, P60756, P85171, Q00560, Q0PMG2, Q0WYX8, Q12866, Q15198, Q15223, Q1WIM2, Q2PFX1, Q52KR2, Q58EG3, Q5BIP2, Q5RJP7, Q60805, Q61490, Q66KX2, Q68FQ2, Q6DJ83, Q6P3A4, Q6PE55, Q6X936, Q7Z553, Q7ZXX1, Q80W68, Q8BLQ9

Diamond homologs: P0DPA2, P0DPA3, P78310, P97792, Q5R764, Q6P3A4, Q8WMV3, Q90Y50, Q9R066, O95297, P0C673, Q08DK1, Q32PI9, Q3TEW6, Q5DX21, Q5U2P2, Q640U3, Q68D85, Q6AYT8, Q8VIM0, Q96IQ7, Q99795, Q9Z109, Q5RFR2, Q8K1G0, Q8NDA2, Q8R373, Q9H6B4, Q96RW7, Q8QHL3, Q91664, Q9JKA5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

960 predictions. Top by Δscore:

Variant	Effect	Δscore
1:159855023:CTCT:C	acceptor_gain	1.0000
1:159855025:CT:C	acceptor_gain	1.0000
1:159855026:TC:T	acceptor_loss	1.0000
1:159855027:C:CC	acceptor_gain	1.0000
1:159855027:CTGTG:C	acceptor_loss	1.0000
1:159855029:G:C	acceptor_gain	1.0000
1:159855174:A:AC	donor_gain	1.0000
1:159855174:ACTGT:A	donor_gain	1.0000
1:159855175:C:CC	donor_gain	1.0000
1:159855175:CTGT:C	donor_gain	1.0000
1:159855175:CTGTC:C	donor_gain	1.0000
1:159855178:T:TA	donor_gain	1.0000
1:159855192:T:A	donor_gain	1.0000
1:159856077:GGAGT:G	acceptor_gain	1.0000
1:159856078:GAGT:G	acceptor_gain	1.0000
1:159856079:AGT:A	acceptor_gain	1.0000
1:159856080:GT:G	acceptor_gain	1.0000
1:159856080:GTCT:G	acceptor_loss	1.0000
1:159856081:TC:T	acceptor_loss	1.0000
1:159856082:C:CC	acceptor_gain	1.0000
1:159856082:CT:C	acceptor_loss	1.0000
1:159856522:A:AC	donor_gain	1.0000
1:159856522:ACCT:A	donor_loss	1.0000
1:159856523:C:CC	donor_gain	1.0000
1:159856525:TGAG:T	donor_gain	1.0000
1:159856639:CAGGC:C	acceptor_gain	1.0000
1:159856640:AGGC:A	acceptor_gain	1.0000
1:159856641:GGC:G	acceptor_gain	1.0000
1:159856641:GGCCT:G	acceptor_loss	1.0000
1:159856642:GC:G	acceptor_gain	1.0000

AlphaMissense

2669 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:159856579:G:C	C239W	1.000
1:159856580:C:G	C239S	1.000
1:159856581:A:G	C239R	1.000
1:159856581:A:T	C239S	1.000
1:159857857:C:A	W180C	1.000
1:159857857:C:G	W180C	1.000
1:159857859:A:G	W180R	1.000
1:159857859:A:T	W180R	1.000
1:159857896:G:C	C167W	1.000
1:159857897:C:G	C167S	1.000
1:159857898:A:G	C167R	1.000
1:159857898:A:T	C167S	1.000
1:159857960:G:T	P146H	1.000
1:159858095:A:T	V142D	1.000
1:159858101:A:T	V140D	1.000
1:159858142:G:C	C126W	1.000
1:159858143:C:G	C126S	1.000
1:159858143:C:T	C126Y	1.000
1:159858144:A:G	C126R	1.000
1:159858144:A:T	C126S	1.000
1:159858150:A:C	Y124D	1.000
1:159858161:T:A	D120V	1.000
1:159858192:A:G	S110P	1.000
1:159858194:G:T	A109D	1.000
1:159858209:G:T	P104Q	1.000
1:159858223:A:C	F99L	1.000
1:159858223:A:T	F99L	1.000
1:159858224:A:C	F99C	1.000
1:159858224:A:G	F99S	1.000
1:159858225:A:G	F99L	1.000

dbSNP variants (sampled 300 via entrez): RS1000290851 (1:159853901 T>G), RS1001205670 (1:159859107 C>T), RS1001886890 (1:159856331 G>A), RS1002216971 (1:159861288 G>A), RS1002229367 (1:159854979 C>A,T), RS1002800604 (1:159857665 A>G), RS1003312622 (1:159860825 G>A,C), RS1003357155 (1:159864050 G>A), RS1003862021 (1:159864258 G>T), RS1004681965 (1:159859809 C>T), RS1005344116 (1:159857039 G>A), RS1006144275 (1:159860633 A>G), RS1006763681 (1:159857171 G>A), RS1007147965 (1:159861409 T>C), RS1007267018 (1:159861597 C>A)

Disease associations

OMIM: gene MIM:621098 | 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
GCST004379_10	Red blood cell density in sickle cell anemia	2.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5169113 (SINGLE PROTEIN)

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

ChEMBL bioactivities

1 potent at pChembl≥5 of 1 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.17	Kd	6700	nM	CHEMBL5190938

PubChem BioAssay actives

1 with measured affinity, of 1 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
1-(5-chloro-2-pyridin-4-yl-1H-indol-3-yl)-3-(3,5-dimethoxyphenyl)urea	1856150: Binding affinity to human VSIG8 assessed as dissociation constant by MST method	kd	6.7000	uM

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenate	decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	increases expression	1
Air Pollutants	affects methylation, increases abundance	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Particulate Matter	affects methylation, increases abundance	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5111028	Binding	Binding affinity to human VSIG8 assessed as dissociation constant by MST method	Development of Inhibitors Targeting the V-Domain Ig Suppressor of T Cell Activation Signal Pathway. — J Med Chem

Clinical trials (associated diseases)

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