VSTM2B

Summary

VSTM2B (V-set and transmembrane domain containing 2B, HGNC:33595) is a protein-coding gene on chromosome 19q12, encoding V-set and transmembrane domain-containing protein 2B (A6NLU5).

Predicted to be active in membrane.

Source: NCBI Gene 342865 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 76 total
• MANE Select transcript: NM_001146339

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33595
Approved symbol	VSTM2B
Name	V-set and transmembrane domain containing 2B
Location	19q12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000187135
Ensembl biotype	protein_coding
Entrez	342865

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 9 protein_coding

ENST00000335523, ENST00000883792, ENST00000883793, ENST00000915702, ENST00000915703, ENST00000915704, ENST00000952476, ENST00000952477, ENST00000952478

RefSeq mRNA: 4 — MANE Select: NM_001146339 NM_001146339, NM_001384640, NM_001384641, NM_001384642

CCDS: CCDS46034

Canonical transcript exons

ENST00000335523 — 5 exons

Exon	Start	End
ENSE00001333426	29529819	29530290
ENSE00001333427	29528433	29528462
ENSE00001333430	29527211	29527395
ENSE00001333439	29525994	29526665
ENSE00001727834	29563846	29564551

Expression profiles

Bgee: expression breadth broad, 75 present calls, max score 94.41.

FANTOM5 (CAGE): breadth broad, TPM avg 2.7132 / max 116.9749, expressed in 230 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
174998	0.6864	105
174999	0.5473	94
174997	0.5255	104
175001	0.3623	127
175000	0.2466	104
175002	0.2420	57
175003	0.0412	22
174996	0.0363	29
174995	0.0254	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 9	UBERON:0013540	94.41	gold quality
superior frontal gyrus	UBERON:0002661	92.99	gold quality
primary visual cortex	UBERON:0002436	92.90	gold quality
nucleus accumbens	UBERON:0001882	92.78	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	92.71	gold quality
temporal lobe	UBERON:0001871	92.66	gold quality
amygdala	UBERON:0001876	92.62	gold quality
anterior cingulate cortex	UBERON:0009835	92.51	gold quality
Ammon’s horn	UBERON:0001954	91.63	gold quality
cerebral cortex	UBERON:0000956	91.49	gold quality
putamen	UBERON:0001874	91.49	gold quality
frontal cortex	UBERON:0001870	91.40	gold quality
prefrontal cortex	UBERON:0000451	91.36	gold quality
right frontal lobe	UBERON:0002810	91.23	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.96	gold quality
substantia nigra	UBERON:0002038	90.89	gold quality
caudate nucleus	UBERON:0001873	90.77	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.45	gold quality
cerebellar hemisphere	UBERON:0002245	89.19	gold quality
cerebellum	UBERON:0002037	89.15	gold quality
cerebellar cortex	UBERON:0002129	89.14	gold quality
hypothalamus	UBERON:0001898	88.36	gold quality
corpus callosum	UBERON:0002336	86.10	gold quality
brain	UBERON:0000955	85.97	gold quality
cortical plate	UBERON:0005343	84.28	gold quality
granulocyte	CL:0000094	77.82	gold quality
ectocervix	UBERON:0012249	65.37	gold quality
ganglionic eminence	UBERON:0004023	58.94	gold quality
endocervix	UBERON:0000458	58.81	gold quality
uterine cervix	UBERON:0000002	58.63	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-8060	no	30.41
E-HCAD-5	no	2.36
E-ANND-3	no	1.14

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

42 targeting VSTM2B, 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-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-LET-7C-3P	99.95	73.42	2862
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-7844-5P	99.55	68.56	1428
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-5009-3P	99.45	69.43	1341
HSA-MIR-3978	99.24	68.39	2201
HSA-MIR-767-3P	98.61	67.69	1192

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	vstm2b	ENSDARG00000098810
mus_musculus	Vstm2b	ENSMUSG00000039257
rattus_norvegicus	Vstm2b	ENSRNOG00000017456

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), VSIG8 (ENSG00000243284)

Protein

Protein identifiers

V-set and transmembrane domain-containing protein 2B — A6NLU5 (reviewed: A6NLU5)

All UniProt accessions (1): A6NLU5

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

RefSeq proteins (4): NP_001139811, NP_001371569, NP_001371570, NP_001371571 (=MANE)

Domains & families (InterPro)

ID	Name	Type
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
IPR051102	IgSF_V-set/TM_domain	Family

Pfam: PF07686

UniProt features (10 total): topological domain 2, compositionally biased region 2, signal peptide 1, chain 1, transmembrane region 1, domain 1, region of interest 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NLU5-F1	68.84	0.33

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 (1): 49–127

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 40 (showing top): MEISSNER_NPC_HCP_WITH_H3K4ME3_AND_H3K27ME3, MEISSNER_BRAIN_HCP_WITH_H3K4ME3_AND_H3K27ME3, MIKKELSEN_NPC_HCP_WITH_H3K4ME3_AND_H3K27ME3, MIKKELSEN_MEF_HCP_WITH_H3K27ME3, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_A, RYBP_TARGET_GENES, MIR1468_3P, MIR19A_3P, MIR19B_3P, MIR493_5P, MIR6797_5P, MIR1249_5P, MIR186_3P, MIR6515_5P, MIR4280

GO Biological Process (0):

GO Molecular Function (0):

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	1

Protein interactions and networks

STRING

1276 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VSTM2B	OR6S1	Q8NH40	506
VSTM2B	TMCC1	O94876	448
VSTM2B	LMCD1	Q9NZU5	447
VSTM2B	IRX2-DT	Q86SI9	447
VSTM2B	DOC2B	Q14184	447
VSTM2B	WHRN	Q9P202	436
VSTM2B	LENEP	Q9Y5L5	410
VSTM2B	CHODL	Q9H9P2	407
VSTM2B	HPSE	Q9Y251	401
VSTM2B	C19orf12	Q9NSK7	389
VSTM2B	ZNF439	Q8NDP4	377
VSTM2B	ZNF773	Q6PK81	370
VSTM2B	SEBOX	Q9HB31	357
VSTM2B	TIPE3	Q5GJ75	356
VSTM2B	FXYD7	P58549	352

IntAct

2 interactions, top by confidence:

A	B	Type	Score
VSTM2B	TCOF1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (1): TCOF1 (Proximity Label-MS)

ESM2 similar proteins: A1XQX1, A4FUY1, A6NFA1, A6NLU5, B1ATG9, C0HL12, D0PRN2, E1BBQ2, E9PUN2, O09112, O14514, O54693, O54951, O60347, O70141, P01346, P07456, P09535, P0DI97, P10764, P16611, P58400, P58401, P97260, Q0IJ12, Q13202, Q14CZ8, Q20FD0, Q28142, Q28143, Q3TZ87, Q3UHD1, Q63373, Q63376, Q640R3, Q6A039, Q6PDS0, Q6ZRP7, Q80UW0, Q86YJ5

Diamond homologs: A6NLU5, Q0IJ12, Q6PDS0, Q8R0A6, Q8TAG5, Q96N03, Q9JME9, P97300, P97546, Q9Y639

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	69
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

933 predictions. Top by Δscore:

Variant	Effect	Δscore
19:29526755:G:GT	donor_gain	1.0000
19:29527203:A:AG	acceptor_gain	1.0000
19:29527204:C:G	acceptor_gain	1.0000
19:29527209:A:AG	acceptor_gain	1.0000
19:29527209:AGCT:A	acceptor_gain	1.0000
19:29527210:G:GA	acceptor_gain	1.0000
19:29527210:GC:G	acceptor_gain	1.0000
19:29527210:GCT:G	acceptor_gain	1.0000
19:29527210:GCTG:G	acceptor_gain	1.0000
19:29527210:GCTGC:G	acceptor_gain	1.0000
19:29527393:AAG:A	donor_loss	1.0000
19:29529817:AGACC:A	acceptor_gain	1.0000
19:29529818:GACC:G	acceptor_gain	1.0000
19:29529818:GACCG:G	acceptor_gain	1.0000
19:29526662:GACG:G	donor_gain	0.9900
19:29526666:G:GG	donor_gain	0.9900
19:29526666:G:T	donor_loss	0.9900
19:29526667:T:G	donor_loss	0.9900
19:29526755:G:T	donor_gain	0.9900
19:29527212:T:A	acceptor_gain	0.9900
19:29527391:GCAAG:G	donor_gain	0.9900
19:29528461:GC:G	donor_gain	0.9900
19:29529816:CA:C	acceptor_loss	0.9900
19:29529817:A:AG	acceptor_gain	0.9900
19:29529817:A:C	acceptor_loss	0.9900
19:29529818:G:GG	acceptor_gain	0.9900
19:29529818:GA:G	acceptor_gain	0.9900
19:29563841:TGCA:T	acceptor_loss	0.9900
19:29563843:CAGG:C	acceptor_loss	0.9900
19:29563844:A:AG	acceptor_gain	0.9900

AlphaMissense

1804 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:29527321:T:A	W65R	1.000
19:29527321:T:C	W65R	1.000
19:29527323:G:C	W65C	1.000
19:29527323:G:T	W65C	1.000
19:29529900:T:A	C127S	1.000
19:29529901:G:C	C127S	1.000
19:29527268:T:C	M47T	0.999
19:29527279:T:C	F51L	0.999
19:29527281:C:A	F51L	0.999
19:29527281:C:G	F51L	0.999
19:29527316:T:C	I63T	0.999
19:29528458:T:C	I98T	0.999
19:29528458:T:G	I98S	0.999
19:29529856:T:C	L112P	0.999
19:29529900:T:C	C127R	0.999
19:29529901:G:A	C127Y	0.999
19:29529902:C:G	C127W	0.999
19:29527229:C:A	P34H	0.998
19:29527268:T:G	M47R	0.998
19:29527273:T:A	C49S	0.998
19:29527273:T:C	C49R	0.998
19:29527274:G:A	C49Y	0.998
19:29527274:G:C	C49S	0.998
19:29527275:C:G	C49W	0.998
19:29527280:T:C	F51S	0.998
19:29527280:T:G	F51C	0.998
19:29527326:G:C	W66C	0.998
19:29527326:G:T	W66C	0.998
19:29529856:T:A	L112H	0.998
19:29529894:T:C	Y125H	0.998

dbSNP variants (sampled 300 via entrez): RS1000075523 (19:29530736 G>A,C), RS1000148578 (19:29530110 C>A,G), RS1000158084 (19:29534175 C>A), RS1000227855 (19:29526493 C>A,T), RS1000248101 (19:29560638 C>T), RS1000258948 (19:29526302 T>C,G), RS1000290089 (19:29558845 A>C,G), RS1000298567 (19:29553975 A>G), RS1000363995 (19:29524359 T>C), RS1000413945 (19:29559044 G>A), RS1000448097 (19:29534447 G>T), RS1000538318 (19:29544079 G>T), RS1000539153 (19:29527607 C>T), RS1000690945 (19:29548945 C>A,T), RS1000716245 (19:29551819 G>A)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001017_14	Diabetic retinopathy	2.000000e-06
GCST001958_5	Bulimia nervosa	4.000000e-06
GCST005951_21	Body mass index	4.000000e-09
GCST010396_181	Gut microbiota (bacterial taxa, hurdle binary method)	3.000000e-06
GCST010577_4	Crohn’s disease	6.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Lead	affects expression, affects methylation	2
perfluorooctanoic acid	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
Benzo(a)pyrene	increases methylation	1
Ivermectin	decreases expression	1
1-Methyl-4-phenylpyridinium	decreases expression	1

Clinical trials (associated diseases)

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