VSTM2A

Summary

VSTM2A (V-set and transmembrane domain containing 2A, HGNC:28499) is a protein-coding gene on chromosome 7p11.2, encoding V-set and transmembrane domain-containing protein 2A (Q8TAG5). Plays a role in the regulation of the early stage of white and brown preadipocyte cell differentiation.

Predicted to enable identical protein binding activity. Involved in several processes, including positive regulation of brown fat cell differentiation; positive regulation of lipid storage; and positive regulation of white fat cell proliferation. Predicted to be located in extracellular region. Predicted to be active in membrane.

Source: NCBI Gene 222008 — RefSeq curated summary.

At a glance

• GWAS associations: 19
• Clinical variants (ClinVar): 32 total
• MANE Select transcript: NM_001301009

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28499
Approved symbol	VSTM2A
Name	V-set and transmembrane domain containing 2A
Location	7p11.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC33530
Ensembl gene	ENSG00000170419
Ensembl biotype	protein_coding
Entrez	222008

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000302287, ENST00000402613, ENST00000404951, ENST00000407838, ENST00000466888, ENST00000469952, ENST00000495904, ENST00000498834

RefSeq mRNA: 3 — MANE Select: NM_001301009 NM_001301009, NM_001317843, NM_182546

CCDS: CCDS5512, CCDS75604, CCDS83185

Canonical transcript exons

ENST00000402613 — 5 exons

Exon	Start	End
ENSE00001859860	54542375	54542809
ENSE00001929460	54569131	54571067
ENSE00003472699	54544622	54544788
ENSE00003540354	54549834	54550170
ENSE00003669407	54546947	54546997

Expression profiles

Bgee: expression breadth ubiquitous, 140 present calls, max score 96.29.

FANTOM5 (CAGE): breadth broad, TPM avg 6.0510 / max 405.8956, expressed in 199 samples.

FANTOM5 promoters (21 alternative TSS)

Promoter ID	TPM avg	Samples expressed
78675	2.1260	117
78674	0.9482	107
78677	0.7075	108
78673	0.4367	99
78671	0.3028	90
78666	0.2529	80
78672	0.2363	82
78669	0.2249	72
78679	0.1817	76
78664	0.0873	49

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	96.29	gold quality
primary visual cortex	UBERON:0002436	96.08	gold quality
endothelial cell	CL:0000115	95.70	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.01	gold quality
occipital lobe	UBERON:0002021	94.91	gold quality
prefrontal cortex	UBERON:0000451	93.30	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	91.48	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.94	gold quality
Brodmann (1909) area 46	UBERON:0006483	90.69	gold quality
superior frontal gyrus	UBERON:0002661	90.58	gold quality
frontal cortex	UBERON:0001870	90.39	gold quality
neocortex	UBERON:0001950	89.72	gold quality
postcentral gyrus	UBERON:0002581	88.69	gold quality
parietal lobe	UBERON:0001872	88.36	gold quality
cerebral cortex	UBERON:0000956	88.30	gold quality
anterior cingulate cortex	UBERON:0009835	88.18	gold quality
nucleus accumbens	UBERON:0001882	88.03	gold quality
entorhinal cortex	UBERON:0002728	87.54	gold quality
temporal lobe	UBERON:0001871	86.63	gold quality
right frontal lobe	UBERON:0002810	85.72	gold quality
amygdala	UBERON:0001876	85.64	gold quality
hypothalamus	UBERON:0001898	85.59	gold quality
caudate nucleus	UBERON:0001873	84.87	gold quality
cortical plate	UBERON:0005343	83.44	gold quality
forebrain	UBERON:0001890	82.76	gold quality
lateral globus pallidus	UBERON:0002476	82.24	gold quality
putamen	UBERON:0001874	81.20	gold quality
Ammon’s horn	UBERON:0001954	80.18	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.04	gold quality
ganglionic eminence	UBERON:0004023	79.43	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-11	yes	683.43
E-GEOD-93593	yes	653.47
E-GEOD-84465	yes	6.63
E-ANND-3	yes	4.24

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

95 targeting VSTM2A, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798

Literature-anchored findings (GeneRIF, showing 4)

• VSTM2A is produced to preserve and amplify the adipogenic capability of adipose precursors. (PMID:28052263)
• VSTM2A overexpression to be a sensitive and specific marker for mucinous tubular and spindle cell carcinoma of the kidney. (PMID:30285995)
• VSTM2A suppresses colorectal cancer and antagonizes Wnt signaling receptor LRP6. (PMID:31588233)
• Gene of the month: VSTM2A. (PMID:38124011)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	vstm2a	ENSDARG00000021909
mus_musculus	Vstm2a	ENSMUSG00000048834
rattus_norvegicus	Vstm2a	ENSRNOG00000005180

Paralogs (5): PTGFRN (ENSG00000134247), CD101 (ENSG00000134256), IGSF3 (ENSG00000143061), IGSF8 (ENSG00000162729), VSTM4 (ENSG00000165633)

Protein

Protein identifiers

V-set and transmembrane domain-containing protein 2A — Q8TAG5 (reviewed: Q8TAG5)

All UniProt accessions (3): Q8TAG5, B5MCX6, F8W8J5

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the regulation of the early stage of white and brown preadipocyte cell differentiation. Promotes adipogenic commitment of preadipocytes by increasing gene expression of the transcription factor PPARG in a BMP4-dependent signaling pathway.

Subunit / interactions. Homodimer.

Subcellular location. Secreted.

Post-translational modifications. N-glycosylated. N-linked glycosylation is critical for secretion but not for preadipocyte cell differentiation activity.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TAG5-1	1	yes
Q8TAG5-2	2

RefSeq proteins (3): NP_001287938, NP_001304772, NP_872352 (=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): glycosylation site 2, signal peptide 1, chain 1, domain 1, region of interest 1, compositionally biased region 1, disulfide bond 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TAG5-F1	72.21	0.39

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): 48–127

Glycosylation sites (2): 35, 175

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 130 (showing top): GOBP_REGULATION_OF_LIPID_STORAGE, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GTTAAAG_MIR302B, GOBP_REGULATION_OF_BROWN_FAT_CELL_DIFFERENTIATION, CAGCTG_AP4_Q5, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION, GOBP_BROWN_FAT_CELL_DIFFERENTIATION, GOBP_FAT_CELL_DIFFERENTIATION, GOBP_RESPONSE_TO_BMP, AACTTT_UNKNOWN, GOBP_RESPONSE_TO_GROWTH_FACTOR, SABATES_COLORECTAL_ADENOMA_DN, GATA1_02, GOBP_POSITIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS

GO Biological Process (6): positive regulation of gene expression (GO:0010628), positive regulation of lipid storage (GO:0010884), cell differentiation (GO:0030154), positive regulation of white fat cell proliferation (GO:0070352), cellular response to BMP stimulus (GO:0071773), positive regulation of brown fat cell differentiation (GO:0090336)

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

GO Cellular Component (2): extracellular region (GO:0005576), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
regulation of lipid storage	1
lipid storage	1
positive regulation of cellular process	1
positive regulation of lipid localization	1
cellular developmental process	1
white fat cell proliferation	1
positive regulation of fat cell proliferation	1
regulation of white fat cell proliferation	1
cellular response to growth factor stimulus	1
response to BMP	1
positive regulation of fat cell differentiation	1
brown fat cell differentiation	1
regulation of brown fat cell differentiation	1
protein binding	1
binding	1

Protein interactions and networks

STRING

826 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VSTM2A	LANCL2	Q9NS86	527
VSTM2A	VOPP1	Q96AW1	522
VSTM2A	SEC61G	P38384	490
VSTM2A	SEPTIN14	Q6ZU15	452
VSTM2A	NINJ2	Q9NZG7	425
VSTM2A	POM121L12	Q8N7R1	393
VSTM2A	TMEM254	Q8TBM7	363
VSTM2A	ZNF713	Q8N859	353
VSTM2A	SUMF2	Q8NBJ7	321
VSTM2A	ZNF716	A6NP11	320
VSTM2A	SNTN	A6NMZ2	315
VSTM2A	OR7D2	Q96RA2	305
VSTM2A	FNDC4	Q9H6D8	299
VSTM2A	LINC03041	A6NGG3	296
VSTM2A	GOLT1A	Q6ZVE7	290
VSTM2A	OR4M2	Q8NGB6	290

IntAct

5 interactions, top by confidence:

A	B	Type	Score
VSTM2A	ACAD8	psi-mi:“MI:0915”(physical association)	0.500
VSTM2A	PTGER4	psi-mi:“MI:0915”(physical association)	0.370
VSTM2A	MSANTD3	psi-mi:“MI:0915”(physical association)	0.370
VSTM2A	POTEF	psi-mi:“MI:0914”(association)	0.350

BioGRID (7): ACAD8 (Affinity Capture-MS), HLA-DPB1 (Affinity Capture-MS), ACAD8 (Affinity Capture-MS), VSTM2A (Two-hybrid), VSTM2A (Two-hybrid), ACAD8 (Affinity Capture-MS), POTEF (Affinity Capture-MS)

ESM2 similar proteins: A0JNA2, A2RRU4, A4FUY1, A5D7V5, A8MVS5, D4A6L0, E1BBQ2, O19131, O54693, O75144, P09564, P15151, P19438, P29590, P31994, P32506, P32507, P50555, P97260, Q14CZ8, Q28110, Q3TEW6, Q53EL9, Q5BJT4, Q5DRQ8, Q5T848, Q61190, Q640R3, Q6AYP5, Q6AYT8, Q6BAA4, Q6GQT6, Q6P6J9, Q6UX15, Q70EL4, Q75VT8, Q7TSK2, Q7Z692, Q8C419, Q8N126

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	29
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1049 predictions. Top by Δscore:

Variant	Effect	Δscore
7:54544617:TGCA:T	acceptor_loss	1.0000
7:54544618:GCAGC:G	acceptor_loss	1.0000
7:54544619:CA:C	acceptor_loss	1.0000
7:54544620:A:AG	acceptor_gain	1.0000
7:54544620:A:AT	acceptor_loss	1.0000
7:54544621:G:GA	acceptor_gain	1.0000
7:54544621:GC:G	acceptor_gain	1.0000
7:54544621:GCA:G	acceptor_gain	1.0000
7:54544621:GCAA:G	acceptor_gain	1.0000
7:54544621:GCAAA:G	acceptor_gain	1.0000
7:54546996:GC:G	donor_gain	1.0000
7:54546998:G:GG	donor_gain	1.0000
7:54542522:G:GT	donor_gain	0.9900
7:54544733:G:GA	donor_gain	0.9900
7:54546941:CCGCA:C	acceptor_loss	0.9900
7:54546942:CGCAG:C	acceptor_loss	0.9900
7:54546943:GCAGG:G	acceptor_loss	0.9900
7:54546944:CAGG:C	acceptor_loss	0.9900
7:54546945:AGG:A	acceptor_loss	0.9900
7:54546993:TCAGC:T	donor_gain	0.9900
7:54546994:CAGCG:C	donor_loss	0.9900
7:54546995:AGCGT:A	donor_loss	0.9900
7:54546997:CG:C	donor_loss	0.9900
7:54546998:G:GA	donor_loss	0.9900
7:54546999:TGAG:T	donor_loss	0.9900
7:54547000:GAGT:G	donor_loss	0.9900
7:54547001:AGTG:A	donor_loss	0.9900
7:54547142:G:GT	donor_gain	0.9900
7:54549824:A:AG	acceptor_gain	0.9900
7:54549825:A:G	acceptor_gain	0.9900

AlphaMissense

1581 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:54544628:T:G	F29C	1.000
7:54544684:T:A	C48S	1.000
7:54544684:T:C	C48R	1.000
7:54544685:G:A	C48Y	1.000
7:54544685:G:C	C48S	1.000
7:54544686:C:G	C48W	1.000
7:54544690:T:C	F50L	1.000
7:54544691:T:C	F50S	1.000
7:54544691:T:G	F50C	1.000
7:54544692:C:A	F50L	1.000
7:54544692:C:G	F50L	1.000
7:54544718:T:C	L59P	1.000
7:54544729:T:A	W63R	1.000
7:54544729:T:C	W63R	1.000
7:54544731:G:C	W63C	1.000
7:54544731:G:T	W63C	1.000
7:54544734:G:C	W64C	1.000
7:54544734:G:T	W64C	1.000
7:54546993:T:C	I98T	1.000
7:54549849:G:T	G105C	1.000
7:54549859:T:A	I108N	1.000
7:54549859:T:G	I108S	1.000
7:54549871:T:A	L112H	1.000
7:54549871:T:C	L112P	1.000
7:54549909:T:G	Y125D	1.000
7:54549915:T:A	C127S	1.000
7:54549915:T:C	C127R	1.000
7:54549916:G:A	C127Y	1.000
7:54549916:G:C	C127S	1.000
7:54549916:G:T	C127F	1.000

dbSNP variants (sampled 300 via entrez): RS1000083370 (7:54552693 C>A), RS1000104547 (7:54560391 T>A,G), RS1000166177 (7:54550922 G>A), RS1000170733 (7:54556963 G>T), RS1000221796 (7:54569667 T>A), RS1000431218 (7:54562942 C>G), RS1000622132 (7:54545165 C>A), RS1000678496 (7:54569344 A>G,T), RS1000781007 (7:54563209 A>G), RS1000850723 (7:54541157 G>A), RS1000856869 (7:54552451 T>G), RS1000864227 (7:54567431 T>G), RS1000908770 (7:54559196 T>C), RS1000909543 (7:54559455 T>A,C), RS1000916530 (7:54567122 A>C)

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

19 associations (top):

Study	Trait	p-value
GCST003564_6	Waist-to-hip ratio adjusted for body mass index	6.000000e-06
GCST006994_1	Logical memory (immediate recall) in Alzheimer’s disease dementia	8.000000e-08
GCST007119_3	Cervical cancer	1.000000e-08
GCST008476_19	Emphysema annual change measurement in smokers (percent low attenuation area)	2.000000e-07
GCST009269_24	Dental caries (decayed and filled deciduous teeth)	3.000000e-06
GCST009391_109	Metabolite levels	7.000000e-06
GCST009391_2021	Metabolite levels	4.000000e-06
GCST009391_2067	Metabolite levels	6.000000e-06
GCST009391_297	Metabolite levels	8.000000e-06
GCST009391_333	Metabolite levels	9.000000e-06
GCST009391_335	Metabolite levels	1.000000e-07
GCST009391_354	Metabolite levels	6.000000e-09
GCST009391_361	Metabolite levels	1.000000e-07
GCST009391_665	Metabolite levels	2.000000e-06
GCST009391_895	Metabolite levels	2.000000e-06
GCST009391_902	Metabolite levels	2.000000e-08
GCST009391_915	Metabolite levels	7.000000e-06
GCST009391_918	Metabolite levels	4.000000e-09
GCST010988_156	Adult body size	5.000000e-08

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004874	memory performance
EFO:0007626	emphysema imaging measurement
EFO:0010353	diacylglycerol 34:2 measurement
EFO:0010348	cholesteryl ester 20:4 measurement
EFO:0010346	cholesteryl ester 18:3 measurement
EFO:0010425	triacylglycerol 54:7 measurement
EFO:0010432	triacylglycerol 56:5 measurement
EFO:0010433	triacylglycerol 56:6 measurement
EFO:0010434	triacylglycerol 56:7 measurement
EFO:0010435	triacylglycerol 56:8 measurement
EFO:0009770	leucine measurement
EFO:0010441	triacylglycerol 58:7 measurement
EFO:0010442	triacylglycerol 58:8 measurement
EFO:0010443	triacylglycerol 58:9 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
GSK-J4	increases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
bisphenol S	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Tretinoin	increases expression	1
Triclosan	decreases expression	1
Valproic Acid	increases expression	1
1-Methyl-4-phenylpyridinium	decreases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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