VSTM2A

Chr 7

V-set and transmembrane domain containing 2A

Also known as: VSTM2

NCBI Gene: 222008ENSG00000170419UniProt: Q8TAG5

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. [provided by Alliance of Genome Resources, Jul 2025]

48
ClinVar variants
11
Pathogenic / LP
0.27
pLI score
0
Active trials
Clinical Summary— VSTM2A
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.
📋
ClinVar Variants
11 Pathogenic / Likely Pathogenic· 35 VUS of 48 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.64LOEUF
pLI 0.273
Z-score 2.44
OE 0.25 (0.11–0.64)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.62Z-score
OE missense 0.85 (0.73–0.99)
114 obs / 134.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.25 (0.11–0.64)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.73–0.99)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.11
0≤1.21.6
LoF obs/exp: 3 / 12.2Missense obs/exp: 114 / 134.4Syn Z: -0.66

ClinVar Variant Classifications

48 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic1
VUS35
Likely Benign2
10
Pathogenic
1
Likely Pathogenic
35
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
0
0
1
0
1
VUS
0
29
6
0
35
Likely Benign
0
1
1
0
2
Benign
0
0
0
0
0
Total03018048

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

VSTM2A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
VSTM2A reverses immunosuppression in colorectal cancer by antagonizing the PD-L1/PD-1 interaction.
Dong Y et al.·Mol Ther
2024
Gene of the month: VSTM2A.
Wang L et al.·J Clin Pathol
2024
VSTM2A Overexpression Is a Sensitive and Specific Biomarker for Mucinous Tubular and Spindle Cell Carcinoma (MTSCC) of the Kidney.
Wang L et al.·Am J Surg Pathol
2018
Amplification of Adipogenic Commitment by VSTM2A.
Secco B et al.·Cell Rep
2017
Contemporary Characterization and Recategorization of Adult Unclassified Renal Cell Carcinoma.
Kwon R et al.·Am J Surg Pathol
2021
Discovery and validation of biomarkers for Parkinson's disease from human cerebrospinal fluid using mass spectrometry-based proteomics analysis.
Oh S et al.·EBioMedicine
2025
Frequency and functional characterization of fusion genes in squamous cell carcinoma of the lung.
Alidousty C et al.·Gene
2024Functional
Prognostic model development for classification of colorectal adenocarcinoma by using machine learning model based on feature selection technique boruta.
Maurya NS et al.·Sci Rep
2023Functional
Integrated analysis of the genomic and transcriptional profile of gliomas with isocitrate dehydrogenase-1 and tumor protein 53 mutations.
Liu HQ et al.·Int J Immunopathol Pharmacol
2022
VSTM2A suppresses colorectal cancer and antagonizes Wnt signaling receptor LRP6.
Dong Y et al.·Theranostics
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Loss of VSTM2A promotes adipocyte hypertrophy and disrupts metabolic homeostasis.
Al Dow M et al.·Obesity (Silver Spring)
2025🔓 Open Access
Control of adipogenic commitment by a STAT3-VSTM2A axis.
Al Dow M et al.·Am J Physiol Endocrinol Metab
2021
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools