VSTM4

Chr 10

V-set and transmembrane domain containing 4

Also known as: C10orf72

NCBI Gene: 196740ENSG00000165633UniProt: Q8IW00

The VSTM4 protein enhances L-type voltage-gated calcium channel currents in retinal photoreceptors and is involved in retinal blood vessel maintenance and vasculature development. Mutations cause autosomal recessive retinal dystrophy with early childhood onset. The gene shows relatively low constraint to loss-of-function variation.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
0
Pubs (1 yr)
59
P/LP submissions
0%
P/LP missense
0.72
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— VSTM4
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.34) despite low pLI — interpret in context.
📋
ClinVar Variants
59 unique Pathogenic / Likely Pathogenic· 80 VUS of 151 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.72LOEUF
pLI 0.034
Z-score 2.34
OE 0.34 (0.18–0.72)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.30Z-score
OE missense 0.94 (0.83–1.06)
174 obs / 185.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.34 (0.18–0.72)
0≤0.351.4
Missense OE0.94 (0.83–1.06)
0≤0.61.4
Synonymous OE0.93
0≤1.21.6
LoF obs/exp: 5 / 14.7Missense obs/exp: 174 / 185.3Syn Z: 0.47
DN
0.76top 25%
GOF
0.7126th %ile
LOF
0.3164th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

151 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic38
Likely Pathogenic21
VUS80
Likely Benign3
38
Pathogenic
21
Likely Pathogenic
80
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
38
0
38
Likely Pathogenic
0
0
21
0
21
VUS
0
50
30
0
80
Likely Benign
0
2
0
1
3
Benign
0
0
0
0
0
Total052891142

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

View in ClinVar →

Protein Context — Lollipop Plot

VSTM4 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients