TRPV3
Chr 17ADtransient receptor potential cation channel subfamily V member 3
Also known as: FNEPPK2, OLMS, OLMS1, VRL3
TRPV3 encodes a temperature-sensitive calcium-permeable cation channel that is activated by warm temperatures (22-40°C) and regulates keratinocyte proliferation and hair follicle cycling. Mutations cause autosomal dominant Olmsted syndrome and focal nonepidermolytic palmoplantar keratoderma, both affecting skin and hair development. The gene shows low constraint against loss-of-function variants, suggesting the pathogenic variants may work through other mechanisms.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
400 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 4 | 20 | 0 | 24 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 3 | 140 | 68 | 1 | 212 |
Likely Benign | 0 | 10 | 20 | 28 | 58 |
Benign | 1 | 13 | 49 | 18 | 81 |
Conflicting | — | 16 | |||
| Total | 4 | 167 | 159 | 47 | 393 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TRPV3 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools