TRPV3

Chr 17AD

transient receptor potential cation channel subfamily V member 3

Also known as: FNEPPK2, OLMS, OLMS1, VRL3

NCBI Gene: 162514ENSG00000167723UniProt: Q8NET8

This gene product belongs to a family of nonselective cation channels that function in a variety of processes, including temperature sensation and vasoregulation. The thermosensitive members of this family are expressed in subsets of sensory neurons that terminate in the skin, and are activated at distinct physiological temperatures. This channel is activated at temperatures between 22 and 40 degrees C. This gene lies in close proximity to another family member gene on chromosome 17, and the two encoded proteins are thought to associate with each other to form heteromeric channels. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

Primary Disease Associations & Inheritance

?Palmoplantar keratoderma, nonepidermolytic, focal 2MIM #616400
AD
Olmsted syndrome 1MIM #614594
AD
552
ClinVar variants
50
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TRPV3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
50 Pathogenic / Likely Pathogenic· 256 VUS of 552 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

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.
1.15LOEUF
pLI 0.000
Z-score 0.82
OE 0.86 (0.65–1.15)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.17Z-score
OE missense 0.98 (0.91–1.06)
467 obs / 477.5 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.0.86 (0.65–1.15)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.91–1.06)
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.1.03
0≤1.21.6
LoF obs/exp: 33 / 38.5Missense obs/exp: 467 / 477.5Syn Z: -0.31

ClinVar Variant Classifications

552 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic46
Likely Pathogenic4
VUS256
Likely Benign76
Benign150
Conflicting20
46
Pathogenic
4
Likely Pathogenic
256
VUS
76
Likely Benign
150
Benign
20
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
9
37
0
46
Likely Pathogenic
0
1
3
0
4
VUS
2
162
91
1
256
Likely Benign
0
12
26
38
76
Benign
1
13
117
19
150
Conflicting
—20
Total319727458552

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.

Gene2Phenotype Curations

TRPV3-related palmoplantar keratoderma, nonepidermolytic, focal

limited
ADUndeterminedAltered Gene Product Structure
Skin
G2P ↗

TRPV3-related Olmsted syndrome

strong
ADUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Palmoplantar keratoderma, nonepidermolytic, focal 2

MIM #616400

Molecular basis of disorder known

Autosomal dominant

Olmsted syndrome 1

MIM #614594

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Global warming and implications for epithelial barrier disruption and respiratory and dermatologic allergic diseases.
Çelebi Sözener Z et al.·J Allergy Clin Immunol
2023Review
TRPV3-Activated PARP1/AIFM1/MIF Axis through Oxidative Stress Contributes to Atopic Dermatitis.
Song Z et al.·J Invest Dermatol
2024
Scutellarein attenuates atopic dermatitis by selectively inhibiting transient receptor potential vanilloid 3 channels.
Wang Y et al.·Br J Pharmacol
2022
TRPV3: Structure, Diseases and Modulators.
Su W et al.·Molecules
2023Review
TRPV3 and Itch: The Role of TRPV3 in Chronic Pruritus according to Clinical and Experimental Evidence.
Um JY et al.·Int J Mol Sci
2022Review
TRPV3 Ion Channel: From Gene to Pharmacology.
Kalinovskii AP et al.·Int J Mol Sci
2023Review
Structural insights into TRPV2 modulation by probenecid.
Rocereta JA et al.·Nat Struct Mol Biol
2025
Pharmacogenetics of new analgesics.
Lötsch J et al.·Br J Pharmacol
2011Review
Genotype‒Phenotype Correlation of TRPV3-Related Olmsted Syndrome.
Zhong W et al.·J Invest Dermatol
2021
TRP channels in cardiac and intestinal fibrosis.
Inoue R et al.·Semin Cell Dev Biol
2019Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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