TRPV1

Chr 17

transient receptor potential cation channel subfamily V member 1

Also known as: VR1

The protein encoded by this gene is a non-selective calcium-permeable cation channel that detects noxious chemical and thermal stimuli, serving as a receptor for capsaicin and temperatures above 42°C, and plays a role in inflammatory pain and hyperalgesia. Mutations in TRPV1 cause autosomal recessive episodic pain syndrome with autonomic dysfunction, characterized by recurrent episodes of severe pain associated with autonomic features. This gene is not highly constrained against loss-of-function variants based on population data.

GeneReviewsOMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.08
Clinical SummaryTRPV1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
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GeneReview available — TRPV1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.08LOEUF
pLI 0.000
Z-score 1.14
OE 0.80 (0.591.08)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.47Z-score
OE missense 0.94 (0.871.02)
475 obs / 504.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.80 (0.591.08)
00.351.4
Missense OE0.94 (0.871.02)
00.61.4
Synonymous OE1.12
01.21.6
LoF obs/exp: 29 / 36.5Missense obs/exp: 475 / 504.5Syn Z: -1.43
DN
0.6743th %ile
GOF
0.79top 10%
LOF
0.3454th %ile

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.

GOFprediction above median
DNprediction 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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TRPV1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
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 5 results · since 2015Search PubMed ↗