TRPV2

Chr 17

transient receptor potential cation channel subfamily V member 2

Also known as: VRL, VRL-1, VRL1

NCBI Gene: 51393 ENSG00000187688 UniProt: Q9Y5S1 OMIM: 606676

The TRPV2 protein functions as a calcium-permeable, non-selective cation channel that is activated by high temperatures above 52°C and regulated by growth factors including IGF1 and PDGF. Mutations in this gene cause autosomal recessive arthrogryposis multiplex congenita with developmental and speech delays. This gene shows very low constraint against loss-of-function variants, indicating tolerance to such mutations in the general population.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes an ion channel that is activated by high temperatures above 52 degrees Celsius. The protein may be involved in transduction of high-temperature heat responses in sensory ganglia. It is thought that in other tissues the channel may be activated by stimuli other than heat. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.86

Clinical Summary— TRPV2

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

91 VUS of 105 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?

0.86LOEUF

pLI 0.000

Z-score 2.26

OE 0.62 (0.46–0.86)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.71Z-score

OE missense 0.78 (0.71–0.85)

359 obs / 462.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.62 (0.46–0.86)

0≤0.351.4

Missense OE?0.78 (0.71–0.85)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 26 / 41.8Missense obs/exp: 359 / 462.5Syn Z: 0.17

This gene — mechanism propensity

0.74top 25%

GOF

0.81top 10%

LOF

0.2093th %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

105 submitted variants in ClinVar

ClinVar

Classification Summary

VUS91

Likely Benign3

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	91	0	91
Likely Benign	3	0	3
Benign	0	1	1
Total	94	1	95

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

View in ClinVar →

26 pathogenic / likely-pathogenic (of 45) ClinVar copy-number / structural variants overlap TRPV2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →