TRPV3

Chr 17AD

transient receptor potential cation channel subfamily V member 3

Also known as: FNEPPK2, OLMS, OLMS1, VRL3

NCBI Gene: 162514 ENSG00000167723 UniProt: Q8NET8 OMIM: 607066

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Palmoplantar keratoderma, nonepidermolytic, focal 2MIM #616400

Olmsted syndrome 1MIM #614594

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Olmsted syndrome 1; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.15

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

0.17Z-score

OE missense 0.98 (0.91–1.06)

467 obs / 477.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.86 (0.65–1.15)

0≤0.351.4

Missense OE?0.98 (0.91–1.06)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 33 / 38.5Missense obs/exp: 467 / 477.5Syn Z: -0.31

Background carrier burden — how many people carry a rare variant somewhere in TRPV3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 60

1,154 rare PASS variants

Rare truncating (LoF)

1 in 490

174 rare PASS variants

Rare synonymous (reference)

1 in 62

479 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TRPV3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 68	1 in 450
South Asian	~43k	1 in 35	1 in 380
Remaining (unassigned)	~30k	1 in 62	1 in 450
European (Finnish)	~27k	1 in 100	1 in 970
Admixed American	~22k	1 in 47	1 in 1,600
African / African American	~21k	1 in 42	1 in 500
East Asian	~20k	1 in 36	1 in 240
Ashkenazi Jewish	~13k	1 in 190	1 in 1,900
Middle Eastern	~2,884	1 in 47	≈ 1 in 960

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 16 of 17 coding exons well covered in gnomAD exomes; exon 14 marginal. Genomes: all 17.? see exons ↓