GeneBe

TRPV3

protein-coding

transient receptor potential cation channel subfamily V member 3, the group of Transient receptor potential cation channels|Ankyrin repeat domain containing

Gene summary

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]

MANE transcript

NM_145068.4

Inheritance

AD

ClinVar variants

P:13U:178B:101

Top phenotype

Olmsted syndrome 1; Palmoplantar keratoderma, nonepidermolytic focal 2

gnomAD constraint

pLI —, LoF o/e 0.86

Max pathogenic AF

—

Genomic locus

chr17:3,510,502-3,557,812

External References & Databases

Ensembl (ENSG00000167723)NCBI Gene (162514)OMIM (607066)HGNC:18084GenCCUniProt (Q8NET8)AlphaFoldClinVar (TRPV3)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~47.3 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

isolated focal non-epidermolytic palmoplantar keratodermaSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0014622

Submitter: Orphanet

Olmsted syndrome 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0100296

Submitter: Labcorp Genetics (formerly Invitae)

mutilating palmoplantar keratoderma with periorificial keratotic plaquesSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0019014

Submitter: Orphanet

Olmsted syndrome 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0100296

Submitter: PanelApp Australia

mutilating palmoplantar keratoderma with periorificial keratotic plaquesSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0019014

Submitter: Genomics England PanelApp

Olmsted syndrome 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0100296

Submitter: G2P

isolated focal non-epidermolytic palmoplantar keratodermaLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0014622

Submitter: Labcorp Genetics (formerly Invitae)

mutilating palmoplantar keratoderma with periorificial keratotic plaquesSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0019014

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Olmsted syndrome 1; Palmoplantar keratoderma, nonepidermolytic focal 2AD

Manifestation: Dermatologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Comments: Infections and skin cancer have been described at arising at the site of skin lesions

Refs: 22405088; 25285920Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TRPV3 variants in ClinVar

6 Conditions Cataloged
not providedTotal: 181
Inborn genetic diseasesTotal: 135
Isolated focal non-epidermolytic palmoplantar keratodermaTotal: 82
not specifiedTotal: 30
TRPV3-related disorderTotal: 20
Olmsted syndrome 1Total: 14

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_145068.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
2
clinvar
50
clinvar
12
clinvar
 64
missense
8
clinvar
5
clinvar
171
clinvar
26
clinvar
11
clinvar
 221
nonsense
2
clinvar
1
clinvar
 3
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
3
clinvar
1
clinvar
 4
Total851787724292

Highest pathogenic variant AF is 0.000012391405

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_145068.4RefSeqNP_659505.117MANE Select
ENST00000576742.6EnsemblENSP00000461518.217MANE Select
NM_001258205.2RefSeqNP_001245134.117Standard
ENST00000301365.8EnsemblENSP00000301365.417Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Inflammatory mediator regulation of TRP channels - Homo sapiens (human)
  • Stimuli-sensing channels
  • Ion channel transport
  • Transport of small molecules
  • TRP channels

Biological Process

  • response to heat
  • negative regulation of hair cycle
  • calcium ion transmembrane transport
  • positive regulation of calcium ion import

Molecular Function

  • ion channel activity
  • calcium channel activity

Cellular Component

  • plasma membrane
  • integral component of plasma membrane
  • receptor complex

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000301365
Coding exons
17
Length
47494
Individuals with no LoFs
125531
Homozygous LoFs
0
Heterozygous LoFs
217
Defined
125748
p
0.000863
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.1714674780.9780.00002895192
Missense (PolyPhen)126146.620.859361622
Synonymous-0.3102152091.030.00001441518
Loss of Function0.8233338.50.8570.00000202434

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000550.00055rare
Latino/Admixed American0.000290.00029rare
Ashkenazi Jewish0.0000990.000099rare
East Asian0.00220.0022notable
Finnish0.000190.00018rare
European (Non-Finnish)0.00130.0012notable
South Asian0.000330.00033rare
Other0.000160.00016rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Putative receptor-activated non-selective calcium permeant cation channel. It is activated by innocuous (warm) temperatures and shows an increased response at noxious temperatures greater than 39 degrees Celsius. Activation exhibits an outward rectification. May associate with TRPV1 and may modulate its activity. Is a negative regulator of hair growth and cycling: TRPV3-coupled signaling suppresses keratinocyte proliferation in hair follicles and induces apoptosis and premature hair follicle regression (catagen). {ECO:0000269|PubMed:12077604, ECO:0000269|PubMed:12077606, ECO:0000269|PubMed:21593771}.;
Disease
DISEASE: Palmoplantar keratoderma, non-epidermolytic, focal 2 (FNEPPK2) [MIM:616400]: A dermatological disorder characterized by non-epidermolytic, abnormal thickening of the skin on the palms and soles. Focal palmoplantar keratoderma consists of localized areas of hyperkeratosis located mainly on pressure points and sites of recurrent friction. {ECO:0000269|PubMed:25285920}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Intolerance Scores

LoFtool
0.192
RVIS EVS
0.23
RVIS percentile EVS
68.58

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.356

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumHigh
CancerMediumMediumMedium
Feedback | API | MCP | Annotate VCF | Sitemap | About | Privacy & Terms
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.