TRPV4

Chr 12

transient receptor potential cation channel subfamily V member 4

Also known as: BCYM3, CMT2C, HMSN2C, OTRPC4, SMAL, SPSMA, SSQTL1, TRP12

NCBI Gene: 59341ENSG00000111199UniProt: Q9HBA0

This gene encodes a member of the OSM9-like transient receptor potential channel (OTRPC) subfamily in the transient receptor potential (TRP) superfamily of ion channels. The encoded protein is a Ca2+-permeable, nonselective cation channel that is thought to be involved in the regulation of systemic osmotic pressure. Mutations in this gene are the cause of spondylometaphyseal and metatropic dysplasia and hereditary motor and sensory neuropathy type IIC. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2010]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtBrachyolmia 3
UniProtSpondylometaphyseal dysplasia Kozlowski type
UniProtMetatropic dysplasia
UniProtNeuronopathy, distal hereditary motor, autosomal dominant 8

Clinical highlights

Gene-disease validity (ClinGen)
TRPV4-related bone disorder · ADDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total
Interpreting a novel variant
Gain of function is the curated mechanism (Gene2Phenotype), so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.Curated gene-level mechanism — a prior for triage, not a per-variant call.
2
Active trials
452
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
1.06
LOEUF
GOF
Mechanism· G2P
📖
GeneReview available — TRPV4
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
1.06LOEUF
pLI 0.000
Z-score 1.28
OE 0.77 (0.58–1.06)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
1.92Z-score
OE missense 0.77 (0.71–0.83)
418 obs / 544.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.77 (0.58–1.06)
0≤0.351.4
Missense OE?0.77 (0.71–0.83)
0≤0.61.4
Synonymous OE?1.00
0≤1.21.6
LoF obs/exp: 29 / 37.4Missense obs/exp: 418 / 544.2Syn Z: 0.03

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

TRPV4 · protein map & ClinVar variants

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

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients