PIEZO2
Chr 18ADARpiezo type mechanosensitive ion channel component 2
Also known as: C18orf30, C18orf58, DA3, DA5, DAIPT, FAM38B, FAM38B2, HsT748
The protein functions as a mechanically-activated cation channel that converts mechanical forces into biological signals and mediates touch and proprioceptive sensation in somatosensory neurons. Mutations cause distal arthrogryposis (types 3 and 5) and arthrogryposis with impaired proprioception and touch, following both autosomal dominant and autosomal recessive inheritance patterns. The pathogenic mechanism involves gain-of-function mutations that disrupt normal mechanosensation.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Highly missense-constrained (top ~0.1%)
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.
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.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
PIEZO2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Growing Up in Multifactorial Risk Conditions
ENROLLING BY INVITATIONMicroneurographic Assessment of Peripheral Nerves in Healthy Volunteers and Individuals With Sensory Dysfunction Caused by Inherited Mutations in the PIEZO2 Gene
RECRUITINGExternal Resources
Links to major genomics databases and tools