PIEZO2

Chr 18ADAR

piezo type mechanosensitive ion channel component 2

Also known as: C18orf30, C18orf58, DA3, DA5, DAIPT, FAM38B, FAM38B2, HsT748

NCBI Gene: 63895ENSG00000154864UniProt: Q9H5I5

The protein encoded by this gene contains more than thirty transmembrane domains and likely functions as part of mechanically-activated (MA) cation channels. These channels serve to connect mechanical forces to biological signals. The encoded protein quickly adapts MA currents in somatosensory neurons. Defects in this gene are a cause of type 5 distal arthrogryposis. Several alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Feb 2014]

Primary Disease Associations & Inheritance

?Marden-Walker syndromeMIM #248700
AD
Arthrogryposis, distal, type 3MIM #114300
AD
Arthrogryposis, distal, type 5MIM #108145
AD
Arthrogryposis, distal, with impaired proprioception and touchMIM #617146
AR
0
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— PIEZO2
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

pubmed: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.37LOEUF
pLI 0.000
Z-score 7.85
OE 0.28 (0.22–0.37)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.44Z-score
OE missense 0.75 (0.71–0.78)
1081 obs / 1450.1 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.28 (0.22–0.37)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.75 (0.71–0.78)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.87
0≤1.21.6
LoF obs/exp: 40 / 140.4Missense obs/exp: 1081 / 1450.1Syn Z: 2.31

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

Gene2Phenotype Curations

PIEZO2-related arthrogryposis, distal

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

PIEZO2-related ataxia, dysmetria, contractures and scoliosis with normal cognition but loss of discriminative touch perception

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Marden-Walker syndrome

MIM #248700

Molecular basis of disorder known

Autosomal dominant

Arthrogryposis, distal, type 3

MIM #114300

Molecular basis of disorder known

Autosomal dominant

Arthrogryposis, distal, type 5

MIM #108145

Molecular basis of disorder known

Autosomal dominant

Arthrogryposis, distal, with impaired proprioception and touch

MIM #617146

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
PIEZO2-Deficiency Syndrome

Microneurographic Assessment of Peripheral Nerves in Healthy Volunteers and Individuals With Sensory Dysfunction Caused by Inherited Mutations in the PIEZO2 Gene

RECRUITING
NCT06052631National Center for Complementary and Integrative Health (NCCIH)Started 2026-03-15

External Resources

Links to major genomics databases and tools