PIEZO2

Chr 18ADAR

piezo type mechanosensitive ion channel component 2

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

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]

GeneReviewsOMIMResearchGenerating clinical summary…

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

Clinical highlights

Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
2
Active trials
200
Pubs (1 yr)
P/LP submissions
P/LP missense
0.37
LOEUF
LOF*
Mechanism· G2P
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GeneReview available — PIEZO2
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Missense constrained — critical functional residues
LoF Constraint?
0.37LOEUF
pLI 0.000
Z-score 7.85
OE 0.28 (0.220.37)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
3.44Z-score
OE missense 0.75 (0.710.78)
1081 obs / 1450.1 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.28 (0.220.37)
00.351.4
Missense OE?0.75 (0.710.78)
00.61.4
Synonymous OE?0.87
01.21.6
LoF obs/exp: 40 / 140.4Missense obs/exp: 1081 / 1450.1Syn Z: 2.31

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.