XIRP2
Chr 2xin actin binding repeat containing 2
Also known as: CMYA3
XIRP2 encodes a protein that protects actin filaments from depolymerization and is essential for cardiomyocyte membrane morphology, intercalated disk maturation, and maintenance of cochlear stereocilia structure. Mutations cause cardiomyopathy with conduction defects and sensorineural hearing loss, inherited in an autosomal recessive pattern. The gene shows tolerance to loss-of-function variants (low pLI score), consistent with recessive inheritance where heterozygous carriers are typically unaffected.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Tolerant to missense variation
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.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
XIRP2 · 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
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools