CAPZA3
Chr 12capping actin protein of muscle Z-line subunit alpha 3
Also known as: CAPPA3, Gsg3, HEL-S-86
The protein caps the fast-growing ends of actin filaments in a calcium-independent manner and is predominantly expressed in sperm where it contributes to sperm architecture and male fertility. Mutations cause autosomal recessive sensorineural hearing loss with onset in infancy or early childhood. The gene shows low constraint to loss-of-function variants, consistent with its autosomal recessive inheritance pattern.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
The highest-scoring mechanism for this gene is dominant-negative.
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
85 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 37 | 0 | 37 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 45 | 2 | 0 | 47 |
Likely Benign | 0 | 0 | 0 | 0 | 0 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 45 | 40 | 0 | 85 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CAPZA3 · 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
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