MYO3A
Chr 10ADARmyosin IIIA
Also known as: DFNA90, DFNB30
This actin-dependent motor protein with kinase activity is essential for cochlear hair bundle development and hearing, transporting actin regulatory factors to stereocilia tips and contributing to the characteristic staircase architecture of auditory hair bundles. Mutations cause nonsyndromic hearing loss with both autosomal dominant and autosomal recessive inheritance patterns. The gene shows very low constraint against loss-of-function variants and is highly expressed in the retina and cochlea.
Primary Disease Associations & Inheritance
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
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
500 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 | 11 | 1 | 15 | 0 | 27 |
Likely Pathogenic | 14 | 0 | 5 | 0 | 19 |
VUS | 6 | 296 | 23 | 4 | 329 |
Likely Benign | 0 | 2 | 35 | 53 | 90 |
Benign | 0 | 0 | 9 | 2 | 11 |
Conflicting | — | 9 | |||
| Total | 31 | 299 | 87 | 59 | 485 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
MYO3A · 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