MYO6
Chr 6ADARmyosin VI
Also known as: DFNA22, DFNB37
MYO6 encodes an unconventional myosin motor protein that moves toward the minus end of actin filaments and functions in intracellular vesicle transport, endocytosis, autophagy, and maintenance of inner ear hair cell structural integrity. Mutations cause non-syndromic hearing loss with both autosomal dominant and autosomal recessive inheritance patterns, with some dominant cases also presenting with hypertrophic cardiomyopathy. The gene is highly constrained against loss-of-function variants (LOEUF 0.419), indicating that such variants are likely pathogenic.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function, dominant-negative and gain-of-function). The Badonyi & Marsh model scores dominant-negative highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). 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.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
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 | 29 | 0 | 8 | 0 | 37 |
Likely Pathogenic | 26 | 3 | 2 | 0 | 31 |
VUS | 6 | 238 | 23 | 4 | 271 |
Likely Benign | 0 | 0 | 36 | 31 | 67 |
Benign | 0 | 0 | 67 | 0 | 67 |
Conflicting | — | 1 | |||
| Total | 61 | 241 | 136 | 35 | 474 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
MYO6 · 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