MYO6

Chr 6ADAR

myosin VI

Also known as: DFNA22, DFNB37

NCBI Gene: 4646ENSG00000196586UniProt: Q9UM54

This gene encodes a reverse-direction motor protein that moves toward the minus end of actin filaments and plays a role in intracellular vesicle and organelle transport. The protein consists of a motor domain containing an ATP- and an actin-binding site and a globular tail which interacts with other proteins. This protein maintains the structural integrity of inner ear hair cells and mutations in this gene cause non-syndromic autosomal dominant and recessive hearing loss. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2014]

Primary Disease Associations & Inheritance

Deafness, autosomal dominant 22MIM #606346
AD
Deafness, autosomal dominant 22, with hypertrophic cardiomyopathyMIM #606346
AD
Deafness, autosomal recessive 37MIM #607821
AR
997
ClinVar variants
123
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— MYO6
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.
📋
ClinVar Variants
123 Pathogenic / Likely Pathogenic· 493 VUS of 997 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.42LOEUF
pLI 0.000
Z-score 5.92
OE 0.30 (0.22–0.42)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.39Z-score
OE missense 0.85 (0.79–0.91)
586 obs / 688.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.30 (0.22–0.42)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.79–0.91)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.95
0≤1.21.6
LoF obs/exp: 25 / 83.4Missense obs/exp: 586 / 688.6Syn Z: 0.59

ClinVar Variant Classifications

997 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic69
Likely Pathogenic54
VUS493
Likely Benign182
Benign100
Conflicting72
69
Pathogenic
54
Likely Pathogenic
493
VUS
182
Likely Benign
100
Benign
72
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
28
1
40
0
69
Likely Pathogenic
28
8
18
0
54
VUS
7
373
106
7
493
Likely Benign
0
5
118
59
182
Benign
0
3
96
1
100
Conflicting
—72
Total6339037867970

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.

Gene2Phenotype Curations

MYO6-related nonsyndromic genetic hearing loss with left ventricular hypertrophy

moderate
ARUndeterminedAltered Gene Product Structure, Decreased Gene Product Level
Cardiac
G2P ↗
splice acceptor variantsplice donor variantframeshift variantstop gainedmissense variant

MYO6-related nonsyndromic genetic hearing loss with left ventricular hypertrophy

moderate
ADUndeterminedAltered Gene Product Structure, Decreased Gene Product Level
Cardiac
G2P ↗
splice acceptor variantsplice donor variantframeshift variantstop gainedmissense variant

MYO6-related nonsyndromic genetic hearing loss

definitive
ARUndeterminedAltered Gene Product Structure, Decreased Gene Product Level
Ear
G2P ↗
splice acceptor variantsplice donor variantframeshift variantstop gainedmissense variant

MYO6-related nonsyndromic genetic hearing loss

definitive
ADUndeterminedAltered Gene Product Structure, Decreased Gene Product Level
Ear
G2P ↗
splice acceptor variantsplice donor variantframeshift variantstop gainedmissense variant

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
MYOSIN VI; MYO6
MIM #600970 · *

Deafness, autosomal dominant 22

MIM #606346

Molecular basis of disorder known

Autosomal dominant

Deafness, autosomal dominant 22, with hypertrophic cardiomyopathy

MIM #606346

Molecular basis of disorder known

Autosomal dominant

Deafness, autosomal recessive 37

MIM #607821

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Association of Genetic Diagnoses for Childhood-Onset Hearing Loss With Cochlear Implant Outcomes.
Carlson RJ et al.·JAMA Otolaryngol Head Neck Surg
2023
Gene Therapy for Hearing Loss: Which Genes Next?
Carlson RJ et al.·Otol Neurotol
2025Review
Myosins and Hearing.
Friedman TB et al.·Adv Exp Med Biol
2020Review
Ultrarare heterozygous pathogenic variants of genes causing dominant forms of early-onset deafness underlie severe presbycusis.
Boucher S et al.·Proc Natl Acad Sci U S A
2020
Gene editing in a Myo6 semi-dominant mouse model rescues auditory function.
Xue Y et al.·Mol Ther
2022Functional
MYO6 contributes to tumor progression and enzalutamide resistance in castration-resistant prostate cancer by activating the focal adhesion signaling pathway.
Zheng S et al.·Cell Commun Signal
2024
Genetic etiology of non-syndromic hearing loss in Europe.
Del Castillo I et al.·Hum Genet
2022Review
Next-generation sequencing identifies three novel missense variants in ILDR1 and MYO6 genes in an Iranian family with hearing loss with review of the literature.
Talebi F et al.·Int J Pediatr Otorhinolaryngol
2017Review
The genomic landscape of Ménière's disease: a path to endolymphatic hydrops.
Fisch KM et al.·BMC Genomics
2024
Clinical Characteristics and In Vitro Analysis of MYO6 Variants Causing Late-Onset Progressive Hearing Loss.
Oka SI et al.·Genes (Basel)
2020
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools