MYO15A

Chr 17

myosin XVA

NCBI Gene: 51168ENSG00000091536UniProt: Q9UKN7

Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Their highly divergent tails are presumed to bind to membranous compartments, which would be moved relative to actin filaments. Required for the arrangement of stereocilia in mature hair bundles (By similarity)

Primary Disease Associations & Inheritance

UniProtDeafness, autosomal recessive, 3
3968
ClinVar variants
137
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— MYO15A
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
137 Pathogenic / Likely Pathogenic· 213 VUS of 3968 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.80LOEUF
pLI 0.000
Z-score 3.78
OE 0.69 (0.59–0.80)
Tolerant

Typical tolerance to LoF variation

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.
0.65Z-score
OE missense 0.96 (0.92–1.00)
1975 obs / 2057.4 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.0.69 (0.59–0.80)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.96 (0.92–1.00)
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.0.93
0≤1.21.6
LoF obs/exp: 116 / 169.1Missense obs/exp: 1975 / 2057.4Syn Z: 1.60

ClinVar Variant Classifications

3968 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic59
Likely Pathogenic78
VUS213
Likely Benign126
Benign1
Conflicting3
59
Pathogenic
78
Likely Pathogenic
213
VUS
126
Likely Benign
1
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
36
2
20
1
59
Likely Pathogenic
34
27
17
0
78
VUS
1
204
4
4
213
Likely Benign
0
7
38
81
126
Benign
0
0
1
0
1
Conflicting
—3
Total712408086480

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MYO15A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

MYO15A-related deafness

definitive
ARLoss Of FunctionAbsent Gene Product
Ear
G2P ↗

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genetic screening of a Chinese cohort of children with hearing loss using a next-generation sequencing panel.
Ma J et al.·Hum Genomics
2023Cohort
Comprehensive Molecular Screening in Chinese Usher Syndrome Patients.
Sun T et al.·Invest Ophthalmol Vis Sci
2018Cohort
Analysis of the genotype-phenotype correlation of MYO15A variants in Chinese non-syndromic hearing loss patients.
Fu Y et al.·BMC Med Genomics
2022Cohort
Molecular diagnose of a large hearing loss population from China by targeted genome sequencing.
Wu J et al.·J Hum Genet
2022
Genetic Epidemiology and Clinical Features of Hereditary Hearing Impairment in the Taiwanese Population.
Wu CC et al.·Genes (Basel)
2019
Myosins and Hearing.
Friedman TB et al.·Adv Exp Med Biol
2020Review
Trends and mechanisms of Alzheimer's disease and hearing impairment: A 20-year perspective.
Li FF et al.·Ageing Res Rev
2025Functional
DNA Diagnostics of Hereditary Hearing Loss: A Targeted Resequencing Approach Combined with a Mutation Classification System.
Sommen M et al.·Hum Mutat
2016
Genetic etiology of non-syndromic hearing loss in Europe.
Del Castillo I et al.·Hum Genet
2022Review
Mutation spectrum of hearing loss patients in Northwest China: Identification of 20 novel variants.
Ma P et al.·Mol Genet Genomic Med
2024Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Computational study of the potential impact of WHRN protein missense SNPs on WHRN-MYO15A protein complex interaction and their association with Usher syndrome.
Chentoufi FE et al.·J Biomol Struct Dyn
2025
The clinical and genetic spectrum of twenty-six individuals with hearing loss affected by MYO15A variants.
Morovvati S et al.·Sci Rep
2025🔓 Open Access
Characteristics and Prognosis of Patients With Non-Syndromic Sensorineural Hearing Loss Associated With Myo15a Mutations.
Wang Y et al.·Otolaryngol Head Neck Surg
2025Cohort
A Novel Mutation Located in the N-Terminal Domain of MYO15A Caused Sensorineural Hearing Loss.
Wang Y et al.·Mol Genet Genomic Med
2024🔓 Open Access
Retracted: Identification of Hearing Loss-Associated Variants of PTPRQ, MYO15A, and SERPINB6 in Pakistani Families.
International BR.·Biomed Res Int
2024🔓 Open Access
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