MYO15A

Chr 17AR

myosin XVA

Also known as: DFNB3, MYO15

This gene encodes an unconventional myosin that functions as an actin-based motor protein with ATPase activity and is required for proper stereocilia arrangement in cochlear hair cell bundles. Mutations cause autosomal recessive nonsyndromic deafness (DFNB3), which presents as profound congenital hearing loss. The gene shows extremely high constraint against loss-of-function variants (pLI ~1.0), indicating intolerance to haploinsufficiency in the general population.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.801 OMIM phenotype
Clinical SummaryMYO15A
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Gene-Disease Validity (ClinGen)
nonsyndromic genetic hearing loss · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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GeneReview available — MYO15A
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.80LOEUF
pLI 0.000
Z-score 3.78
OE 0.69 (0.590.80)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.65Z-score
OE missense 0.96 (0.921.00)
1975 obs / 2057.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.69 (0.590.80)
00.351.4
Missense OE0.96 (0.921.00)
00.61.4
Synonymous OE0.93
01.21.6
LoF obs/exp: 116 / 169.1Missense obs/exp: 1975 / 2057.4Syn Z: 1.60
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveMYO15A-related deafnessLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7325th %ile
GOF
0.6639th %ile
LOF
0.2776th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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