MYO7A

Chr 11ADAR

myosin VIIA

Also known as: DFNA11, DFNB2, MYOVIIA, MYU7A, NSRD2, USH1B

NCBI Gene: 4647 ENSG00000137474 UniProt: Q13402 OMIM: 276903

This unconventional myosin functions as an actin-based motor protein with ATPase activity that plays critical roles in retinal photoreceptor disk renewal, melanosome distribution in retinal pigment epithelium, and cochlear hair cell bundle organization and mechanotransduction. Mutations cause Usher syndrome type 1B, characterized by congenital severe-to-profound sensorineural hearing loss, vestibular dysfunction, and progressive retinal degeneration leading to blindness, with autosomal recessive inheritance. The gene shows extremely low tolerance to loss-of-function variants (pLI approaching 1), indicating that even heterozygous loss-of-function is likely deleterious.

OMIM ResearchSummary from RefSeq, UniProt

This gene is a member of the myosin gene family. Myosins are mechanochemical proteins characterized by the presence of a motor domain, an actin-binding domain, a neck domain that interacts with other proteins, and a tail domain that serves as an anchor. This gene encodes an unconventional myosin with a very short tail. Defects in this gene are associated with the mouse shaker-1 phenotype and the human Usher syndrome 1B which are characterized by deafness, reduced vestibular function, and (in human) retinal degeneration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismAD/ARLOEUF 0.853 OMIM phenotypes

Clinical Summary— MYO7A

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Gene-Disease Validity (ClinGen)

Usher syndrome type 1 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Clinical Trials

2 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.85LOEUF

pLI 0.000

Z-score 2.89

OE 0.70 (0.58–0.85)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.07Z-score

OE missense 0.92 (0.88–0.96)

1242 obs / 1353.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.70 (0.58–0.85)

0≤0.351.4

Missense OE?0.92 (0.88–0.96)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 77 / 109.7Missense obs/exp: 1242 / 1353.0Syn Z: -0.75

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveMYO7A-related deafnessLOFAR

definitiveMYO7A-related Usher syndromeOTHERAR

This gene — mechanism propensity

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

0.7034th %ile

GOF

0.6736th %ile

LOF

0.3066th %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.

Literature Evidence

DNIt has been shown that the coiled-coil region is responsible for the dimerization of MY07A8â¢ Thus it is possible that the DFNAll mutant allele encodes a product that interacts with normal wildtype protein, resulting in a dominant negative effect. Indeed, unlike USHlB and nonsyndromic recessive DFN1

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

References