MYO3A

Chr 10ADAR

myosin IIIA

Also known as: DFNA90, DFNB30

NCBI Gene: 53904 ENSG00000095777 UniProt: Q8NEV4 OMIM: 606808

This actin-dependent motor protein with kinase activity is essential for cochlear hair bundle development and hearing, transporting actin regulatory factors to stereocilia tips and contributing to the characteristic staircase architecture of auditory hair bundles. Mutations cause nonsyndromic hearing loss with both autosomal dominant and autosomal recessive inheritance patterns. The gene shows very low constraint against loss-of-function variants and is highly expressed in the retina and cochlea.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene belongs to the myosin superfamily. Myosins are actin-dependent motor proteins and are categorized into conventional myosins (class II) and unconventional myosins (classes I and III through XV) based on their variable C-terminal cargo-binding domains. Class III myosins, such as this one, have a kinase domain N-terminal to the conserved N-terminal motor domains and are expressed in photoreceptors. The protein encoded by this gene plays an important role in hearing in humans. Three different recessive, loss of function mutations in the encoded protein have been shown to cause nonsyndromic progressive hearing loss. Expression of this gene is highly restricted, with the strongest expression in retina and cochlea. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Deafness, autosomal dominant 90MIM #620722

Deafness, autosomal recessive 30MIM #607101

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · nonsyndromic genetic hearing loss · AR · ClinGen 2023

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.04

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — MYO3A

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.04LOEUF

pLI 0.000

Z-score 1.23

OE 0.86 (0.71–1.04)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.13Z-score

OE missense 1.01 (0.96–1.07)

841 obs / 830.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.86 (0.71–1.04)

0≤0.351.4

Missense OE?1.01 (0.96–1.07)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 76 / 88.5Missense obs/exp: 841 / 830.3Syn Z: -0.95

Background carrier burden — how many people carry a rare variant somewhere in MYO3A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 34

2,126 rare PASS variants

Rare truncating (LoF)

1 in 200

404 rare PASS variants

Rare synonymous (reference)

1 in 54

670 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MYO3A. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 44	1 in 230
South Asian	~43k	1 in 29	1 in 140
Remaining (unassigned)	~30k	1 in 29	1 in 190
European (Finnish)	~27k	1 in 100	1 in 1,100
Admixed American	~22k	1 in 27	1 in 160
African / African American	~21k	1 in 21	1 in 170
East Asian	~20k	1 in 32	1 in 220
Ashkenazi Jewish	~13k	1 in 91	1 in 470
Middle Eastern	~2,884	1 in 24	1 in 110

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 30 of 33 coding exons well covered in gnomAD exomes; exons 12, 24, 33 marginal. Genomes: all 33.? see exons ↓