MYO9A

Chr 15AR

myosin IXA

Also known as: CMS24

NCBI Gene: 4649 ENSG00000066933 UniProt: B2RTY4 OMIM: 604875

This gene encodes an unconventional myosin that functions as an actin-based motor protein with ATPase activity and regulates neurite branching and motor neuron axon guidance. Mutations cause congenital myasthenic syndrome type 24 (presynaptic form), inherited in an autosomal recessive pattern. The gene shows significant constraint against loss-of-function variants (LOEUF 0.304), indicating intolerance to such changes.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the myosin superfamily. The protein represents an unconventional myosin; it should not be confused with the conventional non-muscle myosin-9 (MYH9). Unconventional myosins contain the basic domains of conventional myosins and are further distinguished from class members by their tail domains. They function as actin-based molecular motors. Mutations in this gene have been associated with Bardet-Biedl Syndrome. [provided by RefSeq, Dec 2011]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Myasthenic syndrome, congenital, 24, presynapticMIM #618198

Clinical highlights

Gene–disease validity (ClinGen)

Limited · arthrogryposis syndrome · AR · ClinGen 2016

not for standalone diagnostic reporting

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.30

LOEUF· LoF intol.

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.30LOEUF

pLI 0.489

Z-score 8.31

OE 0.22 (0.17–0.30)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.74Z-score

OE missense 0.87 (0.82–0.91)

1156 obs / 1334.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.22 (0.17–0.30)

0≤0.351.4

Missense OE?0.87 (0.82–0.91)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 30 / 133.7Missense obs/exp: 1156 / 1334.9Syn Z: -0.23

Background carrier burden — how many people carry a rare variant somewhere in MYO9A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 23

3,022 rare PASS variants

Rare truncating (LoF)

1 in 660

285 rare PASS variants

Rare synonymous (reference)

1 in 55

1,127 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MYO9A. 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 28	1 in 940
South Asian	~43k	1 in 20	1 in 590
Remaining (unassigned)	~30k	1 in 19	1 in 610
European (Finnish)	~27k	1 in 51	1 in 2,100
Admixed American	~22k	1 in 20	1 in 640
African / African American	~21k	1 in 16	1 in 580
East Asian	~20k	1 in 20	1 in 680
Ashkenazi Jewish	~13k	1 in 150	≈ 1 in 3,800
Middle Eastern	~2,884	1 in 24	1 in 470

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 28 of 41 coding exons well covered in gnomAD exomes; exon 32 poorly covered; exons 4, 5, 9, 10, 11 and 7 more marginal. Genomes: all 41.? see exons ↓