MYO1B

Chr 2

myosin IB

ENSG00000128641 UniProt: O43795 OMIM: 606537

This gene encodes a motor protein that binds ATP and actin filaments to drive post-Golgi vesicle transport and may participate in neuronal development processes including cell migration and neurite outgrowth. Mutations cause autosomal recessive developmental and epileptic encephalopathy with movement abnormalities. The gene is highly constrained against loss-of-function variants, suggesting complete loss of protein function is likely pathogenic.

OMIM ResearchSummary from RefSeq, UniProt

Motor protein that may participate in process critical to neuronal development and function such as cell migration, neurite outgrowth and vesicular transport

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.43

Clinical Summary— MYO1B

⚡

Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.43LOEUF

pLI 0.000

Z-score 5.54

OE 0.30 (0.21–0.43)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.43Z-score

OE missense 0.72 (0.67–0.78)

446 obs / 615.9 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.30 (0.21–0.43)

0≤0.351.4

Missense OE?0.72 (0.67–0.78)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 22 / 73.1Missense obs/exp: 446 / 615.9Syn Z: -0.40

This gene — mechanism propensity

0.7230th %ile

GOF

0.7126th %ile

LOF

0.2583th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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