MYO1B

Chr 2

myosin IB

Also known as: MMI-alpha, MMIa, MYH-1c, myr1

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.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.43
Clinical SummaryMYO1B
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.43LOEUF
pLI 0.000
Z-score 5.54
OE 0.30 (0.210.43)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.43Z-score
OE missense 0.72 (0.670.78)
446 obs / 615.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.30 (0.210.43)
00.351.4
Missense OE0.72 (0.670.78)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 22 / 73.1Missense obs/exp: 446 / 615.9Syn Z: -0.40
DN
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.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

MYO1B · 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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