MYH4
Chr 17myosin heavy chain 4
Also known as: MYH2B, MyHC-2B, MyHC-IIb
The protein is a myosin heavy chain that enables muscle contraction within myofibrils. Mutations cause autosomal dominant myopathy with early-onset muscle weakness and contractures, as well as autosomal recessive developmental and epileptic encephalopathy with microcephaly. The gene shows very low constraint against loss-of-function variants, suggesting tolerance to such mutations in the general population.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
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
337 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 12 | 0 | 12 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 0 | 291 | 15 | 0 | 306 |
Likely Benign | 0 | 5 | 0 | 2 | 7 |
Benign | 0 | 5 | 0 | 3 | 8 |
Conflicting | — | 1 | |||
| Total | 0 | 301 | 27 | 5 | 334 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
MYH4 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools