MYH3
Chr 17ADARmyosin heavy chain 3
Also known as: CPSFS1A, CPSFS1B, CPSKF1A, CPSKF1B, DA2A, DA2B, DA2B3, DA8
The MYH3 protein is a contractile protein that converts chemical energy into mechanical energy through ATP hydrolysis and is essential for muscle function. Mutations cause multiple arthrogryposis syndromes including Freeman-Sheldon syndrome, Sheldon-Hall syndrome, and contractures-pterygia-spondylocarpotarsal fusion syndrome through dominant-negative mechanisms. These conditions follow autosomal dominant inheritance, though autosomal recessive inheritance has also been reported.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
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.
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
MYH3 · 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
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools