HomeAboutRankingsData Sources
Β© 2026 GeneE
🧬
GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
MYH3
myosin heavy chain 3
Chromosome 17 Β· 17p13.1
NCBI Gene: 4621Ensembl: ENSG00000109063.16HGNC: HGNC:7573UniProt: P11055
61PubMed Papers
24Diseases
0Drugs
126Pathogenic Variants
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
ATP hydrolysis activityATP metabolic processactin filament bindingskeletal muscle contractionFreeman-Sheldon syndromearthrogryposis, distal, type 2B3contractures, pterygia, and spondylocarpotarsal fusion syndrome 1Acontractures, pterygia, and variable skeletal fusions syndrome 1B
✦AI Summary

MYH3 encodes myosin heavy chain 3, an embryonic isoform of skeletal muscle myosin that functions as a molecular motor for muscle contraction through actin filament-based movement and ATP hydrolysis 1. During early muscle development, MYH3 is expressed in fast-twitch skeletal muscle fibers and plays a critical role in sarcomere organization and muscle filament sliding 2. Pathogenic variants in MYH3 cause multiple congenital contracture syndromes inherited in both dominant and recessive patterns 3. These include distal arthrogryposis types 2A and 2B3, Sheldon-Hall syndrome, Freeman-Sheldon syndrome, and contractures, pterygia, and spondylocarpotarsal fusion syndromes (CPSFS) 4 5. Affected individuals present with congenital joint contractures, variable vertebral segmentation anomalies, short stature, and dysmorphic features 3. MYH3-associated disorders represent ultra-rare conditions with non-progressive contractures most severe at birth 4. Pathogenic mechanisms involve disruption of canonical and non-canonical TGF-Ξ² signaling pathways, with monoallelic variants decreasing SMAD3 phosphorylation and biallelic variants potentially causing protein truncation 3. Notably, patients typically exhibit normal life expectancy and cognitive abilities, with management focused on early physical therapy, serial casting, and surgical intervention 4.

Sources cited
1
MYH3 is an embryonic myosin isoform expressed during muscle development; mutations cause distal arthrogryposis syndromes with minimal muscle weakness
PMID: 17434305
2
MYH3 mutations are associated with distal arthrogryposis syndromes as prenatal nonprogressive arthrogrypotic conditions
PMID: 19181095
3
MYH3 variants cause vertebral segmentation anomalies and multiple arthrogryposis syndromes through TGF-Ξ² signaling disruption
PMID: 35169139
4
Sheldon-Hall syndrome caused by MYH3 mutations presents with congenital joint contractures, dysmorphic features, and non-progressive course
PMID: 19309503
5
Bi-allelic MYH3 variants cause recessively-inherited distal arthrogryposis without spondylocarpotarsal fusion features
PMID: 38856159
Disease Associationsβ“˜24
Freeman-Sheldon syndromeOpen Targets
0.80Strong
arthrogryposis, distal, type 2B3Open Targets
0.77Strong
contractures, pterygia, and spondylocarpotarsal fusion syndrome 1AOpen Targets
0.77Strong
contractures, pterygia, and variable skeletal fusions syndrome 1BOpen Targets
0.75Strong
Autosomal dominant multiple pterygium syndromeOpen Targets
0.72Strong
autosomal recessive multiple pterygium syndromeOpen Targets
0.64Moderate
contractures, pterygia, and variable skeletal fusions syndromeOpen Targets
0.64Moderate
spondylocarpotarsal synostosis syndromeOpen Targets
0.62Moderate
Sheldon-hall syndromeOpen Targets
0.56Moderate
genetic disorderOpen Targets
0.50Moderate
Spondylocarpotarsal synostosisOpen Targets
0.46Moderate
distal arthrogryposisOpen Targets
0.46Moderate
distal arthrogryposis type 2B1Open Targets
0.45Moderate
arthrogryposis multiplex congenitaOpen Targets
0.41Moderate
digitotalar dysmorphismOpen Targets
0.40Moderate
rhabdomyolysisOpen Targets
0.26Weak
Meniere diseaseOpen Targets
0.17Weak
arthrogryposis syndromeOpen Targets
0.12Weak
cleft lip/palateOpen Targets
0.12Weak
prostate cancerOpen Targets
0.11Weak
Arthrogryposis, distal, 2AUniProt
Arthrogryposis, distal, 2B3UniProt
Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1AUniProt
Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1BUniProt
Pathogenic Variants126
NM_002470.4(MYH3):c.-9+1G>APathogenic
Spondylocarpotarsal synostosis syndrome;Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A|Contractures, pterygia, and variable skeletal fusions syndrome 1B|Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A|not provided|MYH3-related disorder
β˜…β˜…β˜†β˜†2026
NM_002470.4(MYH3):c.2682+1G>ALikely pathogenic
not provided|MYH3-related disorder|Freeman-Sheldon syndrome
β˜…β˜…β˜†β˜†2026
NM_002470.4(MYH3):c.2014C>T (p.Arg672Cys)Pathogenic
Freeman-Sheldon syndrome|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 672
NM_002470.4(MYH3):c.2776_2779del (p.Arg926fs)Pathogenic
not provided|MYH3-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 926
NM_002470.4(MYH3):c.4525G>T (p.Glu1509Ter)Pathogenic
not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 1509
NM_002470.4(MYH3):c.5563-1G>CLikely pathogenic
not provided
β˜…β˜…β˜†β˜†2025
NM_002470.4(MYH3):c.3329_3330del (p.Lys1110fs)Pathogenic
not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 1110
NM_002470.4(MYH3):c.533C>T (p.Thr178Ile)Pathogenic
Freeman-Sheldon syndrome|Arthrogryposis, distal, type 2B3|not provided|MYH3-related disorder
β˜…β˜…β˜†β˜†2024β†’ Residue 178
NM_002470.4(MYH3):c.3751C>T (p.Arg1251Ter)Pathogenic
Inborn genetic diseases|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 1251
NM_002470.4(MYH3):c.2170C>T (p.Arg724Ter)Pathogenic
not provided|Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A
β˜…β˜…β˜†β˜†2024β†’ Residue 724
NM_002470.4(MYH3):c.724TCC[1] (p.Ser243del)Likely pathogenic
Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A|not provided|Spondylocarpotarsal synostosis syndrome
β˜…β˜…β˜†β˜†2024β†’ Residue 243
NM_002470.4(MYH3):c.533+1G>ALikely pathogenic
not provided|MYH3-related disorder
β˜…β˜…β˜†β˜†2023
NM_002470.4(MYH3):c.4726_4729del (p.Lys1576fs)Pathogenic
not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 1576
NM_002470.4(MYH3):c.2015G>A (p.Arg672His)Pathogenic
Freeman-Sheldon syndrome|not provided|Arthrogryposis, distal, type 2B3;Contractures, pterygia, and variable skeletal fusions syndrome 1B;Freeman-Sheldon syndrome;Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A
β˜…β˜…β˜†β˜†2023β†’ Residue 672
NM_002470.4(MYH3):c.2306G>A (p.Gly769Asp)Likely pathogenic
not provided
β˜…β˜…β˜†β˜†2022β†’ Residue 769
NM_002470.4(MYH3):c.1102A>T (p.Lys368Ter)Pathogenic
not provided
β˜…β˜…β˜†β˜†2022β†’ Residue 368
NM_002470.4(MYH3):c.1581+1G>APathogenic
Spondylocarpotarsal synostosis syndrome;Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A|Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A|Arthrogryposis, distal, type 2B3
β˜…β˜…β˜†β˜†2019
NM_002470.4(MYH3):c.1748A>C (p.Tyr583Ser)Pathogenic
Freeman-Sheldon syndrome|Freeman-Sheldon syndrome;Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A;Contractures, pterygia, and variable skeletal fusions syndrome 1B;Arthrogryposis, distal, type 2B3
β˜…β˜…β˜†β˜†2019β†’ Residue 583
NM_002470.4(MYH3):c.1216A>T (p.Lys406Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 406
NM_002470.4(MYH3):c.4023_4024del (p.Cys1341_Asp1342delinsTer)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 1341
View on ClinVar β†—
Related Genes
MYL12BProtein interaction100%MYL9Protein interaction99%MYL12AProtein interaction99%MYH10Protein interaction99%MYL2Protein interaction96%TNNT2Protein interaction95%
Tissue Expression6 tissues
Liver
100%
Ovary
80%
Lung
46%
Bone Marrow
24%
Heart
17%
Brain
12%
Gene Interaction Network
Click a node to explore
MYH3MYL12BMYL9MYL12AMYH10MYL2TNNT2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt P11055
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.60LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.52 [0.45–0.60]
RankingsWhere MYH3 stands among ~20K protein-coding genes
  • #7,581of 20,598
    Most Researched61
  • #623of 5,498
    Most Pathogenic Variants126 Β· top quartile
  • #4,168of 17,882
    Most Constrained (LOEUF)0.60 Β· top quartile
Genes detectedMYH3
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
A 20-year Clinical and Genetic Neuromuscular Cohort Analysis in Lebanon: An International Effort.
PMID: 34602496
J Neuromuscul Dis Β· 2022
1.00
2
Prenatal whole-exome sequencing for fetal structural anomalies: a retrospective analysis of 145 Chinese cases.
PMID: 37880672
BMC Med Genomics Β· 2023
0.90
3
Expanding the mutation and phenotype spectrum of MYH3-associated skeletal disorders.
PMID: 35169139
NPJ Genom Med Β· 2022
0.80
4
Sheldon-Hall syndrome.
PMID: 19309503
Orphanet J Rare Dis Β· 2009
0.70
5
Hereditary myosin myopathies.
PMID: 17434305
Neuromuscul Disord Β· 2007
0.60