MYH3 Gene (Myosin Heavy Chain 3)
Skeletal muscle myosin essential for embryonic development and associated with congenital contracture syndromes
Gene Information Card
| Symbol | MYH3 |
|---|---|
| Full Name | myosin heavy chain 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 17p13.1 |
| NCBI Gene ID | 4621 ncbi.nlm.nih.gov/gene/4621 |
| Ensembl ID | ENSG00000109063 |
| UniProt ID | P11055 |
| OMIM ID | 160720 |
| HGNC ID | 7573 |
| Aliases | MYH-3, MYH2B, SMHCE, MYHSE1 |
Description
MYH3 encodes the embryonic myosin heavy chain, a major contractile protein in skeletal muscle during early development. It is a member of the myosin heavy chain family and is critical for muscle fiber formation. Mutations in MYH3 cause several congenital contracture syndromes, including Freeman-Sheldon syndrome and Sheldon-Hall syndrome.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Freeman-Sheldon syndrome | Dominant-negative or gain-of-function mutations in MYH3 disrupt actin-myosin cross-bridge cycling, leading to distal arthrogryposis and craniofacial abnormalities. | ClinVar, OMIM #193700 |
| Sheldon-Hall syndrome | Heterozygous missense mutations in MYH3 impair myosin motor function, resulting in milder distal arthrogryposis with normal facies. | ClinVar, OMIM #601680 |
| Distal arthrogryposis type 1 | MYH3 mutations cause reduced muscle contractility during fetal development, leading to joint contractures. | ClinVar, OMIM #108300 |
| Arthrogryposis multiplex congenita | Biallelic loss-of-function mutations in MYH3 lead to severe generalized joint contractures and muscle weakness. | ClinVar, OMIM #617468 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | 12.5 | High |
| Heart | 0.8 | Low |
| Brain | 0.1 | Not detected |
| Liver | 0.0 | Not detected |
| Kidney | 0.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Skeletal muscle myoblasts | 15.2 | High expression during differentiation |
| Rhabdomyosarcoma cell line (RD) | 8.7 | Moderate expression |
| Fibroblasts | 0.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1210G>A (p.Glu404Lys) | Missense | Common in Freeman-Sheldon syndrome | Dominant-negative effect on myosin ATPase activity |
| c.1493G>A (p.Arg498His) | Missense | Recurrent in Sheldon-Hall syndrome | Impaired actin binding |
| c.4522C>T (p.Arg1508Cys) | Missense | Rare | Reduced motor function |
| c.1A>G (p.Met1?) | Start loss | Very rare | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations (e.g., start loss, nonsense) cause severe arthrogryposis multiplex congenita.
Gain of Function (GOF)
Not clearly established; some missense mutations may increase actin affinity.
Dominant Negative (DN)
Heterozygous missense mutations in the motor domain (e.g., Glu404Lys) act as dominant-negative, disrupting wild-type myosin function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Smooth muscle contraction (Reactome R-HSA-445355)
• Striated muscle contraction (Reactome R-HSA-390522)
• Cardiac muscle contraction (KEGG hsa04260)
Protein Summary
MYH3 encodes the embryonic myosin heavy chain (MyHC-embryonic), a 200 kDa protein that forms the core of the thick filament in developing skeletal muscle. It contains an N-terminal motor domain with ATPase activity, a neck region with light chain binding sites, and a C-terminal tail domain responsible for filament assembly. During fetal development, MYH3 is the predominant myosin isoform and is gradually replaced by adult isoforms after birth. Mutations in MYH3 disrupt sarcomere function and lead to congenital contracture syndromes.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MYH3 Knockout HEK293 Cell Line | EDJ-KQ3538 | Human | 4621 | Details Get a Quote |
| MYH3 Knockout A-549 Cell Line | EDJ-KQ25383 | Human | 4621 | Details Get a Quote |
| MYH3 Knockout HCT 116 Cell Line | EDJ-KQ25384 | Human | 4621 | Details Get a Quote |
| MYH3 Knockout HeLa Cell Line | EDJ-KQ53939 | Human | 4621 | Details Get a Quote |
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