The MYH3 gene provides instructions for making a protein called embryonic skeletal muscle myosin heavy chain 3. This protein belongs to a group of proteins called myosins, which are involved in cell movement and transport of materials within and between cells. Thick filaments made of myosin, along with thin filaments of another protein called actin, are the primary components of muscle fibers and are important for muscle tensing (contraction).
Each myosin protein complex consists of two pairs of light chains, which regulate the complex and are produced from several other genes, and two heavy chains such as that produced from the MYH3 gene. The heavy chains each have two parts: a head region and a tail region. The head region interacts with actin and includes a segment that attaches (binds) to ATP. ATP is a molecule that supplies energy for cells' activities, including muscle contraction. The long tail region of the myosin heavy chain interacts with other proteins, including the tail regions of other myosins, enabling them to form thick filaments.
Embryonic skeletal muscle myosin heavy chain 3 forms part of a myosin protein complex that is normally active only before birth and is important for early development of the muscles.
Health Conditions Related to Genetic Changes
At least 26 MYH3 gene mutations have been identified in people with Freeman-Sheldon syndrome. This disorder affects muscle and skeletal development before birth and is characterized by joint deformities (contractures) that restrict movement in the hands and feet. Researchers suggest that the MYH3 mutations that cause Freeman-Sheldon syndrome affect the way the embryonic skeletal muscle myosin heavy chain 3 protein interacts with ATP, reducing the ability of fetal muscle cells to contract. This impairment of muscle contraction may interfere with muscle development in the fetus, resulting in the contractures and other muscle and skeletal abnormalities associated with Freeman-Sheldon syndrome. It is unknown how MYH3 gene mutations relate to other features of this disorder.More About This Health Condition
At least 15 MYH3 gene mutations have been identified in people with Sheldon-Hall syndrome, a muscle and skeletal disorder similar to Freeman-Sheldon syndrome (described above) that impairs joint movement in the hands and feet. The MYH3 gene mutations that cause Sheldon-Hall syndrome are believed to interfere with the ability of embryonic skeletal muscle myosin heavy chain 3 protein to bind with actin and other muscle proteins, and may also impair the formation of thick filaments. The mutations likely prevent muscle contractions from being properly controlled and interfere with muscle development before birth, resulting in the contractures and other muscle and skeletal abnormalities associated with Sheldon-Hall syndrome.More About This Health Condition
Spondylocarpotarsal synostosis syndrome
MedlinePlus Genetics provides information about Spondylocarpotarsal synostosis syndromeMore About This Health Condition
Other Names for This Gene
- muscle embryonic myosin heavy chain
- myosin heavy chain, fast skeletal muscle, embryonic
- myosin, heavy chain 3, skeletal muscle, embryonic
- myosin, heavy polypeptide 3, skeletal muscle, embryonic
- myosin, skeletal, heavy chain, embryonic 1
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- Beck AE, McMillin MJ, Gildersleeve HI, Kezele PR, Shively KM, Carey JC, Regnier M, Bamshad MJ. Spectrum of mutations that cause distal arthrogryposis types 1 and 2B. Am J Med Genet A. 2013 Mar;161A(3):550-5. doi: 10.1002/ajmg.a.35809. Epub 2013 Feb 7. Citation on PubMed or Free article on PubMed Central
- Carapito R, Goldenberg A, Paul N, Pichot A, David A, Hamel A, Dumant-Forest C, Leroux J, Ory B, Isidor B, Bahram S. Protein-altering MYH3 variants are associated with a spectrum of phenotypes extending to spondylocarpotarsal synostosis syndrome. Eur J Hum Genet. 2016 Dec;24(12):1746-1751. doi: 10.1038/ejhg.2016.84. Epub 2016 Jul 6. Citation on PubMed or Free article on PubMed Central
- Oldfors A, Lamont PJ. Thick filament diseases. Adv Exp Med Biol. 2008;642:78-91. Review. Citation on PubMed
- Tajsharghi H, Kimber E, Kroksmark AK, Jerre R, Tulinius M, Oldfors A. Embryonic myosin heavy-chain mutations cause distal arthrogryposis and developmental myosin myopathy that persists postnatally. Arch Neurol. 2008 Aug;65(8):1083-90. doi: 10.1001/archneur.65.8.1083. Erratum in: Arch Neurol. 2008 Dec;65(12):1654. Citation on PubMed
- Toydemir RM, Bamshad MJ. Sheldon-Hall syndrome. Orphanet J Rare Dis. 2009 Mar 23;4:11. doi: 10.1186/1750-1172-4-11. Review. Citation on PubMed or Free article on PubMed Central
- Toydemir RM, Rutherford A, Whitby FG, Jorde LB, Carey JC, Bamshad MJ. Mutations in embryonic myosin heavy chain (MYH3) cause Freeman-Sheldon syndrome and Sheldon-Hall syndrome. Nat Genet. 2006 May;38(5):561-5. Epub 2006 Apr 16. Citation on PubMed