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MYH3 gene

myosin heavy chain 3
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Normal Function

The MYH3 gene provides instructions for making a protein called myosin-3. This protein belongs to a group of proteins called myosins, which are involved in movement and the transport of materials within and between cells. In addition, muscle fibers are primarily composed of thick filaments made of myosin and thin filaments of another protein called actin. Thick and thin filaments are involved in muscle tensing (contraction). Muscle fibers containing myosin-3 are found primarily in the fetus before birth, and they are important for early development of the muscles.

Myosins function when they are part of a group (complex). Each myosin complex consists of two pairs of myosin light chains (produced from other genes), which regulate the complex, and one pair of myosin 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, which allows the thick and thin filaments to move relative to one another so that muscles can contract. The head region also includes a segment that attaches (binds) to ATP, which 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, to form thick filaments.

Health Conditions Related to Genetic Changes

Freeman-Sheldon syndrome

Variants (also known as mutations) in the MYH3 gene cause Freeman-Sheldon syndrome. This disorder affects muscle and skeletal development before birth and is characterized by abnormalities known as contractures that cause a distinctive facial appearance and deformities of the hands and feet. Contractures result from permanent tightening of muscles, skin, and surrounding tissues, and they restrict movement of the affected body part.

Studies suggest that MYH3 gene variants that cause Freeman-Sheldon syndrome prolong the attachment of myosin to actin, possibly because the variants affect the way myosin uses ATP. Prolonged attachment of myosin to actin keeps the muscle tensed and does not allow it to relax, which prevents movement. It is thought that abnormal muscle contraction and limited muscle and limb movement during development leads to stiffening of the muscles and surrounding tissues, causing contractures characteristic of Freeman-Sheldon syndrome. Researchers suggest that limited muscle movement before birth impairs normal development of other parts of the body, which may account for other features of Freeman-Sheldon syndrome. 

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Sheldon-Hall syndrome

MYH3 gene variants can cause Sheldon-Hall syndrome, a muscle and skeletal disorder that impairs joint movement in the hands and feet, similar to but milder than Freeman-Sheldon syndrome (described above). The MYH3 gene variants that cause Sheldon-Hall syndrome are believed to interfere with the ability of the myosin-3 protein to attach to actin and other muscle proteins, and may also impair the formation of thick filaments. The variants likely prevent muscle contractions from being controlled and interfere with muscle development before birth, resulting in the contractures and other muscle and skeletal abnormalities associated with Sheldon-Hall syndrome.

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Spondylocarpotarsal synostosis syndrome

MedlinePlus Genetics provides information about Spondylocarpotarsal synostosis syndrome

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Other Names for This Gene

  • HEMHC
  • muscle embryonic myosin heavy chain
  • MYH3_HUMAN
  • MYHC-EMB
  • MYHSE1
  • 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
  • myosin-3
  • SMHCE

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Research Resources

References

  • 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
  • Poling MI, Dufresne CR, Chamberlain RL. Freeman-Burian syndrome. Orphanet J Rare Dis. 2019 Jan 10;14(1):14. doi: 10.1186/s13023-018-0984-2. Review. Citation on PubMed
  • Racca AW, Beck AE, McMillin MJ, Korte FS, Bamshad MJ, Regnier M. The embryonic myosin R672C mutation that underlies Freeman-Sheldon syndrome impairs cross-bridge detachment and cycling in adult skeletal muscle. Hum Mol Genet. 2015 Jun 15;24(12):3348-58. doi: 10.1093/hmg/ddv084. Epub 2015 Mar 3. Citation on PubMed
  • Schiaffino S, Rossi AC, Smerdu V, Leinwand LA, Reggiani C. Developmental myosins: expression patterns and functional significance. Skelet Muscle. 2015 Jul 15;5:22. doi: 10.1186/s13395-015-0046-6. eCollection 2015. 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
  • Walklate J, Vera C, Bloemink MJ, Geeves MA, Leinwand L. The Most Prevalent Freeman-Sheldon Syndrome Mutations in the Embryonic Myosin Motor Share Functional Defects. J Biol Chem. 2016 May 6;291(19):10318-31. doi: 10.1074/jbc.M115.707489. Epub 2016 Mar 4. Citation on PubMed
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