Open Access Articles- Top Results for MYH6


SymbolsMYH6 ; ASD3; CMD1EE; CMH14; MYHC; MYHCA; SSS3; alpha-MHC
External IDsOMIM160710 MGI97255 HomoloGene124414 GeneCards: MYH6 Gene
RNA expression pattern
File:PBB GE MYH7 204737 s at tn.png
File:PBB GE MYH6 214468 at tn.png
More reference expression data
RefSeq (mRNA)NM_002471NM_001164171
RefSeq (protein)NP_002462NP_001157643
Location (UCSC)Chr 14:
23.85 – 23.88 Mb
Chr 14:
54.94 – 54.97 Mb
PubMed search[1][2]

Myosin-6 is a protein that in humans is encoded by the MYH6 gene.[1][2]


Cardiac muscle myosin is a hexamer consisting of two heavy chain subunits, two light chain subunits, and two regulatory subunits. This gene encodes the alpha heavy chain subunit of cardiac myosin. The gene is located ~4kb downstream of the gene encoding the beta heavy chain subunit of cardiac myosin.[2]

Clinical significance

Mutations in this gene cause familial hypertrophic cardiomyopathy and atrial septal defect 3.[2]

Cardiomyopathy from mutation R403Q

Hypertrophic cardiomyopathy (HCM) is a cardiac disease that has some characteristic abnormalities including hypertrophy of the septal wall, disorganized cardiac myocytes, and increase fibrosis within the myocardium. The majority of familial HCM cases have been linked to a mutation in beta-myosin heavy chains converting a single amino acid from an arginine to a glutamine at the 403rd position.[3] More than half of affected people die by the age of 40 because of HCM due to R403Q.[3] The R403Q mutation interferes with the beta-myosin heavy chain and therefore greatly hinders the functionality of the heart muscle.[4] Specifically, the affected muscle cells have slower contractile velocities, have depressed actin-activated ATPase rates, and have increased stiffness.[4]

Due to the fact that the cause of the R403Q mutation lies within the region that encodes for the globular myosin head, alterations in the myosin head structure greatly impairs its ability to strongly interact with actin and form a stable cross-bridge.[4] The development of HCM is multifaceted, but the R403Q mutation is one of the most influential risk factors. Of the hundreds of pathogenic mutations that give rise to HCM, R403Q mutations in myosin heavy chain genes are present in over half of them.[4][3] Since HCM is such a debilitating disease, investigation into possible therapeutic approaches to treat some of the causes of HCM- or at the very least provide palliative care for people affected by this condition- is of extreme importance.

Myh6 knockout as a therapy for HCM

HCM is an autosomal dominant disease and conventional treatments are ineffective.[5] Gene therapy is currently being investigated as a possible treatment option. Myh6 gene is a possible target for gene therapy.[5] Infected with adeno-associated vectors carrying the siRNA to silence the mutant Mhy6 gene, inhibited expression of R403Q myosin postponed development of HCM for 6 months. Without the dysfunctional myosin protein the heart functioned more efficiently and this prevents the development of myocyte hypertrophy as a compensatory mechanism. Not only was there an absence of HCM, but fibrosis and myocyte disorganization was greatly reduced in the knockout mice.[5] The proposed mechanism for this is the expression of a more normalized ratio of α-myosin chain to β-myosin chain proteins.[4] This enables proper assembly of myofibrils and thus, more organized sarcomeres.[4] It should be noted, however, that all of the mice in the study developed HCM after 11 months and that the gene therapy was only temporarily therapeutic.


  1. Tanigawa G, Jarcho JA, Kass S, Solomon SD, Vosberg HP, Seidman JG, Seidman CE (Oct 1990). "A molecular basis for familial hypertrophic cardiomyopathy: an alpha/beta cardiac myosin heavy chain hybrid gene". Cell 62 (5): 991–8. PMID 2144212. doi:10.1016/0092-8674(90)90273-H. 
  2. 2.0 2.1 2.2 "Entrez Gene: MYH6 myosin, heavy chain 6, cardiac muscle, alpha (cardiomyopathy, hypertrophic 1)". 
  3. 3.0 3.1 3.2 Tyska MJ, Hayes E, Giewat M, Seidman CE, Seidman JG, Warshaw DM (2000). "Single-molecule mechanics of R403Q cardiac myosin isolated from the mouse model of familial hypertrophic cardiomyopathy". Circ. Res. 86 (7): 737–44. PMID 10764406. doi:10.1161/01.res.86.7.737. 
  4. 4.0 4.1 4.2 4.3 4.4 4.5 Geisterfer-Lowrance AA, Kass S, Tanigawa G, Vosberg HP, McKenna W, Seidman CE, Seidman JG (1990). "A molecular basis for familial hypertrophic cardiomyopathy: a beta cardiac myosin heavy chain gene missense mutation". Cell 62 (5): 999–1006. PMID 1975517. doi:10.1016/0092-8674(90)90274-i. 
  5. 5.0 5.1 5.2 Jiang J, Wakimoto H, Seidman JG, Seidman CE (2013). "Allele-specific silencing of mutant Myh6 transcripts in mice suppresses hypertrophic cardiomyopathy". Science 342 (6154): 111–4. PMC 4100553. PMID 24092743. doi:10.1126/science.1236921. 

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