MYH9 gene

The MYH9 gene (MYH9 stands for: Myosin Heavy Chain 9) is a protein-coding gene located on chromosome 22q12.3. The associated signaling pathways include semaphorin interactions and the regulation of actin dynamics. Gene Ontology (GO) annotations for this gene include RNA binding and protein homodimerization activity. An important paralog of this gene is MYH10.

The MYH9 gene encodes a conventional non-muscle myosin (this protein should not be confused with the unconventional myosin-9a or 9b (MYO9A or MYO9B)).

The encoded protein is a myosin IIA heavy chain containing an IQ domain and a myosin head-like domain that is involved in several important functions, including cytokinesis, cell motility and maintenance of cell shape.

Myosins are a large family of motor proteins that share the common features of ATP hydrolysis (ATPase enzyme activity), actin binding and the potential for kinetic energy transfer. Originally isolated from muscle cells, it is known that almost all eukaryotic cells contain myosins.

The encoded MYH9 protein is a cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping. It promotes cell motility in conjunction with S100A4 (Kunishima S et al. (2010). Plays an important role during cell spreading in cytoskeletal reorganization, formation of focal contacts (at the edges but not in the central part of spreading cells) and lamellipodia retraction; this function is mechanistically antagonized by MYH10 (Betapudi V 2010).

Microbial infections: Acts as a receptor for herpes simplex virus 1/HHV-1 envelope glycoprotein B.

MYH9-related disease (MYH9-RD) is an autosomal dominant disorder caused by mutations in the MYH9 gene, which encodes non-muscle myosin heavy chain (NMMHC)-IIA. MYH9-RD has a complex phenotype that includes congenital features such as thrombocytopenia and non-congenital manifestations such as sensorineural hearing loss (SNHL), nephropathy, cataract and liver abnormalities. The disease is caused by a limited number of mutations affecting different regions of the NMMHC IIA protein. SNHL is the most common non-congenital manifestation of MYH9-RD.

Defects in the MYH9 gene are also associated with Epstein syndrome, Alport syndrome with macrothrombocytopenia, Sebastian syndrome, Fechtner syndrome and macrothrombocytopenia with progressive sensorineural deafness.

1. Betapudi V (2010) Myosin II motor proteins with different functions determine the fate of lamellipodia extension during cell spreading. PLoS One 5:e8560
2. Fostier W et al.(2023) Squamous cell carcinoma and MYH9-associated elastin aggregation (MALTA) syndrome. Clin Exp Dermatol 49:105-107.
3. Fewings E et al. (2019) Malta (MYH9 Associated Elastin Aggregation) Syndrome: Germline Variants in MYH9 Cause Rare Sweat Duct Proliferations and Irregular Elastin Aggregations. J Invest Dermatol 139:2238-2241.e6.
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6. Kunishima S et al. (2010) Advances in the understanding of MYH9 disorders. Curr Opin Hematol 17:405-410.