MYOM2, encoding endosarcomeric cytoskeletal M-protein, is a major component of the myofibrillar M-band of the sarcomere and a hub gene within sarcomere gene interactions. It likely plays a role in maintaining the structure and function of the sarcomere, which is crucial for muscle contraction. As such, it is important for normal cardiac and muscle function [2].

Mutations in MYOM2 have been identified in patients with Tetralogy of Fallot (TOF) and hypertrophic cardiomyopathy (HCM), who do not exhibit mutations in known disease genes. Patient-derived cardiomyocytes show myofibrillar disarray and reduced passive force. In a Drosophila model, partial loss of function or moderate cardiac knockdown of the ortholog of MYOM2 results in cardiac dilation, while more severe reduction causes a constricted phenotype and an increase in sarcomere myosin protein. Also, compound heterozygous combinations with the sarcomere gene Mhc exhibit synergistic genetic interactions, suggesting MYOM2 is a candidate gene for these heart diseases [2]. A rare heterozygous missense variant in MYOM2 was found to cause TOF in a Chinese family, further emphasizing its role in this condition [3]. Additionally, in rats, diacetylmorphine-induced abnormal cardiac rhythms are associated with regulation of MYOM2 protein expression via increased autophosphorylation of CaMKII [1].

In summary, MYOM2 is essential for maintaining robust heart function, especially in relation to sarcomere structure and function. Studies in model organisms like Drosophila and observations in patients with heart diseases such as TOF and HCM, as well as in rats with drug-induced cardiac issues, highlight the significance of MYOM2 in cardiac-related biological processes and disease conditions.

References:

1. Ji, Min, Su, Liping, Liu, Li, Ma, Lijuan, Pu, Hongwei. 2023. CaMKII regulates the proteins TPM1 and MYOM2 and promotes diacetylmorphine-induced abnormal cardiac rhythms. In Scientific reports, 13, 5827. doi:10.1038/s41598-023-32941-6. https://pubmed.ncbi.nlm.nih.gov/37037889/

2. Auxerre-Plantié, Emilie, Nielsen, Tanja, Grunert, Marcel, Vogler, Georg, Sperling, Silke R. 2020. Identification of MYOM2 as a candidate gene in hypertrophic cardiomyopathy and Tetralogy of Fallot, and its functional evaluation in the Drosophila heart. In Disease models & mechanisms, 13, . doi:10.1242/dmm.045377. https://pubmed.ncbi.nlm.nih.gov/33033063/

3. Wang, Jing, Wang, Chunyan, Xie, Haiyang, Pi, Mingan, Gong, Li. 2022. Case Report: Tetralogy of Fallot in a Chinese Family Caused by a Novel Missense Variant of MYOM2. In Frontiers in cardiovascular medicine, 9, 863650. doi:10.3389/fcvm.2022.863650. https://pubmed.ncbi.nlm.nih.gov/35872890/