The Role of MYBPC3 in Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is an inherited condition and one of the leading causes of sudden cardiac death in young individuals. It is primarily caused by the inheritance of pathogenic variants in sarcomere genes, including MYBPC3, encoding cardiac myosin-binding protein C. Genetic variants, often truncating, disrupt sarcomere structure and function via haploinsufficiency, impaired protein quality control, and less commonly, dominant-negative effects. The clinical manifestation of the disease is highly variable due to incomplete penetrance, genetic modifiers, and environmental factors. Recent advances include cardiac myosin inhibitors such as Mavacamten, while gene therapies targeting MYBPC3 remain under investigation. These approaches aim to address the molecular mechanisms of HCM alongside established symptomatic treatments. Understanding genotype–phenotype relationships, molecular mechanisms and the use of diverse population groups is essential to revolutionize HCM care. We summarize the role of MYBPC3 in pathogenicity in HCM.