Key result
Pathogenic MYBPC3 variants drive hypertrophic cardiomyopathy through haploinsufficiency, opening avenues for targeted therapies.
Why the study?
Hypertrophic cardiomyopathy caused by MYBPC3 variants has highly variable clinical manifestations, and understanding its molecular mechanisms and genotype-phenotype relationships is essential to advance care, prompts this summary of MYBPC3 pathogenicity in HCM.
This review summarizes the molecular mechanisms of MYBPC3 pathogenic variants in hypertrophic cardiomyopathy and discusses emerging targeted therapies including cardiac myosin inhibitors like mavacamten and investigational gene therapies.
Answers are grounded in this paper and cite their sources.
Supports genotype-guided management in MYBPC3-related HCM, though novel gene therapies should not yet change practice; leaves open long-term clinical efficacy pending prospective trials.
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.
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Harris et al. (2026) conducted a review in Hypertrophic cardiomyopathy. MYBPC3 pathogenic variants was evaluated. Pathogenic MYBPC3 variants cause hypertrophic cardiomyopathy via haploinsufficiency and impaired protein quality control, targeted by myosin inhibitors and investigational gene therapies.
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