Myosin-binding protein C, cardiac-type (MYBPC3)

Myosin-binding protein C, cardiac-type (MYBPC3) is a critical structural and regulatory protein located within the A-band of the cardiac sarcomere, where it interacts with both myosin and actin (UniProt P12139). It functions as a molecular brake on the cross-bridge cycle, modulating the kinetics of muscle contraction and ensuring efficient cardiac relaxation (PubMed: 30135443). Mutations in the MYBPC3 gene are the most frequent genetic cause of hypertrophic cardiomyopathy (HCM), typically resulting in a state of haploinsufficiency where reduced protein levels lead to myofibrillar disarray and pathological cardiac remodeling (NCBI Gene: 4607). This deficiency manifests clinically as ventricular hypertrophy, diastolic dysfunction, and an increased risk of sudden cardiac death. Therapeutic development for this target focuses on gene replacement strategies, such as TN-201 and LX2020, which aim to restore functional MYBPC3 expression in cardiomyocytes using viral vectors (Tenaya Therapeutics; Lexeo Therapeutics). By addressing the underlying genetic deficiency, these therapies seek to normalize sarcomere function and potentially reverse the progression of HCM.

Other names

Cardiac myosin-binding protein CC-protein, cardiacMYBP-CMYBPC3

Gene replacement therapy utilizing adeno-associated virus (AAV) vectors to deliver a functional MYBPC3 transgene to cardiomyocytes, thereby restoring protein expression and sarcomere function.