Myosin-7 (MYH7) (MYH7)

Cardiac β-myosin, primarily encoded by the MYH7 gene, is the fundamental motor protein responsible for generating the mechanical force required for heart contraction [6, 9, 16]. As a class II myosin and a mechanoenzyme, it utilizes ATP hydrolysis to drive the sliding of thick and thin filaments within the cardiac sarcomere [6, 9]. This protein is predominantly expressed in the human ventricles and slow-twitch skeletal muscle fibers, playing a critical role in maintaining cardiac output and systemic circulation [6, 8]. Mutations in the MYH7 gene are a major cause of inherited heart conditions, most notably hypertrophic cardiomyopathy (HCM), where they typically result in sarcomere hypercontractility and impaired diastolic relaxation [6, 11, 15]. These genetic variants can also lead to dilated cardiomyopathy (DCM) and various skeletal myopathies [8, 9]. Modern therapeutic strategies involve small-molecule allosteric modulators that directly bind to the myosin head to correct these functional imbalances [1, 16]. Inhibitors such as mavacamten and aficamten are used to stabilize the super-relaxed state of myosin, thereby reducing excessive cross-bridge formation in HCM [2, 4, 15]. Conversely, activators like omecamtiv mecarbil have been investigated to enhance the rate of phosphate release and improve systolic function in heart failure with reduced ejection fraction [3, 13]. Monitoring of patients on these therapies often involves tracking biomarkers like NT-proBNP and left ventricular ejection fraction to ensure safety and efficacy [11, 12, 15].

Other names

Cardiac β-myosinMyosin heavy chain 7Myosin heavy chain slow isoformMyHC-betaMHC-betaMYH7

Allosteric modulation of myosin ATPase activity; inhibitors (e.g., mavacamten) stabilize the super-relaxed (SRX) state to reduce hypercontractility, while activators (e.g., omecamtiv mecarbil) enhance phosphate release to increase systolic force [2, 3, 4, 13, 15].