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Myh7Edit

Myh7 is the gene that encodes the beta (β) heavy chain of the motor protein myosin, a central component of the thick filament in muscle cells. In humans, the product of this gene plays a pivotal role in the contraction of cardiac muscle and, to a lesser extent, in slow-twitch skeletal muscle. The beta-myosin heavy chain is a large, enzymatic protein that couples ATP hydrolysis to mechanical work, enabling the heart to pump blood and skeletal muscles to sustain posture and endurance activities. MYH7 is widely studied as a key player in both normal physiology and inherited muscle disease, and its study offers insight into how genetic variation can shape cardiac and skeletal muscle performance.

Structure and expression

The beta-myosin heavy chain is a major component of the thick filament within the sarcomere, the basic contractile unit of striated muscle. The protein consists of motor domains that bind actin and hydrolyze ATP, a neck region that acts as a lever to amplify small structural changes into large movements, and a tail that mediates filament assembly. The MYH7 gene product is a large molecular motor with an estimated mass of around 200 kDa, and it is evolutionarily conserved across vertebrates due to its essential role in muscle force generation. In humans, MYH7 is expressed predominantly in the ventricular myocardium, where it contributes to the slower, sustained contractile phenotype suited to continuous cardiac work, and in slow-twitch skeletal muscle fibers, where endurance-related movements rely on efficient, fatigue-resistant contraction. myosin cardiac muscle skeletal muscle

Function in muscle contraction

Within the sarcomere, beta-myosin heavy chain forms the thick filament backbone and provides the catalytic activity that powers contraction. The motor domain of the protein interacts with actin thin filaments, and the hydrolysis of ATP induces conformational changes that produce sliding of the filaments relative to one another. This process converts chemical energy into mechanical force, enabling the heart to generate stroke work and maintain systemic circulation. The relative predominance of MYH7 expression in ventricular tissue helps define the heart’s characteristic contractile kinetics, including slower contraction and relaxation dynamics compared with other myosin isoforms. In skeletal muscle, the beta-myosin heavy chain contributes to the endurance-oriented, slow-twitch fiber function. sarcomere actin ATPase beta-myosin heavy chain

Genetic variation and disease

Mutations in MYH7 are a major cause of inherited muscle disease and are among the most common genetic contributors to cardiomyopathy. The gene can harbor a variety of sequence changes, including missense, nonsense, frameshift, and splice-site variants, which can disrupt motor function, filament assembly, or regulation of contraction. The clinical consequences depend on the specific mutation and its effect on protein function, but several general patterns have emerged:

  • Hypertrophic cardiomyopathy (HCM): A substantial proportion of familial HCM cases are linked to MYH7 mutations. Patients typically exhibit thickened ventricular walls, diastolic dysfunction, and an increased risk of arrhythmias and heart failure. The disease reflects altered force generation and energetic inefficiency in the left ventricle. hypertrophic cardiomyopathy
  • Dilated cardiomyopathy (DCM): MYH7 variants can also cause dilated cardiomyopathy, characterized by thinning and dilation of the ventricular walls and reduced systolic function. This form of disease underscores how perturbations in myosin mechanics can weaken the heart’s pumping capacity. dilated cardiomyopathy
  • Skeletal myopathies: MYH7 mutations may present with skeletal muscle weakness, often in a distal or proximal pattern, depending on the allele. Conditions associated with MYH7 include Laing distal myopathy and myosin storage myopathy, which reflect disruptions in muscle fiber maintenance and protein handling. Laing distal myopathy myosin storage myopathy
  • Disease mechanisms: Many pathogenic MYH7 variants affect the motor domain or the mechanical lever arm, altering ATPase activity, actin interaction, or the timing of contraction. Some mutations likely have dominant-negative effects, while others lead to haploinsufficiency. The net result is impaired force production, abnormal energy utilization, or disrupted sarcomere integrity. genetics cardiomyopathy

In the clinical setting, MYH7 testing is part of genetic evaluation for cardiomyopathy and related myopathies, guiding family screening, prognosis, and, in some cases, treatment decisions. genetic testing family history

Clinical significance and management

The identification of MYH7 mutations informs risk assessment for relatives and can influence surveillance strategies. Cardiomyopathy patients with MYH7 variants may undergo regular imaging (echocardiography, cardiac MRI) and rhythm monitoring to detect hypertrophy, dilation, or arrhythmic risk. Management is tailored to the specific cardiomyopathy phenotype and may include medications to control blood pressure and heart rate, devices for rhythm control or heart failure management, and lifestyle considerations to reduce cardiac strain. Research continues into therapies that directly target myosin function to improve contractility and energy efficiency in affected individuals. Notably, targeted myosin inhibitors have emerged as a therapeutic strategy for certain forms of hypertrophic cardiomyopathy, illustrating how a detailed understanding of myosin biology can translate into clinical options. hypertrophic cardiomyopathy cardiac device heart failure mavacamten

Therapies that modulate myosin activity, such as mavacamten, illustrate the translational potential of MYH7 biology. By dampening excessive myosin activity in obstructive HCM, such agents aim to reduce left ventricular outflow tract obstruction and improve symptoms, guiding a new era of mechanism-based treatment for genetic heart disease. mavacamten cardiac myosin

Research and implications

Ongoing research in MYH7 covers basic questions about motor protein mechanics, the regulation of filament assembly, and how specific genetic changes translate into the clinical spectrum of disease. Comparative studies across vertebrates help illuminate how changes in MYH7 expression and structure influence cardiac performance and endurance. The gene remains a central example of how single-gene variation can have wide-ranging effects on heart and skeletal muscle health, and it continues to motivate advances in genetic testing, precision medicine, and targeted pharmacology. myosin sarcomere genetics

See also