Gene TPM1
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Also known as
Tropomyosin 1, Alpha-tropomyosin, CMH3, CMD1G, LVNC9Overview
TPM1 (Tropomyosin 1) encodes alpha-tropomyosin, a major component of the thin filament in cardiac and skeletal muscle. Tropomyosin is a coiled-coil protein that wraps around actin filaments in a helical fashion, with each tropomyosin molecule spanning seven actin monomers. In the absence of calcium, tropomyosin sterically blocks myosin-binding sites on actin, preventing muscle contraction. The troponin complex binds to tropomyosin, and when calcium binds to troponin C, the resulting conformational changes move tropomyosin to expose myosin-binding sites, allowing contraction. TPM1 is essential for the calcium-dependent regulation of muscle contraction and maintaining the structural integrity of the sarcomere.Mutations in TPM1 cause familial hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and left ventricular noncompaction (LVNC), all inherited in autosomal dominant patterns. TPM1 mutations account for approximately 3-5% of HCM cases and smaller percentages of DCM. These mutations typically alter the interaction between tropomyosin and either actin or the troponin complex, disrupting normal calcium-dependent regulation of contraction. Clinical presentations range from asymptomatic mutation carriers to severe heart failure, arrhythmias, and sudden cardiac death. Some TPM1 mutations are associated with particularly malignant phenotypes with early onset and high sudden death risk. Genetic testing enables early diagnosis, family screening, and implementation of preventive strategies including medications, lifestyle modifications, and consideration of implantable cardioverter-defibrillators in high-risk individuals.