Gene TNNI3
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Also known as
Troponin I3, Cardiac, cTnI, CMH7, RCM1, CMD2AOverview
TNNI3 (Troponin I3) encodes cardiac troponin I, the inhibitory subunit of the troponin complex specific to cardiac muscle. Troponin I binds to actin and tropomyosin in the absence of calcium, preventing muscle contraction during diastole. When calcium binds to troponin C during systole, conformational changes release troponin I's inhibition, allowing actin-myosin cross-bridge formation and muscle contraction. Cardiac troponin I is also subject to phosphorylation by protein kinase A during beta-adrenergic stimulation, which modulates myofilament calcium sensitivity and contributes to enhanced relaxation during increased heart rate. This protein is highly specific to cardiac tissue and is widely used as a biomarker for myocardial injury in clinical practice.Mutations in TNNI3 cause familial hypertrophic cardiomyopathy (HCM) and restrictive cardiomyopathy (RCM), both inherited in autosomal dominant patterns. These mutations typically alter the calcium sensitivity of the myofilament or affect the regulation of contraction-relaxation dynamics. HCM-associated mutations often increase calcium sensitivity, leading to hypercontractility, while some mutations cause restrictive physiology with impaired diastolic function. Clinical presentations range from asymptomatic carriers to severe heart failure and sudden cardiac death. TNNI3 mutations account for approximately 5% of HCM cases. Genetic testing allows for early identification of at-risk family members, implementation of surveillance protocols, and informed reproductive counseling.