TNNT2

TNNT2, or troponin T type 2, is a human gene that encodes the cardiac isoform of troponin T, a component of the troponin complex that regulates muscle contraction in striated muscle. In the heart, troponin T works with troponin I and troponin C to control the interaction of actin and myosin in response to intracellular calcium. The TNNT2 gene is located on chromosome 1 (1q32.1) and undergoes alternative splicing to produce cardiac-specific isoforms, distinguishing it from the skeletal troponin T genes TNNT1 (slow skeletal) and TNNT3 (fast skeletal).

The cardiac troponin T protein binds to tropomyosin along the thin filament and helps position the inhibitory region of troponin I. When Ca2+ rises, conformational changes in the troponin complex relieve inhibition and allow actin–myosin cross-bridge cycling, enabling coordinated cardiac contraction. The cardiac isoforms are expressed in atrial and ventricular myocardium and contribute to the regulation of both systolic and diastolic function.

Mutations in TNNT2 are a major cause of inherited cardiomyopathies. Pathogenic variants are commonly associated with familial hypertrophic cardiomyopathy (HCM) and can also be found in dilated cardiomyopathy (DCM). These mutations are typically inherited in an autosomal dominant manner and can lead to altered calcium sensitivity of the myofilaments or disruptions in TnT–tropomyosin interactions, resulting in abnormal contractile performance, energetic inefficiency, and an increased risk of arrhythmias. Phenotypes show variable penetrance and expressivity.

Genetic testing panels for inherited cardiomyopathies frequently include TNNT2. Research uses cellular and animal models to study how specific mutations affect calcium handling and contractility, aiming to clarify mechanisms and guide potential therapies.

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