tnni

TNNI is a gene family that encodes the I subunit of the troponin complex, a regulatory component of the contractile apparatus in striated muscle. In humans, three main genes generate tissue-specific isoforms: TNNI1 encodes slow skeletal troponin I, TNNI2 encodes fast skeletal troponin I, and TNNI3 encodes cardiac troponin I. These isoforms differ in their amino-terminal regions and regulatory properties, reflecting the distinct functional demands of skeletal and cardiac muscle.

Troponin I forms part of the troponin complex, together with troponin T and troponin C, on the actin-containing thin filament. In the absence of Ca2+, TnI inhibits actin–myosin ATPase activity, stabilizing the inhibited state. Upon Ca2+ binding to troponin C, conformational changes relieve this inhibition, enabling cross-bridge cycling and muscle contraction. The skeletal and cardiac isoforms show differences in calcium sensitivity and regulatory kinetics, aligning with the physiological requirements of their respective muscle types.

Expression patterns are developmentally regulated. Cardiac TnI is the predominant isoform in mature heart muscle, while skeletal muscles express the corresponding TNNI isoforms according to fiber type and developmental stage. Post-translational modifications, particularly phosphorylation of cardiac TnI by protein kinase A, modulate calcium sensitivity and relaxation kinetics, contributing to the heart’s response to adrenergic stimulation.

Clinical relevance: Cardiac troponin I, encoded by TNNI3, is a widely used biomarker of myocardial injury. Mutations in TNNI3 have been linked to familial cardiomyopathies, and rare variants in TNNI1 or TNNI2 have been associated with skeletal muscle disorders. Research on TNNI isoforms informs understanding of muscle physiology and related diseases.