TNNT3

TNNT3, or troponin T type 3, is a gene that encodes the fast skeletal muscle isoform of troponin T, a component of the troponin complex that regulates contraction in striated muscle. In fast-twitch skeletal fibers, troponin T anchors the troponin complex to tropomyosin on the actin-containing thin filament, helping position the calcium-sensitive subunits for regulation of actin–myosin interaction.

Functionally, the troponin complex binds calcium through troponin C; when calcium levels rise, conformational changes in the complex relieve inhibition of actin–myosin interaction, enabling contraction. Troponin T’s anchoring role ensures proper alignment of the regulatory complex along the thin filament, and isoform differences influence regulatory properties in different fiber types.

TNNT3 is predominantly expressed in fast-twitch skeletal muscle, including limb and trunk muscles. Alternative splicing of TNNT3 generates multiple mRNA and protein isoforms, with tissue- and development-specific expression patterns.

Variants in TNNT3 have been linked to distal arthrogryposis and related congenital contracture disorders in some families. Most pathogenic changes are missense or splice-site variants that affect the interaction of troponin T with tropomyosin or other components, thereby altering calcium-regulated contraction. The gene is also studied in normal muscle physiology and disease models of skeletal muscle regulation.

The TNNT3-encoded protein binds tropomyosin and forms part of the troponin complex, interacting with troponin I and troponin C to regulate the transition of thin filaments between blocked and active states in response to calcium.