alphaactinin3

Alpha-actinin-3 is a cytoskeletal protein encoded by the ACTN3 gene in humans. It is predominantly expressed in type II fast-twitch skeletal muscle fibers and localizes to the Z-disc of the sarcomere, where it functions as a major actin-binding and crosslinking protein. By anchoring actin filaments and interacting with other Z-disc components such as titin, alpha-actinin-3 helps maintain the structural integrity of the muscle fiber during rapid and forceful contractions. The ACTN3 gene belongs to the alpha-actinin family, whose other members are expressed in various tissues and can partially compensate in some contexts.

A common genetic variation is a nonsense polymorphism, resulting in a premature stop codon (p.R577X; rs1815739). This variant can produce a nonfunctional protein, and individuals who are homozygous for the X allele (XX) lack detectable alpha-actinin-3 in fast fibers, whereas heterozygotes (RX) have partial expression. Allele frequencies vary among populations, and the XX genotype does not cause disease but is associated with differences in muscle function.

In the field of sports genetics, ACTN3 has been linked to sprint and power performance, with functional R allele carriers often showing advantages in high-velocity strength activities. Conversely, those with the XX genotype may exhibit a relative shift toward oxidative, slower-twitch muscle metabolism in some studies. Animal models lacking ACTN3 display reduced sprint capacity but can show enhanced oxidative properties in fast fibers, illustrating functional redundancy with other alpha-actinins.

Overall, alpha-actinin-3 is a muscle-specific structural component whose presence or absence influences muscle fiber function and athletic performance, rather than serving a direct disease-related role.