How are ACTN3 and fatigue related?

The relationship between ACTN3 and fatigue is not clearly established in the scientific literature. ACTN3 encodes α-actinin-3, a protein predominantly expressed in fast-twitch (type II) muscle fibers. A common nonsense variant (R577X) results in complete deficiency of this protein in about 18 % of the global population. Mechanistically, the lack of α-actinin-3 may shift muscle fiber composition toward slower fibers, potentially improving fatigue resistance during endurance activities. Some studies have associated the X‑allele with better endurance performance and reduced muscle damage after exercise. However, evidence for a direct effect on perceived fatigue or recovery in everyday life is weak. Most research focuses on athletic performance rather than general fatigue. Effect sizes are small and findings are not always replicated. For the average person, ACTN3 genotype likely has no noticeable impact on fatigue. The provided context contains no specific information on ACTN3 and fatigue. This answer is based on general physiological knowledge. Evidence level: mechanistic. Caveat: No clinical recommendation can be derived.