ACTN3

Official Full Name

actinin alpha 3

Organism

Homo sapiens

GeneID

Background

This gene encodes a member of the alpha-actin binding protein gene family. The encoded protein is primarily expressed in skeletal muscle and functions as a structural component of sarcomeric Z line. This protein is involved in crosslinking actin containing thin filaments. An allelic polymorphism in this gene results in both coding and non-coding variants; the reference genome represents the coding allele. The non-functional allele of this gene is associated with elite athlete status. [provided by RefSeq, Apr 2024]

Synonyms

ACTN3D;

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Detailed Information

α-Actinin 3(ACTN3) is a structural protein of the Z-line of skeletal muscle fast muscle fibers that maintains the orderly alignment and normal contraction of muscle fibers by binding to actin in thin filaments. The ACTN3 gene is located at 11q13.1 and encodes α-Auxiliary 3 protein. There are four forms of existence in the α-actin family. ACTN1 and 4 are present in non-striated muscles and act as anchors for cell scaffolds. ACTN2 and 3 are present in skeletal muscle fibers, and ACTN2 is present in all types of skeletal muscle fibers. While ACTN3 is present only in fast muscle fibers, fast muscle fibers produce the shrinkage required for explosiveness. Recent studies have shown that ACTN3 polymorphisms may affect other motor-related variables, including training adaptation, post-exercise recovery, and exercise-related impairment.

ACTN3 Figure 1. A summary of the potential wider implications of ACTN3 genotype on outcomes from exercise. (Craig Pickring., et al. 2017)

ACTN3 Gene Polymorphism

Currently, studies on the ACTN3 gene polymorphism are focused on the exon 16 R577X polymorphism. The C-T polymorphism at this locus results in a change in the amino acid encoding position 577 from arginine (577R) to termination coding (577X), and when terminated, α-actinin-3 is deleted. The frequency of occurrence of the 577X allele varies from race to race, such as less than 10% in some African populations and 50% in Eurasian populations. The XX genotype of ACTN3 R577X is characterized by a complete absence of ACTN3, which is estimated to be 1.5 billion people worldwide. Deletion of ACTN3 does not cause any disease because ACTN2, which is 80% identical in structure to ACTN3, compensates for up-regulated expression. However, the expression of ACTN3 has a special effect on fast muscle fibers. Beginning with the Australian scholar Yang et al., many scholars and researchers in the field of sports science are concerned about whether the presence or absence of ACTN3 in the fast muscle fibers of the human body affects the quality of exercise and performance. In particular, the explosive quality, that is, whether the ACTN3 gene R577X polymorphism is associated with explosive quality.

ACTN3 and Athletic Ability

The earliest research on the association between ACTN3 R577X polymorphism and athletic performance of elite athletes was conducted with Caucasian athletes as subjects. As a result, it was found that the absence of α-actinin-3 (XX genotype) was significantly higher in the elite endurance athletes than in the healthy controls. In subsequent studies, some studies showed that the X allele or XX genotype was associated with outstanding endurance quality, while others did not. In contrast, the ACTN3 R577X polymorphism is more consistent with the findings associated with superior explosiveness. The study found that the frequency of XX genotype distribution of ACTN3R577X polymorphism was lower in elite explosive quality athletes than in elite endurance athletes and control populations. Since then, there have been many repetitive studies that have yielded significant results in different elite athletes (such as sprinters, long jumps, high jumps, throws) and weightlifters. Some studies have shown that the ACTN3 577XX genotype is distributed at a frequency of excellent explosive quality athletes and excellent endurance athletes, but there is no significant difference between the control population. Inconsistent findings may be related to sample size and ethnic differences.

The distribution frequency of ACTN3 577XX is also different among explosive athletes with different levels of exercise. If studies have found that the ACTN3 577XX genotype distribution frequency of short-distance swimmers in Taiwan's Olympic level is significantly lower than that of non-Olympic athletes. The ACTN3 R577X polymorphism is sometimes combined with other genetic polymorphisms to explore the preferred multi-gene combination that affects the explosive quality.

To further understand the effects of the ACTN3 R577X polymorphism on physiological and metabolic functions, the researchers established a mouse model of ACTN3 knockout. Compared with wild-type mice, ACTN3 knockout mice had a faster diameter of the fast muscle fibers, a decrease in muscle mass, a marked decrease in paw grip, and a marked increase in endurance. It can be seen that the absence of ACTN3 directly leads to a tendency of mouse muscle properties to transform into slow muscle fiber properties. Through anatomical analysis, it was found that the activity of anaerobic metabolic enzymes in the fast muscle fibers of mice decreased, and the activity of aerobic metabolic enzymes increased, but the distribution of muscle fiber types did not change. The activity of lactate dehydrogenase in the oxygen metabolism pathway is lowered, resulting in the insufficient conversion of pyruvic acid to lactic acid. A part of the aerobic metabolic pathway enters the tricarboxylic acid cycle; on the other hand, the activity of citrate synthase and succinate dehydrogenase in the aerobic metabolic pathway is increased, which further promotes the entry of pyruvic acid into the aerobic metabolism pathway. Then it will cause a decrease in anaerobic metabolism and an increase in aerobic capacity. A related study of ACTN3 knockout mice can roughly explain why the ACTN3 XX genotype has poorer burst quality and better endurance quality.

References:

Eynon, N., Hanson, E. D., Lucia, A., Houweling, P. J., Garton, F., & North, K. N., et al. (2013). Genes for elite power and sprint performance: actn3 leads the way. Sports Medicine, 43(9), 803-817.
Craig Pickring., John Kiely. (2017). Actn3: more than just a gene for speed. Frontiers in Physiology, 18 December 2017.
Pimenta, E. M., Coelho, D. B., Veneroso, C. E., Barros Coelho, E. J., Cruz, I. R., & Morandi, R. F., et al. (2013). Effect of actn3 gene on strength and endurance in soccer players. Journal of Strength & Conditioning Research, 27(12), 3286-3292.
Ruiz JR, Santiago C, Yvert T, et al. (2013). ACTN3 genotype in Spanish elite swimmers：No "heterozygous advantage". Scand J Med Sci Sports, 23(3) :162.
Mikami, E., Fuku, N., Murakami, H., Tsuchie, H., Takahashi, H., & Ohiwa, N., et al. (2014). Actn3 r577x genotype is associated with sprinting in elite japanese athletes. International Journal of Sports Medicine, 35(02), 172-177.

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