rs1815739

mixedMag 4.5

This is a stop gained variant in the ACTN3 gene.

Key Literature Trait Associations

Sprint / Power Athletic Performance

The ACTN3 R577X variant. Alpha-actinin-3 is expressed exclusively in fast-twitch (type II) muscle fibers responsible for explosive power and speed. The C allele (X) introduces a premature stop codon, preventing protein production. ~18% of people are XX and entirely alpha-actinin-3 deficient. TT (RR) individuals are over-represented among elite sprinters; CC (XX) may be better suited to endurance events.

Tharabenjasin P et al. “Association of the ACTN3 R577X (rs1815739) polymorphism with elite power sports: A meta-analysis.” Plos One (2019)
Allele C
OR 1.21
p 2.0e-3
Meta-analysis
multi-ancestry
Yang N et al. “ACTN3 genotype is associated with human elite athletic performance.” American Journal of Human Genetics 73(3):627-631 (2003)
Allele C
OR —
p 1.0e-3
Candidate gene study
Weyerstraß J et al. “Nine genetic polymorphisms associated with power athlete status - A Meta-Analysis.” Journal of Science and Medicine in Sport (2018)
Allele C
OR —
p —
N 19,852
Meta-analysis
multi-ancestry
Tamuno Alfred et al. “<i>ACTN3</i> genotype, athletic status, and life course physical capability: meta‐analysis of the published literature and findings from nine studies” Human Mutation (2011)
Allele C
OR —
p —
N 15,511
Meta-analysis
European
El Ouali EM et al. “A Systematic Review and Meta-analysis of the Association Between ACTN3 R577X Genotypes and Performance in Endurance Versus Power Athletes and Non-athletes.” Sports Medicine - Open (2024)
Allele C
OR 4.26
p 1.0e-5
N 14,541
Meta-analysis
multi-ancestry

Myostatin levels

rs1815739-C (R allele) is among the strongest genetic determinants of circulating myostatin (GDF8/GDF11) protein levels in plasma, identified in large-scale protein QTL studies. The R allele, which encodes functional alpha-actinin-3 in fast-twitch fibers, is associated with higher myostatin levels (p = 9×10⁻²⁹ for body composition/GDF8 measurement; p = 8×10⁻¹² for GDF11/8 measurement). This likely reflects a direct cis or trans regulatory connection between muscle fiber type composition and systemic myostatin signaling, a key regulator of muscle mass. The biological plausibility is strong as myostatin is produced in skeletal muscle and feeds back to regulate fiber hypertrophy.

Loya H et al. “A scalable variational inference approach for increased mixed-model association power.” Nature Genetics 57(2):461-468 (2025)
Allele C
OR —
β 11.130
p 9.0e-29
N 47,745
Large GWAS
European
Sun BB et al. “Genomic atlas of the human plasma proteome.” Nature 558(7708):73-79 (2018)
Allele C
OR —
β 0.170
p 8.0e-12
N 3,301
Large GWAS
European

Muscle mass

The C (R) allele of ACTN3 R577X is associated with preservation of muscle mass in community-dwelling older adults. In a Japanese cohort study, RR homozygotes had significantly lower odds of low muscle mass (sarcopenia criterion) compared to X-allele carriers (OR 0.39, p=0.013). This finding aligns with the known role of alpha-actinin-3 in fast-twitch fiber maintenance and structural integrity. However, the study was small (n=265) and no association was found with grip strength or walking speed, suggesting the effect is specific to muscle mass rather than broader functional measures.

Shiratsuchi D et al. “Association of alpha-actinin-3 genotype with muscle mass and physical function in community-dwelling older adults.” European Geriatric Medicine (2025)
Allele C
OR 0.39
p 1.3e-2
N 265
Candidate gene study
East Asian

Insomnia

A large genome-wide meta-analysis of over 2.3 million individuals identified rs1815739-T as a genome-wide significant risk locus for insomnia (p = 6×10⁻¹³, beta = 0.007). This association is notable because ACTN3 is a muscle-expressed gene, and the mechanism linking the T (stop-gain) allele to insomnia is not fully established — possible pathways include altered muscle metabolism, sleep microarchitecture changes, or pleiotropic effects through shared neural or metabolic pathways. The effect size is small, and the clinical significance of this finding for individual sleep health remains uncertain.

Watanabe K et al. “Genome-wide meta-analysis of insomnia prioritizes genes associated with metabolic and psychiatric pathways.” Nature Genetics 54(8):1125-1132 (2022)
Allele T
OR —
β 0.007 ±0.001
p 6.0e-13
N 2,365,010
Meta-analysisLarge GWAS
European

Sleep apnea

A multi-trait GWAS meta-analysis integrating sleep apnea and snoring phenotypes identified rs1815739 as a genome-wide significant locus (p = 2×10⁻⁸, beta = 0.019). The T allele, which eliminates alpha-actinin-3 expression, is associated with increased sleep apnea risk, though the biological mechanism remains unclear. Fast-twitch muscle fiber composition differences in upper airway musculature may contribute. The effect size is modest and the clinical implications for individual risk stratification are limited.

Campos AI et al. “Discovery of genomic loci associated with sleep apnea risk through multi-trait GWAS analysis with snoring.” Sleep (2023)
Allele T
OR —
β 0.019
p 2.0e-8
N 159,255
Large GWAS
European
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GWAS Catalog Trait Associations (5)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

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ClinVar annotation

Benign★☆☆☆
2 submitters10 publications

Sprinting performance; ACTININ, ALPHA-3 POLYMORPHISM; Actn3 deficiency; INCREASED COLD TOLERANCE; not specified

View on ClinVar →
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Research that mentions this SNP (2)

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Association of the matrix metalloproteinase 3 (MMP3) single nucleotide polymorphisms with tendinopathies: case-control study in high-level athletes
Case reportNina Briški et al.(2021)· International Orthopaedics

This is a Turkish-language personalized nutrigenetics and epigenetics coaching report for individual Mehmet Efe Yildirim (Report No. 1332, dated 2023-11-21). The report analyzes the individual's genetic polymorphisms related to nutritional metabolism, food sensitivities, detoxification pathways, and other health-related traits, providing personalized dietary and lifestyle recommendations based on cited scientific literature. This is a direct-to-consumer genetic test report, not a peer-reviewed research study.

Traits studied:Alcohol metabolismAnxiety and panic disorderCaffeine sensitivityCholine metabolismCircadian rhythmExercise performanceFolate metabolismFood allergiesGluten sensitivityHistamine sensitivityHomocysteinemiaInflammatory markersLactose intoleranceLiver healthMicrobiota metabolismNFE2L2 pathwayObesity and weight managementOmega-3 metabolismPhase I detoxificationPhase II glutathione transferasePlant sterols metabolismRiboflavin metabolismSelenium metabolismSleep qualityUGT metabolismVitamin A metabolismVitamin B12 metabolismVitamin B6 metabolismVitamin C metabolismVitamin D metabolismVitamin K metabolismZinc metabolism
PubMedDOIMetascience Observatory
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ACTN3 genotype, athletic status, and life course physical capability: meta‐analysis of the published literature and findings from nine studies
Meta-analysisN=17,835Tamuno Alfred et al.(2011)· Human Mutation

Meta-analysis of ACTN3 R577X (rs1815739) genotype and athletic status, plus analysis of 17,835 individuals from nine population-based studies on physical capability. The RR genotype is more common among sprint/power athletes compared with controls in Europeans (OR showed evidence for association), but no evidence supported the X allele being advantageous for endurance athleticism. No significant associations were found between R577X and grip strength (P=0.09 in males, P=0.90 in females), standing balance, timed get up and go, or chair rises in the general population.

Traits studied:Body mass indexChair risesEndurance athletic statusGrip strengthHeightPhysical activityPhysical capabilitySprint/power athletic statusStanding balanceTimed get up and goWaist-to-hip ratioWeight
PubMedDOIMetascience Observatory

Gene information from NCBI Gene. Variant classifications from ClinVar.

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