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rs1815739

From SNPedia

muscle performance
Orientationplus
Stabilizedplus
Geno Mag Summary
(C;C) 2.2 Better performing muscles. Likely sprinter.
(C;T) 2.1 Mix of muscle types. Likely sprinter.
(T;T) 2.2 Impaired muscle performance. Likely endurance athlete.
ReferenceGRCh38 38.1/141
Chromosome11
Position66560624
GeneACTN3
is asnp
is mentioned by
dbSNPrs1815739
dbSNP (classic)rs1815739
ClinGenrs1815739
ebirs1815739
HLIrs1815739
Exacrs1815739
Gnomadrs1815739
Varsomers1815739
LitVarrs1815739
Maprs1815739
PheGenIrs1815739
Biobankrs1815739
1000 genomesrs1815739
hgdprs1815739
ensemblrs1815739
geneviewrs1815739
scholarrs1815739
googlers1815739
pharmgkbrs1815739
gwascentralrs1815739
openSNPrs1815739
23andMers1815739
SNPshotrs1815739
SNPdbers1815739
MSV3drs1815739
GWAS Ctlgrs1815739
Merged fromRs2228325
GMAF0.3742
Max Magnitude2.2
? (C;C) (C;T) (T;T) 28


This SNP, in the ACTN3 gene, encodes a premature stop codon in a muscle protein called alpha-actinin-3. The polymorphism alters position 577 of the alpha-actinin-3 protein. In publications the (C;C) genotype is often called RR, whereas the (T;T) genotype is often called XX.


According to [PMID 18043716OA-icon.png] (T;T) is under-represented in elite strength athletes, consistent with previous reports indicating that alpha-actinin-3 deficiency appears to impair muscle performance. However in 2016 [PMID 26824906OA-icon.png] failed to replicate casting some doubt.

The most common nucleotide at this position, (C), encodes an arginine (amino acid code R), the alternative T allele encodes a stop codon (X). Hence, the SNP is referred to as R577X, with homozygotes being either RR or XX and heterozygotes being RX. XX individuals completely lack the expression of alpha-actinin-3.

One of the earliest report studying a relatively small number of Australian elite (i.e. ~Olympic) athletes found that, at least in females, the R allele (ie rs1815739(C)) is associated with sprinters, while the X allele (rs1815739(T)) is associated with endurance athletes. No female or Olympic-level sprinters were XX homozygotes (rs1815739(T;T)). The association tended the same way but was statistically weaker in males. [PMID 12879365OA-icon.png]. There have been several subsequent studies, but few with large sample sizes and thus few with much statistical power. An example of a typical study: no increase in endurance ability was associated with the X allele in elite male cyclists. [PMID 16612741]

An extensive blog post from one of the original authors of this research.

One paper has found that the X allele profile of centenarians resembles that of world-class elite endurance athletes. [PMID 21407828OA-icon.png]

This is one of the SNPs reported by NutraHacker.

OMIM102574
Desc
Variant0001
Relatedalso


ClinVar
Risk Rs1815739(C;C)
Alt Rs1815739(C;C)
Reference Rs1815739(T;T)
Significance Other
Disease ACTININ ACTN3 deficiency Sprinting performance
Variation info
Gene ACTN3
CLNDBN ACTININ, ALPHA-3 POLYMORPHISM ACTN3 deficiency Sprinting performance
Reversed 0
HGVS NC_000011.9:g.66328095T\x3d
CLNSRC OMIM Allelic Variant
CLNACC RCV000019974.2, RCV000019975.27, RCV000019976.27,



[PMID 18852891OA-icon.png] Distribution and effects of nonsense polymorphisms in human genes.

[PMID 19237423OA-icon.png] Is there an optimum endurance polygenic profile?

[PMID 19544227] ACTN3 R577X polymorphism and Israeli top-level athletes.

[PMID 20005538] Is the interaction between HIF1A P582S and ACTN3 R577X determinant for power/sprint performance?

[PMID 20561285] ACTN3 R577X polymorphism does not influence explosive leg muscle power in elite volleyball players.

[PMID 20585627OA-icon.png] Web-based, participant-driven studies yield novel genetic associations for common traits.

[PMID 20845221] ACTN3 R577X and other polymorphisms are not associated with elite endurance athlete status in the Genathlete study.

[PMID 20936592] Association between the ACTN3 R577X polymorphism and female endurance athletes in China.

[PMID 21407828OA-icon.png] Are 'endurance' alleles 'survival' alleles? Insights from the ACTN3 R577X polymorphism.

[PMID 21542061OA-icon.png] ACTN3 genotype, athletic status, and life course physical capability: meta-analysis of the published literature and findings from nine studies.

[PMID 22224919] ACTN3 R577X polymorphism and performance phenotypes in young Chinese male soldiers.



[PMID 22891846] Human alpha-actinin-3 genotype association with exercise-induced muscle damage and the repeated-bout effect.


[PMID 25761735] The ACTN3 R577X genotype is associated with muscle function in a Japanese population


[PMID 26324221] ACTN3 R577X genotype and athletic performance in a large cohort of Japanese athletes