Journal article

Is evolutionary loss our gain? The role of ACTN3 p.Arg577Ter (R577X) genotype in athletic performance, ageing, and disease

Peter J Houweling, Ioannis D Papadimitriou, Jane T Seto, Laura M Perez, Juan Del Coso, Kathryn N North, Alejandro Lucia, Nir Eynon

HUMAN MUTATION | WILEY | Published : 2018


A common null polymorphism in the ACTN3 gene (rs1815739:C>T) results in replacement of an arginine (R) with a premature stop codon (X) at amino acid 577 in the fast muscle protein α-actinin-3. The ACTN3 p.Arg577Ter allele (aka p.R577* or R577X) has undergone positive selection, with an increase in the X allele frequency as modern humans migrated out of Africa into the colder, less species-rich Eurasian climates suggesting that the absence of α-actinin-3 may be beneficial in these conditions. Approximately 1.5 billion people worldwide are completely deficient in α-actinin-3. While the absence of α-actinin-3 influences skeletal muscle function and metabolism this does not result in overt muscl..

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Awarded by Australian Research Council Discovery Early Career Research Award

Awarded by National Health & Medical Research Council

Awarded by HHMRC Project

Funding Acknowledgements

Australian Research Council Discovery Early Career Research Award, Award/Grant number: ARC DECRA DE#140100864; National Health & Medical Research Council. Award/Grant number: NHMRC CDF#APP1140644; and HHMRC Project, Award/Grant number:#APP 1130215.