Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
Symbol ACTN3 contributors: mct - updated : 24-03-2021
HGNC name actinin, alpha 3
HGNC id 165
corresponding disease(s) ACTN3D
Other morbid association(s)
TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
changes the overall protein composition of fast fiber Z-disks and alters their elastic properties, providing a mechanistic explanation for the loss of force generation and increased susceptibility to eccentric damage in ACTN3-deficient individuals
constitutional       loss of function
reduces the activity of glycogen phosphorylase and results in a fundamental shift toward more oxidative pathways of energy utilization
constitutional       loss of function
is underrepresented in elite sprint/power athletes and has been associated with reduced muscle mass and strength in humans
constitutional       loss of function
is accompanied by a shift toward a slower skeletal muscle phenotype, and deficient humans exhibit improved cold tolerance during cold-water immersion
changes in Ca2+ handling in the absence of ACTN3 are consistent with cold acclimatisation and thermogenesis, and offer an additional explanation for the positive selection of the ACTN3 577X null allele in populations living in cold environments during recent evolution
tumoral     --over  
adversely affected the survival of AML patients
  • to passive muscle stiffness
  • Variant & Polymorphism other
  • R577X associated to elite athlete status (overrepresentation of the 577XX genotype among elite endurance athletes)
  • R577X polymorphism of the ACTN3 has been associated
  • with passive muscle stiffness
  • ACTN3 R577X genotype is a modifier of clinical phenotype in DMD patients
  • ACTN3 R577X polymorphism could be a novel target for readthrough therapy, which may affect athletic and muscle performance
  • Candidate gene
    Therapy target
  • Actn3 KO mice showing reductions in muscle strength, increased endurance capacity, reduced fast fiber size, shifts in fast fiber metabolism toward oxidative metabolism
  • Actn3(-/-) mouse displays significantly reduced bone mass, with reduced cortical bone volume (-14p100) and trabecular number (-61p100) seen by microCT
  • deficiency in the Actn3 KO mouse results in a shift in fast-twitch fibres towards oxidative metabolism, which would be more "energy efficient" in famine, and beneficial to endurance performance
  • Actn3 KO mice were significantly lighter than their WT counterparts and therefore showed an improved cold tolerance after normalizing for body weight