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FLASH GENE

Symbol

ACTN3

contributors: mct - updated : 24-03-2021

HGNC name	actinin, alpha 3
HGNC id	165

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

ASSOCIATED DISORDERS

corresponding disease(s)

ACTN3D

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional         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 constitutional         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

Susceptibility

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

Marker

Therapy target

ANIMAL & CELL MODELS

	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