Gene "ACTN3"
Found 1 record
Gene information
Gene symbol:
ACTN3
See related:
Ensembl: ENSG00000248746, Gene ID: 89
Additive variants :
Undetected
Genetic interaction partners
No data
Modifier statisitcs
Record:
1 
Disorder:
1 
Vriant:
1 
Reference:
1 
Effect type:
Penetrance(1)  
Modifier effect:
Altered incidence(1)  
Detail：
  • Variant 1:
    ACTN3:c.1729C>T(p.Arg577*)
    Gene:
    ACTN3
    Genomic location:
    dbSNP ID:
    rs1815739
    Target disease:
    Duchenne Muscular Dystrophy(DOID_11723)
    Effect type:
    Penetrance 
    Modifier effect:
    Altered incidence 
    Evidence:
    Study on animal models 
    Effect:
    The α-actinin-3 deficiency triggers an increase in oxidative muscle metabolism through activation of calcineurin, which likely confers the protective effect. ACTN3 R577X genotype is a modifier of clinical phenotype in DMD patients.
    Reference:
    PMID28139640
    Title:
    Evidence for ACTN3 as a genetic modifier of Duchenne muscular dystrophy.
    Species studied:
    Human
    Abstract:
    Duchenne muscular dystrophy (DMD) is characterized by muscle degeneration and progressive weakness. There is considerable inter-patient variability in disease onset and progression, which can confound the results of clinical trials. Here we show that a common null polymorphism (R577X) in ACTN3 results in significantly reduced muscle strength and a longer 10m walk test time in young, ambulant patients with DMD; both of which are primary outcome measures in clinical trials. We have developed a double knockout mouse model, which also shows reduced muscle strength, but is protected from stretch-induced eccentric damage with age. This suggests that α-actinin-3 deficiency reduces muscle performance at baseline, but ameliorates the progression of dystrophic pathology. Mechanistically, we show that α-actinin-3 deficiency triggers an increase in oxidative muscle metabolism through activation of calcineurin, which likely confers the protective effect. Our studies suggest that ACTN3 R577X genotype is a modifier of clinical phenotype in DMD patients.