Gene "ATXN2"
Found 2 records
Gene information
Gene symbol:
ATXN2
See related:
Ensembl: ENSG00000204842, Gene ID: 6311
Additive variants :
Detected
Genetic interaction partners
No data
Modifier statisitcs
Record:
2 
Disorder:
2 
Vriant:
2 
Reference:
2 
Effect type:
Expressivity(2)  
Modifier effect:
Risk factor(1) ,Risk of respiratory failure or death(1)  
Details：
  • Variant 1:
    ATXN2:variant
    Gene:
    ATXN2
    Genomic location:
    dbSNP ID:
    Target disease:
    Alzheimer's Disease(DOID_10652)
    Effect type:
    Expressivity 
    Modifier effect:
    Risk factor 
    Evidence:
    P<0.05 
    Effect:
    Intermediate repeat lengths in ATXN2 might modify the disease phenotype of C9ORF72 expansion carriers.
    Reference:
    PMID24866401
    Title:
    Ataxin-2 as potential disease modifier in C9ORF72 expansion carriers.
    Species studied:
    Human
    Abstract:
    Repeat expansions in chromosome 9 open reading frame 72 (C9ORF72) are an important cause of both motor neuron disease (MND) and frontotemporal dementia (FTD). Currently, little is known about factors that could account for the phenotypic heterogeneity detected in C9ORF72 expansion carriers. In this study, we investigated 4 genes that could represent genetic modifiers: ataxin-2 (ATXN2), non-imprinted in Prader-Willi/Angelman syndrome 1 (NIPA1), survival motor neuron 1 (SMN1), and survival motor neuron 2 (SMN2). Assessment of these genes, in a unique cohort of 331 C9ORF72 expansion carriers and 376 control subjects, revealed that intermediate repeat lengths in ATXN2 possibly act as disease modifier in C9ORF72 expansion carriers; no evidence was provided for a potential role of NIPA1, SMN1, or SMN2. The effects of intermediate ATXN2 repeats were most profound in probands with MND or FTD/MND (2.1% vs. 0% in control subjects, p = 0.013), whereas the frequency in probands with FTD was identical to control subjects. Though intermediate ATXN2 repeats were already known to be associated with MND risk, previous reports did not focus on individuals with clear pathogenic mutations, such as repeat expansions in C9ORF72. Based on our present findings, we postulate that intermediate ATXN2 repeat lengths may render C9ORF72 expansion carriers more susceptible to the development of MND; further studies are needed, however, to validate our findings.
  • Variant 2:
    ATXN2:rs201755263
    Gene:
    ATXN2
    Genomic location:
    dbSNP ID:
    rs201755263
    Target disease:
    Amyotrophic Lateral Sclerosis(DOID_332)
    Effect type:
    Expressivity 
    Modifier effect:
    Risk of respiratory failure or death 
    Evidence:
    After adjusting forother factors, each additional rare variant increased the risk of respiratory failure or death by 60% (p=0.0098). 
    Effect:
    The presence of the rare variant was associated with the risk of ALS
    Reference:
    PMID28709720
    Title:
    Burden of rare variants in ALS genes influences survival in familial and sporadic ALS.
    Species studied:
    Human
    Abstract:
    Genetic variants are implicated in the development of amyotrophic lateral sclerosis (ALS), but it is unclear whether the burden of rare variants in ALS genes has an effect on survival. We performed whole genome sequencing on 8 familial ALS (FALS) patients with superoxide dismutase 1 (SOD1) mutation and whole exome sequencing on 46 sporadic ALS (SALS) patients living in Hong Kong and found that 67% had at least 1 rare variant in the exons of 40 ALS genes; 22% had 2 or more. Patients with 2 or more rare variants had lower probability of survival than patients with 0 or 1 variant (p = 0.001). After adjusting for other factors, each additional rare variant increased the risk of respiratory failure or death by 60% (p = 0.0098). The presence of the rare variant was associated with the risk of ALS (Odds ratio 1.91, 95% confidence interval 1.03-3.61, p = 0.03), and ALS patients had higher rare variant burden than controls (MB, p = 0.004). Our findings support an oligogenic basis with the burden of rare variants affecting the development and survival of ALS.