Gene "CNOT3"
Found 2 records
Gene information
Gene symbol:
CNOT3
See related:
Ensembl: ENSG00000274616, Gene ID: 4849
Additive variants :
Undetected
Genetic interaction partners
No data
Modifier statisitcs
Record:
2 
Disorder:
2 
Vriant:
2 
Reference:
2 
Effect type:
Penetrance(2)  
Modifier effect:
Altered incidence(2)  
Details：
  • Variant 1:
    CNOT3:rs36643
    Gene:
    CNOT3
    Genomic location:
    dbSNP ID:
    rs36643
    Target disease:
    Long QT Syndrome(DOID_2843)
    Effect type:
    Penetrance 
    Modifier effect:
    Altered incidence 
    Evidence:
    From review article 
    Effect:
    Protective effect
    Reference:
    PMID23856471
    Title:
    Identification of a KCNQ1 polymorphism acting as a protective modifier against arrhythmic risk in long-QT syndrome.
    Species studied:
    Human
    Abstract:
    Long-QT syndrome (LQTS) is characterized by such striking clinical heterogeneity that, even among family members carrying the same mutation, clinical outcome can range between sudden death and no symptoms. We investigated the role of genetic variants as modifiers of risk for cardiac events in patients with LQTS.
  • Variant 2:
    CNOT3:c.*1582A>G
    Gene:
    CNOT3
    Genomic location:
    chr19:54657877
    dbSNP ID:
    rs4806718
    Target disease:
    Cone-Rod Dystrophy(DOID_0050572)
    Effect type:
    Penetrance 
    Modifier effect:
    Altered incidence 
    Evidence:
    Pedigree analysis 
    Effect:
    Reduced incidence
    Reference:
    PMID23144630
    Title:
    CNOT3 is a modifier of PRPF31 mutations in retinitis pigmentosa with incomplete penetrance.
    Species studied:
    Human
    Abstract:
    Heterozygous mutations in the PRPF31 gene cause autosomal dominant retinitis pigmentosa (adRP), a hereditary disorder leading to progressive blindness. In some cases, such mutations display incomplete penetrance, implying that certain carriers develop retinal degeneration while others have no symptoms at all. Asymptomatic carriers are protected from the disease by a higher than average expression of the PRPF31 allele that is not mutated, mainly through the action of an unknown modifier gene mapping to chromosome 19q13.4. We investigated a large family with adRP segregating an 11-bp deletion in PRPF31. The analysis of cell lines derived from asymptomatic and affected individuals revealed that the expression of only one gene among a number of candidates within the 19q13.4 interval significantly correlated with that of PRPF31, both at the mRNA and protein levels, and according to an inverse relationship. This gene was CNOT3, encoding a subunit of the Ccr4-not transcription complex. In cultured cells, siRNA-mediated silencing of CNOT3 provoked an increase in PRPF31 expression, confirming a repressive nature of CNOT3 on PRPF31. Furthermore, chromatin immunoprecipitation revealed that CNOT3 directly binds to a specific PRPF31 promoter sequence, while next-generation sequencing of the CNOT3 genomic region indicated that its variable expression is associated with a common intronic SNP. In conclusion, we identify CNOT3 as the main modifier gene determining penetrance of PRPF31 mutations, via a mechanism of transcriptional repression. In asymptomatic carriers CNOT3 is expressed at low levels, allowing higher amounts of wild-type PRPF31 transcripts to be produced and preventing manifestation of retinal degeneration.