Gene "KCNN4"
Found 1 record
Gene information
Gene symbol:
KCNN4
See related:
Ensembl: ENSG00000104783, Gene ID: 3783
Additive variants :
Undetected
Genetic interaction partners
No data
Modifier statisitcs
Record:
1 
Disorder:
1 
Vriant:
1 
Reference:
1 
Effect type:
Pleiotropy(1)  
Modifier effect:
Altered intestinal secretion(1)  
Detail：
  • Variant 1:
    KCNN4:deletion*
    Gene:
    KCNN4
    Genomic location:
    dbSNP ID:
    Target disease:
    Cystic fibrosis(DOID_1485)
    Effect type:
    Pleiotropy 
    Modifier effect:
    Altered intestinal secretion 
    Evidence:
    Study on animal models 
    Effect:
    Kcnn4 is an intestinal CF modifier gene partially acting through a STAT6-dependent mechanism.
    Reference:
    PMID29915289
    Title:
    Kcnn4 is a modifier gene of intestinal cystic fibrosis preventing lethality in the Cftr-F508del mouse.
    Species studied:
    Mouse
    Abstract:
    Nearly 70% of cystic fibrosis (CF) patients bear the phenylalanine-508 deletion but disease severity differs greatly, andis not explained by the existence of different mutations in compound heterozygous. Studies demonstrated that genes other than CFTR relate to intestinal disease in humans and CF-mouse. Kcnn4, the gene encoding the calcium-activated potassium channel KCa3.1, important for intestinal secretion, is present in a locus linked with occurrence of intestinal CF-disease in mice and humans. We reasoned that it might be a CF-modifier gene and bred a CF-mouse with Kcnn4 silencing, finding that lethality was almost abolished. Silencing of Kcnn4 did not improve intestinal secretory functions, but rather corrected increased circulating TNF-α level and reduced intestinal mast cell increase. Given the importance of mast cells in intestinal disease additional double mutant CF-animals were tested, one lacking mast cells (C-kitW-sh/W-sh) and Stat6-/- to block IgE production. While mast cell depletion had no effect, silencing Stat6 significantly reduced lethality. Our results show that Kcnn4 is an intestinal CF modifier gene partially acting through a STAT6-dependent mechanism.