Gene "PLN"
Found 3 records
Gene information
Gene symbol:
PLN
See related:
Ensembl: ENSG00000198523, Gene ID: 5350
Additive variants :
Undetected
Genetic interaction partners
No data
Modifier statisitcs
Record:
3 
Disorder:
2 
Vriant:
3 
Reference:
2 
Effect type:
Expressivity(2) ,Penetrance(1)  
Modifier effect:
Altered contractility and functional deterioration in heart failure(1) ,Altered incidence(1) ,Risk factor(1)  
Details：
  • Variant 1:
    PLN:rs77186188
    Gene:
    PLN
    Genomic location:
    dbSNP ID:
    rs77186188
    Target disease:
    Dilated Cardiomyopathy(DOID_12930)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered contractility and functional deterioration in heart failure 
    Evidence:
    Gene activity study 
    Effect:
    the g.203A>C genetic variant in the human PLN promoter may contribute to depressed contractility and accelerate functional deterioration in heart failure.
    Reference:
    PMID18241046
    Title:
    A human phospholamban promoter polymorphism in dilated cardiomyopathy alters transcriptional regulation by glucocorticoids
    Species studied:
    Human
    Abstract:
    Depressed calcium handling by the sarcoplasmic reticulum (SR) Ca-ATPase and its regulator phospholamban (PLN) is a key characteristic of human and experimental heart failure. Accumulating evidence indicates that increases in the relative levels of PLN to Ca-ATPase in failing hearts and resulting inhibition of Ca sequestration during diastole, impairs contractility. Here, we identified a genetic variant in the PLN promoter region, which increases its expression and may serve as a genetic modifier in dilated cardiomyopathy (DCM). The variant AF177763.1:g.203A>C (at position -36 bp relative to the PLN transcriptional start site) was found only in the heterozygous form in 1 out of 296 normal subjects and in 22 out of 381 cardiomyopathy patients (heart failure at age of 18-44 years, ejection fraction=22+/-9%). In vitro analysis, using luciferase as a reporter gene in rat neonatal cardiomyocytes, indicated that the PLN-variant increased activity by 24% compared to the wild type. Furthermore, the g.203A>C substitution altered the specific sequence of the steroid receptor for the glucocorticoid nuclear receptor (GR)/transcription factor in the PLN promoter, resulting in enhanced binding to the mutated DNA site. These findings suggest that the g.203A>C genetic variant in the human PLN promoter may contribute to depressed contractility and accelerate functional deterioration in heart failure.
  • Variant 2:
    PLN:rs12210810
    Gene:
    PLN
    Genomic location:
    dbSNP ID:
    rs12210810
    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 3:
    PLN:rs11970286
    Gene:
    PLN
    Genomic location:
    dbSNP ID:
    rs11970286
    Target disease:
    Long QT Syndrome(DOID_2843)
    Effect type:
    Expressivity 
    Modifier effect:
    Risk factor 
    Evidence:
    From review article 
    Effect:
    Risk factor
    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.