PhenoModifier-Variant Detail

Variant "DCTN4:c.809A>G(p.Tyr263Cys)"

Search results: 2 records

Variant information

Gene:

DCTN4

Variant:

DCTN4:c.809A>G(p.Tyr263Cys)

Genomic location:

chr5:150110239(hg19)

HGVS:

SO Term	RefSeq
protein_coding	NM_001135643.1:c.809A>G(p.Tyr270Cys)
protein_coding	NM_016221.3:c.788A>G(p.Tyr263Cys)
protein_coding	NM_001135644.1:c.617A>G(p.Tyr206Cys)

dbSNP ID:

rs35772018

GWAS trait:

lung adenocarcinoma

Modifier statisitcs

Record:

2

Disorder:

1

Reference:

2

Effect type:

Expressivity(2)

Modifier effect:

Altered onset time of P. aeruginosa airway infection(1) ,Altered response to pulmonary infection with Pa(1)

Details：

Target disease:

Cystic fibrosis (DOID_1485)

Effect type:

Expressivity

Modifier effect:

Altered onset time of P. aeruginosa airway infection

Evidence:

P<0.05

Effect:

Variants in DCTN4 are associated with time to first Pseudomonas aeruginosa (P. aeruginosa) airway infection, chronic P. aeruginosa infection and mucoid P. aeruginosa among individuals with cystic fibrosis (MIM219700).

Reference:

PMID22772370

Title:

Exome sequencing of extreme phenotypes identifies DCTN4 as a modifier of chronic Pseudomonas aeruginosa infection in cystic fibrosis.

Species studied:

Human

Abstract:

Exome sequencing has become a powerful and effective strategy for the discovery of genes underlying Mendelian disorders. However, use of exome sequencing to identify variants associated with complex traits has been more challenging, partly because the sample sizes needed for adequate power may be very large. One strategy to increase efficiency is to sequence individuals who are at both ends of a phenotype distribution (those with extreme phenotypes). Because the frequency of alleles that contribute to the trait are enriched in one or both phenotype extremes, a modest sample size can potentially be used to identify novel candidate genes and/or alleles. As part of the National Heart, Lung, and Blood Institute (NHLBI) Exome Sequencing Project (ESP), we used an extreme phenotype study design to discover that variants in DCTN4, encoding a dynactin protein, are associated with time to first P. aeruginosa airway infection, chronic P. aeruginosa infection and mucoid P. aeruginosa in individuals with cystic fibrosis.
Target disease:

Cystic fibrosis (DOID_1485)

Effect type:

Expressivity

Modifier effect:

Altered response to pulmonary infection with Pa

Evidence:

P=0.06

Effect:

p.Tyr263Cys tend to be more frequently observed in CF patients with CPA than in patients without CPA

Reference:

PMID25763772

Title:

DCTN4 as a modifier of chronic Pseudomonas aeruginosa infection in cystic fibrosis.

Species studied:

Human

Abstract:

Pseudomonas aeruginosa (Pa) infection in cystic fibrosis (CF) patients is associated with worse long-term pulmonary disease and shorter survival, and chronic Pa infection (CPA) is associated with reduced lung function, faster rate of lung decline, increased rates of exacerbations and shorter survival. By using exome sequencing and extreme phenotype design, it was recently shown that isoforms of dynactin 4 (DCTN4) may influence Pa infection in CF, leading to worse respiratory disease. The purpose of this study was to investigate the role of DCTN4 missense variants on Pa infection incidence, age at first Pa infection and chronic Pa infection incidence in a cohort of adult CF patients from a single centre.