|Cystic Fibrosis related|
|(A;A)||5||Double homozygote for cystic fibrosis G551D allele|
|(A;G)||3||Carrier for cystic fibrosis G551D allele|
|(G;G)||0||common in clinvar|
Known primarily as G551D (although sometimes also called G511D) and also known as i4000305 by 23andMe, rs75527207 is a rare variant in the cystic fibrosis CFTR gene is thought to be present in ~1,200 patients in the US. The risk allele is rs75527207(A). G551D is termed a 'gating mutant', and is considered to be a somewhat different class of cystic fibrosis mutation compared to variants that lead to misfolded proteins.
Like almost all cystic fibrosis variants, individuals must inherit two defective CFTR alleles to manifest the disease; since G551D is ~20 times rarer than the most common CFTR variant, deltaF508, patients carrying one G551D variant are likely to be compound heterozygotes harboring an additional CFTR variant.
In early 2012, the biotech company Vertex Pharmaceutics received FDA approval to sell the drug Kalydeco (ivacaftor) to G551D cystic fibrosis patients over the age of 6. In phase 3 trials, Kalydeco increased lung function by 10% (in 161 patients) compared to placebo, and showed improvements in weight gain along with reductions in cough and sputum production.10.1038/nbt0312-201a
See also: OMIM 602421.0013
|Disease||Cystic fibrosis Hereditary pancreatitis ivacaftor response - Efficacy|
|CLNDBN||Cystic fibrosis Hereditary pancreatitis ivacaftor response - Efficacy|
|CLNSRC||CFTR2 OMIM Allelic Variant PharmGKB Clinical Annotation PharmGKB UniProtKB (protein)|
|CLNACC||RCV000007540.10, RCV000119040.2, RCV000211289.1,|
[PMID 7522329] Phosphatase inhibitors activate normal and defective CFTR chloride channels.
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[PMID 10341008] Screening for cystic fibrosis transmembrane conductance regulator gene mutations in men included in an intracytoplasmic sperm injection programme.
[PMID 10653141] Study of mutant and polyvariant mutant CFTR genes in patients with congenital absence of the vas deferens.
[PMID 12767731] Effect of genotype on phenotype and mortality in cystic fibrosis: a retrospective cohort study.