ABCMdb

PMID: 24534272

Cant N, Pollock N, Ford RC
CFTR structure and cystic fibrosis.
Int J Biochem Cell Biol. 2014 Jul;52:15-25. doi: 10.1016/j.biocel.2014.02.004. Epub 2014 Feb 15., [PubMed]

Sentences

No. Mutations Sentence Comment

2401 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* CFTR mutations are classified into 5 groups (Prickett and Jain, 2013): Class 1 mutations cause a defect in CFTR protein synthesis, such as the premature stop codon W1282X; Class 2 mutations, including the common F508, are translated into full-length nascent polypeptide chains but are defective in folding and are thus targeted for degradation rather than trafficked to the PM; Class 3 mutants of CFTR are able to reach the PM but have channel gating defects that decrease channel opening time and decrease chloride flux, e.g. the second most common mutation G551D; Class 4 mutants reach the PM, but have decreased channel conductance even when the gate is open; and Class 5 represent a fully functional CFTR at the PM but with reduced abundance due to defective mRNA splicing. Login to comment 2429 ABCC7 p.Gly551Asp Potentiators are compounds that can stimulate channel activity of CFTR that has already reached the PM, for example the recently FDA-approved drug Kalydeco (or Ivacaftor), which stimulates the activity of the otherwise inactive G551D-CFTR mutant (http://www.cff.org/research/drugdevelopmentpipeline). Login to comment 2431 ABCC7 p.Gly551Asp However, only 4% of CF patients carry the G551D mutation, so efforts are continuing to find a similarly successful corrector compound for the F508-CFTR mutation. Login to comment