Defective CFTR does not transport Cl- from cytosol to extracellular region

Stable Identifier
Reaction [transition]
Homo sapiens
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Cystic fibrosis transmembrane conductance regulator (CFTR) is a low conductance chloride-selective channel that mediates the transport of chloride ions in human airway epithelial cells. Chloride ions plays a key role in maintaining homoeostasis of epithelial secretions in the lungs. Defects in CFTR can cause cystic fibrosis (CF; MIM:602421), a common generalised disorder in Caucasians affecting the exocrine glands. CF results in an ionic imbalance that impairs clearance of secretions, not only in the lung, but also in the pancreas, gastrointestinal tract and liver. Wide-ranging manifestations of the disease include chronic lung disease, exocrine pancreatic insufficiency, blockage of the terminal ileum, male infertility and salty sweat.

The most common mutation that causes CF is F508del (Kerem et al. 1989). Although more than 1,500 mutations of CFTR have been identified, only four mutations besides F508del reach a frequency of 1% to 3%: G551D, W1282X, G542X, and N1303K (Rogan et al. 2011, Cutting et al. 1990, Vidaud et al. 1990, Kerem et al. 1990, Cuppens et al. 1990, Osborne et al. 1991).

Literature References
PubMed ID Title Journal Year
21652558 Cystic fibrosis transmembrane conductance regulator intracellular processing, trafficking, and opportunities for mutation-specific treatment

Rogan, MP, Stoltz, DA, Hornick, DB

Chest 2011
2135388 A child, homozygous for a stop codon in exon 11, shows milder cystic fibrosis symptoms than her heterozygous nephew

Van den Berghe, H, De Boeck, C, De Baets, F, Marynen, P, Cassiman, JJ, Cuppens, H, Eggermont, E

J. Med. Genet. 1990
1695717 A cluster of cystic fibrosis mutations in the first nucleotide-binding fold of the cystic fibrosis conductance regulator protein

Antonarakis, SE, Kazazian, HH, Cutting, GR, Kasch, LM, Tsui, LC, Rosenstein, BJ, Zielenski, J

Nature 1990
2236053 Identification of mutations in regions corresponding to the two putative nucleotide (ATP)-binding folds of the cystic fibrosis gene

Markiewicz, D, Collins, FS, Kennedy, D, Gazit, E, Bozon, D, Riordan, JR, Kerem, BS, Yahav, J, Rommens, JM, Zielenski, J

Proc. Natl. Acad. Sci. U.S.A. 1990
2210768 Three point mutations in the CFTR gene in French cystic fibrosis patients: identification by denaturing gradient gel electrophoresis

Martin, J, Nicolas, S, Goossens, M, Ghanem, N, Fanen, P, Vidaud, M

Hum. Genet. 1990
2570460 Identification of the cystic fibrosis gene: genetic analysis

Markiewicz, D, Buchanan, JA, Buchwald, M, Kerem, B, Cox, TK, Tsui, LC, Chakravarti, A, Rommens, JM

Science 1989
1998343 A mutation in the second nucleotide binding fold of the cystic fibrosis gene

Hodson, M, Santis, G, Knight, R, Osborne, L

Am. J. Hum. Genet. 1991
Catalyst Activity

chloride transmembrane transporter activity of CFTR mutants [plasma membrane]

Normal reaction
Functional status

Loss of function of CFTR mutants [plasma membrane]

Name Identifier Synonyms
cystic fibrosis DOID:1485 mucoviscidosis, CF
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