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CFTR C
Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
Overview
CFTR is a member of the ABC transporter superfamily, but, uniquely, it is an ion channel, allowing electrodiffusion of Cl- and HCO3-. It is activated by phosphorylation, mainly by PKA on its regulatory domain (R domain). Conserved nucleotide binding domains (NBD1 and NBD2) couple ATP binding and hydrolysis to gate opening and closing, respectively [7]. CFTR is expressed apically in polarized epithelial cells in various organs where it controls volume and pH of fluid secretions as well as mucin unfolding and release [20]. CFTR transcripts are present in secretory and ionocyte cells in airway epithelia [23,25], crypt enterocytes, goblet and CFTR-high expressing cells in the intestine [2-3], pancreatic duct cells [10], intra- and extra-hepatic cholangiocytes [38] and others.
Mutations in the CFTR gene cause the genetic disease cystic fibrosis (CF) [29]. The most common mutation, F508del, is present in at least one gene copy in ~80% of patients worldwide, but there are ~1000 different variants known to cause CF. Mutations affect CFTR biogenesis (folding, maturation, trafficking, metabolic stability) and/or ion-channel function. Vertex Pharmaceuticals developed small-molecule CFTR modulator drugs that improve biogenesis ("correctors") or open probability ("potentiators") of defective CFTR variants. Triple combination therapies, including two correctors and one potentiator (e.g. Trikafta®: elexacaftor, tezacaftor, ivacaftor), are standard of care for patients carrying at least one copy of the F508del variant. Patients carrying mutations only affecting ion-channel function ("gating mutations" e.g. G551D) are treated with ivacaftor (potentiator) alone. Cryo-EM structures of Trikafta-bound F508del-E1371Q-CFTR reveal that all three compounds bind at the protein-membrane interface, in shallow pockets on CFTR's surface [11].
While low/absent CFTR activity causes CF, over-activation of CFTR (due to bacterial toxins such as cholera toxin) results in secretory diarrhoeas, causing large intestinal loss of fluid and alkali [8]. No inhibitors have been approved yet for emergency treatment of secretory diarrhoeas.
Channels and Subunits
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CFTR
C
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How to cite this family page
Database page citation (select format):
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Striessnig J, Gibb AJ, Mathie AA, Veale EL, Kelly E, Peach CJ, Armstrong JF, Faccenda E, Harding SD, Southan C, Davies JA et al. (2025) The Concise Guide to PHARMACOLOGY 2025/26: Ion channels. Br J Pharmacol. 182: S152-S241.
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Cystic fibrosis mouse models have been useful in studies of the intestinal symptoms of CF (e.g. [34]). However, they do not develop severe lung symptoms typically observed in humans with CF [14]. CF pigs [32] exhibit respiratory defects and mucus accumulation similar to humans [31]. More recently, several ferret (Mustela putorius furo) CF models have also been developed, by providing in utero treatment with CFTR modulators to reduce mortality in the foetal and neonatal period [9,33].