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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 33318612 [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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Further reading
Citation information
Database page citation:
Paola Vergani. CFTR. Accessed on 12/09/2025. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=129.
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Mathie AA, Peters JA, Veale EL, Striessnig J, Kelly E, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Ion channels. Br J Pharmacol. 180 Suppl 2:S145-S222.
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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].