Alt. symbols: CF | ABCC7 | MRP7 | ABC35 | TNR-CFTR | dJ760C5.1 | CFTR/MRP

Approved name: CF transmembrane conductance regulator
Alt. names: cystic fibrosis transmembrane conductance regulator, ATP-binding cassette (sub-family C, member 7) | ATP-binding cassette sub-family C, member 7

Location: 7q31.2: 117287120 - 117715971 (+)
Gene type: protein_coding, 38 transcripts.

Scores: LoFtool: 0.023500 | pLI: 0.00000000 | LOEUF: 1.307

HGNC: 1884

NCBI: 1080, RefSeq: NG_016465.4

Ensembl: ENSG00000001626.18

LRG_663 | Status: public

OMIM: 602421

Expression | ProteinAtlas

The CFTR gene encodes the cystic fibrosis transmembrane conductance regulator (CFTR), a member of the ATP-binding cassette (ABC) transporter superfamily. This protein functions as a channel transporting negatively charged chloride ions across the membrane of cells that produce mucus, sweat, saliva, tears, and digestive enzymes. The transport of chloride ions helps control the movement of water in tissues, which is necessary for the production of thin, freely flowing mucus. Mucus lubricates and protects the lining of the airways, digestive system, reproductive system, and other organs and tissues. In addition, the CFTR protein regulates the function of other channels, such as those that transport positively charged sodium ions across cell membranes, which is necessary for the normal function of organs such as the lungs and pancreas. Channel activation is mediated by cycles of regulatory domain phosphorylation, ATP-binding by the nucleotide-binding domains, and ATP hydrolysis.

Biallelic mutations in CFTR cause cystic fibrosis [MIM:219700] (Abulí 2016 Hum Mutat 37: 516 PubMed: 26990548), or congenital bilateral absence of vas deferens [MIM:277180] (Anguiano 1992 JAMA 267: 1794 PubMed: 1545465); both, autosomal recessive conditions. However, monoallelic (class IV-V) mutations in the gene have also been associated with pancreatitis (Masson 2013 PLoS One 8: e73522 PubMed: 23951356), sweat chloride elevation without CF, neonatal hypertrypsinemia, and bronchiectasis with or without elevated sweat chloride. To date, over 1,000 mutations (mostly missense) in the CFTR gene have been associated with cystic fibrosis. These mutations are classified as class I (no mRNA or protein is produced), class II (protein is synthesized but it misfolds and does not reach the cell surface), class III (impaired channel gating), class IV (decreased conductance), class V (insufficient protein synthesis). The most common mutation, delta F508 belongs to class II, nonsense or splice-site mutations belong to class I (e.g. p.G542X, W1282X, p.R553X), missense mutations can be either class III (e.g. p.G551D, p.S549N) or class IV (e.g. p.R117H, p.R334W, and p.A455E), and class V includes some missense and some intronic mutations (e.g. c.3272-26A>G, p.A455E). Pathogenic mutations in CFTR either alter the production, the structure, or the stability of the channel; thus, impairing the transport of chloride ions and the movement of water across cell membranes. As a result, cells that line the passageways of the lungs, pancreas, and other organs produce an abnormally thick and sticky mucus, which obstructs the airways and glands. [Load More]