CFTR

Chr 7

CF transmembrane conductance regulator

This gene encodes CFTR, an ATP-gated chloride channel that regulates ion and water transport across epithelial tissues and maintains fluid homeostasis in airways, pancreas, and other organs. Mutations cause cystic fibrosis (autosomal recessive), congenital bilateral absence of vas deferens, and milder phenotypes including bronchiectasis, pancreatitis, and isolated sweat chloride elevation (autosomal dominant or recessive depending on the condition). The gene shows tolerance to loss-of-function variants (LOEUF 1.31), reflecting the spectrum of phenotype severity associated with different mutation types.

ResearchSummary from RefSeq, OMIM, UniProt

Epithelial ion channel that plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis (PubMed:26823428). Mediates the transport of chloride ions across the cell membrane (PubMed:10792060, PubMed:11524016, PubMed:11707463, PubMed:12519745, PubMed:12529365, PubMed:12588899, PubMed:12727866, PubMed:15010471, PubMed:17036051, PubMed:1712898, PubMed:17182731, PubMed:19398555, PubMed:19621064, PubMed:22178883, PubMed:25330774, PubMed:26846474, PubMed:28087700, PubMed:8910473, PubMed:9804160). Possesses an intrinsic ATPase activity and utilizes ATP to gate its channel; the passive flow of anions through the channel is gated by cycles of ATP binding and hydrolysis by the ATP-binding domains (PubMed:11524016, PubMed:15284228, PubMed:26627831, PubMed:8910473). The ion channel is also permeable to HCO(3)(-); selectivity depends on the extracellular chloride concentration (PubMed:15010471, PubMed:19019741). In vitro, mediates ATP-dependent glutathione flux (PubMed:12727866). Exerts its function also by modulating the activity of other ion channels and transporters (PubMed:12403779, PubMed:22121115, PubMed:22178883, PubMed:27941075). Plays an important role in airway fluid homeostasis (PubMed:16645176, PubMed:19621064, PubMed:26823428). Contributes to the regulation of the pH and the ion content of the airway surface fluid layer and thereby plays an important role in defense against pathogens (PubMed:14668433, PubMed:16645176, PubMed:26823428). Modulates the activity of the epithelial sodium channel (ENaC) complex, in part by regulating the cell surface expression of the ENaC complex (PubMed:17182731, PubMed:17434346, PubMed:27941075). Inhibits the activity of the ENaC channel containing subunits SCNN1A, SCNN1B and SCNN1G (PubMed:17182731). Inhibits the activity of the ENaC channel containing subunits SCNN1D, SCNN1B and SCNN1G, but not of the ENaC channel containing subunits SCNN1A, SCNN1B and SCNN1G (PubMed:17182731, PubMed:27941075). May regulate bicarbonate secretion and salvage in epithelial cells by regulating the transporter SLC4A7 (PubMed:12403779). Can inhibit the chloride channel activity of ANO1 (PubMed:22178883). Plays a role in the chloride and bicarbonate homeostasis during sperm epididymal maturation and capacitation (PubMed:19923167, PubMed:27714810, PubMed:29393851)

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCystic fibrosis

UniProtCongenital bilateral absence of the vas deferens

Clinical highlights

Gene-disease validity (ClinGen)

cystic fibrosis · ARDefinitivesufficient evidence for diagnostic panels

Active trials

1302

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.31

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (2)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.31LOEUF

pLI 0.000

Z-score -0.73

OE 1.09 (0.91–1.31)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-3.14Z-score

OE missense 1.32 (1.25–1.39)

996 obs / 753.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.09 (0.91–1.31)

0≤0.351.4

Missense OE?1.32 (1.25–1.39)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 84 / 77.0Missense obs/exp: 996 / 753.5Syn Z: 0.77

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

CFTR · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Cystic Fibrosis

Testing Drug Efficacy in Cystic Fibrosis Through N-of-1 Trials

RECRUITING

NCT04580368Phase NAChildren's Hospital Medical Center, CincinnatiStarted 2021-05-01

CFTR Modulators

Cystic Fibrosis

Impact of a Coordinated Dietetic-adapted Physical Activity Program on the Percentage of Lean Body Mass in Adults With Cystic Fibrosis Treated With Elexacaftor-Tezacaftor-Ivacaftor: Multicentre Randomised Controlled Trial

RECRUITING

NCT06457451Phase NAUniversity Hospital, ToursStarted 2024-11-25

DIAPASOM program

Cystic Fibrosis

Study to Evaluate Elexacaftor/Tezacaftor/Ivacaftor (ELX/TEZ/IVA) Long-term Safety and Efficacy in Subjects Without F508del

ACTIVE NOT RECRUITING

NCT05331183Phase PHASE3Vertex Pharmaceuticals IncorporatedStarted 2022-11-23

ELX/TEZ/IVAIVA

Cystic Fibrosis-related DiabetesCystic Fibrosis

Metformin for People With CFRD on CFTR Modulator Therapy to Improve Ion Channel Function

RECRUITING

NCT04530383Phase PHASE2University of Kansas Medical CenterStarted 2022-02-14