CFTR

Chr 7ADAR

CF transmembrane conductance regulator

Also known as: ABC35, ABCC7, CF, CFTR/MRP, MRP7, TNR-CFTR, dJ760C5.1

NCBI Gene: 1080 ENSG00000001626 UniProt: P13569 OMIM: 602421

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the ATP-binding cassette (ABC) transporter superfamily. The encoded protein functions as a chloride channel, making it unique among members of this protein family, and controls ion and water secretion and absorption in epithelial tissues. Channel activation is mediated by cycles of regulatory domain phosphorylation, ATP-binding by the nucleotide-binding domains, and ATP hydrolysis. Mutations in this gene cause cystic fibrosis, the most common lethal genetic disorder in populations of Northern European descent. The most frequently occurring mutation in cystic fibrosis, DeltaF508, results in impaired folding and trafficking of the encoded protein. Multiple pseudogenes have been identified in the human genome. [provided by RefSeq, Aug 2017]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Bronchiectasis with or without elevated sweat chloride 1, modifier of}MIM #211400

{Hypertrypsinemia, neonatal}

{Pancreatitis, hereditary}MIM #167800

Congenital bilateral absence of vas deferensMIM #277180

Cystic fibrosisMIM #219700

Sweat chloride elevation without CF

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · cystic fibrosis · AR · ClinGen 2022

Active trials

1387

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.31

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — CFTR

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

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

Background carrier burden — how many people carry a rare variant somewhere in CFTR?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 18

2,119 rare PASS variants

Rare truncating (LoF)

1 in 170

373 rare PASS variants

Rare synonymous (reference)

1 in 89

624 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CFTR. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 21	1 in 180
South Asian	~43k	1 in 18	1 in 190
Remaining (unassigned)	~30k	1 in 17	1 in 130
European (Finnish)	~27k	1 in 100	1 in 680
Admixed American	~22k	1 in 21	1 in 160
African / African American	~21k	1 in 23	1 in 240
East Asian	~20k	1 in 24	1 in 450
Ashkenazi Jewish	~13k	1 in 87	1 in 840
Middle Eastern	~2,884	1 in 20	1 in 220

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 17 of 27 coding exons well covered in gnomAD exomes; exons 2, 3, 5, 9, 12 and 5 more marginal. Genomes: all 27.? see exons ↓

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

📖

GeneReview available — CFTR

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Cystic Fibrosis (CF)Type 2 Inflammatory Disorders

Type 2 Inflammation in Adults With Cystic Fibrosis

NOT YET RECRUITING

NCT07892443University of VirginiaStarted 2026-11-01

Cystic FibrosisLiver Disease

Genetic Modifiers of Cystic Fibrosis (CF) Liver Disease

ACTIVE NOT RECRUITING

NCT00804583University of North Carolina, Chapel HillStarted 2004-03

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

Monitoring Response to Orkambi in Cystic Fibrosis Lung Disease by Inhaled Xenon MRI

ACTIVE NOT RECRUITING

NCT02848560Children's Hospital Medical Center, CincinnatiStarted 2016-03

Hyperpolarized Xenon

Cystic Fibrosis

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

RECRUITING

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