Protein / target

Cystic fibrosis transmembrane conductance regulator

CFTRP13569Homo sapiensSwiss-Prot

UniProt: P13569 Ensembl: ENSG00000001626 HGNC: HGNC:1884 NCBI Gene: 1080

Clinically validated

Therapeutic maturity

Approved medicines

Clinical trials

Small-molecule tractable

Druggability

Approved Drug

Protein at a glance

Biological role

ATP-gated chloride channel activity

Strongest disease association

congenital bilateral aplasia of vas deferens from CFTR mutation

Genetic evidence · score 0.98

Therapeutic maturity

Clinically validated target

7 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

7 approved · 6 in clinical development

30 linked trials

Research activity

Emerging research

8 papers · latest 2025

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function

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)

Subcellular location

Apical cell membraneEarly endosome membraneCell membraneRecycling endosome membraneEndoplasmic reticulum membraneNucleus

Domains and Gene Ontology detail (53)

Domains & features

ABC transmembrane type-1 1ABC transporter 1ABC transmembrane type-1 2ABC transporter 2

Gene Ontology

Capical plasma membrane
Cbasolateral plasma membrane
Ccell surface
Cchloride channel complex
Cclathrin-coated endocytic vesicle membrane
Ccytoplasm
Ccytosol
Cearly endosome
Cearly endosome membrane
Cendoplasmic reticulum membrane
Cendosome membrane
CGolgi-associated vesicle membrane

1480 aa · 168 kDa · 3 isoforms

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Chloride transportUniProt · GOProteolysisReactome

View supporting evidence

Chloride transport

·Epithelial ion channel that plays an important role in the regulation of epithelial ion…
·chloride channel complex
·chloride channel activity
·chloride channel inhibitor activity

Proteolysis

·Ub-specific processing proteases

View underlying pathways (11)

ABC-family protein mediated transport

RHO GTPases regulate CFTR trafficking

Defective CFTR causes cystic fibrosis

Ub-specific processing proteases

Cargo recognition for clathrin-mediated endocytosis

Clathrin-mediated endocytosis

RHOQ GTPase cycle

Chaperone Mediated Autophagy

Late endosomal microautophagy

Aggrephagy

Developmental Lineage of Pancreatic Ductal Cells

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Drugs targeting this protein

Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.

tezacaftor

Narrow target profileApprovedPositive modulator

Cystic fibrosis transmembrane conductance regulator positive modulator

Appears in clinical studies involving acute lung injury, cystic fibrosis, cystic fibrosis-related diabetes, Impaired glucose tolerance

Direct interaction with this protein · Only this protein recorded as a target

ivacaftor

Narrow target profileApprovedPositive modulator

Cystic fibrosis transmembrane conductance regulator positive modulator

Appears in clinical studies involving cystic fibrosis, acute lung injury, respiratory system disorder, cystic fibrosis-related diabetes

Direct interaction with this protein · Only this protein recorded as a target

elexacaftor

Narrow target profileApprovedPositive modulator

Cystic fibrosis transmembrane conductance regulator positive modulator

Appears in clinical studies involving cystic fibrosis, cystic fibrosis-related diabetes, Impaired glucose tolerance, Dyspnea

Direct interaction with this protein · Only this protein recorded as a target

ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.

Translational evidence

Open Targets 26

Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.

Strongest genetic associations

Human genetic evidence — the most direct causal link between this target and a disease.

congenital bilateral aplasia of vas deferens from CFTR mutation0.98

Genetic · overall 0.82

cystic fibrosis0.97

Genetic · overall 0.92

bronchiectasis with or without elevated sweat chloride 10.95

Genetic · overall 0.70

hereditary chronic pancreatitis0.95

Genetic · overall 0.72

Obstructive azoospermia0.88

Genetic · overall 0.54

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

Diarrhea0.89

Clinical · overall 0.55

acute lung injury0.87

Clinical · overall 0.54

bronchiectasis0.12

Clinical · overall 0.56

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

congenital bilateral absence of vas deferens0.60

Genetic literature

cholestasis0.47

Genetic literature

Show all associations

cystic fibrosis0.92

congenital bilateral aplasia of vas deferens from CFTR mutation0.82

hereditary chronic pancreatitis0.72

bronchiectasis with or without elevated sweat chloride 10.70

congenital bilateral absence of vas deferens0.60

bronchiectasis0.56

Diarrhea0.55

acute lung injury0.54

Obstructive azoospermia0.54

cholestasis0.47

Open Targets ranks 1,987 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.

Known drugs · 13 total

GALICAFTORPhase 2

cystic fibrosis

OLACAFTORPhase 2

cystic fibrosis

BAMOCAFTORPhase 3

cystic fibrosis

DEUTIVACAFTORApproval

cystic fibrosis

TEZACAFTORApproval

acute lung injury · cystic fibrosis · cystic fibrosis-related diabetes

ICENTICAFTORPhase 2

chronic obstructive pulmonary disease · bronchiectasis · cystic fibrosis

IVACAFTORApproval

cystic fibrosis · acute lung injury · respiratory system disorder

CROFELEMERApproval

Diarrhea · irritable bowel syndrome · breast cancer

NAVOCAFTORPhase 2

cystic fibrosis

ELEXACAFTORApproval

cystic fibrosis · cystic fibrosis-related diabetes · Impaired glucose tolerance

Tractability

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · UniProt UbiquitinationPR · Database UbiquitinationPR · Small Molecule Binder

Safety liabilities

adverse events

Clinical trials

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Safety and Efficacy of VX-770 in Subjects Aged 12 Years and Older With Cystic Fibrosis Who Are Homozygous for the F508del-CFTR MutationPHASE2

TERMINATED · via ivacaftor · NCT00953706

A Phase 3, Randomized, Double Blind, Placebo Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Lumacaftor in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Homozygous for the F508del CFTR MutationPHASE3

COMPLETED · via ivacaftor · NCT01807949

A Phase 2, Multicenter, Double-Blinded, Placebo-Controlled, Multiple-Dose Study to Evaluate Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of Lumacaftor Monotherapy, and Lumacaftor and Ivacaftor Combination Therapy in Subjects With Cystic Fibrosis, Homozygous or Heterozygous for the F508del-CFTR MutationPHASE2

COMPLETED · via ivacaftor · NCT01225211

A Multicenter Randomized, Double-blind, Phase 2, Placebo Controlled Study to Determine the Safety and Efficacy of Ivacaftor (VX-770) for the Treatment of Chronic Obstructive Pulmonary Disease (The Multicenter Topic Trial)PHASE2

WITHDRAWN · via ivacaftor · NCT04066751

A Phase 3b, 2-part, Randomized, Double-blind, Placebo-controlled Crossover Study With a Long-term Open-label Period to Investigate Ivacaftor in Subjects With Cystic Fibrosis Aged 3 Through 5 Years Who Have a Specified CFTR Gating MutationPHASE3

TERMINATED · via ivacaftor · NCT02742519

A Phase 2, Randomized, Placebo-Controlled, Double-blind Study to Evaluate the Effect of VX-661 in Combination With Ivacaftor on Chest Imaging Endpoints in Subjects Aged 12 Years and Older With Cystic Fibrosis, Homozygous for the F508del CFTR MutationPHASE2

COMPLETED · via ivacaftor · NCT02730208

Show remaining trials (24)

A Phase 3, 2-Arm, Roll-Over Study to Evaluate the Long-term Safety and Pharmacodynamics of Ivacaftor Treatment in Pediatric Subjects With Cystic Fibrosis and a CFTR Gating MutationPHASE3

COMPLETED · via ivacaftor · NCT01946412

A Randomized, Double-Blind, Placebo Controlled Pilot Study to Determine the Safety and Efficacy of Ivacaftor (VX-770) for the Treatment of Chronic Obstructive Pulmonary Disease (The TOPIC Trial)EARLY_PHASE1

COMPLETED · via ivacaftor · NCT02135432

A Phase 1, Open-Label Study to Examine the Effect of Ciprofloxacin, Itraconazole, and Rifampin on the Pharmacokinetics of Lumacaftor in Combination With Ivacaftor in Healthy Adult SubjectsPHASE1

COMPLETED · via ivacaftor · NCT01768663

An Efficacy and Safety Study of Ivacaftor in Patients With Cystic Fibrosis and Two Splicing MutationsPHASE3

COMPLETED · via ivacaftor · NCT02934698

A Phase 1, Randomized, Placebo and Active Controlled, Double-Blind, Parallel, Electrocardiogram Study to Evaluate the Effect of Lumacaftor in Combination With Ivacaftor on the QT/QTc Interval in Healthy SubjectsPHASE1

COMPLETED · via ivacaftor · NCT01910415

A Phase 3, Open-label Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Lumacaftor in Combination With Ivacaftor in Subjects 6 Through 11 Years of Age With Cystic Fibrosis, Homozygous for the F508del-CFTR MutationPHASE3

COMPLETED · via ivacaftor · NCT01897233

A Phase 1/2, Multicenter Study Evaluating the Safety, Tolerability, and Biodistribution of RCT2100 With Single-Ascending Doses in Healthy Participants and Multiple-Ascending Doses and Proof-of-Concept in Participants With Cystic FibrosisPHASE2

RECRUITING · via ivacaftor · NCT06237335

A Phase 3b, Open-Label Study to Evaluate Lumacaftor and Ivacaftor Combination Therapy in Subjects 12 Years and Older With Cystic Fibrosis and Advanced Lung Disease, Homozygous for the F508del-CFTR MutationPHASE3

COMPLETED · via ivacaftor · NCT02390219

An Open-Label, Phase 1 Study in Healthy Adult Subjects to Examine the Effects of Multiple-Dose Ciprofloxacin on the Multiple-Dose Pharmacokinetics of Ivacaftor and on the Multiple-Dose Pharmacokinetics of VX-661 Administered in Combination With IvacaftorPHASE1

COMPLETED · via ivacaftor · NCT02015507

An Open-Label, Rollover Study to Evaluate the Long Term Safety and Efficacy of VX-770 in Subjects With Cystic FibrosisPHASE3

COMPLETED · via ivacaftor · NCT01117012

A Phase 2 Open Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Dose Levels of Subcutaneously Administered ELX-02 in Patients With Cystic Fibrosis With at Least One G542X AllelePHASE2

COMPLETED · via ivacaftor · NCT04126473

A Phase 2, Randomized, Multicenter, Double Blind, Placebo Controlled Study to Evaluate Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of VX-661 in Combination With Ivacaftor for 12 Weeks in Subjects With Cystic Fibrosis, Homozygous for the F508del CFTR Mutation With an Open-Label ExtensionPHASE2

COMPLETED · via ivacaftor · NCT02070744

A Phase 3, 2-Part, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Pharmacokinetics, Efficacy and Safety of VX-770 in Subjects Aged 6 to 11 Years With Cystic Fibrosis and the G551D MutationPHASE3

COMPLETED · via ivacaftor · NCT00909727

Ivacaftor for Acquired CFTR Dysfunction in Chronic Rhinosinusitis (Randomized Pilot Study Utilizing Ivacaftor for the Treatment of Refractory Gram-Negative Bacterial CRS)EARLY_PHASE1

RECRUITING · via ivacaftor · NCT03439865

An Open Label Study to Investigate the Role of Ivacaftor (VX-770) for the Treatment of Chronic Bronchitis With CFTR DysfunctionPHASE4

WITHDRAWN · via ivacaftor · NCT03251911

Phase 3b, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Assess the Safety, Efficacy, and Tolerability of Tezacaftor/Ivacaftor (TEZ/IVA) in an Orkambi-experienced Population Who Are Homozygous for the F508del CFTR MutationPHASE3

COMPLETED · via ivacaftor · NCT03150719

Airway Infection, Inflammatory Markers and Exercise Capacity in Patients With Cystic Fibrosis and at Least One G551D Mutation Taking VX770 (Ivacaftor)PHASE4

UNKNOWN · via ivacaftor · NCT01937325

Short Term Effects of Ivacaftor in Non-G551D Cystic Fibrosis PatientsNA

COMPLETED · via ivacaftor · NCT01784419

A Phase 3, 2-Part, Open-Label Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of Ivacaftor in Subjects With Cystic Fibrosis Who Are 2 Through 5 Years of Age and Have a CFTR Gating MutationPHASE3

COMPLETED · via ivacaftor · NCT01705145

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Efficacy and Safety of Ivacaftor and VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Heterozygous for the F508del-CFTR Mutation, and a Second Allele With a CFTR Mutation Predicted to Have Residual FunctionPHASE3

COMPLETED · via ivacaftor · NCT02392234

A Phase 3, Two-Part, Randomized, Double-Blind, Placebo-Controlled, Crossover Study With an Open-Label Period to Evaluate the Efficacy and Safety of Ivacaftor in Subjects With Cystic Fibrosis Who Have a Non-G551D CFTR Gating MutationPHASE3

COMPLETED · via ivacaftor · NCT01614470

A Phase 1, Randomized, Single-Dose, Open-Label Crossover Study to Investigate the Effect of Food on the Relative Bioavailability of 2 Fixed-Dose Combinations of Lumacaftor and Ivacaftor Tablet Formulations in Healthy Adult SubjectsPHASE1

COMPLETED · via ivacaftor · NCT01899105

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Effect of VX-770 on Lung Clearance Index in Subjects With Cystic Fibrosis, the G551D Mutation, and FEV1 >90% PredictedPHASE2

COMPLETED · via ivacaftor · NCT01262352

A Randomized, Double-blind, Phase 2, Placebo Controlled Study to Determine the Safety and Efficacy of Ivacaftor (VX-770) for the Treatment of Chronic Obstructive Pulmonary Disease (The Topic Trial)PHASE2

COMPLETED · via ivacaftor · NCT03085485

ClinicalTrials.gov via the drug-target graph.

Research activity

8 papers · to 2025

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Long-term expanding human airway organoids for disease modeling.846 cites

Sachs N · The EMBO journal · 2019

Lung SORT LNPs enable precise homology-directed repair mediated CRISPR/Cas genome correction in cystic fibrosis models.103 cites

Wei T · Nature communications · 2023

Intestinal Bacteroides modulates inflammation, systemic cytokines, and microbial ecology via propionate in a mouse model of cystic fibrosis.45 cites

Price CE · mBio · 2024

Prime editing functionally corrects cystic fibrosis-causing CFTR mutations in human organoids and airway epithelial cells.44 cites

Bulcaen M · Cell reports. Medicine · 2024

Systematic optimization of prime editing for the efficient functional correction of CFTR F508del in human airway epithelial cells.43 cites

Sousa AA · Nature biomedical engineering · 2025

Recent

Systematic optimization of prime editing for the efficient functional correction of CFTR F508del in human airway epithelial cells.

Sousa AA · Nature biomedical engineering · 2025

Prime editing-installed suppressor tRNAs for disease-agnostic genome editing.

Pierce SE · Nature · 2025

Intestinal Bacteroides modulates inflammation, systemic cytokines, and microbial ecology via propionate in a mouse model of cystic fibrosis.

Price CE · mBio · 2024

Prime editing functionally corrects cystic fibrosis-causing CFTR mutations in human organoids and airway epithelial cells.

Bulcaen M · Cell reports. Medicine · 2024

Tissue-Specific Regulation of CFTR Gene Expression.

Blotas C · International journal of molecular sciences · 2023

Lung SORT LNPs enable precise homology-directed repair mediated CRISPR/Cas genome correction in cystic fibrosis models.

Wei T · Nature communications · 2023

Longitudinal microbial and molecular dynamics in the cystic fibrosis lung after Elexacaftor-Tezacaftor-Ivacaftor therapy.

Martin C · Respiratory research · 2023

Long-term expanding human airway organoids for disease modeling.

Sachs N · The EMBO journal · 2019

Europe PMC papers linked directly to this protein.

Forefront confidence

Synthesis

Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.

cystic fibrosisWell supported

1.00

agreement 0.91–1.00

Genetic39%Clinical30%Pathway15%Animal model9%Literature6%Genetic literaturedup

Open Targets aggregate 0.92 · 5 independent evidence families · 1 not counted as duplicate

congenital bilateral aplasia of vas deferens from CFTR mutationWell supported

0.98

agreement 0.86–1.00

Genetic77%Animal model13%Literature10%Genetic literaturedup

Open Targets aggregate 0.82 · 3 independent evidence families · 1 not counted as duplicate

hereditary chronic pancreatitisWell supported

0.96

agreement 0.84–1.00

Genetic84%Animal model15%Literature2%Genetic literaturedup

Open Targets aggregate 0.72 · 3 independent evidence families · 1 not counted as duplicate

bronchiectasis with or without elevated sweat chloride 1Well supported

0.96

agreement 0.83–1.00

Genetic86%Animal model14%Genetic literaturedup

Open Targets aggregate 0.70 · 2 independent evidence families · 1 not counted as duplicate

Obstructive azoospermiaWell supported

0.88

agreement 0.74–1.00

Genetic99%Literature1%

Open Targets aggregate 0.54 · 2 independent evidence families

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.

What's happening now

Recent activity around this target, drawn from one canonical event stream. Every item is reached through 2 drugs that target this protein, so each event is news about that drug rather than about the protein directly.

New publication2023-12-16
Longitudinal microbial and molecular dynamics in the cystic fibrosis lung after Elexacaftor-Tezacaftor-Ivacaftor therapy.
Respiratory research · 2023 · 24 citations · Europe PMC · via tezacaftor
New publication2017-01-09
In vivo and in vitro ivacaftor response in cystic fibrosis patients with residual CFTR function: N-of-1 studies.
Pediatric pulmonology · 2017 · 50 citations · Europe PMC · via ivacaftor
Accelerated approval granted2012-07-23
Accelerated approval: Kalydeco (EMA)
ema · regulatory · ema · via ivacaftor

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.