Protein / target

Cystic fibrosis transmembrane conductance regulator

Encoded byCFTRP13569Homo sapiensSwiss-Prot

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

Clinically validated

Therapeutic maturity

Approved medicines

Open Targets target-level

View by indication →

Clinical trials

Small-molecule tractable

Druggability

Approved Drug

Protein at a glance

Biological role

ATP-gated chloride channel

Strongest disease association

congenital bilateral aplasia of vas deferens from CFTR mutation

Via encoding gene CFTR · Genetic evidence · score 0.98

Therapeutic position

Established drug target

Small molecules

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 overview

Epithelial ion channel that plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis.

View complete UniProt function annotation

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 · GO

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

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.

Approved medicines with mapped indications

2 medicines · 2 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Cystic Fibrosis2 medicines

ivacaftor tezacaftor

Broader indication categories (1)

Respiratory Tract Diseases1 medicine

ivacaftor

Broad umbrella indications (e.g. “Neoplasms”). Shown here because every medicine also appears under a more specific disease above — kept for completeness, de-emphasised for clarity.

7 medicines meet Open Targets' target-level approved-medicine definition; the 2 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

tezacaftor

Narrow target profileApprovedPositive modulator

Cystic fibrosis transmembrane conductance regulator positive modulator

Indicated for Cystic Fibrosis

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

ivacaftor

Narrow target profileApprovedPositive modulator

Cystic fibrosis transmembrane conductance regulator positive modulator

Indicated for Cystic Fibrosis, Respiratory Tract Diseases

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

elexacaftor

Narrow target profileApprovedPositive modulator

Cystic fibrosis transmembrane conductance regulator positive modulator

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

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

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene CFTR

Gene-level evidence surfaced through the gene CFTRthat encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Cystic Fibrosis

1.00Well supported

Genetic evidence dominant · Open Targets 0.92

congenital bilateral aplasia of vas deferens from CFTR mutation

0.98Well supported

Genetic evidence dominant · Open Targets 0.82

Hereditary chronic pancreatitis

0.96Well supported

Genetic evidence dominant · Open Targets 0.72

Bronchiectasis with or without elevated sweat chloride 1

0.96Well supported

Genetic evidence dominant · Open Targets 0.70

Acute Lung Injury

0.72Moderately supported

Clinical evidence dominant · Open Targets 0.54

View evidence synthesis (5)

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

Acute Lung InjuryModerately supported

0.72

agreement 0.59–0.85

Clinical75%Animal model23%Literature1%

Open Targets aggregate 0.54 · 3 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 per-type scores above show the calculation.

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

Acute Lung Injury0.54

Cholestasis0.47

Drug development

13 compounds recorded · 7 approved · 6 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 3 drugs that target this protein in Forefront's canonical graph (2 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)

GALICAFTORPhase 2

OLACAFTORPhase 2

BAMOCAFTORPhase 3

DEUTIVACAFTORApproval

TEZACAFTORApproval

ICENTICAFTORPhase 2

IVACAFTORApproval

CROFELEMERApproval

NAVOCAFTORPhase 2

ELEXACAFTORApproval

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small molecules — Strong

Approved Drug and Structure with Ligand support this modality.

Antibodies — Emerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (uniprot ubiquitination and database ubiquitination) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (11)

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

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

adverse eventsClinPGx

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

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. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

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 1, Study of VX-828 in Healthy Subjects and in Subjects With Cystic FibrosisPHASE1

ACTIVE_NOT_RECRUITING · via tezacaftor · NCT06154447

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

View all trials (26)

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

A Randomized, Double-blind, Placebo-controlled, Crossover Study to Evaluate the Efficacy of Ivacaftor in Subjects With Cystic Fibrosis Who Are 6 Years of Age and Older and Have Either a 3849 + 10KB C→T or D1152H-CFTR MutationPHASE3

COMPLETED · via ivacaftor · NCT03068312

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

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

COMPLETED · via ivacaftor · NCT02934698

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 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Heterozygous for the F508del-CFTR Mutation and With a Second CFTR Mutation That Is Not Likely to Respond to VX-661 and/or Ivacaftor Therapy (F508del/NR)PHASE3

COMPLETED · via ivacaftor · NCT02516410

A Phase 3, Randomized, Double-Blind, Ivacaftor-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of 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 CFTR Allele With a Gating Defect That Is Clinically Demonstrated to be Ivacaftor ResponsivePHASE3

COMPLETED · via ivacaftor · NCT02412111

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

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, Randomized, Double Blind, Placebo Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Homozygous for the F508del CFTR MutationPHASE3

COMPLETED · via ivacaftor · NCT02347657

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 Phase 3, Rollover Study to Evaluate the Safety and Efficacy of Long-term Treatment With Lumacaftor in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Homozygous or Heterozygous for the F508del-CFTR MutationPHASE3

COMPLETED · via ivacaftor · NCT01931839

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 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 · NCT01807923

COMPLETED · via ivacaftor · NCT01807949

A Phase 3, Two-Arm, Rollover Study to Evaluate the Safety of Long Term Ivacaftor Treatment in Subjects 6 Years of Age and Older With Cystic Fibrosis and a Non-G551D CFTR MutationPHASE3

COMPLETED · via ivacaftor · NCT01707290

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, Parallel-Group Study to Evaluate the Efficacy and Safety of Ivacaftor in Subjects With Cystic Fibrosis Who Have the R117H-CFTR MutationPHASE3

COMPLETED · via ivacaftor · NCT01614457

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

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 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

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

COMPLETED · via ivacaftor · NCT00909532

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 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 · NCT04135495

COMPLETED · via ivacaftor · NCT04126473

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.

What's happening now

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for a drug that targets this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

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.