CFTR

Summary

CFTR (CF transmembrane conductance regulator, HGNC:1884) is a protein-coding gene on chromosome 7q31.2, encoding Cystic fibrosis transmembrane conductance regulator (P13569). Epithelial ion channel that plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis.

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.

Source: NCBI Gene 1080 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cystic fibrosis (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 9
• Clinical variants (ClinVar): 6,148 total — 925 pathogenic, 395 likely-pathogenic (top 1% of genes corpus-wide)
• GTEx eGene: eQTL in 14 tissues, sQTL in 5 (q < 0.05)
• Phenotypes (HPO): 103
• Drug target: yes — 13 curated mechanism-of-action drugs; 14 molecules with ChEMBL bioactivity (top 2% of genes corpus-wide)
• Approved drugs (ChEMBL mechanism of action): 7 — Crofelemer, Deutivacaftor, Elexacaftor, +4 more
• Pharmacogenomics (PharmGKB): 2 CPIC/DPWG dosing guidelines (e.g. ivacaftor)
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.15 (unconstrained)
• MANE Select transcript: NM_000492
• Interaction hub: 3,544 STRING partners (top 1% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1884
Approved symbol	CFTR
Name	CF transmembrane conductance regulator
Location	7q31.2
Locus type	gene with protein product
Status	Approved
Aliases	MRP7, ABC35, TNR-CFTR, dJ760C5.1, CFTR/MRP
Ensembl gene	ENSG00000001626
Ensembl biotype	protein_coding
OMIM	602421
Entrez	1080

Gene structure

Transcript identifiers

Ensembl transcripts: 45 — 21 protein_coding, 11 protein_coding_CDS_not_defined, 11 nonsense_mediated_decay, 2 retained_intron

MANE Select: ENST00000003084

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 1, TSL 4: 1, TSL 5: 8

ENST00000003084, ENST00000426809, ENST00000429014, ENST00000436097, ENST00000446805, ENST00000468795, ENST00000472848, ENST00000546407, ENST00000600166, ENST00000608965, ENST00000610149, ENST00000621535, ENST00000647639, ENST00000647720, ENST00000647978, ENST00000648260, ENST00000649406, ENST00000649781, ENST00000649850, ENST00000673785, ENST00000685018, ENST00000687278, ENST00000689011, ENST00000692802, ENST00000693465, ENST00000693480, ENST00000699585, ENST00000699596, ENST00000699597, ENST00000699598, ENST00000699599, ENST00000699600, ENST00000699601, ENST00000699602, ENST00000699603, ENST00000699604, ENST00000699605, ENST00000699606, ENST00000889206, ENST00000889207, ENST00000889208, ENST00000889209, ENST00000889210, ENST00000950799, ENST00001140285

RefSeq mRNA: 1 — MANE Select: NM_000492 NM_000492

CCDS: CCDS5773

Canonical transcript exons

ENST00000003084 — 27 exons

Exon	Start	End
ENSE00000718611	117530899	117531114
ENSE00000718620	117534276	117534365
ENSE00000718626	117535248	117535411
ENSE00000718630	117536548	117536673
ENSE00000718634	117540100	117540346
ENSE00000718637	117542016	117542108
ENSE00000718699	117614613	117614713
ENSE00000977443	117611581	117611808
ENSE00001343851	117480025	117480147
ENSE00003833777	117652842	117652931
ENSE00003835972	117665459	117665564
ENSE00003840813	117664688	117664860
ENSE00003925242	117642438	117642593
ENSE00003936498	117627522	117627770
ENSE00003976975	117509034	117509142
ENSE00003976986	117548641	117548823
ENSE00003976987	117504253	117504363
ENSE00003977038	117591934	117592657
ENSE00003977041	117590353	117590439
ENSE00003977044	117602826	117602863
ENSE00003977054	117606674	117606753
ENSE00003977055	117603532	117603782
ENSE00003977056	117610519	117610669
ENSE00003977066	117587739	117587833
ENSE00003977072	117594930	117595058
ENSE00003977079	117559464	117559655
ENSE00004796618	117666908	117668665

Expression profiles

Bgee: expression breadth ubiquitous, 193 present calls, max score 99.02.

FANTOM5 (CAGE): breadth broad, TPM avg 1.7950 / max 364.2383, expressed in 193 samples.

Highest expression (Bgee): body of pancreas, gall bladder, pancreas, rectum, mucosa of sigmoid colon.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CFTR is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 14 tissues and its splicing (sQTL) in 5 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

19 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	sqtl	7.6e-09	+0.56	7:117290908:A:G
Pancreas	sqtl	3.0e-07	+2.15	7:117551272:C:T
Brain Hippocampus	eqtl	6.1e-07	-0.28	7:117372187:A:G
Brain Caudate basal ganglia	eqtl	1.9e-05	-0.24	7:117571799:T:C
Testis	eqtl	3.2e-05	-0.31	7:117637872:G:A
Brain Substantia nigra	eqtl	1.6e-04	-0.30	7:117443526:T:C
Brain Cerebellum	eqtl	2.8e-04	+0.40	7:117309232:C:T
Brain Hypothalamus	eqtl	4.5e-04	-0.25	7:117687541:A:C
Colon Transverse	sqtl	1.5e-03	+1.57	7:117551272:C:T
Prostate	sqtl	1.8e-03	-2.77	7:117441663:G:A
Brain Spinal cord cervical c-1	eqtl	1.1e-02	-0.26	7:117374018:A:G
Skin Sun Exposed Lower leg	eqtl	1.4e-02	+0.20	7:116542178:C:G
Stomach	eqtl	2.1e-02	+0.53	7:117172037:A:G
Brain Putamen basal ganglia	eqtl	2.3e-02	-0.32	7:117789745:CA:C
Brain Cortex	eqtl	2.5e-02	-0.23	7:117382550:A:G
Brain Amygdala	eqtl	2.9e-02	-0.32	7:117343659:T:C
Pancreas	eqtl	4.0e-02	-0.19	7:117383183:A:G
Skin Sun Exposed Lower leg	sqtl	4.8e-02	+1.25	7:116943735:T:C
Esophagus Mucosa	eqtl	4.8e-02	-0.69	7:117326105:T:G

FANTOM5 promoters

showing 10 of 12 alternative TSS:

Promoter ID	TPM avg	Samples expressed
80712	1.4391	176
80713	0.0732	28
80718	0.0586	5
80716	0.0579	4
80715	0.0526	3
80711	0.0262	16
80717	0.0260	3
80720	0.0233	4
80724	0.0171	7
204668	0.0099	2

Top tissues by expression

showing 100 of 284 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	99.02	gold quality
gall bladder	UBERON:0002110	96.99	gold quality
pancreas	UBERON:0001264	96.76	gold quality
rectum	UBERON:0001052	95.92	gold quality
mucosa of sigmoid colon	UBERON:0004993	95.82	gold quality
colonic mucosa	UBERON:0000317	95.77	gold quality
islet of Langerhans	UBERON:0000006	95.45	gold quality
duodenum	UBERON:0002114	95.09	gold quality
mucosa of transverse colon	UBERON:0004991	92.93	gold quality
jejunal mucosa	UBERON:0000399	92.39	gold quality
transverse colon	UBERON:0001157	88.98	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	87.52	gold quality
minor salivary gland	UBERON:0001830	86.75	gold quality
saliva-secreting gland	UBERON:0001044	86.69	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.40	gold quality
parotid gland	UBERON:0001831	84.91	gold quality
large intestine	UBERON:0000059	83.66	gold quality
intestine	UBERON:0000160	83.25	gold quality
colon	UBERON:0001155	83.14	gold quality
mouth mucosa	UBERON:0003729	82.90	gold quality
spinal cord	UBERON:0002240	82.59	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	82.57	gold quality
colonic epithelium	UBERON:0000397	81.31	gold quality
small intestine Peyer’s patch	UBERON:0003454	81.14	gold quality
small intestine	UBERON:0002108	81.07	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.67	gold quality
caput epididymis	UBERON:0004358	80.63	gold quality
body of uterus	UBERON:0009853	79.82	gold quality
palpebral conjunctiva	UBERON:0001812	79.80	gold quality
epithelium of bronchus	UBERON:0002031	79.53	gold quality
right testis	UBERON:0004534	79.41	gold quality
left testis	UBERON:0004533	79.37	gold quality
type B pancreatic cell	CL:0000169	79.10	silver quality
mucosa of stomach	UBERON:0001199	78.72	gold quality
bronchial epithelial cell	CL:0002328	78.65	gold quality
left uterine tube	UBERON:0001303	78.38	gold quality
right lung	UBERON:0002167	78.37	gold quality
metanephros cortex	UBERON:0010533	78.34	gold quality
bronchus	UBERON:0002185	78.30	gold quality
right frontal lobe	UBERON:0002810	78.25	gold quality
epithelial cell of pancreas	CL:0000083	78.10	gold quality
esophagus mucosa	UBERON:0002469	77.08	gold quality
upper lobe of left lung	UBERON:0008952	76.50	gold quality
endocervix	UBERON:0000458	76.49	gold quality
Brodmann (1909) area 9	UBERON:0013540	76.37	gold quality
vermiform appendix	UBERON:0001154	76.27	gold quality
right uterine tube	UBERON:0001302	76.20	gold quality
caudate nucleus	UBERON:0001873	76.10	gold quality
amniotic fluid	UBERON:0000173	75.75	silver quality
caecum	UBERON:0001153	75.73	gold quality
testis	UBERON:0000473	75.68	gold quality
upper lobe of lung	UBERON:0008948	75.52	gold quality
smooth muscle tissue	UBERON:0001135	75.34	gold quality
pancreatic ductal cell	CL:0002079	75.32	silver quality
amygdala	UBERON:0001876	75.13	gold quality
sigmoid colon	UBERON:0001159	75.10	gold quality
putamen	UBERON:0001874	74.64	gold quality
mucosa of paranasal sinus	UBERON:0005030	74.60	silver quality
skin of leg	UBERON:0001511	74.53	gold quality
lower esophagus mucosa	UBERON:0035834	74.30	gold quality
nucleus accumbens	UBERON:0001882	74.23	gold quality
esophagus	UBERON:0001043	74.22	gold quality
corpus callosum	UBERON:0002336	74.03	gold quality
lung	UBERON:0002048	73.97	gold quality
tibial nerve	UBERON:0001323	73.75	gold quality
ectocervix	UBERON:0012249	73.41	gold quality
skin of abdomen	UBERON:0001416	73.34	gold quality
jejunum	UBERON:0002115	73.08	gold quality
tibial artery	UBERON:0007610	72.90	gold quality
popliteal artery	UBERON:0002250	72.88	gold quality
cingulate cortex	UBERON:0003027	72.56	gold quality
zone of skin	UBERON:0000014	72.29	gold quality
anterior cingulate cortex	UBERON:0009835	72.23	gold quality
right ovary	UBERON:0002118	72.15	gold quality
substantia nigra	UBERON:0002038	72.00	gold quality
cortical plate	UBERON:0005343	71.98	gold quality
prostate gland	UBERON:0002367	71.53	gold quality
lower esophagus muscularis layer	UBERON:0035833	71.31	gold quality
lower esophagus	UBERON:0013473	71.29	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	71.24	gold quality
right lobe of thyroid gland	UBERON:0001119	71.09	gold quality
omental fat pad	UBERON:0010414	71.00	gold quality
peritoneum	UBERON:0002358	70.92	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	70.80	gold quality
endometrium	UBERON:0001295	70.65	gold quality
left lobe of thyroid gland	UBERON:0001120	70.52	gold quality
left ovary	UBERON:0002119	70.52	gold quality
vagina	UBERON:0000996	70.50	gold quality
muscle layer of sigmoid colon	UBERON:0035805	70.37	gold quality
hypothalamus	UBERON:0001898	70.36	gold quality
visceral pleura	UBERON:0002401	70.08	gold quality
tonsil	UBERON:0002372	70.00	gold quality
uterus	UBERON:0000995	69.73	gold quality
aorta	UBERON:0000947	69.67	gold quality
right hemisphere of cerebellum	UBERON:0014890	69.44	gold quality
right lobe of liver	UBERON:0001114	69.35	gold quality
adipose tissue of abdominal region	UBERON:0007808	69.35	gold quality
thyroid gland	UBERON:0002046	69.25	gold quality
esophagus squamous epithelium	UBERON:0006920	69.21	silver quality
left coronary artery	UBERON:0001626	68.94	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-GEOD-81547	yes	6704.17
E-GEOD-83139	yes	2299.92
E-MTAB-5061	yes	2258.11
E-ENAD-27	yes	2239.71
E-GEOD-81608	yes	963.64
E-GEOD-125970	yes	45.59
E-CURD-114	yes	11.21
E-MTAB-6386	no	13.16
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 65 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Pancreas	tissue	187.0	high
Gallbladder	tissue	47.0	medium
Colon	tissue	42.2	not detected
Rectum	tissue	40.5	not detected
Duodenum	tissue	32.5	medium
Salivary gland	tissue	21.7	medium
Small intestine	tissue	18.5	medium
Cervix	tissue	8.7	not detected
Lung	tissue	7.7	not detected
Olfactory bulb	tissue	7.3
Appendix	tissue	4.3	not detected
Basal ganglia	tissue	3.0	not detected
Cerebellum	tissue	3.0	not detected
Nucleus accumbens	tissue	2.7
Periaqueductal gray	tissue	2.7
Stomach 1	tissue	2.6	not detected
Ventral forebrain	tissue	2.6
Putamen	tissue	2.4
Medulla oblongata	tissue	2.2
Septum	tissue	2.2
Hypothalamus	tissue	2.1
Cerebral cortex	tissue	2.0	not detected
Spinal cord	tissue	2.0
Corpus callosum	tissue	2.0
Prostate	tissue	2.0	not detected
Hippocampal formation	tissue	2.0
Retrosplenial and cingulate cortex	tissue	2.0
Amygdala	tissue	1.9
Temporal cortex	tissue	1.9
Occipital cortex	tissue	1.9
Insular cortex	tissue	1.9
Smooth muscle	tissue	1.8	not detected
Midbrain	tissue	1.8
Superior colliculi	tissue	1.8
Entorhinal cortex	tissue	1.8
Fallopian tube	tissue	1.8	not detected
Retrosplenial cortex	tissue	1.8
Pons	tissue	1.7
Thalamus	tissue	1.7
Somatosensory cortex	tissue	1.7
Prefrontal cortex	tissue	1.6
Epididymis	tissue	1.6	not detected
Substantia nigra	tissue	1.6
Liver	tissue	1.6	not detected
Motor cortex	tissue	1.5
Caudate putamen	tissue	1.3
Testis	tissue	1.2	not detected
Locus coeruleus	tissue	1.2
Endometrium 1	tissue	1.0	not detected
Esophagus	tissue	0.9	not detected
Hippocampus	tissue	0.9	not detected
Urinary bladder	tissue	0.8	not detected
Kidney	tissue	0.8	high
Postcentral gyrus	tissue	0.8
Seminal vesicle	tissue	0.5	not detected
Placenta	tissue	0.5	not detected
Breast	tissue	0.4	not detected
Parathyroid gland	tissue	0.4	not detected
Tonsil	tissue	0.4	not detected
Adipose tissue	tissue	0.3	not detected

Brain sub-regions (HPA Brain Atlas): detected in 188; highest nTPM — Parieto-temporal junction (white matter) (6.2), Temporal white matter (4.7), Corpus callosum, genu (white matter) (4.2), Corpus callosum, splenium (white matter) (4.0), Globus pallidus, internus (3.7).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF1, CDX2, CEBPA, CEBPB, CEBPD, CEBPG, CTCF, CUX1, DNMT1, ESR1, FOXA1, FOXA2, FOXI1, FOXJ1, HIF1A, HNF1A, HNF1B, KAT7, NFE2L2, NFKB1, NFKB, NR3C1, PBX1, RELA, SP1, SP3, SRF, STAT1, TBP, TCF4, TFAP2A, TXK, USF1, USF2, YY1

miRNA regulators (miRDB)

Targeting CFTR by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 91 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-12136	99.98	72.81	5713
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-652-5P	99.91	67.49	505
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-5582-3P	99.86	72.48	4221

Functional genomics

gnomAD constraint: pLI 2.38e-39, LOEUF 1.15, missense Z -1.07 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000003084 — one region, missense o/e 1.13. ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• CFTR gene transcription is regulated by a DNase I hypersensitive site (PMID:10561583)
• mutational analysis of the entire coding region in idiopathic pancreatitis (PMID:11462247)
• TG(m)T(n) polymorphism has an effect on splicing in transgenic mice (PMID:11597137)
• ‘Chronic complications’ reveal mainly the effect of a long-term absence of previously recognized CFTR functions. In contrast, the ‘unique presentations’ provide new insight into the role of CFTR in different tissues. Review. (PMID:11667976)
• disulfide bond structure (PMID:11688981)
• mutations and phylogeny (place of origin) (PMID:11713719)
• wild type CFTR elevates the acid-gated Na(+) current of ASIC1a/2a in part by altering the kinetics of extracellular Na(+) interaction. (PMID:11748227)
• non-conventional trafficking through the early secretory pathway (PMID:11799116)
• Cl(-) channel and a regulator of other transport proteins and the large number of disease-causing CFTR mutations is the reason for a variable genotype-phenotype correlation and sometimes unpredictable clinical manifestation (PMID:11845294)
• CFTR may play a role in regulated secretion by lymphocytes: a new hypothesis for the pathophysiology of cystic fibrosis. (PMID:11845300)
• role for functional CFTR in regulation of lysozyme secretion in human airways. (PMID:11845302)
• actin must be directly associated with CFTR to elicit its activation, further suggesting that this channel protein may bind actin as well. (PMID:11845308)
• CFTR is an apically resident ion channel whose activity is regulated by the activation of the cAMP mediated second messenger cascade. (PMID:11845310)
• Cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels are regulated tightly by protein kinases and phosphatases (PMID:11845311)
• Localisation of wild-type and DeltaF508-CFTR in nasal epithelial cells. (PMID:11845316)
• mapping of DNase I hypersensitive sites (DHS) within the locus (PMID:11856314)
• Cysteine residues in the nucleotide binding domains regulate the conductance state of CFTR channels (PMID:11867445)
• Tyrosine kinase c-Src constitutes a bridge between cystic fibrosis transmembrane regulator channel failure and MUC1 overexpression in cystic fibrosis (PMID:11872746)
• Evidence for direct interaction between actin and the cystic fibrosis transmembrane conductance regulator. (PMID:11908853)
• Discrimination between CF cells and CFTR-corrected epithelial cells by a membrane potential-sensitive probe and digital imaging technique that detects response to cAMP in the majority of CFTR-corrected cells, but only in a small proportion of CF cells. (PMID:11936773)
• data support a model where nucleotide-binding domains form dimers with the ATP-binding sites at the domain-domain interface (PMID:11940532)
• A short segment of the R domain of cystic fibrosis transmembrane conductance regulator contains channel stimulatory and inhibitory activities that are separable by sequence modification (PMID:11950844)
• Protein kinase C epsilon-dependent regulation of cystic fibrosis transmembrane regulator involves binding to a receptor for activated C kinase (RACK1) and RACK1 binding to Na+/H+ exchange regulatory factor. (PMID:11956211)
• calcium channel inhibitors induce surface expression in cystic fibrosis cultured epithelial cells of mutated protein (PMID:11984593)
• Men with the CFTR mutation, the 5T allele only, and those without CFTR mutation have few differences in genital phenotype. Low testicular volume is observed in men without the CFTR mutation and those with the 5T allele only. (PMID:12009340)
• Glutathione levels and BAX activation during apoptosis due to oxidative stress in cells expressing wild-type and mutant protein (PMID:12023951)
• Csp has a role in regulated CFTR trafficking at the plasma membrane. [CYSTEINE STRING PROTEIN] (PMID:12039948)
• Sequence alignment of representative vertebrate CFTR with the aim of generating hypotheses on the functional significance of conserved and variable residues. (PMID:12054472)
• The allele and genotype frequencies of the tetranucleotide tandem repeat (TTR) of CFTR intron 6B were analyzed in eight ethnic populations of the Volga-Ural region, including Bashkir, Tatar, Chuvash, Mari, Mordvinian, Udmurt, Komi-Permyak, and Russian (PMID:12068629)
• Role of Hsp40 co-chaperone Hdj-1 in CFTR turnover with HSP70 (PMID:12069690)
• Introduction of the most common mutations into human P-glycoprotein disrupts packing of the transmembrane segments. (PMID:12070134)
• A novel natural product compound enhances cAMP-regulated chloride conductance of cells expressing CFTR[delta]F508 (PMID:12080183)
• These studies demonstrate that luc-containing YAC vectors can be used to study CFTR expression in human cells, and that regulatory elements responsible for decreased CFTR expression in response to PMA are not located in the 5’-flanking sequence. (PMID:12084577)
• substitution of two residues eliminates aggregation of a 111-amino acid peptide derived from the C-terminal portion of the cystic fibrosis transmembrane conductance regulator (CFTR). (PMID:12084728)
• mutations in CFTR nucleotide binding domain region rescue the CFTRDeltaF508 defect (PMID:12110684)
• The comparison of primary sclerosing cholangitis patients with healthy controls showed no significant difference in the frequency of CFTR mutations (PMID:12127423)
• CFTR gene mutation is observed with trypsinogen levels more than 60 ng/mL. (PMID:12139895)
• CFTR may contribute to blastocoele formation in the early human embryo (PMID:12149408)
• Analysis by mass spectrometry of 100 cystic fibrosis gene mutations in 92 patients with congenital bilateral absence of the vas deferens. Compound heterozygosity. (PMID:12151438)
• CFTR channels are regulated by a t-SNARE complex that may tune CFTR activity to rates of membrane traffic in epithelial cells. (PMID:12209004)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
danio_rerio	cftr	ENSDARG00000041107
mus_musculus	Cftr	ENSMUSG00000041301
rattus_norvegicus	Cftr	ENSRNOG00000055103
drosophila_melanogaster	l(2)03659	FBGN0010549
drosophila_melanogaster	CG7627	FBGN0032026
drosophila_melanogaster	MRP	FBGN0032456
drosophila_melanogaster	CG9270	FBGN0032908
drosophila_melanogaster	CG10505	FBGN0034612
drosophila_melanogaster	Mrp5	FBGN0038740
drosophila_melanogaster	rdog	FBGN0039644
drosophila_melanogaster	CG11898	FBGN0039645
drosophila_melanogaster	CG31792	FBGN0051792
drosophila_melanogaster	Mrp4	FBGN0263316
caenorhabditis_elegans		WBGENE00000477

Paralogs (11): ABCC8 (ENSG00000006071), ABCC2 (ENSG00000023839), ABCC9 (ENSG00000069431), ABCC6 (ENSG00000091262), ABCC1 (ENSG00000103222), ABCC3 (ENSG00000108846), ABCC5 (ENSG00000114770), ABCC11 (ENSG00000121270), ABCC10 (ENSG00000124574), ABCC4 (ENSG00000125257), ABCC12 (ENSG00000140798)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:88388) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 110 distinct phenotype terms.

Mouse phenotype (MP)	Records
intestinal obstruction	13
postnatal lethality, incomplete penetrance	13
premature death	8
decreased respiratory epithelial chloride transmembrane transport	8
decreased body weight	6
postnatal growth retardation	6
abnormal intestine goblet cell morphology	6
decreased body size	5
peritoneal inflammation	5
meconium ileus	5
abnormal intestine morphology	4
abnormal crypts of Lieberkuhn morphology	4
lung inflammation	4
decreased intestinal epithelial chloride transmembrane transport	4
dilated crypt of Lieberkuhn	4
abnormal colon morphology	3
abnormal digestive system physiology	3
decreased respiratory epithelial sodium ion transmembrane transport	3
impaired fertilization	2
abnormal intestinal mucosa morphology	2
female infertility	2
decreased litter size	2
abnormal pancreas morphology	2
abnormal small intestine crypts of Lieberkuhn morphology	2
abnormal large intestine crypts of Lieberkuhn morphology	2

+85 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Macaca mulatta	Q00553	100.0%	Diamond
Macaca fuscata fuscata	Q7JII7	100.0%	Diamond
Macaca fascicularis	Q7JII8	100.0%	Diamond
Papio anubis	Q9TSP5	99.9%	Diamond
Macaca nemestrina	Q9TUQ2	99.9%	Diamond
Muntiacus reevesi	Q07DW5	99.7%	Diamond
Muntiacus muntjak	Q09YJ4	99.7%	Diamond
Chlorocebus aethiops	Q2IBA1	99.7%	Diamond
Gorilla gorilla gorilla	Q2IBF6	99.7%	Diamond
Pan troglodytes	Q2QLE5	99.7%	Diamond
Pongo abelii	Q2IBE4	99.1%	Diamond
Nomascus leucogenys	Q07DX5	99.0%	Diamond
Colobus guereza	Q07DY5	99.0%	Diamond
Aotus nancymaae	Q07DV2	98.9%	Diamond
Saimiri boliviensis boliviensis	Q09YH0	98.9%	Diamond
Plecturocebus moloch	Q2QLB4	98.7%	Diamond
Callithrix jacchus	Q2QLF9	98.5%	Diamond
Bos taurus	P35071	98.4%	Diamond
Ovis aries	Q00555	98.4%	Diamond
Ateles geoffroyi	Q09YK5	98.4%	Diamond
Microcebus murinus	Q2QL83	95.1%	Diamond
Otolemur garnettii	Q2QLH0	95.1%	Diamond
Equus caballus	Q2QLA3	94.6%	Diamond
Sus scrofa	Q6PQZ2	94.6%	Diamond
Mustela putorius furo	Q07E16	93.9%	Diamond
Didelphis virginiana	Q2QL74	93.2%	Diamond
Trichosurus vulpecula	Q5D1Z7	93.2%	Diamond
Atelerix albiventris	Q00PJ2	92.9%	Diamond
Oryctolagus cuniculus	Q00554	92.8%	Diamond
Canis lupus familiaris	Q5U820	92.5%	Diamond
Dasypus novemcinctus	Q07E42	92.4%	Diamond
Cavia porcellus	Q00552	91.8%	Diamond
Loxodonta africana	Q108U0	91.8%	Diamond
Rhinolophus ferrumequinum	Q2IBB3	90.9%	Diamond
Carollia perspicillata	Q2QLC5	90.3%	Diamond
Ornithorhynchus anatinus	Q07DZ6	84.7%	Diamond
Xenopus laevis	P26363	77.6%	Diamond
Squalus acanthias	P26362	71.6%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
CFTR-AS1	ncRNA	111082987
ASZ1	protein-coding	136991
WNT2	protein-coding	7472
CFTR-AS2	ncRNA	140577507
LSM8	protein-coding	51691
CTTNBP2	protein-coding	83992
ANKRD7	protein-coding	56311

Protein

Protein identifiers

Cystic fibrosis transmembrane conductance regulator — P13569 (reviewed: P13569)

Alternative names: ATP-binding cassette sub-family C member 7, Channel conductance-controlling ATPase, cAMP-dependent chloride channel

All UniProt accessions (20): P13569, A0A3B3IT97, A0A3B3ITE0, A0A3B3ITW0, A0A3B3ITW5, A0A669KBE8, A0A8I5KVL1, A0A8I5KVV2, A0A8I5KXQ9, A0A8V8TNG7, A0A8V8TNH2, A0A8V8TNN0, A0A8V8TNN7, A0A8V8TPV6, A0A8V8TQ89, A0A8V8TQ94, C9J6L5, E7EPB6, H0Y8A9, M0QYZ3

UniProt curated annotations — full annotation on UniProt →

Function. Epithelial ion channel that plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis. Mediates the transport of chloride ions across the cell membrane. 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. The ion channel is also permeable to HCO(3)(-); selectivity depends on the extracellular chloride concentration. In vitro, mediates ATP-dependent glutathione flux. Exerts its function also by modulating the activity of other ion channels and transporters. Plays an important role in airway fluid homeostasis. 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. Modulates the activity of the epithelial sodium channel (ENaC) complex, in part by regulating the cell surface expression of the ENaC complex. Inhibits the activity of the ENaC channel containing subunits SCNN1A, SCNN1B and SCNN1G. 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. May regulate bicarbonate secretion and salvage in epithelial cells by regulating the transporter SLC4A7. Can inhibit the chloride channel activity of ANO1. Plays a role in the chloride and bicarbonate homeostasis during sperm epididymal maturation and capacitation.

Subunit / interactions. Monomer; does not require oligomerization for channel activity. May form oligomers in the membrane. Interacts with SLC26A3, SLC26A6 and SHANK2. Interacts with NHERF1 and MYO6. Interacts (via C-terminus) with GOPC (via PDZ domain); this promotes CFTR internalization and thereby decreases channel activity. Interacts with SLC4A7 through NHERF1. Found in a complex with MYO5B and RAB11A. Interacts with ANO1. Interacts with SLC26A8. Interacts with AHCYL1; the interaction increases CFTR activity. Interacts with CSE1L. The core-glycosylated form interacts with GORASP2 (via PDZ GRASP-type 1 domain) in respone to ER stress. Interacts with MARCHF2; the interaction leads to CFTR ubiquitination and degradation. Interacts with ADGRG2.

Subcellular location. Apical cell membrane. Early endosome membrane. Cell membrane. Recycling endosome membrane. Endoplasmic reticulum membrane. Nucleus.

Tissue specificity. Expressed in the respiratory airway, including bronchial epithelium, and in the female reproductive tract, including oviduct (at protein level). Detected in pancreatic intercalated ducts in the exocrine tissue, on epithelial cells in intralobular striated ducts in sublingual salivary glands, on apical membranes of crypt cells throughout the small and large intestine, and on the reabsorptive duct in eccrine sweat glands. Detected on the equatorial segment of the sperm head (at protein level). Detected in nasal and bronchial superficial epithelium. Expressed by the central cells on the sebaceous glands, dermal adipocytes and, at lower levels, by epithelial cells.

Post-translational modifications. N-glycosylated. Phosphorylated; cAMP treatment promotes phosphorylation and activates the channel. Dephosphorylation decreases the ATPase activity (in vitro). Phosphorylation at PKA sites activates the channel. Phosphorylation at PKC sites enhances the response to phosphorylation by PKA. Phosphorylated by AMPK; this inhibits channel activity. Ubiquitinated, leading to its degradation in the lysosome. Deubiquitination by USP10 in early endosomes enhances its endocytic recycling to the cell membrane. Ubiquitinated by RNF185 during ER stress. Ubiquitinated by MARCHF2.

Disease relevance. Cystic fibrosis (CF) [MIM:219700] A common generalized disorder of the exocrine glands which impairs clearance of secretions in a variety of organs. It is characterized by the triad of chronic bronchopulmonary disease (with recurrent respiratory infections), pancreatic insufficiency (which leads to malabsorption and growth retardation) and elevated sweat electrolytes. It is the most common genetic disease in Caucasians, with a prevalence of about 1 in 2'000 live births. Inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry. There is some evidence that the functional defect caused by the most common variant Phe-508 DEL can be corrected by the binding to the snake phospholipase A2 crotoxin basic subunit CB. This toxin both disrupts the Phe-508 DEL-cytokeratin 8 complex, allowing for the escape from degradation, and increases the chloride channel current. Congenital bilateral absence of the vas deferens (CBAVD) [MIM:277180] An autosomal recessive disease characterized by vas deferens aplasia resulting in azoospermia and male infertility. CBAVD may occur in isolation or as a manifestation of cystic fibrosis. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Binds and hydrolyzes ATP via the two cytoplasmic ABC transporter nucleotide-binding domains. The two ATP-binding domains interact with each other, forming a head-to-tail dimer. Normal ATPase activity requires interaction between the two domains. The first ABC transporter nucleotide-binding domain has no ATPase activity by itself. The PDZ-binding motif mediates interactions with GOPC and with the SLC4A7, NHERF1/EBP50 complex. The R region is intrinsically disordered. It mediates channel activation when it is phosphorylated, but not in the absence of phosphorylation.

Miscellaneous. Exon 9 splicing depends upon 2 polymorphic tracts within intron 8, a T(n) tract and TG(n) tract, where the number of T and/or TG repeats affect the extent of correct splicing of exon 9. Low numbers of T residues and high numbers of TG repeats give rise to less efficient splicing. Transcripts that lack exon 9 sequences fail to mature. Causes congenital bilateral absence of the vas deferens (CBAVD). Alternative acceptor site favored by mutation in an exonic splicing enhancer (ESE). Causes cystic fibrosis (CF).

Similarity. Belongs to the ABC transporter superfamily. ABCC family. CFTR transporter (TC 3.A.1.202) subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P13569-1	1	yes
P13569-2	2
P13569-3	3

RefSeq proteins (1): NP_000483* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003439	ABC_transporter-like_ATP-bd	Domain
IPR003593	AAA+_ATPase	Domain
IPR009147	CFTR/ABCC7	Family
IPR011527	ABC1_TM_dom	Domain
IPR017871	ABC_transporter-like_CS	Conserved_site
IPR025837	CFTR_reg_dom	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036640	ABC1_TM_sf	Homologous_superfamily
IPR047082	CFTR1_ATP-bd_dom1	Domain
IPR050173	ABC_transporter_C-like	Family

Pfam: PF00005, PF00664, PF14396

Enzyme classification (BRENDA)

• EC 2.7.4.3 — adenylate kinase (BRENDA: 73 organisms, 259 substrates, 134 inhibitors, 192 Km, 47 kcat entries)
• EC 5.6.1.6 — channel-conductance-controlling ATPase (BRENDA: 13 organisms, 102 substrates, 71 inhibitors, 16 Km, 3 kcat entries)

Substrate kinetics (BRENDA)

11 substrates with measured Km, best-characterized 11. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
AMP	0.0014–1.9	59
ATP	0.0001–7	58
ADP	0.003–16.8	27
ATP	0.0033–2.2	13
2 ADP	0.006–0.15	5
DAMP	0.507–2	2
2’-DAMP	0.85	1
7-DEAZAADENOSINE 5’-MONOPHOSPHATE	0.73	1
ADP3-	0.03	1
CMP	0.0002	1
MGATP2-	0.15	1

Catalyzed reactions (Rhea)

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)
• hydrogencarbonate(in) = hydrogencarbonate(out) (RHEA:28695)
• chloride(in) = chloride(out) (RHEA:29823)

UniProt features (406 total): sequence variant 209, helix 76, strand 31, modified residue 15, topological domain 13, mutagenesis site 13, transmembrane region 12, turn 11, binding site 6, domain 4, region of interest 3, splice variant 3, sequence conflict 2, lipid moiety-binding region 2, glycosylation site 2, chain 1, short sequence motif 1, compositionally biased region 1, cross-link 1

Structure

Experimental structures (PDB)

showing 30 of 60 structures by resolution:

PDB	Title	Method	Resolution (Å)
2PZE	Minimal human CFTR first nucleotide binding domain as a head-to-tail dimer	X-RAY DIFFRACTION	1.7
7QI1	Crystal structure of human 14-3-3 protein beta in complex with CFTR peptide pS753pS768 …	X-RAY DIFFRACTION	1.76
2PZG	Minimal human CFTR first nucleotide binding domain as a monomer	X-RAY DIFFRACTION	1.8
5TFJ	Nucleotide-binding domain 1 of the human cystic fibrosis transmembrane conductance …	X-RAY DIFFRACTION	1.85
6WBS	Human CFTR first nucleotide binding domain with dF508/V510D	X-RAY DIFFRACTION	1.86
6HEP	Crystal structure of human 14-3-3 beta in complex with CFTR R-domain peptide pS753-pS768	X-RAY DIFFRACTION	1.86
5TF8	Nucleotide-binding domain 1 of the human cystic fibrosis transmembrane conductance …	X-RAY DIFFRACTION	1.86
5TFA	Nucleotide-binding domain 1 of the human cystic fibrosis transmembrane conductance …	X-RAY DIFFRACTION	1.87
5TFB	Nucleotide-binding domain 1 of the human cystic fibrosis transmembrane conductance …	X-RAY DIFFRACTION	1.87
5TFD	Nucleotide-binding domain 1 of the human cystic fibrosis transmembrane conductance …	X-RAY DIFFRACTION	1.89
5TFF	Nucleotide-binding domain 1 of the human cystic fibrosis transmembrane conductance …	X-RAY DIFFRACTION	1.89
5TFI	Nucleotide-binding domain 1 of the human cystic fibrosis transmembrane conductance …	X-RAY DIFFRACTION	1.89
5TFG	Nucleotide-binding domain 1 of the human cystic fibrosis transmembrane conductance …	X-RAY DIFFRACTION	1.91
5TGK	Nucleotide-binding domain 1 of the human cystic fibrosis transmembrane conductance …	X-RAY DIFFRACTION	1.91
5TFC	Nucleotide-binding domain 1 of the human cystic fibrosis transmembrane conductance …	X-RAY DIFFRACTION	1.92
5TF7	Nucleotide-binding domain 1 of the human cystic fibrosis transmembrane conductance …	X-RAY DIFFRACTION	1.93
6GJS	Human NBD1 of CFTR in complex with nanobodies D12 and T4	X-RAY DIFFRACTION	1.95
2PZF	Minimal human CFTR first nucleotide binding domain as a head-to-tail dimer with delta F508	X-RAY DIFFRACTION	2
2BBS	Human deltaF508 NBD1 with three solubilizing mutations	X-RAY DIFFRACTION	2.05
4WZ6	Human CFTR aa389-678 (NBD1), deltaF508 with three solubilizing mutations, bound ATP	X-RAY DIFFRACTION	2.05
5D2D	Crystal structure of human 14-3-3 zeta in complex with CFTR R-domain peptide pS753-pS768	X-RAY DIFFRACTION	2.1
9MXL	Complex of the phosphorylated human cystic fibrosis transmembrane conductance regulator …	ELECTRON MICROSCOPY	2.1
1XMI	Crystal structure of human F508A NBD1 domain with ATP	X-RAY DIFFRACTION	2.25
1XMJ	Crystal structure of human deltaF508 human NBD1 domain with ATP	X-RAY DIFFRACTION	2.3
2BBT	Human deltaF508 NBD1 with two solublizing mutations.	X-RAY DIFFRACTION	2.3
6GJQ	human NBD1 of CFTR in complex with nanobody T27	X-RAY DIFFRACTION	2.49
2BBO	Human NBD1 with Phe508	X-RAY DIFFRACTION	2.55
6GJU	human NBD1 of CFTR in complex with nanobodies T2a and T4	X-RAY DIFFRACTION	2.6
6UK1	Crystal structure of nucleotide-binding domain 2 (NBD2) of the human Cystic Fibrosis …	X-RAY DIFFRACTION	2.69
3GD7	Crystal structure of human NBD2 complexed with N6-Phenylethyl-ATP (P-ATP)	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P13569-F1	75.96	0.33

Antibody-complex structures (SAbDab)

6 antibodies co-crystallized with this protein: 6GJQ, 6GJS, 6GJU, 6GK4, 6GKD, 6ZE1

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Isomerase, Transporters, Primary Active Transporters, Predicted membrane proteins, Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Candidate cancer biomarkers, Disease related genes, FDA approved drug targets, Small molecule drugs, Human disease related genes, Congenital disorders of metabolism, Congenital disorders of ion transport and metabolism, Congenital malformations, Congenital malformations of genital organs

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH enhanced

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (6)

Position	Role
401	ATP
434	ATP
458–465	ATP
493	ATP
1219	ATP
1244–1251	ATP

Post-translational modifications (18)

Type	Positions
Phosphoserine	549, 660, 670, 686, 700, 712, 737, 753, 768, 790, 795, 813, 1444, 1456
Phosphothreonine	717
S-palmitoyl cysteine	524, 1395
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in ubiquitin)	688

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	894, 900

Mutagenesis-validated functional residues (13)

Position	Phenotype
347	decreases glutathione uptake. increases affinity for glutathione.
464	decreases glutathione uptake.
464	impaired maturation of glycan chains indicating impaired trafficking from the endoplasmic reticulum to the cell membrane.
508	impaired maturation of glycan chains indicating impaired trafficking from the endoplasmic reticulum to the cell membrane.
539	enhances trafficking from the endoplasmic reticulum to the cell membrane.
894	abolishes n-glycosylation, enhances endocytosis and impairs subsequent recycling to the cell surface; when associated with d-900.
900	abolishes n-glycosylation, enhances endocytosis and impairs subsequent recycling to the cell surface; when associated with d-894.
1137	abolishes channel activity. impairs protein maturation, suggesting the protein is retained in the endoplasmic reticulum.
1139	decreases channel activity, no visible effect on protein maturation.
1154	decreases channel activity, no visible effect on protein maturation.
1250	decreases glutathione uptake.
1250	no effect on maturation of glycans, suggesting that trafficking to the plasma membrane is not altered.
1478–1480	reduces interaction with marchf2 and abolishes subsequent marchf2-mediated degradation. no effect on localization to the golgi.

Function

Pathways and Gene Ontology

Reactome pathways

8 curated (TAS) of 31; 4 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

31 pathways:

ID	Pathway	Evidence
R-HSA-5678895	Defective CFTR causes cystic fibrosis ⚕	curated
R-HSA-382556	ABC-family protein mediated transport	curated
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis	curated
R-HSA-8856828	Clathrin-mediated endocytosis	curated
R-HSA-9925563	Developmental Lineage of Pancreatic Ductal Cells	curated
R-HSA-5627083	RHO GTPases regulate CFTR trafficking	curated
R-HSA-9013406	RHOQ GTPase cycle	curated
R-HSA-5689880	Ub-specific processing proteases	curated
R-HSA-5619084	ABC transporter disorders ⚕	—
R-HSA-1643685	Disease ⚕	—
R-HSA-5619115	Disorders of transmembrane transporters ⚕	—
R-HSA-9646399	Aggrephagy	electronic
R-HSA-9612973	Autophagy	—
R-HSA-9613829	Chaperone Mediated Autophagy	electronic
R-HSA-5688426	Deubiquitination	—
R-HSA-1266738	Developmental Biology	—
R-HSA-9734767	Developmental Cell Lineages	—
R-HSA-9820448	Developmental Cell Lineages of the Exocrine Pancreas	—
R-HSA-9615710	Late endosomal microautophagy	electronic
R-HSA-1632852	Macroautophagy	—
R-HSA-199991	Membrane Trafficking	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-597592	Post-translational protein modification	—
R-HSA-195258	RHO GTPase Effectors	—
R-HSA-9012999	RHO GTPase cycle	—
R-HSA-9663891	Selective autophagy	—
R-HSA-162582	Signal Transduction	—
R-HSA-194315	Signaling by Rho GTPases	—
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3	—
R-HSA-382551	Transport of small molecules	—
R-HSA-5653656	Vesicle-mediated transport	—

MSigDB gene sets: 498 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, MIDORIKAWA_AMPLIFIED_IN_LIVER_CANCER, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOCC_VACUOLAR_MEMBRANE, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOCC_CELL_SURFACE, GOBP_INORGANIC_ANION_TRANSPORT, GOBP_MALE_GAMETE_GENERATION, REACTOME_MEMBRANE_TRAFFICKING, GOBP_TOOTH_MINERALIZATION, GGGTGGRR_PAX4_03, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, KEGG_ABC_TRANSPORTERS, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, GOBP_SPERM_CAPACITATION

GO Biological Process (17): water transport (GO:0006833), bicarbonate transport (GO:0015701), response to endoplasmic reticulum stress (GO:0034976), transepithelial water transport (GO:0035377), sperm capacitation (GO:0048240), multicellular organismal-level water homeostasis (GO:0050891), intracellular pH elevation (GO:0051454), transmembrane transport (GO:0055085), membrane hyperpolarization (GO:0060081), positive regulation of enamel mineralization (GO:0070175), cellular response to cAMP (GO:0071320), amelogenesis (GO:0097186), chloride transmembrane transport (GO:1902476), cellular response to forskolin (GO:1904322), monoatomic ion transport (GO:0006811), chloride transport (GO:0006821), monoatomic ion transmembrane transport (GO:0034220)

GO Molecular Function (19): chloride channel activity (GO:0005254), intracellularly ATP-gated chloride channel activity (GO:0005260), ATP binding (GO:0005524), bicarbonate transmembrane transporter activity (GO:0015106), chloride transmembrane transporter activity (GO:0015108), ATP hydrolysis activity (GO:0016887), chloride channel regulator activity (GO:0017081), chloride channel inhibitor activity (GO:0019869), enzyme binding (GO:0019899), PDZ domain binding (GO:0030165), ATPase-coupled transmembrane transporter activity (GO:0042626), identical protein binding (GO:0042802), protein-folding chaperone binding (GO:0051087), 14-3-3 protein binding (GO:0071889), Sec61 translocon complex binding (GO:0106138), ABC-type transporter activity (GO:0140359), nucleotide binding (GO:0000166), protein binding (GO:0005515), isomerase activity (GO:0016853)

GO Cellular Component (19): nucleus (GO:0005634), cytoplasm (GO:0005737), lysosomal membrane (GO:0005765), early endosome (GO:0005769), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), plasma membrane (GO:0005886), cell surface (GO:0009986), endosome membrane (GO:0010008), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), Golgi-associated vesicle membrane (GO:0030660), clathrin-coated endocytic vesicle membrane (GO:0030669), early endosome membrane (GO:0031901), protein-containing complex (GO:0032991), chloride channel complex (GO:0034707), recycling endosome (GO:0055037), recycling endosome membrane (GO:0055038)

Reactome top-level categories

13 top-level categories:

Category	Pathways
Autophagy	3
Transport of small molecules	1
RHO GTPase Effectors	1
ABC transporter disorders	1
Deubiquitination	1
Clathrin-mediated endocytosis	1
Membrane Trafficking	1
RHO GTPase cycle	1
Selective autophagy	1
Developmental Cell Lineages of the Exocrine Pancreas	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Vesicle-mediated transport	1

GO top-level categories

showing 60 of 86 GO namespaces:

Category	Terms
protein binding	4
cellular anatomical structure	4
transport	3
chloride channel activity	3
endosome	3
ATP-dependent activity	2
cytoplasmic vesicle membrane	2
bounding membrane of organelle	2
plasma membrane region	2
endosome membrane	2
fluid transport	1
cellular response to stress	1
water transport	1
epithelial fluid transport	1
developmental process involved in reproduction	1
spermatid development	1
cellular process involved in reproduction in multicellular organism	1
cell maturation	1
regulation of body fluid levels	1
multicellular organismal-level chemical homeostasis	1
regulation of intracellular pH	1
cellular process	1
regulation of membrane potential	1
enamel mineralization	1
positive regulation of tooth mineralization	1
regulation of enamel mineralization	1
response to cAMP	1
cellular response to nitrogen compound	1
cellular response to oxygen-containing compound	1
odontogenesis of dentin-containing tooth	1
anatomical structure formation involved in morphogenesis	1
chloride transport	1
monoatomic anion transmembrane transport	1
cellular response to lipid	1
cellular response to alcohol	1
cellular response to ketone	1
response to forskolin	1
monoatomic anion transport	1
inorganic anion transport	1
monoatomic ion transport	1
transmembrane transport	1
monoatomic anion channel activity	1
chloride transmembrane transporter activity	1
ligand-gated monoatomic anion channel activity	1
intracellularly ATP-gated ion channel activity	1
polypeptide conformation or assembly isomerase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
bicarbonate transport	1
transmembrane transporter activity	1
monoatomic anion transmembrane transporter activity	1
chloride transmembrane transport	1
ribonucleoside triphosphate phosphatase activity	1
ion channel regulator activity	1
ion channel inhibitor activity	1
chloride channel regulator activity	1
protein domain specific binding	1
primary active transmembrane transporter activity	1
ATP hydrolysis activity	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 27 of 55 annotations. The rest are phylogenetic / computational / electronic (IEA).

27 experimentally-supported GO terms:

GO term	NS	Evidence
bicarbonate transport	BP	direct assay
cellular response to forskolin	BP	direct assay
chloride transmembrane transport	BP	direct assay
multicellular organismal-level water homeostasis	BP	mutant phenotype
response to endoplasmic reticulum stress	BP	direct assay
transepithelial water transport	BP	mutant phenotype
apical plasma membrane	CC	direct assay
cell surface	CC	direct assay
cytoplasm	CC	direct assay
cytosol	CC	direct assay
early endosome	CC	direct assay
endoplasmic reticulum membrane	CC	direct assay
membrane	CC	direct assay
plasma membrane	CC	direct assay
protein-containing complex	CC	direct assay
recycling endosome	CC	direct assay
14-3-3 protein binding	MF	mutant phenotype
ATP hydrolysis activity	MF	direct assay
PDZ domain binding	MF	direct assay
Sec61 translocon complex binding	MF	direct assay
bicarbonate transmembrane transporter activity	MF	direct assay
chloride channel activity	MF	direct assay
chloride channel inhibitor activity	MF	direct assay
enzyme binding	MF	physical interaction
identical protein binding	MF	physical interaction
intracellularly ATP-gated chloride channel activity	MF	mutant phenotype
protein-folding chaperone binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 3,544 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CFTR	SCNN1B	P51168	889
CFTR	SPINK1	P00995	872
CFTR	SLC26A6	Q9BXS9	862
CFTR	PRSS1	P07477	841
CFTR	CTRC	Q99895	838
CFTR	SCNN1G	P51170	821
CFTR	SLC9A3	P48764	820
CFTR	GUCY2C	P25092	807
CFTR	SCNN1A	P37088	791
CFTR	SLC26A3	P40879	790
CFTR	GUCA2A	Q02747	780
CFTR	NHERF1	O14745	759
CFTR	SLC26A9	Q7LBE3	745
CFTR	GUCA2B	Q16661	744
CFTR	RNF5	Q99942	744

IntAct

Human interaction partners of CFTR in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 542 partners by confidence:

Partner	Interaction type	MIscore	Records
NHERF1	direct interaction	0.940	11
NHERF2	physical association	0.940	10
PPP2R1A	physical association	0.890	4
CANX	physical association	0.890	3
HSPD1	physical association	0.790	2
VPS4A	physical association	0.790	2
CLIC1	physical association	0.790	1
COPG1	physical association	0.790	1
PDZK1	physical association	0.780	7
GOPC	physical association	0.770	2
GORASP2	physical association	0.750	4
PTBP1	direct interaction	0.750	1
HACD3	colocalization	0.740	2
DSTN	physical association	0.740	1
PDIA4	colocalization	0.740	1
SDHA	physical association	0.740	1
ACTB	physical association	0.730	2
CAP1	physical association	0.720	3
CAPZB	physical association	0.720	3
PDIA3	physical association	0.720	3
RNF5	colocalization	0.720	3
CALM1	physical association	0.720	1
GNB2	physical association	0.720	1
STAU1	physical association	0.720	1
ESYT2	association	0.710	13
TRAFD1	physical association	0.710	3
CASK	direct interaction	0.710	2
TFG	physical association	0.710	2
XPO1	association	0.710	2
KRT18	association	0.710	1

BioGRID (1,949 interactions; top human partners by supporting records in a sample of 600 records): MARCH2 (Affinity Capture-Western; 3 records), HSPA8 (Affinity Capture-Western; 2 records), HSPB1 (Affinity Capture-Western; 2 records), MYO6 (Affinity Capture-Western; 2 records), RNF185 (Affinity Capture-Western; 2 records), SLC4A7 (Affinity Capture-Western; 2 records), SQSTM1 (Affinity Capture-Western; 2 records), A2M (Affinity Capture-MS), AARS (Affinity Capture-MS), AARS2 (Affinity Capture-MS), ABCB10 (Affinity Capture-MS), ABCB7 (Affinity Capture-MS), ABCC11 (Affinity Capture-MS), ACADVL (Affinity Capture-MS), ACLY (Affinity Capture-MS)

SIGNOR signaling

showing 23 of 38 signaling interactions:

A	Effect	B	Mechanism
GOPC	down-regulates	CFTR	binding
CSNK2A1	up-regulates	CFTR	phosphorylation
CSNK2A1	down-regulates	CFTR	phosphorylation
PRKACA	“down-regulates activity”	CFTR	phosphorylation
PRKG1	up-regulates	CFTR	phosphorylation
ivacaftor	down-regulates	CFTR	“chemical inhibition”
PRKACA	up-regulates	CFTR	phosphorylation
AMPK	“down-regulates activity”	CFTR	phosphorylation
FOXI1	“up-regulates quantity by expression”	CFTR	“transcriptional regulation”
PRKAA1	“down-regulates activity”	CFTR	phosphorylation
STK39	“down-regulates activity”	CFTR	phosphorylation
HSPA8	“down-regulates quantity”	CFTR	binding
RNF5	“down-regulates quantity by destabilization”	CFTR	ubiquitination
STUB1	“down-regulates quantity by destabilization”	CFTR	polyubiquitination
LMTK2	“down-regulates activity”	CFTR	phosphorylation
MARCHF2	“down-regulates quantity by destabilization”	CFTR	ubiquitination
STUB1	“down-regulates quantity by destabilization”	CFTR	ubiquitination
glyburide	“down-regulates activity”	CFTR	“chemical inhibition”
tolbutamide	“down-regulates activity”	CFTR	“chemical inhibition”
PP1	“up-regulates activity”	CFTR	dephosphorylation
PRKCA	“up-regulates activity”	CFTR	phosphorylation
PRKG1	“up-regulates activity”	CFTR	phosphorylation
PRKACA	“up-regulates activity”	CFTR	phosphorylation

Protein complexes (CORUM) (4)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

4 complexes by size:

Complex	Subunits	Members
★ C-CFTR-NHERF-ezrin complex	3	CFTR, EZR, NHERF1
★ ADRB2-CFTR-NHERF1 complex	3	ADRB2, CFTR, NHERF1
★ CFTR-GOPC-STX6 complex	3	CFTR, GOPC, STX6
★ ANO1-CFTR complex	2	ANO1, CFTR

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 542 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	6	10.0×	5e-03
Unblocking of NMDA receptors, glutamate binding and activation	6	9.5×	5e-03
Negative regulation of NMDA receptor-mediated neuronal transmission	6	9.5×	5e-03
Neurexins and neuroligins	13	7.5×	1e-05
Assembly and cell surface presentation of NMDA receptors	10	7.4×	4e-04
Protein-protein interactions at synapses	9	7.0×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	12.0×	1e-05
protein localization to synapse	7	11.1×	1e-03
receptor clustering	7	9.0×	4e-03

Disease & clinical

Genetic variants

Variant evidence for CFTR: 6,148 ClinVar records (1,320 pathogenic / likely pathogenic); 2 PharmGKB dosing guidelines; 9 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

6,148 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	925
Likely pathogenic	395
Uncertain significance	2481
Likely benign	1486
Benign	69

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 1,320 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
7105	NM_000492.3(CFTR):c.1521_1523del (p.Phe508del)	Pathogenic	practice guideline	101
7136	NM_000492.4(CFTR):c.3909C>G (p.Asn1303Lys)	Pathogenic	practice guideline	52
7109	NM_000492.4(CFTR):c.350G>A (p.Arg117His)	Pathogenic	practice guideline	49
7115	NM_000492.4(CFTR):c.1624G>T (p.Gly542Ter)	Pathogenic	practice guideline	45
7129	NM_000492.4(CFTR):c.3846G>A (p.Trp1282Ter)	Pathogenic	practice guideline	43
38497	NM_000492.4(CFTR):c.2657+5G>A	Pathogenic	practice guideline	38
7120	NM_000492.4(CFTR):c.1652G>A (p.Gly551Asp)	Pathogenic	practice guideline	36
7139	NM_000492.4(CFTR):c.1000C>T (p.Arg334Trp)	Pathogenic	practice guideline	36
38799	NM_000492.4(CFTR):c.489+1G>T	Pathogenic	practice guideline	36
7106	NM_000492.4(CFTR):c.1516ATC[1] (p.Ile507del)	Pathogenic	practice guideline	34
7112	NM_000492.4(CFTR):c.1585-1G>A	Pathogenic	practice guideline	33
7122	NM_000492.4(CFTR):c.1657C>T (p.Arg553Ter)	Pathogenic	practice guideline	33
7224	NM_000492.4(CFTR):c.2988+1G>A	Pathogenic	practice guideline	33
7137	NM_000492.4(CFTR):c.3484C>T (p.Arg1162Ter)	Pathogenic	practice guideline	31
7166	NM_000492.3(CFTR):c.3718-2477C>T	Pathogenic	practice guideline	31

Per-variant reference — Sugi Variant

Explore CFTR’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 33 predictions of 3,687):

Position(s)	Effect	Δscore	Sites
7:117531079	donor_gain	1.0000
7:117534274–117534275	acceptor_loss	1.0000	2
7:117534366–117534367	donor_loss	1.0000	2
7:117535316	donor_gain	1.0000
7:117536546–117536547	acceptor_loss	1.0000	6
7:117536674–117536675	donor_loss	1.0000	5
7:117559462–117559463	acceptor_loss	1.0000	4
7:117559656–117559657	donor_loss	1.0000	4
7:117602824–117602825	acceptor_loss	1.0000	5
7:117602864–117602865	donor_loss	1.0000	3

AlphaMissense

3,068 missense substitutions predicted likely pathogenic (of 9,721 scored), across 857 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M150	9	0.839	0.953
D579	8	0.977	0.990
D979	8	0.974	0.993
D572	8	0.967	0.985
D984	8	0.959	0.986
F337	8	0.957	0.988
N505	8	0.955	0.997
D1370	8	0.948	0.979
H1402	8	0.927	0.963
D993	8	0.924	0.976
F1078	8	0.923	0.985
F508	8	0.917	0.978
F575	8	0.904	0.967
F1099	8	0.904	0.979
D192	8	0.902	0.970
D1154	8	0.900	0.955
D924	8	0.895	0.984
F1107	8	0.887	0.984
S549	8	0.882	0.995
N1303	8	0.877	0.991

HPA cancer prognostics

RNA cancer specificity: Group enriched (Colon Adenocarcinoma, Kidney Chromophobe, Pancreatic Adenocarcinoma, Rectum Adenocarcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Colon Adenocarcinoma (validation)	favorable	0.000143
Lung Adenocarcinoma (TCGA)	favorable	0.000302

Disease associations

OMIM: gene MIM:602421 | disease phenotypes: MIM:211400, MIM:219700, MIM:167800, MIM:277180, MIM:606719, MIM:125853, MIM:415000

GenCC curated gene-disease

4 curated gene-disease records:

Disease	Classification	Inheritance	Records
cystic fibrosis	Definitive	Autosomal recessive	6
congenital bilateral aplasia of vas deferens from CFTR mutation	Definitive	Autosomal recessive
congenital bilateral absence of vas deferens	Supportive	Autosomal recessive
hereditary chronic pancreatitis	Limited	Autosomal dominant

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
cystic fibrosis	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (10 panels, 9 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

10 panels:

Panel	Rating
Additional findings reproductive carrier status	green
COVID-19 research	green
Cholestasis	green
Cystic fibrosis - Diagnostic	green
Fetal anomalies	green
Neonatal cholestasis	green
Non-CF bronchiectasis	green
Pancreatitis	green
Respiratory ciliopathies including non-CF bronchiectasis	green
Primary immunodeficiency or monogenic inflammatory bowel disease	amber

Mondo (9): bronchiectasis with or without elevated sweat chloride 1 (MONDO:0008887), cystic fibrosis (MONDO:0009061), CFTR-related disorder (MONDO:7770004), hereditary chronic pancreatitis (MONDO:0008185), congenital bilateral aplasia of vas deferens from CFTR mutation (MONDO:0010178), melanoma-pancreatic cancer syndrome (MONDO:0011713), type 2 diabetes mellitus (MONDO:0005148), spermatogenic failure, Y-linked, 2 (MONDO:0010767), congenital bilateral absence of vas deferens (MONDO:0018801)

Orphanet (6): Cystic fibrosis (Orphanet:586), Idiopathic bronchiectasis (Orphanet:60033), Congenital bilateral absence of vas deferens (Orphanet:48), Autosomal dominant hereditary chronic pancreatitis (Orphanet:676), Familial atypical multiple mole melanoma syndrome (Orphanet:404560), Chromosome Y microdeletion syndrome (Orphanet:1646)

HPO phenotypes

showing 60 of 103 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000027	Azoospermia
HP:0000118	Phenotypic abnormality
HP:0000122	Unilateral renal agenesis
HP:0000246	Sinusitis
HP:0000365	Hearing impairment
HP:0000716	Depression
HP:0000739	Anxiety
HP:0000787	Kidney stone
HP:0000798	Oligozoospermia
HP:0000819	Diabetes mellitus
HP:0000837	Increased circulating gonadotropin level
HP:0000938	Osteopenia
HP:0000939	Osteoporosis
HP:0000969	Edema
HP:0000982	Palmoplantar keratoderma
HP:0001047	Atopic dermatitis
HP:0001217	Clubbing
HP:0001392	Abnormality of the liver
HP:0001394	Cirrhosis
HP:0001433	Hepatosplenomegaly
HP:0001508	Failure to thrive
HP:0001648	Cor pulmonale
HP:0001658	Myocardial infarction
HP:0001733	Pancreatitis
HP:0001738	Exocrine pancreatic insufficiency
HP:0001944	Dehydration
HP:0001945	Fever
HP:0001977	Abnormal thrombosis
HP:0002014	Diarrhea
HP:0002020	Gastroesophageal reflux
HP:0002024	Malabsorption
HP:0002027	Abdominal pain
HP:0002035	Rectal prolapse
HP:0002094	Dyspnea
HP:0002097	Emphysema
HP:0002099	Asthma
HP:0002105	Hemoptysis
HP:0002107	Pneumothorax
HP:0002110	Bronchiectasis
HP:0002150	Hypercalciuria
HP:0002202	Pleural effusion
HP:0002205	Recurrent respiratory infections
HP:0002240	Hepatomegaly
HP:0002570	Steatorrhea
HP:0002595	Ileus
HP:0002613	Biliary cirrhosis
HP:0002724	Recurrent Aspergillus infection
HP:0002725	Systemic lupus erythematosus
HP:0002726	Recurrent Staphylococcus aureus infection
HP:0002783	Recurrent lower respiratory tract infections
HP:0002795	Abnormal respiratory system physiology
HP:0002842	Recurrent Burkholderia cepacia infection
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0003251	Male infertility
HP:0003593	Infantile onset
HP:0004326	Cachexia
HP:0004401	Meconium ileus
HP:0004469	Chronic bronchitis

GWAS associations

9 associations:

Study	Trait	p-value
GCST90014023_16	Type 1 diabetes	2e-16
GCST003740_3	Barrett’s esophagus or Esophageal adenocarcinoma	5e-10
GCST005956_33	Waist-to-hip ratio adjusted for BMI	5e-9
GCST006395_12	Glaucoma	3e-8
GCST001356_12	Gout	1e-7
GCST005962_14	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	3e-7
GCST001629_2	Response to platinum-based chemotherapy in non-small-cell lung cancer	4e-7
GCST002408_2	Response to methotrexate in juvenile idiopathic arthritis	5e-7
GCST002408_3	Response to methotrexate in juvenile idiopathic arthritis	6e-6

EFO canonical traits (from GWAS)

3 canonical traits:

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement

MeSH disease descriptors

6 disease descriptors:

Descriptor	Name	Tree numbers
D003550	Cystic Fibrosis	C06.689.202; C08.381.187; C16.320.190; C16.614.213
D003924	Diabetes Mellitus, Type 2	C18.452.394.750.149; C19.246.300
C567618	Bronchiectasis With Or Without Elevated Sweat Chloride 1 *(supp.)*
C537262	Hereditary pancreatitis *(supp.)*
C563985	Melanoma-Pancreatic Cancer Syndrome *(supp.)*
C564030	Spermatogenic Failure, Nonobstructive, Y-Linked *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3885559 (PROTEIN-PROTEIN INTERACTION), CHEMBL4051 (SINGLE PROTEIN)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the CFTR protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

13 curated-mechanism drugs:

Drug	Modality	Max phase
CROFELEMER	Small molecule	4
DEUTIVACAFTOR	Small molecule	4
ELEXACAFTOR	Small molecule	4
IVACAFTOR	Small molecule	4
LUMACAFTOR	Small molecule	4
TEZACAFTOR	Small molecule	4
VANZACAFTOR	Small molecule	4
BAMOCAFTOR	Small molecule	3
GALICAFTOR	Small molecule	2
ICENTICAFTOR	Small molecule	2
IOWH-032	Small molecule	2
NAVOCAFTOR	Small molecule	2
OLACAFTOR	Small molecule	2

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 240,652 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

14 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL4298128	ELEXACAFTOR	4	568
CHEMBL2010601	IVACAFTOR	4	2,748
CHEMBL2103870	LUMACAFTOR	4	2,446
CHEMBL3544914	TEZACAFTOR	4	1,511
CHEMBL472	GLYBURIDE	4	53,640
CHEMBL4297849	BAMOCAFTOR	3	281
CHEMBL50	QUERCETIN	3	75,572
CHEMBL226335	RUTIN	3	58,533
CHEMBL4101487	GALICAFTOR	2	308
CHEMBL4650318	ICENTICAFTOR	2	253
CHEMBL4802150	NAVOCAFTOR	2	156
CHEMBL44	GENISTEIN	2	44,589
CHEMBL6068548	GLPG-2737	2	45
CHEMBL6068031	RISELCAFTOR	2	2

PharmGKB: 1 entry (CPIC guideline: yes)

PharmGKB clinical annotations

showing 60 of 78 annotations by evidence level (1 strongest → 4):

Variant	Association	Level	Drugs	Phenotypes
rs113993958	Efficacy	1A	ivacaftor	Cystic Fibrosis
rs113993960	Efficacy	1A	ivacaftor / lumacaftor	Cystic Fibrosis
rs113993960	Efficacy	1A	ivacaftor / tezacaftor	Cystic Fibrosis
rs115545701	Efficacy	1A	ivacaftor	Cystic Fibrosis
rs11971167	Efficacy	1A	ivacaftor	Cystic Fibrosis
rs121908751	Efficacy	1A	elexacaftor / tezacaftor / ivacaftor	Cystic Fibrosis
rs121908752	Efficacy	1A	ivacaftor	Cystic Fibrosis
rs121908753	Efficacy	1A	ivacaftor	Cystic Fibrosis
rs121908755	Efficacy	1A	ivacaftor	Cystic Fibrosis
rs121908757	Efficacy	1A	ivacaftor	Cystic Fibrosis
rs121909005	Efficacy	1A	ivacaftor	Cystic Fibrosis
rs121909013	Efficacy	1A	ivacaftor	Cystic Fibrosis
rs121909020	Efficacy	1A	ivacaftor	Cystic Fibrosis
rs121909041	Efficacy	1A	ivacaftor	Cystic Fibrosis
rs141033578	Efficacy	1A	ivacaftor	Cystic Fibrosis
rs150212784	Efficacy	1A	ivacaftor	Cystic Fibrosis
rs1800076	Efficacy	1A	elexacaftor / tezacaftor / ivacaftor;ivacaftor	Cystic Fibrosis
rs1800100	Efficacy	1A	ivacaftor	Cystic Fibrosis
rs1800111	Efficacy	1A	ivacaftor	Cystic Fibrosis
rs186045772	Efficacy	1A	ivacaftor	Cystic Fibrosis
rs186089140	Efficacy	1A	elexacaftor / tezacaftor / ivacaftor;ivacaftor	Cystic Fibrosis
rs193922525	Efficacy	1A	ivacaftor	Cystic Fibrosis
rs202179988	Efficacy	1A	ivacaftor	Cystic Fibrosis
rs267606723	Efficacy	1A	ivacaftor	Cystic Fibrosis
rs35516286	Efficacy	1A	elexacaftor / tezacaftor / ivacaftor;ivacaftor	Cystic Fibrosis
rs36210737	Efficacy	1A	elexacaftor / tezacaftor / ivacaftor	Cystic Fibrosis
rs368505753	Efficacy	1A	ivacaftor	Cystic Fibrosis
rs397508256	Efficacy	1A	ivacaftor	Cystic Fibrosis
rs397508288	Efficacy	1A	ivacaftor	Cystic Fibrosis
rs397508442	Efficacy	1A	ivacaftor	Cystic Fibrosis
rs397508513	Efficacy	1A	ivacaftor	Cystic Fibrosis
rs397508537	Efficacy	1A	ivacaftor	Cystic Fibrosis
rs397508572	Efficacy	1A	elexacaftor / tezacaftor / ivacaftor;ivacaftor	Cystic Fibrosis
rs397508573	Efficacy	1A	elexacaftor / tezacaftor / ivacaftor;ivacaftor	Cystic Fibrosis
rs397508602	Efficacy	1A	ivacaftor	Cystic Fibrosis
rs397508759	Efficacy	1A	ivacaftor	Cystic Fibrosis
rs74503330	Efficacy	1A	ivacaftor	Cystic Fibrosis
rs74551128	Efficacy	1A	ivacaftor	Cystic Fibrosis
rs75039782	Efficacy	1A	elexacaftor / tezacaftor / ivacaftor;ivacaftor	Cystic Fibrosis
rs75527207	Efficacy	1A	ivacaftor	Cystic Fibrosis
rs75541969	Efficacy	1A	ivacaftor	Cystic Fibrosis
rs77409459	Efficacy	1A	ivacaftor	Cystic Fibrosis
rs77834169	Efficacy	1A	ivacaftor	Cystic Fibrosis
rs77932196	Efficacy	1A	elexacaftor / tezacaftor / ivacaftor	Cystic Fibrosis
rs77932196	Efficacy	1A	ivacaftor	Cystic Fibrosis
rs78655421	Efficacy	1A	ivacaftor	Cystic Fibrosis
rs78769542	Efficacy	1A	ivacaftor	Cystic Fibrosis
rs80224560	Efficacy	1A	elexacaftor / tezacaftor / ivacaftor;ivacaftor	Cystic Fibrosis
rs80282562	Efficacy	1A	ivacaftor	Cystic Fibrosis
rs113993959	Other	3	ataluren	Cystic Fibrosis
rs113993960	Toxicity	3	ivacaftor / lumacaftor	Cystic Fibrosis
rs113993960	Efficacy	3	cysteamine	Cystic Fibrosis
rs113993960	Efficacy	3	lumacaftor	Cystic Fibrosis
rs113993960	Efficacy	3	cavosonstat	Cystic Fibrosis
rs121909011	Efficacy	3	ivacaftor / lumacaftor	Cystic Fibrosis
rs121909011	Efficacy	3	ivacaftor	Cystic Fibrosis
rs121909011	Efficacy	3	elexacaftor / tezacaftor / ivacaftor	Cystic Fibrosis
rs121909019	Efficacy	3	ivacaftor	Cystic Fibrosis
rs121909019	Efficacy	3	elexacaftor / tezacaftor / ivacaftor	Cystic Fibrosis
rs121909047	Efficacy	3	lumacaftor	Cystic Fibrosis

PharmGKB variants

showing 60 of 61 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs74503330	CFTR	1A	202.00	1	ivacaftor
rs75039782	CFTR	1A	200.00	2	elexacaftor / tezacaftor / ivacaftor;ivacaftor;ataluren
rs75527207	CFTR	1A	237.62	2	ivacaftor;ivacaftor;tezacaftor
rs77010898	CFTR	3	4.50	3	ataluren;curcumin;ivacaftor;ivacaftor
rs78655421	CFTR	1A	206.25	1	ivacaftor
rs80282562	CFTR	1A	202.00	1	ivacaftor
rs113993959	CFTR	3	4.50	1	ataluren
rs113993960	CFTR	1A	123.38	7	lumacaftor;ivacaftor / tezacaftor;ivacaftor;cavosonstat;cysteamine;ivacaftor / lumacaftor
rs121908755	CFTR	1A	202.50	1	ivacaftor
rs121908757	CFTR	1A	204.75	1	ivacaftor
rs121909005	CFTR	1A	202.25	1	ivacaftor
rs121909013	CFTR	1A	202.00	1	ivacaftor
rs121909041	CFTR	1A	202.00	1	ivacaftor
rs193922525	CFTR	1A	202.00	1	ivacaftor
rs267606723	CFTR	1A	202.00	1	ivacaftor
rs77932196	CFTR	1A	201.25	2	elexacaftor / tezacaftor / ivacaftor;ivacaftor
rs121909011	CFTR	3	1.50	3	ivacaftor / lumacaftor;ivacaftor;elexacaftor / tezacaftor / ivacaftor
rs80034486	CFTR	3	2.88	1	elexacaftor / tezacaftor / ivacaftor
rs80224560	CFTR	1A	200.25	1	elexacaftor / tezacaftor / ivacaftor;ivacaftor
rs75961395	CFTR	3	0.62	1	elexacaftor / tezacaftor / ivacaftor
rs74551128	CFTR	1A	200.00	2	ivacaftor;ivacaftor / lumacaftor
rs397508256	CFTR	1A	200.00	1	ivacaftor
rs368505753	CFTR	1A	200.00	1	ivacaftor
rs115545701	CFTR	1A	200.00	1	ivacaftor
rs397508537	CFTR	1A	200.00	1	ivacaftor
rs113993958	CFTR	1A	200.00	1	ivacaftor
rs77834169	CFTR	1A	200.00	1	ivacaftor
rs397508759	CFTR	1A	200.00	1	ivacaftor
rs121908752	CFTR	1A	200.00	1	ivacaftor
rs121908753	CFTR	1A	200.00	1	ivacaftor
rs397508288	CFTR	1A	200.00	1	ivacaftor
rs397508442	CFTR	1A	200.25	1	ivacaftor
rs141033578	CFTR	1A	200.00	1	ivacaftor
rs150212784	CFTR	1A	200.00	1	ivacaftor
rs397508513	CFTR	1A	200.00	1	ivacaftor
rs121909020	CFTR	1A	200.00	1	ivacaftor
rs78769542	CFTR	1A	200.00	1	ivacaftor
rs202179988	CFTR	1A	200.00	1	ivacaftor
rs186045772	CFTR	1A	200.00	1	ivacaftor
rs75541969	CFTR	1A	200.00	1	ivacaftor
rs11971167	CFTR	1A	200.00	1	ivacaftor
rs34911792	CFTR	3	0.00	1	ivacaftor
rs1800100	CFTR	1A	100.00	1	ivacaftor
rs1800111	CFTR	1A	100.00	1	ivacaftor
rs121909019	CFTR	3	0.12	2	ivacaftor;elexacaftor / tezacaftor / ivacaftor
rs77409459	CFTR	1A	100.00	1	ivacaftor
rs397508139	CFTR	3	0.00	1	ivacaftor
rs397508510	CFTR	3	0.00	1	ivacaftor
rs397508328	CFTR	3	0.00	1	ivacaftor
rs121908751	CFTR	1A	100.00	1	elexacaftor / tezacaftor / ivacaftor
rs397508435	CFTR	3	0.00	1	ivacaftor
rs36210737	CFTR	1A	100.25	1	elexacaftor / tezacaftor / ivacaftor
rs121909047	CFTR	3	1.50	3	lumacaftor;ivacaftor;elexacaftor / tezacaftor / ivacaftor
rs75549581	CFTR	3	0.12	1	elexacaftor / tezacaftor / ivacaftor
rs397508453	CFTR	3	2.00	1	ivacaftor
rs397508602	CFTR	1A	100.25	1	ivacaftor
rs186089140	CFTR	1A	200.12	1	elexacaftor / tezacaftor / ivacaftor;ivacaftor
rs35516286	CFTR	1A	200.00	1	elexacaftor / tezacaftor / ivacaftor;ivacaftor
rs397508573	CFTR	1A	200.00	1	elexacaftor / tezacaftor / ivacaftor;ivacaftor
rs397508572	CFTR	1A	200.00	1	elexacaftor / tezacaftor / ivacaftor;ivacaftor

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

showing 58 of 138 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs75527207	ivacaftor	Efficacy	Allele A is associated with response to ivacaftor in people with Cystic Fibrosis.	PMID:23757359
rs75527207	ivacaftor	Efficacy	Allele A is associated with increased activity of CFTR when treated with ivacaftor in transfected CHO cells.	PMID:23757361
rs75527207	ivacaftor	Efficacy	Allele A is associated with activity of CFTR when treated with ivacaftor in FRT cell lines.	PMID:23891399
rs113993960	lumacaftor	Toxicity	Genotype del/del is associated with increased change in sweat chloride when treated with lumacaftor in people with Cystic Fibrosis.	PMID:21825083
rs80282562	ivacaftor	Efficacy	Allele A is associated with increased response to ivacaftor.	PMID:22293084
rs121908755	ivacaftor	Efficacy	Allele A is associated with increased response to ivacaftor.	PMID:22293084
rs121908757	ivacaftor	Efficacy	Allele C is associated with increased response to ivacaftor.	PMID:22293084
rs121909005	ivacaftor	Efficacy	Allele G is associated with increased response to ivacaftor.	PMID:22293084
rs121909013	ivacaftor	Efficacy	Allele A is associated with increased response to ivacaftor.	PMID:22293084
rs267606723	ivacaftor	Efficacy	Allele A is associated with increased response to ivacaftor.	PMID:22293084
rs74503330	ivacaftor	Efficacy	Allele A is associated with increased response to ivacaftor.	PMID:22293084
rs121909041	ivacaftor	Efficacy	Allele C is associated with increased response to ivacaftor.	PMID:22293084
rs193922525	ivacaftor	Efficacy	Allele A is associated with increased response to ivacaftor.	PMID:22293084
rs75527207	ivacaftor	Efficacy	Allele A is associated with response to ivacaftor in people with Cystic Fibrosis.	PMID:25049054
rs75527207	ivacaftor	Efficacy	Genotypes AA + AG are associated with response to ivacaftor in people with Cystic Fibrosis.	PMID:24461666
rs113993960	ivacaftor / lumacaftor	Efficacy	Genotype del/del is associated with response to ivacaftor / lumacaftor in people with Cystic Fibrosis.	PMID:24973281
rs113993959	ataluren	Efficacy	Allele T is associated with response to ataluren in people with Cystic Fibrosis as compared to allele G.	PMID:21233271
rs77010898	ataluren	Efficacy	Allele A is associated with response to ataluren in people with Cystic Fibrosis as compared to allele G.	PMID:21233271
rs77010898	ataluren	Efficacy	Allele A is associated with response to ataluren in people with Cystic Fibrosis as compared to allele G.	PMID:18722008
rs75039782	ataluren	Efficacy	Allele T is associated with response to ataluren in people with Cystic Fibrosis as compared to allele C.	PMID:18722008
rs113993959	ataluren	Efficacy	Allele T is associated with response to ataluren in people with Cystic Fibrosis as compared to allele G.	PMID:18722008
rs113993959	ataluren	Efficacy	Allele T is associated with response to ataluren in children with Cystic Fibrosis as compared to allele G.	PMID:20622033
rs77010898	ataluren	Efficacy	Allele A is associated with response to ataluren in children with Cystic Fibrosis as compared to allele G.	PMID:20622033
rs75039782	ataluren	Efficacy	Allele T is associated with response to ataluren in children with Cystic Fibrosis as compared to allele C.	PMID:20622033
rs113993960	cysteamine	Efficacy	Genotypes CTT/del + del/del are associated with increased response to cysteamine in people with Cystic Fibrosis as compared to genotype CTT/CTT.	PMID:27035618
rs77010898	curcumin, ivacaftor	Efficacy	Genotypes AA + AG are associated with response to curcumin and ivacaftor in people with Cystic Fibrosis as compared to genotype GG.	PMID:27007499
rs113993960	ivacaftor	Efficacy	Allele del is associated with increased response to ivacaftor in people with Cystic Fibrosis.	PMID:26968770
rs78655421	ivacaftor	Efficacy	Genotypes AA + AG is associated with response to ivacaftor in people with Cystic Fibrosis.	PMID:26070913
rs75527207	ivacaftor	Efficacy	Genotypes AA + AG are associated with increased response to ivacaftor in people with Cystic Fibrosis as compared to genotype GG.	PMID:27158673
rs113993960	corr-4a, ivacaftor, lumacaftor	Efficacy	Genotype del/del is associated with increased activity of CFTR when treated with corr-4a, ivacaftor and lumacaftor as compared to genotype CTT/CTT.	PMID:27214033
rs113993960	ivacaftor / lumacaftor	Efficacy	Genotype del/del is associated with increased response to ivacaftor / lumacaftor in people with Cystic Fibrosis as compared to genotypes CTT/CTT + CTT/del.	PMID:27298017
rs78655421	ivacaftor / lumacaftor	Efficacy	Allele A is associated with increased activity of CFTR when treated with ivacaftor / lumacaftor as compared to allele G.	PMID:27402691
rs75527207	ivacaftor, nppb	Efficacy	Allele A is associated with increased activity of CFTR when treated with ivacaftor and nppb Chinese hamster ovary cells as compared to allele G.	PMID:27413118
rs77010898	ivacaftor	Efficacy	Genotype AA is associated with increased response to ivacaftor in people with Cystic Fibrosis as compared to genotype GG.	PMID:27707539
rs77010898	ivacaftor	Efficacy	Allele A is associated with increased activity of CFTR when treated with ivacaftor as compared to allele G.	PMID:27707539
rs75527207	ivacaftor	Efficacy	Genotypes AA + AG is associated with decreased severity of bone density when treated with ivacaftor in people with Cystic Fibrosis as compared to genotype GG.	PMID:27745802
rs75527207	ivacaftor	Efficacy	Genotypes AA + AG is associated with increased response to ivacaftor in people with Cystic Fibrosis as compared to genotype GG.	PMID:27773592
rs77932196	ivacaftor	Efficacy	Allele A is associated with increased response to ivacaftor in people with Cystic Fibrosis as compared to allele G.	PMID:27812499
rs121909011	ivacaftor	Efficacy	Allele C is associated with increased response to ivacaftor in people with Cystic Fibrosis as compared to allele T.	PMID:27812499
rs113993960	cavosonstat	Efficacy	Genotype del/del is associated with response to cavosonstat in people with Cystic Fibrosis as compared to genotypes CTT/CTT + CTT/del.	PMID:28209466
rs113993960	ivacaftor, tezacaftor	Efficacy	Genotype del/del is associated with increased response to ivacaftor and tezacaftor in people with Cystic Fibrosis.	PMID:29099344
rs113993960	ivacaftor, tezacaftor	Other	Genotype del/del is associated with decreased cystic fibrosis pulmonary exacerbation when treated with ivacaftor and tezacaftor in people with Cystic Fibrosis.	PMID:29099344
rs113993960	ivacaftor, tezacaftor	Efficacy	Genotype CTT/del is associated with increased response to ivacaftor and tezacaftor in people with Cystic Fibrosis.	PMID:29099333
rs113993960	ivacaftor	Efficacy	Genotype CTT/del is associated with increased response to ivacaftor in people with Cystic Fibrosis.	PMID:29099333
rs121908757	ivacaftor	Efficacy	Allele C is associated with response to ivacaftor in people with Cystic Fibrosis.	PMID:28947035
rs150212784	ivacaftor	Efficacy	Allele G is associated with activity of CFTR when treated with ivacaftor in FRT cell lines.	PMID:23891399
rs34911792	ivacaftor	Efficacy	Allele G is associated with activity of CFTR when treated with ivacaftor in FRT cell lines.	PMID:23891399
rs75541969	ivacaftor	Efficacy	Allele C is associated with activity of CFTR when treated with ivacaftor in FRT cell lines.	PMID:23891399
rs11971167	ivacaftor	Efficacy	Allele T is associated with activity of CFTR when treated with ivacaftor in FRT cell lines.	PMID:23891399
rs1800100	ivacaftor	Efficacy	Allele T is associated with activity of CFTR when treated with ivacaftor in FRT cell lines.	PMID:23891399
rs397508513	ivacaftor	Efficacy	Allele C is associated with activity of CFTR when treated with ivacaftor in FRT cell lines.	PMID:23891399
rs115545701	ivacaftor	Efficacy	Allele T is associated with activity of CFTR when treated with ivacaftor in FRT cell lines.	PMID:23891399
rs78655421	ivacaftor	Efficacy	Allele A is associated with activity of CFTR when treated with ivacaftor in FRT cell lines.	PMID:23891399
rs397508759	ivacaftor	Efficacy	Allele A is associated with activity of CFTR when treated with ivacaftor in FRT cell lines.	PMID:23891399
rs121909020	ivacaftor	Efficacy	Allele A is associated with activity of CFTR when treated with ivacaftor in FRT cell lines.	PMID:23891399
rs1800111	ivacaftor	Efficacy	Allele C is associated with activity of CFTR when treated with ivacaftor in FRT cell lines.	PMID:23891399
rs78769542	ivacaftor	Efficacy	Allele A is associated with activity of CFTR when treated with ivacaftor in FRT cell lines.	PMID:23891399
rs397508537	ivacaftor	Efficacy	Allele A is associated with activity of CFTR when treated with ivacaftor in FRT cell lines.	PMID:23891399

PharmGKB dosing guidelines

CPIC / DPWG genotype-guided dosing for this gene (drug × pharmacogene).

2 dosing guidelines:

Guideline	Source	Drug	Dosing?	Recommendation?
Annotation of CPIC Guideline for ivacaftor and CFTR	CPIC	ivacaftor		yes
Annotation of CFF Guideline for ivacaftor and CFTR	CFF	ivacaftor		yes

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other ic — CFTR

Most potent curated ligand interactions (17 total), top 17:

Ligand	Action	Affinity	Parameter
ivacaftor	Potentiation	8.52	pEC50
(R)-BPO-27	Inhibition	8.4	pIC50
felodipine	Potentiation	8.4	pKi
compound 16d [PMID: 36573286]	Activation	7.64	pEC50
bamocaftor	Binding	7.52	pEC50
icenticaftor	Potentiation	7.33	pEC50
elexacaftor	Activator	7.15	pEC50
CFTRinh-172	Inhibition	7.1	pIC50
GaTx1	Inhibition	7.0	pIC50
GLPG1837	Potentiation	6.64	pEC50
deutivacaftor	Potentiation	6.59	pEC50
tezacaftor	Activator	6.57	pEC50
GLPG2737	Activator	6.16	pEC50
lumacaftor	Binding	5.59	pEC50
GlyH-101	Pore blocker	5.37	pIC50
crofelemer	Inhibition	5.15	pIC50
glibenclamide	Pore blocker	4.66	pKi

Binding affinities (BindingDB)

885 measured of 1264 human assays (1267 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
BDBM301432	EC50	0.2 nM	US-10131670: Bicyclic heteroaryl derivatives as CFTR potentiators
4-amino-5-[2-(difluoromethyl)pyrimidin-5-yl]-7-{1-[1-(2-fluorophenyl)-1H-pyrazol-4-yl]ethyl}pyrrolo[2,1-f][1,2,4]triazine-6-carbonitrile,enantiomer 1	EC50	0.4 nM	US-10131670: Bicyclic heteroaryl derivatives as CFTR potentiators
CHEMBL5178232	EC50	0.4 nM
4-amino-5-[2-(difluoromethyl)pyrimidin-5-yl]-7-{[1-(2-fluorophenyl)-1H-pyrazol-4-yl]methyl}pyrrolo[2,1-f][1,2,4]triazine-6-carbonitrile	EC50	0.41 nM	US-10131670: Bicyclic heteroaryl derivatives as CFTR potentiators
4-amino-7-[1-[1-(2-fluorophenyl)pyrazol-4-yl]ethyl]-5-[2-(trifluoromethyl)pyrimidin-5-yl]pyrrolo[2,1-f][1,2,4]triazine-6-carbonitrile	EC50	0.42 nM	US-10131670: Bicyclic heteroaryl derivatives as CFTR potentiators
BDBM301434	EC50	0.42 nM	US-10131670: Bicyclic heteroaryl derivatives as CFTR potentiators
CHEMBL4558190	EC50	0.5 nM
CHEMBL5193680	EC50	0.51 nM
4-amino-7-{[1-(2-fluorophenyl)-1H-pyrazol-4-yl]methyl}-5-[2-(trifluoromethyl)pyrimidin-5-yl]pyrrolo[2,1-f][1,2,4]triazine-6-carbonitrile	EC50	0.57 nM	US-10131670: Bicyclic heteroaryl derivatives as CFTR potentiators
4-amino-7-{(1R)-1-[1-(2,4-difluorophenyl)-1H-pyrazol-4-yl]ethyl}-5-[2-(trifluoromethyl)pyrimidin-5-yl]pyrrolo[2,1-f][1,2,4]triazine-6-carbonitrile,enantiomer 2	EC50	0.66 nM	US-10131670: Bicyclic heteroaryl derivatives as CFTR potentiators
CHEMBL5178488	EC50	0.66 nM
CHEMBL5202275	EC50	0.8 nM
CHEMBL5186971	EC50	0.84 nM
2,2-dimethylbutyric acid, 8-ester with (4R,6R)-6-(2-((1S,2S,6R,8S,8aR)-1,2,6,7,8,8a-hexahydro-8-hydroxy-2,6-dimethyl-1-naphthyl)ethyl)tetrahydro-4-hydroxy-2H-pyran-2-one	IC50	0.9 nM
CHEMBL5171054	EC50	0.9 nM
CHEMBL4799994	EC50	1.1 nM
CHEMBL6170767	EC50	1.1 nM
1-[1-[1-(2-fluorophenyl)pyrazol-4-yl]propyl]-3-[2-(trifluoromethyl)pyrimidin-5-yl]pyrazolo[3,4-d]pyrimidin-4-amine	EC50	1.53 nM	US-10131670: Bicyclic heteroaryl derivatives as CFTR potentiators
CHEMBL6170689	EC50	1.6 nM
4-amino-7-{1-[3-(2-fluorophenyl)-1,2-oxazol-5-yl]ethyl}-5-[2-(trifluoromethyl)pyrimidin-5-yl]pyrrolo[2,1-f][1,2,4]triazine-6-carbonitrile, enantiomer 1	EC50	1.67 nM	US-10131670: Bicyclic heteroaryl derivatives as CFTR potentiators
CHEMBL6143326	EC50	1.8 nM
7-[1-[1-(2-fluorophenyl)triazol-4-yl]propyl]-5-[2-(trifluoromethyl)pyrimidin-5-yl]pyrrolo[2,1-f][1,2,4]triazin-4-amine	EC50	1.88 nM	US-10131670: Bicyclic heteroaryl derivatives as CFTR potentiators
CHEMBL3357142	EC50	2 nM
CHEMBL6175200	EC50	2 nM
CHEMBL6167971	EC50	2 nM
CHEMBL6148174	EC50	2 nM
CHEMBL3354672	EC50	2.1 nM
4-amino-7-{1-[1-(2-fluorophenyl)-1H-1,2,3-triazol-4-yl]propyl}-5-[2-(trifluoromethyl)pyrimidin-5-yl]pyrrolo[2,1-f][1,2,4]triazine-6-carbonitrile,enantiomer 1	EC50	2.13 nM	US-10131670: Bicyclic heteroaryl derivatives as CFTR potentiators
(R)-3-methyl-1-((S)-3-phenyl-2-(pyrazine-6-carboxamido)propanamido)butylboronic acid	IC50	2.4 nM
CHEMBL4083374	EC50	2.7 nM
CHEMBL4787310	EC50	2.8 nM
CHEMBL3357141	EC50	3 nM
CHEMBL6171349	EC50	3 nM
CHEMBL4077574	EC50	3 nM
CHEMBL6177322	EC50	3.3 nM
CHEMBL4798183	EC50	3.4 nM
(S)-2-(3-Isopropoxy-4-methoxy-benzoyl)-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid (4-pentyl-phenyl)-amide	EC50	3.5 nM
4-amino-5-[2-(difluoromethyl)pyrimidin-5-yl]-7-{1-[1-(2-fluorophenyl)-1H-pyrazol-4-yl]ethyl}pyrrolo[2,1-f][1,2,4]triazine-6-carbonitrile,enantiomer 2	EC50	3.87 nM	US-10131670: Bicyclic heteroaryl derivatives as CFTR potentiators
4-Amino-7-{[3-(2-fluorophenyl)-1,2-oxazol-5-yl]methyl}-5-[2-(trifluoromethyl)pyrimidin-5-yl]pyrrolo[2,1-f][1,2,4]triazine-6-carbonitrile	EC50	4 nM	US-10131670: Bicyclic heteroaryl derivatives as CFTR potentiators
CHEMBL2386374	IC50	4 nM
CHEMBL6160710	EC50	4 nM
CHEMBL6167563	EC50	4 nM
CHEMBL6168993	EC50	4 nM
4-amino-7-{1-[1-(propan-2-yl)-1H-pyrazol-4-yl]propyl}-5-[2-(trifluoromethyl)pyrimidin-5-yl]pyrrolo[2,1-f][1,2,4]triazine-6-carbonitrile,enantiomer 1	EC50	4.17 nM	US-10131670: Bicyclic heteroaryl derivatives as CFTR potentiators
2,4-dimethylpyrido[1,2-a]pyrimidin-5-ium-3-olate	IC50	5 nM
CHEMBL4781857	EC50	5 nM
CHEMBL6170120	EC50	5 nM
CHEMBL6142699	EC50	5 nM
CHEMBL6162901	EC50	5 nM
Galicaftor	EC50	5 nM

ChEMBL bioactivities

1202 potent at pChembl≥5 of 1359 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.70	EC50	0.2	nM	CHEMBL5863288
9.40	EC50	0.4	nM	CHEMBL5178232
9.40	EC50	0.4	nM	CHEMBL5861582
9.39	EC50	0.41	nM	CHEMBL5802461
9.38	EC50	0.42	nM	CHEMBL6033456
9.38	EC50	0.42	nM	CHEMBL5892004
9.30	EC50	0.5	nM	CHEMBL4558190
9.29	EC50	0.51	nM	CHEMBL5193680
9.27	EC50	0.54	nM	CHEMBL4084934
9.25	EC50	0.56	nM	CHEMBL5863288
9.25	EC50	0.56	nM	CHEMBL5892004
9.24	EC50	0.57	nM	CHEMBL6009312
9.21	EC50	0.62	nM	CHEMBL6033456
9.18	EC50	0.66	nM	CHEMBL5178488
9.18	EC50	0.66	nM	CHEMBL5881985
9.10	EC50	0.8	nM	CHEMBL5202275
9.08	EC50	0.84	nM	CHEMBL5186971
9.07	EC50	0.86	nM	CHEMBL6009312
9.05	EC50	0.9	nM	CHEMBL5171054
8.98	EC50	1.05	nM	CHEMBL5802461
8.96	EC50	1.1	nM	CHEMBL4799994
8.96	EC50	1.1	nM	CHEMBL6170767
8.81	EC50	1.53	nM	CHEMBL5860580
8.80	EC50	1.6	nM	CHEMBL6170689
8.78	EC50	1.67	nM	CHEMBL5889215
8.74	EC50	1.8	nM	CHEMBL6143326
8.73	EC50	1.88	nM	CHEMBL6000653
8.70	EC50	2	nM	CHEMBL3357142
8.70	EC50	2	nM	CHEMBL4087529
8.70	EC50	2	nM	CHEMBL4066158
8.70	EC50	2	nM	CHEMBL5863288
8.70	EC50	2	nM	CHEMBL6000653
8.70	EC50	2	nM	CHEMBL5869365
8.70	EC50	2	nM	CHEMBL6175200
8.70	EC50	2	nM	CHEMBL6167971
8.70	EC50	2	nM	CHEMBL6148174
8.67	EC50	2.13	nM	CHEMBL5964878
8.57	EC50	2.7	nM	CHEMBL4102980
8.57	EC50	2.7	nM	CHEMBL4083374
8.55	EC50	2.8	nM	CHEMBL4787310
8.52	EC50	3	nM	IVACAFTOR
8.52	EC50	3	nM	CHEMBL3357143
8.52	EC50	3	nM	CHEMBL3357141
8.52	EC50	3	nM	CHEMBL4103906
8.52	EC50	3	nM	CHEMBL4075348
8.52	EC50	3.02	nM	CHEMBL5964878
8.52	EC50	3	nM	CHEMBL5892004
8.52	EC50	3	nM	CHEMBL6171349
8.52	EC50	3	nM	CHEMBL4077574
8.51	EC50	3.1	nM	CHEMBL5889215

PubChem BioAssay actives

1021 with measured affinity, of 2755 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
3-amino-N-[(2R)-3,3,3-trifluoro-2-hydroxypropyl]-5-[2-(trifluoromethoxy)phenyl]sulfonylpyridine-2-carboxamide	1744464: Potentiation of CFTR F508del mutant (unknown origin) expressed in human CFBE41o- cells co-expressing YFP incubated for 10 mins by halide potentiator assay	ec50	0.0003	uM
2-[6-(difluoromethyl)-2-pyridinyl]-1-(2-methoxy-5-methylphenyl)-N-(2-methylquinolin-5-yl)sulfonylcyclopropane-1-carboxamide	1875523: Modulation of homozygous F508del/F508del CFTR mutant in HBE cells incubated for 18 to 24 hrs by trans-epithelial current clamp assay	ec50	0.0004	uM
2-[(2-hydroxy-4,4-dimethylpentanoyl)amino]-5,5,7,7-tetramethyl-4H-thieno[2,3-c]pyran-3-carboxamide	1471893: Potentiation of CFTR F508del mutant (unknown origin) expressed in human CFBE41o cells incubated for 10 mins in presence of forskolin measured for 7 secs by YFP halide assay	ec50	0.0005	uM
4-[4-[[1-(2,2-difluoro-1,3-benzodioxol-5-yl)cyclopropanecarbonyl]amino]-7-(difluoromethoxy)-3,4-dihydro-2H-chromen-2-yl]benzoic acid	1570126: Corrector activity at CFTR F508del mutant (unknown origin)	ec50	0.0005	uM
1-(2-methoxy-5-methylphenyl)-N-(2-methylquinolin-5-yl)sulfonyl-2-[3-(trifluoromethyl)phenyl]cyclopropane-1-carboxamide	1875523: Modulation of homozygous F508del/F508del CFTR mutant in HBE cells incubated for 18 to 24 hrs by trans-epithelial current clamp assay	ec50	0.0005	uM
1-(2-methoxy-5-methylphenyl)-2-(4-methoxyphenyl)-N-(2-methylquinolin-5-yl)sulfonylcyclopropane-1-carboxamide	1875523: Modulation of homozygous F508del/F508del CFTR mutant in HBE cells incubated for 18 to 24 hrs by trans-epithelial current clamp assay	ec50	0.0007	uM
1-(2-methoxy-5-methylphenyl)-2-(3-methoxyphenyl)-N-(2-methylquinolin-5-yl)sulfonylcyclopropane-1-carboxamide	1875523: Modulation of homozygous F508del/F508del CFTR mutant in HBE cells incubated for 18 to 24 hrs by trans-epithelial current clamp assay	ec50	0.0008	uM
1-(2-methoxy-5-methylphenyl)-2-(4-methylphenyl)-N-(2-methylquinolin-5-yl)sulfonylcyclopropane-1-carboxamide	1875523: Modulation of homozygous F508del/F508del CFTR mutant in HBE cells incubated for 18 to 24 hrs by trans-epithelial current clamp assay	ec50	0.0008	uM
1-(2-methoxy-5-methylphenyl)-N-(2-methylquinolin-5-yl)sulfonyl-2-(6-propan-2-yloxy-2-pyridinyl)cyclopropane-1-carboxamide	1875523: Modulation of homozygous F508del/F508del CFTR mutant in HBE cells incubated for 18 to 24 hrs by trans-epithelial current clamp assay	ec50	0.0009	uM
[3-amino-5-(4-fluorophenyl)sulfonyl-2-pyridinyl]-[3-hydroxy-3-(trifluoromethyl)azetidin-1-yl]methanone	1744464: Potentiation of CFTR F508del mutant (unknown origin) expressed in human CFBE41o- cells co-expressing YFP incubated for 10 mins by halide potentiator assay	ec50	0.0011	uM
(S)-[5-[3-amino-5-[4-(trifluoromethoxy)phenyl]sulfonyl-2-pyridinyl]-1,3,4-oxadiazol-2-yl]-phenylmethanol	2252594: Activation of CFTR F508del mutant (unknown origin)	ec50	0.0011	uM
[5-[3-amino-5-[4-(trifluoromethyl)phenyl]sulfonyl-2-pyridinyl]-1,3,4-oxadiazol-2-yl]methanol	2252594: Activation of CFTR F508del mutant (unknown origin)	ec50	0.0016	uM
2-[5-[3-amino-5-[4-(trifluoromethoxy)phenyl]sulfonyl-2-pyridinyl]-1,3,4-oxadiazol-2-yl]-1,1,1-trifluoropropan-2-ol	2252594: Activation of CFTR F508del mutant (unknown origin)	ec50	0.0018	uM
N-(3-carbamoyl-5,5,7,7-tetramethyl-4H-thieno[2,3-c]pyran-2-yl)-4-methyl-1H-pyrazole-5-carboxamide	1471893: Potentiation of CFTR F508del mutant (unknown origin) expressed in human CFBE41o cells incubated for 10 mins in presence of forskolin measured for 7 secs by YFP halide assay	ec50	0.0020	uM
N-(3-carbamoyl-5,5,7,7-tetramethyl-4H-thieno[2,3-c]pyran-2-yl)-4-chloro-1H-pyrazole-5-carboxamide	1471893: Potentiation of CFTR F508del mutant (unknown origin) expressed in human CFBE41o cells incubated for 10 mins in presence of forskolin measured for 7 secs by YFP halide assay	ec50	0.0020	uM
4-[[6-[[6-(2-ethylphenyl)-5-(trifluoromethyl)-2-pyridinyl]sulfamoyl]-2-pyridinyl]-propan-2-ylamino]butanoic acid	2252594: Activation of CFTR F508del mutant (unknown origin)	ec50	0.0020	uM
2-[(3S)-1-[6-[[6-(5-fluoro-2-methylphenyl)-5-(trifluoromethyl)-2-pyridinyl]sulfamoyl]-2-pyridinyl]-3-methylpiperidin-3-yl]acetic acid	2252594: Activation of CFTR F508del mutant (unknown origin)	ec50	0.0020	uM
N-[(6-amino-2-pyridinyl)sulfonyl]-1-(2-cycloheptyl-5-methylphenoxy)cyclopropane-1-carboxamide	2252594: Activation of CFTR F508del mutant (unknown origin)	ec50	0.0020	uM
N-(4-tert-butyl-2-fluoro-5-hydroxyphenyl)-4-oxo-1H-quinoline-3-carboxamide	1172572: Potentiation of human CFTR F508del mutant expressed in mouse NIH-3T3 cells after 30 mins by fluorescent voltage sensing optical assay	ec50	0.0020	uM
N,N-dibenzyl-4-oxo-1H-quinoline-3-carboxamide	1979275: Inhibition of CFTR F508 deletion mutant (unknown origin)	ec50	0.0021	uM
2-[[(2S)-2-hydroxy-3,3-dimethylbutanoyl]amino]-5,5,7,7-tetramethyl-4H-thieno[2,3-c]pyran-3-carboxamide	1471893: Potentiation of CFTR F508del mutant (unknown origin) expressed in human CFBE41o cells incubated for 10 mins in presence of forskolin measured for 7 secs by YFP halide assay	ec50	0.0027	uM
2-[[1-(hydroxymethyl)cyclopropanecarbonyl]amino]-5,5,7,7-tetramethyl-4H-thieno[2,3-c]pyran-3-carboxamide	2252594: Activation of CFTR F508del mutant (unknown origin)	ec50	0.0027	uM
3-amino-N-[(1-hydroxycyclopropyl)methyl]-5-[4-(trifluoromethoxy)phenyl]sulfonylpyridine-2-carboxamide	1744464: Potentiation of CFTR F508del mutant (unknown origin) expressed in human CFBE41o- cells co-expressing YFP incubated for 10 mins by halide potentiator assay	ec50	0.0028	uM
N-(3-carbamoyl-5,5,7,7-tetramethyl-4H-thieno[2,3-c]pyran-2-yl)-1H-pyrazole-5-carboxamide	1471893: Potentiation of CFTR F508del mutant (unknown origin) expressed in human CFBE41o cells incubated for 10 mins in presence of forskolin measured for 7 secs by YFP halide assay	ec50	0.0030	uM
2-[[(2R)-2-hydroxy-3,3-dimethylbutanoyl]amino]-5,5,7,7-tetramethyl-4H-thieno[2,3-c]pyran-3-carboxamide	2252594: Activation of CFTR F508del mutant (unknown origin)	ec50	0.0030	uM
N-(3-carbamoyl-5,5,7,7-tetramethyl-4H-thieno[2,3-c]pyran-2-yl)-5-(trifluoromethyl)-1H-pyrazole-3-carboxamide	1471893: Potentiation of CFTR F508del mutant (unknown origin) expressed in human CFBE41o cells incubated for 10 mins in presence of forskolin measured for 7 secs by YFP halide assay	ec50	0.0030	uM
4-[[(7S)-1-[3-[(2,2-difluoro-1,3-benzodioxol-5-yl)-methylcarbamoyl]phenyl]-3-(trifluoromethyl)-4,5,6,7-tetrahydroindazol-7-yl]oxy]benzoic acid	2269168: Corrector activity at CFTR F508del mutant (unknown origin) expressed in human CFBE41o- cells co-expressing HS-YFP assessed as restoration of channel function incubated for 24 hrs by florescence based analysis	ec50	0.0030	uM
3-[19,19-dioxo-24-(trifluoromethyl)-19lambda6-thia-13,20,25,26-tetrazatetracyclo[19.3.1.114,18.02,7]hexacosa-1(24),2,4,6,14(26),15,17,21(25),22-nonaen-13-yl]-2,2-dimethylpropan-1-ol	2252594: Activation of CFTR F508del mutant (unknown origin)	ec50	0.0030	uM
Ivacaftor	1170917: Corrector activity at CFTR mutant (unknown origin) by phenotypic screening assay	ec50	0.0030	uM
3-[(7S)-7-[4-[2-(3-but-3-ynyldiazirin-3-yl)ethylcarbamoyl]phenoxy]-3-(trifluoromethyl)-4,5,6,7-tetrahydroindazol-1-yl]-N-(2,2-difluoro-1,3-benzodioxol-5-yl)-N-methylbenzamide	2269168: Corrector activity at CFTR F508del mutant (unknown origin) expressed in human CFBE41o- cells co-expressing HS-YFP assessed as restoration of channel function incubated for 24 hrs by florescence based analysis	ec50	0.0030	uM
N-(4-tert-butyl-3-hydroxyphenyl)-4-oxo-1H-quinoline-3-carboxamide	1172572: Potentiation of human CFTR F508del mutant expressed in mouse NIH-3T3 cells after 30 mins by fluorescent voltage sensing optical assay	ec50	0.0030	uM
N-[4-tert-butyl-5-hydroxy-2-(trifluoromethyl)phenyl]-4-oxo-1H-quinoline-3-carboxamide	1172572: Potentiation of human CFTR F508del mutant expressed in mouse NIH-3T3 cells after 30 mins by fluorescent voltage sensing optical assay	ec50	0.0030	uM
N-(2,2-difluoro-1,3-benzodioxol-5-yl)-3-[(7S)-7-(4-ethynylphenoxy)-3-(trifluoromethyl)-4,5,6,7-tetrahydroindazol-1-yl]-N-methylbenzamide	2269168: Corrector activity at CFTR F508del mutant (unknown origin) expressed in human CFBE41o- cells co-expressing HS-YFP assessed as restoration of channel function incubated for 24 hrs by florescence based analysis	ec50	0.0033	uM
3-amino-N-[(2R)-3,3,3-trifluoro-2-hydroxypropyl]-5-[4-(trifluoromethoxy)phenyl]sulfonylpyridine-2-carboxamide	1744464: Potentiation of CFTR F508del mutant (unknown origin) expressed in human CFBE41o- cells co-expressing YFP incubated for 10 mins by halide potentiator assay	ec50	0.0034	uM
(3S)-2-(4-methoxy-3-propan-2-yloxybenzoyl)-N-(4-pentylphenyl)-3,4-dihydro-1H-isoquinoline-3-carboxamide	246453: Effective concentration for cellular chloride transport in C127 mouse epithelial cell transfected with recombinant Delta F508 CFTR	ec50	0.0035	uM
2-[(2-hydroxybenzoyl)amino]-5,5,7,7-tetramethyl-4H-thieno[2,3-c]pyran-3-carboxamide	1471893: Potentiation of CFTR F508del mutant (unknown origin) expressed in human CFBE41o cells incubated for 10 mins in presence of forskolin measured for 7 secs by YFP halide assay	ec50	0.0040	uM
2-[(2-hydroxybenzoyl)amino]-5,7-dimethyl-5,7-dihydro-4H-thieno[2,3-c]pyran-3-carboxamide	1471893: Potentiation of CFTR F508del mutant (unknown origin) expressed in human CFBE41o cells incubated for 10 mins in presence of forskolin measured for 7 secs by YFP halide assay	ec50	0.0040	uM
3-[19,19-dioxo-24-(trifluoromethyl)-19lambda6-thia-13,20,25,26-tetrazatetracyclo[19.3.1.114,18.02,7]hexacosa-1(24),2,4,6,14(26),15,17,21(25),22-nonaen-13-yl]-2,2-dimethylpropanoic acid	2252594: Activation of CFTR F508del mutant (unknown origin)	ec50	0.0040	uM
4-[ethyl-[6-[[6-(2-ethylphenyl)-5-(trifluoromethyl)-2-pyridinyl]sulfamoyl]-2-pyridinyl]amino]butanoic acid	2252594: Activation of CFTR F508del mutant (unknown origin)	ec50	0.0040	uM
N-[[6-[4-amino-4-(trifluoromethyl)piperidin-1-yl]-2-pyridinyl]sulfonyl]-1-(2-cyclohexyl-5-methylphenoxy)cyclopropane-1-carboxamide	2252594: Activation of CFTR F508del mutant (unknown origin)	ec50	0.0040	uM
(9R)-9-(5-bromofuran-2-yl)-12,14-dimethyl-13,15-dioxo-17-phenyl-8-oxa-1,12,14-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-2(7),3,5,10,16-pentaene-4-carboxylic acid;propan-2-amine	748579: Inhibition of wild type human CFTR chloride conductance expressed in forskolin-stimulated rat FRT cells by short-circuit current analysis in presence of transepithelial chloride gradient	ic50	0.0040	uM
2,4-dimethylpyrido[1,2-a]pyrimidin-5-ium-3-olate	598317: Inhibition of wild type CFTR expressed in CHO cells by [125I]iodide efflux assay	ic50	0.0050	uM
4-[(2R,4R)-4-[[1-(2,2-difluoro-1,3-benzodioxol-5-yl)cyclopropanecarbonyl]amino]-7-(difluoromethoxy)-3,4-dihydro-2H-chromen-2-yl]benzoic acid	1467971: Corrector activity at CFTR F508del/F508del mutant in primary HBE cells assessed as increase in chloride ion current across apical membrane measured 18 to 24 hrs post compound treatment on basolateral side of cells in presence of channel potentiator GLPG1837 by trans-epithelial current clamp method	ec50	0.0050	uM
3-amino-N-(3,3,3-trifluoro-2-hydroxypropyl)-5-[4-(trifluoromethoxy)piperidin-1-yl]sulfonylpyridine-2-carboxamide	1744464: Potentiation of CFTR F508del mutant (unknown origin) expressed in human CFBE41o- cells co-expressing YFP incubated for 10 mins by halide potentiator assay	ec50	0.0050	uM
trans-(1S,2R)-1-(2-methoxy-5-methylphenyl)-N-(2-methylquinolin-5-yl)sulfonyl-2-[3-(trifluoromethyl)phenyl]cyclopropane-1-carboxamide	2252594: Activation of CFTR F508del mutant (unknown origin)	ec50	0.0050	uM
trans-(1S,2S)-2-(6-ethoxy-2-pyridinyl)-1-(2-methoxy-5-methylphenyl)-N-(2-methylquinolin-5-yl)sulfonylcyclopropane-1-carboxamide	2252594: Activation of CFTR F508del mutant (unknown origin)	ec50	0.0050	uM
3-amino-N-(2-hydroxypropyl)-5-[4-(trifluoromethoxy)piperidin-1-yl]sulfonylpyridine-2-carboxamide	2252594: Activation of CFTR F508del mutant (unknown origin)	ec50	0.0050	uM
[5-[3-amino-5-[4-(trifluoromethoxy)phenyl]sulfonyl-2-pyridinyl]-1,3,4-oxadiazol-2-yl]methanol	2252594: Activation of CFTR F508del mutant (unknown origin)	ec50	0.0056	uM
1-[5-[3-amino-5-[4-(trifluoromethoxy)phenyl]sulfonyl-2-pyridinyl]-1,3,4-oxadiazol-2-yl]-2,2,2-trifluoroethanol	2252594: Activation of CFTR F508del mutant (unknown origin)	ec50	0.0058	uM
(3S)-N-(4-pentylphenyl)-2-(4-propan-2-yloxypyridine-2-carbonyl)-3,4-dihydro-1H-isoquinoline-3-carboxamide	246453: Effective concentration for cellular chloride transport in C127 mouse epithelial cell transfected with recombinant Delta F508 CFTR	ec50	0.0060	uM

CTD chemical–gene interactions

170 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Chlorides	increases secretion, decreases expression, affects transport, decreases secretion, increases transport (+7 more)	15
Colforsin	increases activity, increases transport, affects localization, decreases activity, increases phosphorylation (+5 more)	15
Glyburide	affects binding, decreases activity, decreases reaction, increases activity, affects cotreatment (+1 more)	10
fenamic acid	increases transport, decreases activity, affects cotreatment, decreases reaction, increases activity	7
3-((3-trifluoromethyl)phenyl)-5-((3-carboxyphenyl)methylene)-2-thioxo-4-thiazolidinone	increases export, increases reaction, affects cotreatment, increases activity, increases transport (+2 more)	7
5-nitro-2-(3-phenylpropylamino)benzoic acid	affects binding, increases activity, decreases activity	5
N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide	affects localization, decreases reaction, increases activity, increases phosphorylation, decreases activity	5
ivacaftor	affects transport, increases secretion, affects cotreatment, increases activity, decreases activity (+1 more)	5
Tobacco Smoke Pollution	affects expression, decreases activity, decreases expression	5
Valproic Acid	affects cotreatment, increases expression	5
Genistein	decreases reaction, increases activity, increases transport, increases reaction, affects localization (+2 more)	5
5-butyl-6-hydroxy-10-chlorobenzo(c)quinolizinium chloride	decreases reaction, increases transport, increases stability, affects localization, affects cotreatment (+1 more)	4
Resveratrol	affects cotreatment, decreases expression, increases activity	4
Adenosine Triphosphate	decreases reaction, increases export, increases reaction, affects reaction, increases activity (+2 more)	4
1-Methyl-3-isobutylxanthine	affects cotreatment, increases activity, affects export, increases reaction	4
4-phenylbutyric acid	affects localization, increases activity, increases stability	3
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases expression, increases activity, decreases expression, affects localization	3
U 0126	decreases reaction, increases activity, decreases expression, decreases activity	3
5-butyl-7-chloro-6-hydroxybenzo(c)quinolizinium	affects localization, affects cotreatment, decreases reaction, increases transport, increases activity (+2 more)	3
Cyclic AMP	increases reaction, increases transport, increases activity	3
Ascorbic Acid	decreases activity, decreases reaction, increases reaction, increases secretion, increases activity (+1 more)	3
Bicarbonates	decreases transport, increases transport, increases reaction, affects cotreatment, increases activity (+1 more)	3
Curcumin	increases reaction, affects reaction, increases activity, decreases reaction, increases export (+1 more)	3
Gentamicins	increases activity, increases expression	3
Glutathione	affects cotreatment, increases activity, decreases activity, decreases reaction	3
sodium arsenite	decreases expression, decreases reaction, increases secretion, increases expression, decreases activity	2
mercuric bromide	increases expression, affects cotreatment	2
7,8-benzoquinoline	affects secretion, increases reaction, increases activity	2
6-hydroxy-10-chlorobenzo(c)quinolizinium	affects cotreatment, decreases reaction, increases transport, increases activity	2
4-chlorobenzo(f)isoquinoline	increases activity	2

ChEMBL screening assays

520 unique, capped per target: 497 binding, 17 functional, 5 admet, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1737974	Binding	PUBCHEM_BIOASSAY: Fluorescence Polarization with Cer CAL-PDZ Measured in Biochemical System Using Plate Reader - 2109-01_Inhibitor_Dose_CherryPick_Activity. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID50443	PubChem BioAssay data set
CHEMBL1963993	Functional	PUBCHEM_BIOASSAY: Fluorescence Polarization with Cer CAL-PDZ Measured in Biochemical System Using Plate Reader - 2109-01_Inhibitor_Dose_DryPowder_Activity. (Class of assay: confirmatory)	PubChem BioAssay data set
CHEMBL4310428	ADMET	Inhibition of wild type human CFTR expressed in FRT cells assessed as reduction in forskolin-induced chloride current at 30 to 100 uM after 20 mins by electrophysiological assay	Synthesis and biological evaluation of novel Ani9 derivatives as potent and selective ANO1 inhibitors. — *Eur J Med Chem*

Cellosaurus cell lines

283 cell lines: 157 transformed cell line, 54 induced pluripotent stem cell, 44 finite cell line, 21 embryonic stem cell, 4 cancer cell line, 3 telomerase immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_0338	IB3-1	Transformed cell line	Male
CVCL_0486	PLJ-4.7	Cancer cell line	Male
CVCL_0M12	GM01957	Finite cell line	Male
CVCL_0M13	GM01958	Finite cell line	Male
CVCL_0M14	GM01959	Finite cell line	Male
CVCL_0M15	GM02801	Finite cell line	Male
CVCL_0M16	GM02803	Finite cell line	Male
CVCL_0M17	GM02826	Finite cell line	Female
CVCL_0M18	GM02827	Finite cell line	Female
CVCL_0M19	GM02828	Finite cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00157690	Phase 4	COMPLETED	Study of Alendronate to Prevent and Treat Osteoporosis in Cystic Fibrosis Patients
NCT00208078	Phase 4	TERMINATED	Effect of Non-Invasive Ventilation in Cystic Fibrosis Patient With Chronic Respiratory Failure.
NCT00244270	Phase 4	COMPLETED	Cystic Fibrosis and Totally Implantable Vascular Access Devices
NCT00333385	Phase 4	TERMINATED	Continuous Versus Short Infusions of Ceftazidime in Cystic Fibrosis
NCT00411736	Phase 4	COMPLETED	Scandinavian Cystic Fibrosis Azithromycin Study
NCT00418470	Phase 4	TERMINATED	Prolonging the Duration of Peripheral Venous Catheters in Cystic Fibrosis People
NCT00431964	Phase 4	COMPLETED	Effect of Azithromycin on Lung Function in 6-18 Year-olds With Cystic Fibrosis (CF) Not Infected With P. Aeruginosa
NCT00434278	Phase 4	TERMINATED	A Trial of Pulmozyme Withdrawal on Exercise Tolerance in Cystic Fibrosis Subjects With Severe Lung Disease (TOPIC)
NCT00483769	Phase 4	COMPLETED	One Year Glargine Treatment in CFRD Children and Adolescents
NCT00528190	Phase 4	COMPLETED	Treatment of Aspergillus Fumigatus (a Fungal Infection) in Patients With Cystic Fibrosis
NCT00557089	Phase 4	COMPLETED	The Effect of rhDNase on Ventilation Inhomogeneity in Patients With Cystic Fibrosis
NCT00572975	Phase 4	COMPLETED	Malabsorption Blood Test:Toward a Novel Approach to Quantify Steatorrhea
NCT00680316	Phase 4	TERMINATED	A Study of Pulmozyme® (Dornase Alpha) in 3- to 5-Year-Old Patients With Cystic Fibrosis
NCT00685035	Phase 4	COMPLETED	Comparison of Airway Clearance Therapy in Cystic Fibrosis Using the Same VEST Therapy Device But With Different Settings
NCT00744250	Phase 4	TERMINATED	Intraduodenal Aspiration Study to Assess the Bioavailability of Oral Pancrecarb® Compared to Placebo Control
NCT00787917	Phase 4	TERMINATED	An Exploratory Study to Assess Multiple Doses of Omalizumab in Patients With Cystic Fibrosis Complicated by Acute Bronchopulmonary Aspergillosis (ABPA)
NCT00843817	Phase 4	COMPLETED	RhDNase and Biodistribution of PMN Serine Proteases in Cystic Fibrosis Sputum
NCT00890370	Phase 4	COMPLETED	Should Any One Airway Clearance Technique be Recommended for People With Cystic Fibrosis?
NCT00996424	Phase 4	TERMINATED	The Effect of Inhaled N-Acetylcysteine Compared to Normal Saline on Sputum Rheology and Lung Function
NCT01044719	Phase 4	UNKNOWN	Duration of Antibiotics in Infective Exacerbations of Cystic Fibrosis
NCT01100606	Phase 4	COMPLETED	A Study to Evaluate the Mode of Administration and Safety of EUR-1008 (APT-1008) in Infants 1 to 12 Months of Age
NCT01131507	Phase 4	COMPLETED	PR-018: An Open-Label, Safety Extension of Study PR-011
NCT01207245	Phase 4	COMPLETED	Circadian Rhythm In Tobramycin Elimination In Cystic Fibrosis
NCT01323101	Phase 4	COMPLETED	Doxycycline Effects on Inflammation in Cystic Fibrosis
NCT01327703	Phase 4	COMPLETED	Control of Steatorrhea in Participants With Cystic Fibrosis and Exocrine Pancreatic Insufficiency
NCT01377792	Phase 4	COMPLETED	Study of Long-term Treatment With Hypertonic Saline in Patients With Cystic Fibrosis
NCT01400750	Phase 4	COMPLETED	Comparison of 2 Treatment Regimens for Eradication of P Aeruginosa Infection in Children With Cystic Fibrosis
NCT01429259	Phase 4	COMPLETED	Population Pharmacokinetics of Prolonged Infusion Meropenem in Cystic Fibrosis (CF) Children
NCT01608555	Phase 4	COMPLETED	Tobramycin 300 mg Once-a-day (o.d.) Aerosol in Adults With Cystic Fibrosis
NCT01667094	Phase 4	UNKNOWN	A Study Comparing Continuous Infusion Antibiotics to Standard Treatment for Lung Infections in Cystic Fibrosis
NCT01694069	Phase 4	TERMINATED	Continuous Infusion Piperacillin-tazobactam for the Treatment of Cystic Fibrosis
NCT01702415	Phase 4	WITHDRAWN	Zoledronic Acid in Cystic Fibrosis
NCT01712334	Phase 4	COMPLETED	A Study of the Comparable Efficacy and Safety of Pulmozyme (Dornase Alfa) Delivered by the eRapid Nebulizer System in Patients With Cystic Fibrosis
NCT01737983	Phase 4	COMPLETED	Effect of Lactobacillus Reuteri in Cystic Fibrosis
NCT01844778	Phase 4	COMPLETED	Ease of Use and Microbial Contamination of Tobramycin Inhalation Powder (TIP) Versus Nebulised Tobramycin Inhalation Solution (TIS) and Nebulised Colistimethate (COLI)
NCT01880346	Phase 4	COMPLETED	Comparison of Absorption of Vitamin D in Cystic Fibrosis
NCT01882400	Phase 4	COMPLETED	Assessment of Response to Treatment of Osteoporosis With Oral Bisphosphonates in Patients With Muscular Dystrophy
NCT01937325	Phase 4	UNKNOWN	CPET in CF Patients With One G551D Mutation Taking VX770
NCT02015663	Phase 4	TERMINATED	Tobramycin Inhalation Powder (TIP) Administered Once Daily Continuously Versus TIP Administered BID in 28 Day on / 28 Day Off Cycles
NCT02048592	Phase 4	UNKNOWN	Impact of Immunonutrition on the Patients With Cystic Fibrosis
NCT02178540	Phase 4	COMPLETED	Study to Validate the Instructions for Use of TOBI® Podhaler™ in Cystic Fibrosis Patients
NCT02277626	Phase 4	COMPLETED	Electro Flo 5000 and Vest Therapy
NCT02421120	Phase 4	COMPLETED	Population Pharmacokinetics and Safety of Intravenous Ceftolozane/Tazobactam in Adult Cystic Fibrosis Patients
NCT02444234	Phase 4	COMPLETED	Pharmacokinetics of Tedizolid Phosphate in Cystic Fibrosis
NCT02504827	Phase 4	COMPLETED	Steady-state Pharmacokinetics of Ceftazidime/Avibactam in Cystic Fibrosis
NCT02547116	Phase 4	WITHDRAWN	Epidemiology and Treatment of Small-colony Variant Staphylococcus Aureus in Cystic Fibrosis
NCT02677701	Phase 4	COMPLETED	Testing the Effect of Adding Chronic Oral Azithromycin to Inhaled Tobramycin in People With Cystic Fibrosis (CF)
NCT02700282	Phase 4	COMPLETED	Backpack Carrying in Children With Cystic Fibrosis
NCT02823470	Phase 4	TERMINATED	A Pilot Study to Evaluate the Use of Smart Adherence Technology to Measure Lumacaftor/Ivacaftor Adherence in CF Subjects Homozygous for the F508del CFTR Mutation
NCT02823964	Phase 4	COMPLETED	EASY: Extended Access to Sollpura Over Years
NCT02875366	Phase 4	COMPLETED	A Study of the Effects of Lumacaftor/Ivacaftor (LUM/IVA) on Exercise Tolerance in Subjects With Cystic Fibrosis (CF), Homozygous for the F508del-CFTR Mutation
NCT02894684	Phase 4	COMPLETED	Aztreonam for Inhalation Solution (AZLI) for the Treatment of Exacerbations of Cystic Fibrosis
NCT02918409	Phase 4	COMPLETED	IV Colistin for Pulmonary Exacerbations: Improving Safety and Efficacy
NCT03045198	Phase 4	UNKNOWN	Effect of Azithromycin on Fatty Acids in CF
NCT03172793	Phase 4	COMPLETED	Telavancin Pharmacokinetics in Cystic Fibrosis Patients
NCT03256799	Phase 4	COMPLETED	Evaluation of Ivacaftor in Patients Using Ataluren for Nonsense Mutations
NCT03256968	Phase 4	COMPLETED	PTC Study to Evaluate Ataluren in Combination With Ivacaftor
NCT03502070	Phase 4	COMPLETED	Human Factors Study to Validate the User Interface of TOBI Podhaler Using Placebo Capsules
NCT03624101	Phase 4	TERMINATED	Novel Therapeutic Approaches for Treatment of CF Patients With W1282X Premature Termination Codon Mutations
NCT03632525	Phase 4	COMPLETED	Intravenous Iron in Adults With Cystic Fibrosis

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for CFTR across ~30M SureChEMBL compounds — explore on Sugi Predict.