Details of the Drug Transporter (DTP)

General Information of Drug Transporter (DTP) (ID: DTEJNUG)

• DTP Name: Cystic fibrosis transmembrane conductance regulator (ABCC7)
• Gene Name: ABCC7
• UniProt ID: P13569 (CFTR_HUMAN)
• VARIDT ID: DTD0060
• Synonyms: CFTR; ATP-binding cassette sub-family C member 7; Channel conductance-controlling ATPase; cAMP-dependent chloride channel; ABCC7
• DTP Family: ATP-Binding Cassette (ABC) Superfamily
• Tissue Specificity: Expressed in the respiratory airway, includingbronchial epithelium, and in the female reproductive tract,including oviduct (at protein level) (PubMed:22207244,PubMed:15716351). Detected in pancreatic intercalated ducts in theexocrine tissue, on epithelial cells in intralobular striatedducts in sublingual salivary glands, on apical membranes of cryptcells throughout the small and large intestine, and on thereabsorptive duct in eccrine sweat glands (PubMed:1284548,PubMed:28130590). Detected on the equatorial segment of the spermhead (at protein level) (PubMed:19923167). Detected in nasal andbronchial superficial epithelium (PubMed:15716351). Expressed bythe central cells on the sebaceous glands, dermal adipocytes and,at lower levels, by epithelial cells (PubMed:28130590).
• Sequence:
  MQRSPLEKASVVSKLFFSWTRPILRKGYRQRLELSDIYQIPSVDSADNLSEKLEREWDRE
  LASKKNPKLINALRRCFFWRFMFYGIFLYLGEVTKAVQPLLLGRIIASYDPDNKEERSIA
  IYLGIGLCLLFIVRTLLLHPAIFGLHHIGMQMRIAMFSLIYKKTLKLSSRVLDKISIGQL
  VSLLSNNLNKFDEGLALAHFVWIAPLQVALLMGLIWELLQASAFCGLGFLIVLALFQAGL
  GRMMMKYRDQRAGKISERLVITSEMIENIQSVKAYCWEEAMEKMIENLRQTELKLTRKAA
  YVRYFNSSAFFFSGFFVVFLSVLPYALIKGIILRKIFTTISFCIVLRMAVTRQFPWAVQT
  WYDSLGAINKIQDFLQKQEYKTLEYNLTTTEVVMENVTAFWEEGFGELFEKAKQNNNNRK
  TSNGDDSLFFSNFSLLGTPVLKDINFKIERGQLLAVAGSTGAGKTSLLMVIMGELEPSEG
  KIKHSGRISFCSQFSWIMPGTIKENIIFGVSYDEYRYRSVIKACQLEEDISKFAEKDNIV
  LGEGGITLSGGQRARISLARAVYKDADLYLLDSPFGYLDVLTEKEIFESCVCKLMANKTR
  ILVTSKMEHLKKADKILILHEGSSYFYGTFSELQNLQPDFSSKLMGCDSFDQFSAERRNS
  ILTETLHRFSLEGDAPVSWTETKKQSFKQTGEFGEKRKNSILNPINSIRKFSIVQKTPLQ
  MNGIEEDSDEPLERRLSLVPDSEQGEAILPRISVISTGPTLQARRRQSVLNLMTHSVNQG
  QNIHRKTTASTRKVSLAPQANLTELDIYSRRLSQETGLEISEEINEEDLKECFFDDMESI
  PAVTTWNTYLRYITVHKSLIFVLIWCLVIFLAEVAASLVVLWLLGNTPLQDKGNSTHSRN
  NSYAVIITSTSSYYVFYIYVGVADTLLAMGFFRGLPLVHTLITVSKILHHKMLHSVLQAP
  MSTLNTLKAGGILNRFSKDIAILDDLLPLTIFDFIQLLLIVIGAIAVVAVLQPYIFVATV
  PVIVAFIMLRAYFLQTSQQLKQLESEGRSPIFTHLVTSLKGLWTLRAFGRQPYFETLFHK
  ALNLHTANWFLYLSTLRWFQMRIEMIFVIFFIAVTFISILTTGEGEGRVGIILTLAMNIM
  STLQWAVNSSIDVDSLMRSVSRVFKFIDMPTEGKPTKSTKPYKNGQLSKVMIIENSHVKK
  DDIWPSGGQMTVKDLTAKYTEGGNAILENISFSISPGQRVGLLGRTGSGKSTLLSAFLRL
  LNTEGEIQIDGVSWDSITLQQWRKAFGVIPQKVFIFSGTFRKNLDPYEQWSDQEIWKVAD
  EVGLRSVIEQFPGKLDFVLVDGGCVLSHGHKQLMCLARSVLSKAKILLLDEPSAHLDPVT
  YQIIRRTLKQAFADCTVILCEHRIEAMLECQQFLVIEENKVRQYDSIQKLLNERSLFRQA
  ISPSDRVKLFPHRNSSKCKSKPQIAALKEETEEEVQDTRL
• Function: This transporter plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis and it mediates the transport of chloride ions across the cell membrane.
• Endogenous Substrate(s): Cl-; Glutathione
• TCDB ID: 3.A.1.202.1
• Gene ID: 1080
• KEGG Pathway:
  ABC transporters (hsa02010)
  cAMP signaling pathway (hsa04024)
  AMPK signaling pathway (hsa04152)
  Tight junction (hsa04530)
  Gastric acid secretion (hsa04971)
  Pancreatic secretion (hsa04972)
  Bile secretion (hsa04976)
  Vibrio cholerae infection (hsa05110)
• Reactome Pathway:
  RHO GTPases regulate CFTR trafficking (R-HSA-5627083)
  Defective CFTR causes cystic fibrosis (R-HSA-5678895)
  Ub-specific processing proteases (R-HSA-5689880)
  Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825)
  Clathrin-mediated endocytosis (R-HSA-8856828)
  RHOQ GTPase cycle (R-HSA-9013406)
  Chaperone Mediated Autophagy (R-HSA-9613829)
  Late endosomal microautophagy (R-HSA-9615710)
  Aggrephagy (R-HSA-9646399)
  ABC-family proteins mediated transport (R-HSA-382556)
• BioCyc Pathway: MetaCyc:HS00075-MON

Molecular Expression Atlas (MEA) of This DTP

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Acute myelocytic leukaemia	2B33.1	Bone marrow	4.04E-01	1.82E-03	2.03E-02
Adrenocortical carcinoma	2D11.Z	Kidney	6.08E-01	-1.84E-02	-2.14E-01
Alopecia	ED70	Skin from scalp	1.70E-03	9.70E-02	3.89E-01
Alzheimer's disease	8A20	Entorhinal cortex	5.90E-02	2.21E-02	2.74E-01
Ankylosing spondylitis	FA92.0	Pheripheral blood	7.34E-02	3.40E-02	3.15E-01
Aortic stenosis	BB70	Calcified aortic valve	8.68E-01	-2.86E-02	-1.10E-01
Apnea	7A40	Hyperplastic tonsil	1.22E-01	-4.41E-02	-6.85E-01
Arthropathy	FA00-FA5Z	Peripheral blood	1.66E-02	6.59E-02	1.03E+00
Asthma	CA23	Nasal and bronchial airway	6.33E-01	8.93E-02	1.93E-01
Atopic dermatitis	EA80	Skin	5.08E-01	-5.40E-02	-5.09E-01
Autism	6A02	Whole blood	7.79E-01	1.14E-02	1.13E-01
Autoimmune uveitis	9A96	Peripheral monocyte	6.74E-01	-2.18E-02	-2.47E-01
Autosomal dominant monocytopenia	4B04	Whole blood	2.43E-01	1.03E-01	7.88E-01
Bacterial infection of gingival	1C1H	Gingival tissue	1.51E-03	-4.64E-02	-4.95E-01
Batten disease	5C56.1	Whole blood	1.15E-01	2.49E-02	3.12E-01
Behcet's disease	4A62	Peripheral blood	1.78E-01	6.25E-02	7.17E-01
Bipolar disorder	6A60-6A6Z	Prefrontal cortex	5.82E-01	-4.90E-03	-6.75E-02
Bladder cancer	2C94	Bladder tissue	7.38E-02	1.73E-01	9.41E-01
Breast cancer	2C60-2C6Z	Breast tissue	7.66E-01	-3.51E-03	-3.08E-02
Cardioembolic stroke	8B11.20	Whole blood	3.05E-07	1.38E-01	1.32E+00
Cervical cancer	2C77	Cervical tissue	5.97E-01	-1.00E-02	-2.26E-02
Childhood onset rheumatic disease	FA20.Z	Peripheral blood	7.11E-01	2.14E-02	2.29E-01
Chronic hepatitis C	1E51.1	Whole blood	5.77E-01	-5.52E-02	-3.42E-01
Chronic obstructive pulmonary disease	CA22	Lung tissue	8.34E-01	-2.30E-02	-8.87E-02
Chronic obstructive pulmonary disease	CA22	Small airway epithelium	8.85E-01	-3.07E-02	-2.98E-01
Chronic rhinosinusitis	CA0A	Sinus mucosa tissue	5.90E-01	-2.52E-02	-2.10E-01
Colon cancer	2B90	Colon tissue	2.39E-01	9.42E-02	3.25E-01
Coronary artery disease	BA80-BA8Z	Peripheral blood	6.04E-01	2.59E-03	2.09E-02
Diffuse large B-cell lymphoma	2A81	Tonsil tissue	6.40E-01	-7.22E-02	-4.77E-01
Endometriosis	GA10	Endometrium tissue	2.35E-01	6.14E-02	4.22E-01
Familial hypercholesterolemia	5C80.00	Peripheral blood	7.49E-01	1.07E-02	1.75E-01
Familial hypercholesterolemia	5C80.00	Whole blood	2.15E-01	7.54E-02	8.58E-01
Gastric cancer	2B72	Gastric tissue	8.39E-03	2.96E-01	3.30E+00
Glioblastopma	2A00.00	Nervous tissue	9.01E-01	4.91E-03	4.17E-02
Glioma	2A00.0Y-2A00.0Z	White matter tissue	4.84E-02	-9.29E-02	-5.27E-01
Head and neck cancer	2D42	Head and neck tissue	3.13E-10	-1.18E-01	-7.22E-01
HIV-associated neurocognitive impairment	8A2Y-8A2Z	White matter tissue	2.35E-01	2.77E-02	1.60E-01
Huntington's disease	8A01.10	Whole blood	6.35E-01	-1.88E-02	-2.46E-01
Idiopathic pulmonary fibrosis	CB03.4	Lung tissue	1.27E-01	-2.39E-01	-6.06E-01
Immunodeficiency	4A00-4A20	Peripheral blood	2.35E-01	-5.10E-02	-6.54E-01
Influenza	1.00E+30	Whole blood	5.80E-04	2.08E-01	6.20E+00
Interstitial cystitis	GC00.3	Bladder tissue	1.12E-01	9.97E-02	1.56E+00
Intracranial aneurysm	8B01.0	Intracranial artery	9.39E-01	-5.37E-03	-5.51E-02
Irritable bowel syndrome	DD91.0	Rectal colon tissue	3.61E-01	-1.02E-01	-2.57E-01
Ischemic stroke	8B11	Peripheral blood	3.86E-01	1.83E-02	2.41E-01
Juvenile idiopathic arthritis	FA24	Peripheral blood	8.69E-02	1.76E-02	1.02E-01
Lateral sclerosis	8B60.4	Cervical spinal cord	9.36E-01	1.46E-02	1.48E-01
Lateral sclerosis	8B60.4	Skin	7.32E-01	3.55E-02	7.33E-01
Liver cancer	2C12.0	Liver tissue	6.62E-02	-9.96E-02	-9.55E-01
Liver failure	DB99.7-DB99.8	Liver tissue	1.83E-03	5.05E-01	3.21E+00
Lung cancer	2C25	Lung tissue	4.70E-31	-4.35E-01	-9.54E-01
Lupus erythematosus	4A40	Whole blood	5.08E-08	5.99E-02	5.88E-01
Major depressive disorder	6A70-6A7Z	Whole blood	8.61E-01	-2.77E-02	-2.04E-01
Major depressive disorder	6A70-6A7Z	Hippocampus	6.77E-01	1.96E-02	2.32E-01
Melanoma	2C30	Skin	1.68E-03	-3.08E-01	-4.05E-01
Multiple myeloma	2A83.1	Bone marrow	5.49E-01	-4.19E-02	-3.92E-01
Multiple myeloma	2A83.1	Peripheral blood	4.31E-02	4.82E-02	7.40E-01
Multiple sclerosis	8A40	Plasmacytoid dendritic cells	5.02E-02	-1.16E-01	-1.03E+00
Myelodysplastic syndrome	2A36-2A3Z	Bone marrow	9.36E-01	-1.31E-02	-1.37E-01
Myelofibrosis	2A20.2	Whole blood	2.18E-01	-3.47E-03	-4.27E-02
Myocardial infarction	BA41-BA50	Peripheral blood	1.90E-02	5.39E-02	2.11E-01
Myopathy	8C70.6	Muscle tissue	7.43E-01	3.77E-03	3.85E-02
Neonatal sepsis	KA60	Whole blood	7.29E-01	7.15E-04	7.34E-03
Neuroectodermal tumour	2A00.11	Brain stem tissue	8.69E-02	-1.14E-01	-6.63E-01
Non-alcoholic fatty liver disease	DB92	Liver tissue	7.50E-01	1.51E-02	1.89E-01
Obesity related type 2 diabetes	5A11	Omental adipose tissue	2.01E-01	3.96E-03	8.94E-02
Olive pollen allergy	CA08.00	Peripheral blood	5.17E-01	2.27E-02	1.77E-01
Oral cancer	2B6E	Oral tissue	1.83E-01	-5.57E-02	-1.26E-01
Osteoarthritis	FA00-FA0Z	Synovial tissue	4.55E-01	-2.10E-02	-3.34E-01
Osteoporosis	FB83.1	Bone marrow	3.07E-02	9.39E-02	1.88E+00
Ovarian cancer	2C73	Ovarian tissue	2.66E-05	2.83E-02	4.98E-01
Pancreatic cancer	2C10	Pancreas	2.97E-03	-1.17E+00	-1.42E+00
Parkinson's disease	8A00.0	Substantia nigra tissue	8.95E-01	-6.62E-03	-7.23E-02
Pediatric respiratory syncytial virus infection	CA40.11	Peripheral blood	6.58E-01	2.11E-02	3.26E-01
Pituitary cancer	2D12	Pituitary tissue	4.61E-01	3.81E-02	3.06E-01
Pituitary gonadotrope tumour	2D12	Pituitary tissue	4.32E-01	8.04E-02	5.11E-01
Polycystic ovary syndrome	5A80.1	Vastus lateralis muscle	6.68E-01	-2.17E-02	-2.81E-01
Polycythemia vera	2A20.4	Whole blood	1.28E-01	1.50E-02	1.70E-01
Pompe disease	5C51.3	Biceps muscle	3.72E-01	-4.44E-02	-3.18E-01
Preterm birth	KA21.4Z	Myometrium	2.66E-01	4.91E-02	7.02E-01
Prostate cancer	2C82	Prostate	8.93E-01	-3.29E-02	-6.84E-02
Psoriasis	EA90	Skin	7.40E-01	1.22E-02	5.68E-02
Rectal cancer	2B92	Rectal colon tissue	3.81E-01	-1.01E-01	-5.94E-01
Renal cancer	2C90-2C91	Kidney	1.40E-01	3.48E-02	2.82E-01
Retinoblastoma	2D02.2	Uvea	1.00E-01	-3.04E-02	-1.03E+00
Rheumatoid arthritis	FA20	Synovial tissue	4.49E-03	-2.77E-01	-2.22E+00
Rhinovirus infection	CA42.1	Nasal epithelium tissue	1.51E-01	-1.96E-02	-1.58E-01
Schizophrenia	6A20	Prefrontal cortex	8.06E-02	2.62E-02	3.32E-01
Schizophrenia	6A20	Superior temporal cortex	6.43E-01	-3.09E-02	-4.89E-01
Scleroderma	4A42.Z	Whole blood	3.66E-01	-2.38E-02	-3.20E-01
Seizure	8A60-8A6Z	Whole blood	9.58E-01	1.83E-03	1.51E-02
Sensitive skin	EK0Z	Skin	8.40E-01	4.49E-02	5.76E-01
Sepsis with septic shock	1G41	Whole blood	6.79E-01	1.14E-02	8.45E-02
Shwachman-Diamond syndrome	3A70.0	Bone marrow	4.27E-01	5.73E-02	4.65E-01
Sickle cell disease	3A51.0-3A51.3	Peripheral blood	6.41E-01	-1.08E-02	-1.35E-01
Simpson golabi behmel syndrome	LD2C	Adipose tissue	1.50E-01	2.09E-02	9.49E-01
Sjogren's syndrome	4A43.2	Salivary gland tissue	3.30E-01	-2.61E-02	-1.68E-01
Skin cancer	2C30-2C3Z	Skin	1.41E-29	-2.32E-01	-8.27E-01
Thrombocythemia	3B63	Whole blood	5.34E-01	3.54E-03	3.77E-02
Thrombocytopenia	3B64	Whole blood	7.76E-01	6.28E-02	7.41E-01
Thyroid cancer	2D10	Thyroid	3.22E-01	2.68E-03	2.58E-02
Tibial muscular dystrophy	8C75	Muscle tissue	3.25E-05	-1.51E-01	-1.83E+00
Tuberous sclerosis complex	LD2D.2	Perituberal tissue	2.67E-01	8.56E-02	8.79E-01
Type 2 diabetes	5A11	Liver tissue	5.19E-01	-4.76E-02	-8.33E-01
Ureter cancer	2C92	Urothelium	4.50E-01	1.97E-02	2.53E-01
Uterine cancer	2C78	Endometrium tissue	3.90E-02	1.32E-02	4.34E-02
Vitiligo	ED63.0	Skin	7.43E-01	-1.78E-01	-6.48E-01

The Drug Therapeutic Target (DTT) Role of This DTP

• DTP DTT Name: cAMP-dependent chloride channel (CFTR) DTT Info
• DTP DTT Type: Successful

3 Approved Drug(s) Targeting This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Crofelemer	DM4AMQZ	HIV-associated diarrhoea	1A2Z	Approved	[1]
Ivacaftor	DMZC1HS	Cystic fibrosis	CA25	Approved	[2]
Tezacaftor and ivacaftor	DMY62FC	Acute lung injury	NB32.3	Approved	[3]

10 Clinical Trial Drug(s) Targeting This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
VX-661	DMJBXO3	Cystic fibrosis	CA25	Phase 3	[4]
ABBV-2222	DM4ZLTY	Cystic fibrosis	CA25	Phase 2	[5]
GLPG-1837	DMOCRYB	Cystic fibrosis	CA25	Phase 2	[5]
iOWH032	DM5TMYC	Diarrhea	ME05.1	Phase 2	[6]
Lumacaftor	DMCLWDJ	Cystic fibrosis	CA25	Phase 2	[7]
QBW251	DMQ5APT	Chronic obstructive pulmonary disease	CA22	Phase 2	[8]
ABBV-2451	DMUCF9L	Cystic fibrosis	CA25	Phase 1	[5]
ABBV-2737	DMU6K37	Cystic fibrosis	CA25	Phase 1	[5]
ABBV-3067	DMB01L5	Cystic fibrosis	CA25	Phase 1	[5]
VX-522	DMO1D9E	Cystic fibrosis	CA25	Phase 1	[9]

8 Investigative Drug(s) Targeting This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CBIQ	DMDIW1M	Discovery agent	N.A.	Investigative	[10]
CFTRinh-172	DM8TJW3	Discovery agent	N.A.	Investigative	[10]
GlyH-101	DM67FQ1	Discovery agent	N.A.	Investigative	[10]
phenylglycine-01	DMHT9AR	Discovery agent	N.A.	Investigative	[10]
sulfonamide-01	DMU0BW9	Discovery agent	N.A.	Investigative	[10]
UCCF-029	DMO9S5P	Discovery agent	N.A.	Investigative	[10]
UCCF-339	DM3I9JG	Discovery agent	N.A.	Investigative	[10]
UCCF-853	DMN9QO4	Discovery agent	N.A.	Investigative	[10]

References

• [1] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [3] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [4] CFTR Modulators for the Treatment of Cystic Fibrosis. P T. 2014 Jul;39(7):500-11.
• [5] Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
• [6] Developing novel antisecretory drugs to treat infectious diarrhea. Future Med Chem. 2011 Aug;3(10):1317-25.
• [7] A CFTR corrector (lumacaftor) and a CFTR potentiator (ivacaftor) for treatment of patients with cystic fibrosis who have a phe508del CFTR mutation: a phase 2 randomised controlled trial. Lancet Respir Med. 2014 Jul;2(7):527-38.
• [8] Safety and efficacy of the cystic fibrosis transmembrane conductance regulator potentiator icenticaftor (QBW251). J Cyst Fibros. 2021 Mar;20(2):250-256.
• [9] Clinical pipeline report, company report or official report of Vertex
• [10] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 707).