Target General Infomation
Target ID
T50066
Former ID
TTDS00287
Target Name
Chloride channel protein 2
Gene Name
CLCN2
Synonyms
ClC-2; ClC-2 Cl- channel; ClC-2 chloride channel; CLCN2
Target Type
Successful
Disease Alopecia [ICD9: 704.09; ICD10: L65.9]
Chronic idiopathic constipation [ICD9: 564; ICD10: K59]
Function
Voltage-gated chloride channel. Chloride channels have several functions including the regulation of cell volume; membrane potential stabilization, signal transduction and transepithelial transport.
BioChemical Class
Chloride channel
UniProt ID
Sequence
MAAAAAEEGMEPRALQYEQTLMYGRYTQDLGAFAKEEAARIRLGGPEPWKGPPSSRAAPE
LLEYGRSRCARCRVCSVRCHKFLVSRVGEDWIFLVLLGLLMALVSWVMDYAIAACLQAQQ
WMSRGLNTSILLQYLAWVTYPVVLITFSAGFTQILAPQAVGSGIPEMKTILRGVVLKEYL
TLKTFIAKVIGLTCALGSGMPLGKEGPFVHIASMCAALLSKFLSLFGGIYENESRNTEML
AAACAVGVGCCFAAPIGGVLFSIEVTSTFFAVRNYWRGFFAATFSAFIFRVLAVWNRDEE
TITALFKTRFRLDFPFDLQELPAFAVIGIASGFGGALFVYLNRKIVQVMRKQKTINRFLM
RKRLLFPALVTLLISTLTFPPGFGQFMAGQLSQKETLVTLFDNRTWVRQGLVEELEPPST
SQAWNPPRANVFLTLVIFILMKFWMSALATTIPVPCGAFMPVFVIGAAFGRLVGESMAAW
FPDGIHTDSSTYRIVPGGYAVVGAAALAGAVTHTVSTAVIVFELTGQIAHILPVMIAVIL
ANAVAQSLQPSLYDSIIRIKKLPYLPELGWGRHQQYRVRVEDIMVRDVPHVALSCTFRDL
RLALHRTKGRMLALVESPESMILLGSIERSQVVALLGAQLSPARRRQHMQERRATQTSPL
SDQEGPPTPEASVCFQVNTEDSAFPAARGETHKPLKPALKRGPSVTRNLGESPTGSAESA
GIALRSLFCGSPPPEAASEKLESCEKRKLKRVRISLASDADLEGEMSPEEILEWEEQQLD
EPVNFSDCKIDPAPFQLVERTSLHKTHTIFSLLGVDHAYVTSIGRLIGIVTLKELRKAIE
GSVTAQGVKVRPPLASFRDSATSSSDTETTEVHALWGPHSRHGLPREGSPSDSDDKCQ
Drugs and Mode of Action
Drug(s) Lubiprostone Drug Info Approved Chronic idiopathic constipation [467577], [528715], [531566], [536527]
RK-023 Drug Info Phase 2 Alopecia [548944]
Activator Acid-activated omeprazole Drug Info [535191]
Lubiprostone Drug Info [534851], [535703], [537096]
Blocker (channel blocker) diphenylamine-2-carboxylic acid Drug Info [543920]
NPPB Drug Info [543920]
Modulator RK-023 Drug Info [1572591]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Mineral absorption
Reactome Stimuli-sensing channels
WikiPathways Iron uptake and transport
References
Ref 467577(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. (Ligand id: 4242).
Ref 5287152006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
Ref 531566Long-term safety and effectiveness of lubiprostone, a chloride channel (ClC-2) activator, in patients with chronic idiopathic constipation. Dig Dis Sci. 2011 Sep;56(9):2639-45.
Ref 536527Emerging drugs for postoperative ileus. Expert Opin Emerg Drugs. 2007 Nov;12(4):619-26.
Ref 548944Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800030641)
Ref
Ref 534851Expression of CLCN voltage-gated chloride channel genes in human blood vessels. J Mol Cell Cardiol. 1999 Mar;31(3):657-66.
Ref 535191ClC-2 Cl- channels in human lung epithelia: activation by arachidonic acid, amidation, and acid-activated omeprazole. Am J Physiol Cell Physiol. 2001 Jul;281(1):C46-54.
Ref 535703Mutations in CLCN2 encoding a voltage-gated chloride channel are associated with idiopathic generalized epilepsies. Nat Genet. 2003 Apr;33(4):527-32. Epub 2003 Mar 3.
Ref 537096Lubiprostone stimulates secretion from tracheal submucosal glands of sheep, pigs, and humans. Am J Physiol Lung Cell Mol Physiol. 2009 May;296(5):L811-24. Epub 2009 Feb 20.
Ref 543920(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: 699).
Ref 1572591Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.

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