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Gene Review

CLCN6  -  chloride channel, voltage-sensitive 6

Homo sapiens

Synonyms: CLC-6, Chloride channel protein 6, Chloride transport protein 6, ClC-6, KIAA0046
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Disease relevance of CLCN6


High impact information on CLCN6


Biological context of CLCN6

  • A novel CA-repeat polymorphism identified within intron 2 of the CLCN6 gene may be useful in assessing loss of heterozygosity in such tumors [3].
  • Thus, the CLCN6 type of alternative splicing and the ensuing structural diversity is not conserved within the CLC gene family [4].
  • The human and murine CLCN6 genes both consist of 23 exons and share a nearly identical genomic structure [5].
  • Comparison of the genomic organization of CLCN6 and CLCN7 genes shows that just eight introns are located at corresponding cDNA positions [5].
  • The four plant genes are homologous to a recently isolated chloride channel gene from tobacco (CLC-Nt1; Lurin, C., Geelen, D., Barbier-Brygoo, H., Guern, J., and Maurel, C. (1996) Plant Cell 8, 701-711) and are about 30% identical in sequence to the most closely related CLC-6 and CLC-7 putative chloride channels from mammalia [6].

Anatomical context of CLCN6


Associations of CLCN6 with chemical compounds

  • ClC-6 has a highly conserved glycosylation site between transmembrane domains D8 and D9, while ClC-7 is the only known eukaryotic ClC protein which lacks this site [7].

Other interactions of CLCN6

  • CLCN6 and CLCN7 belong to a novel, poorly characterized subbranch of this family [5].
  • Complete genomic structure of the CLCN6 and CLCN7 putative chloride channel genes(1) [5].
  • Experiments using antisense oligoribonucleotides to ClC-5 or ClC-6 channel m-RNA also inhibit topographic reactions, which provides further confirmation of the hypothesis [8].


  1. Lysosomal storage disease upon disruption of the neuronal chloride transport protein ClC-6. Poët, M., Kornak, U., Schweizer, M., Zdebik, A.A., Scheel, O., Hoelter, S., Wurst, W., Schmitt, A., Fuhrmann, J.C., Planells-Cases, R., Mole, S.E., Hübner, C.A., Jentsch, T.J. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  2. Expression of human pICln and ClC-6 in Xenopus oocytes induces an identical endogenous chloride conductance. Buyse, G., Voets, T., Tytgat, J., De Greef, C., Droogmans, G., Nilius, B., Eggermont, J. J. Biol. Chem. (1997) [Pubmed]
  3. The human and mouse methylenetetrahydrofolate reductase (MTHFR) genes: genomic organization, mRNA structure and linkage to the CLCN6 gene. Gaughan, D.J., Barbaux, S., Kluijtmans, L.A., Whitehead, A.S. Gene (2000) [Pubmed]
  4. The exon-intron architecture of human chloride channel genes is not conserved. Eggermont, J. Biochim. Biophys. Acta (1998) [Pubmed]
  5. Complete genomic structure of the CLCN6 and CLCN7 putative chloride channel genes(1). Kornak, U., Bösl, M.R., Kubisch, C. Biochim. Biophys. Acta (1999) [Pubmed]
  6. A family of putative chloride channels from Arabidopsis and functional complementation of a yeast strain with a CLC gene disruption. Hechenberger, M., Schwappach, B., Fischer, W.N., Frommer, W.B., Jentsch, T.J., Steinmeyer, K. J. Biol. Chem. (1996) [Pubmed]
  7. ClC-6 and ClC-7 are two novel broadly expressed members of the CLC chloride channel family. Brandt, S., Jentsch, T.J. FEBS Lett. (1995) [Pubmed]
  8. Chloride channels and the reactions of cells to topography. Tobasnick, G., Curtis, A.S. European cells & materials [electronic resource]. (2001) [Pubmed]
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