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Gene Review

CLCNKA  -  chloride channel, voltage-sensitive Ka

Homo sapiens

Synonyms: CLCK1, Chloride channel Ka, Chloride channel protein ClC-Ka, ClC-K1, hClC-Ka
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Disease relevance of CLCNKA

  • As ClC-K channels are involved in human kidney disease the frog pronephros may be a useful system in which to study the in vivo activity of this channel [1].

High impact information on CLCNKA

  • Some of the deletions are shown to have arisen by unequal crossing over between CLCNKB and the nearby related gene, CLCNKA [2].
  • Barttin modulates trafficking and function of ClC-K channels [3].
  • Whereas the transmembrane core is necessary and sufficient to promote ClC-K channel exit from the endoplasmic reticulum, a short cytoplasmic segment following the second transmembrane helix modifies the unitary conductance [3].
  • Further, the lower renal inner medullary interstitial NaCl concentration that occurs chronically in ClCK1(-/-) mice and acutely in normal mice given furosemide is associated with lower NTE mRNA and protein [4].
  • After injection of ClC-K cRNAs into oocytes, corresponding proteins were made and glycosylated, though no additional Cl- currents were detectable [5].

Biological context of CLCNKA

  • K+ taken up by cells bordering these interstitial spaces is accompanied by Cl-. Maintaining appropriate electrolyte balance and membrane potentials in these cells requires a mechanism for exit of the resorbed Cl-. One possible candidate for regulating this Cl- efflux is ClC-K, a chloride channel previously thought to be kidney specific [6].

Anatomical context of CLCNKA

  • These results indicate a role for ClC-K in mediating Cl- recycling in the cochlea [6].
  • These data support the hypothesis that both isoforms of ClC-K are co-expressed in some cell membranes and account for the preservation of hearing in the presence of a mutation in only one channel isoform [6].
  • Here, we demonstrate the expression of both known isoforms of ClC-K in the organ of Corti, spiral ligament and stria vascularis of the rat cochlea by immunohistochemical, Western blot and RT-PCR analysis [6].

Associations of CLCNKA with chemical compounds


Regulatory relationships of CLCNKA

  • We previously isolated KLF15 as a transcription factor that regulates the expression of the ClC-K1 chloride channel [9].

Other interactions of CLCNKA


Analytical, diagnostic and therapeutic context of CLCNKA


  1. The chloride conductance channel ClC-K is a specific marker for the Xenopus pronephric distal tubule and duct. Vize, P.D. Gene Expr. Patterns (2003) [Pubmed]
  2. Mutations in the chloride channel gene, CLCNKB, cause Bartter's syndrome type III. Simon, D.B., Bindra, R.S., Mansfield, T.A., Nelson-Williams, C., Mendonca, E., Stone, R., Schurman, S., Nayir, A., Alpay, H., Bakkaloglu, A., Rodriguez-Soriano, J., Morales, J.M., Sanjad, S.A., Taylor, C.M., Pilz, D., Brem, A., Trachtman, H., Griswold, W., Richard, G.A., John, E., Lifton, R.P. Nat. Genet. (1997) [Pubmed]
  3. Barttin modulates trafficking and function of ClC-K channels. Scholl, U., Hebeisen, S., Janssen, A.G., Müller-Newen, G., Alekov, A., Fahlke, C. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  4. Neuropathy target esterase catalyzes osmoprotective renal synthesis of glycerophosphocholine in response to high NaCl. Gallazzini, M., Ferraris, J.D., Kunin, M., Morris, R.G., Burg, M.B. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  5. Two highly homologous members of the ClC chloride channel family in both rat and human kidney. Kieferle, S., Fong, P., Bens, M., Vandewalle, A., Jentsch, T.J. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  6. Expression of CLC-K chloride channels in the rat cochlea. Qu, C., Liang, F., Hu, W., Shen, Z., Spicer, S.S., Schulte, B.A. Hear. Res. (2006) [Pubmed]
  7. Assignment of the genes encoding the human chloride channels, CLCNKA and CLCNKB, to 1p36 and of CLCN3 to 4q32-q33 by in situ hybridization. Saito-Ohara, F., Uchida, S., Takeuchi, Y., Sasaki, S., Hayashi, A., Marumo, F., Ikeuchi, T. Genomics (1996) [Pubmed]
  8. Functional and structural analysis of ClC-K chloride channels involved in renal disease. Waldegger, S., Jentsch, T.J. J. Biol. Chem. (2000) [Pubmed]
  9. Postnatal expression of KLF12 in the inner medullary collecting ducts of kidney and its trans-activation of UT-A1 urea transporter promoter. Suda, S., Rai, T., Sohara, E., Sasaki, S., Uchida, S. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  10. Polymorphism (1339G>A; A447T) in exon 13 of human kidney chloride channel gene CLCNKA. Lin, R.C., Morris, B.J. Hum. Mutat. (2000) [Pubmed]
  11. A common sequence variation of the CLCNKB gene strongly activates ClC-Kb chloride channel activity. Jeck, N., Waldegger, P., Doroszewicz, J., Seyberth, H., Waldegger, S. Kidney Int. (2004) [Pubmed]
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