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Gene Review

CLCA4  -  chloride channel accessory 4

Homo sapiens

Synonyms: CaCC, CaCC-2, CaCC2, Calcium-activated chloride channel family member 4, Calcium-activated chloride channel protein 2, ...
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Disease relevance of CLCA4

  • CaCC is preserved and seems to be up-regulated in the airways of cystic fibrosis (CF) patients [1].
  • Co-activation of hKvLQT1 improves CaCC-mediated Cl- secretion in native CF airway epithelia, and may have a therapeutic effect in the treatment of CF lung disease [1].
  • However, the expression levels of all the CaCC genes were significantly decreased in nasal polyp [2].

High impact information on CLCA4

  • ASL volume is maintained by the predominantly ciliated epithelium via coordinated regulation of (a) absorption, by the epithelial Na(+) channel, and (b) secretion, by the Ca(2+) -activated Cl() channel (CaCC) and CFTR [3].
  • At the apical membrane, the secretion of moderate concentrations of HCO3- can be explained by the parallel activity of a Cl-/HCO3- exchanger and a Cl- conductance, either the cystic fibrosis transmembrane conductance regulator (CFTR) or a Ca2+-activated Cl- channel (CaCC) [4].
  • Expression of hCLCA1 and hCLCA4 in human rectal mucosa was proven by microarray analysis [5].
  • Transmission disequilibrium and the significance of the association decreased within the locus from hCLCA2 towards hCLCA4 [5].
  • CaCC-dependent ion transport was inhibited by the chromanol 293B, an inhibitor of cAMP-activated hKvLQT1 K+ channels, and by clotrimazole, an inhibitor of Ca2+-activated hSK4 K+ channels [1].

Biological context of CLCA4

  • In the present study, we examined the role of basolateral K+ channels in CaCC-mediated Cl- secretion in native nasal tissues from normal individuals and CF patients by measuring ion transport in perfused micro Ussing chambers [1].
  • Treatment with these CaCC inhibitors (NA, FA, NPPB, and DIDS) markedly prevented the CsA-induced apoptosis [6].

Anatomical context of CLCA4


Associations of CLCA4 with chemical compounds

  • Taken together these findings demonstrate the existence of several CaCC-like genes in humans, some of which display distinct tissue specificity patterns within the CaCC subfamily of chloride channels [9].
  • The K+ channel opener 1-ethyl-2-benzimidazolinone further increased CaCC-mediated Cl- secretion in normal and CF tissues [1].


  1. Modulation of Ca2+-activated Cl- secretion by basolateral K+ channels in human normal and cystic fibrosis airway epithelia. Mall, M., Gonska, T., Thomas, J., Schreiber, R., Seydewitz, H.H., Kuehr, J., Brandis, M., Kunzelmann, K. Pediatr. Res. (2003) [Pubmed]
  2. Expression and distribution of ion transport mRNAs in human nasal mucosa and nasal polyps. Lee, S.H., Park, J.H., Jung, H.H., Lee, S.H., Oh, J.W., Lee, H.M., Jun, H.S., Cho, W.J., Lee, J.Y. Acta Otolaryngol. (2005) [Pubmed]
  3. Regulation of normal and cystic fibrosis airway surface liquid volume by phasic shear stress. Tarran, R., Button, B., Boucher, R.C. Annu. Rev. Physiol. (2006) [Pubmed]
  4. Mechanisms of bicarbonate secretion in the pancreatic duct. Steward, M.C., Ishiguro, H., Case, R.M. Annu. Rev. Physiol. (2005) [Pubmed]
  5. The CLCA gene locus as a modulator of the gastrointestinal basic defect in cystic fibrosis. Ritzka, M., Stanke, F., Jansen, S., Gruber, A.D., Pusch, L., Woelfl, S., Veeze, H.J., Halley, D.J., Tümmler, B. Hum. Genet. (2004) [Pubmed]
  6. Role of Ca2+-activated Cl- channels in the mechanism of apoptosis induced by cyclosporin A in a human hepatoma cell line. Kim, J.A., Kang, Y.S., Lee, Y.S. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  7. Modulation of the Ca(2+)-activated Cl(-) channel by 14-3-3epsilon. Chan, H.C., Wu, W.L., So, S.C., Chung, Y.W., Tsang, L.L., Wang, X.F., Yan, Y.C., Luk, S.C., Siu, S.S., Tsui, S.K., Fung, K.P., Lee, C.Y., Waye, M.M. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  8. Molecular characterisation of pancreatic zymogen granule ion channel and regulator proteins involved in exocytosis. Thévenod, F., Braun, M., Roussa, E., Fuller, C.M. J. Korean Med. Sci. (2000) [Pubmed]
  9. Identification of three novel members of the calcium-dependent chloride channel (CaCC) family predominantly expressed in the digestive tract and trachea. Agnel, M., Vermat, T., Culouscou, J.M. FEBS Lett. (1999) [Pubmed]
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