CLCN4 explained

H(+)/Cl(-) exchange transporter 4 is a protein that in humans is encoded by the CLCN4 gene.^{[1] [2]}

Function

The CLCN family of voltage-dependent chloride channel genes comprises nine members (CLCN1-7, Ka and Kb) which demonstrate quite diverse functional characteristics while sharing significant sequence homology. Chloride channel 4 has an evolutionary conserved CpG island and is conserved in both mouse and hamster. This gene is mapped in close proximity to APXL (Apical protein Xenopus laevis-like) and OA1 (Ocular albinism type I), which are both located on the human X chromosome at band p22.3. The physiological role of chloride channel 4 remains unknown but may contribute to the pathogenesis of neuronal disorders.

Clinical significance

Mutations in this gene have been linked to cases of early onset epilepsy^[3]

See also

• Chloride channel

Further reading

• Schnur RE, Wick PA . Intragenic TaqI restriction fragment length polymorphism (RFLP) in CICN4, between the loci for X-linked ocular albinism (OA1) and microphthalmia with linear skin defects syndrome (MLS) . Hum. Genet. . 95 . 5 . 594–5 . 1995 . 7759088 . 10.1007/BF00223880 . 6494341 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Dinulos MB, Bassi MT, Rugarli EI, Chapman V, Ballabio A, Disteche CM . A new region of conservation is defined between human and mouse X chromosomes . Genomics . 35 . 1 . 244–7 . 1996 . 8661129 . 10.1006/geno.1996.0347 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Lamb FS, Clayton GH, Liu BX, Smith RL, Barna TJ, Schutte BC . Expression of CLCN voltage-gated chloride channel genes in human blood vessels . J. Mol. Cell. Cardiol. . 31 . 3 . 657–66 . 1999 . 10198195 . 10.1006/jmcc.1998.0901 .
• Kawasaki M, Fukuma T, Yamauchi K, Sakamoto H, Marumo F, Sasaki S . Identification of an acid-activated Cl(-) channel from human skeletal muscles . Am. J. Physiol. . 277 . 5 Pt 1 . C948–54 . 1999 . 10.1152/ajpcell.1999.277.5.C948 . 10564087 .
• Wang T, Weinman SA . Involvement of chloride channels in hepatic copper metabolism: ClC-4 promotes copper incorporation into ceruloplasmin . Gastroenterology . 126 . 4 . 1157–66 . 2004 . 15057754 . 10.1053/j.gastro.2004.01.015 . free .
• Suzuki Y, Yamashita R, Shirota M, Sakakibara Y, Chiba J, Mizushima-Sugano J, Nakai K, Sugano S . Sequence Comparison of Human and Mouse Genes Reveals a Homologous Block Structure in the Promoter Regions . Genome Res. . 14 . 9 . 1711–8 . 2004 . 15342556 . 515316 . 10.1101/gr.2435604 .
• Picollo A, Pusch M . Chloride/proton antiporter activity of mammalian CLC proteins ClC-4 and ClC-5 . Nature . 436 . 7049 . 420–3 . 2005 . 16034421 . 10.1038/nature03720 . 2005Natur.436..420P . 4389450 .
• Huang L, Cao J, Wang H, Vo LA, Brand JG . Identification and Functional Characterization of a Voltage-gated Chloride Channel and Its Novel Splice Variant in Taste Bud Cells . J. Biol. Chem. . 280 . 43 . 36150–7 . 2006 . 16129671 . 2367165 . 10.1074/jbc.M507706200 . free .
• Littler DR, Assaad NN, Harrop SJ, Brown LJ, Pankhurst GJ, Luciani P, Aguilar MI, Mazzanti M, Berryman MA, Breit SN, Curmi PM . Crystal structure of the soluble form of the redox-regulated chloride ion channel protein CLIC4 . FEBS J. . 272 . 19 . 4996–5007 . 2005 . 16176272 . 10.1111/j.1742-4658.2005.04909.x . free .
• Okkenhaug H, Weylandt KH, Carmena D, Wells DJ, Higgins CF, Sardini A . The human ClC-4 protein, a member of the CLC chloride channel/transporter family, is localized to the endoplasmic reticulum by its N-terminus . FASEB J. . 20 . 13 . 2390–2 . 2006 . 17023393 . 10.1096/fj.05-5588fje . free . 24433478 .

Notes and References

1. Huda Zoghbi . van Slegtenhorst MA, Bassi MT, Borsani G, Wapenaar MC, Ferrero GB, de Conciliis L, Rugarli EI, Grillo A, Franco B, Zoghbi HY, Ballabio A . A gene from the Xp22.3 region shares homology with voltage-gated chloride channels . Hum Mol Genet . 3 . 4 . 547–52 . Sep 1994 . 8069296 . 10.1093/hmg/3.4.547 .
2. Web site: Entrez Gene: CLCN4 chloride channel 4.
3. Veeramah KR, Johnstone L, Karafet TM, Wolf D, Sprissler R, Salogiannis J, Barth-Maron A, Greenberg ME, Stuhlmann T, Weinert S, Jentsch TJ, Pazzi M, Restifo LL, Talwar D, Erickson RP, Hammer MF . Exome sequencing reveals new causal mutations in children with epileptic encephalopathies . Epilepsia . 54 . 7 . 1270–81 . 2013 . 23647072 . 3700577 . 10.1111/epi.12201 .