CLCN3 explained

2Cl^-/H⁺ exchanger 3 is a protein that in humans is encoded by the CLCN3 gene.^[1]

Interactions

CLCN3 has been shown to interact with PDZK1^[2] and TMEM9.^[3]

See also

• Chloride channel

Further reading

• Planells-Cases R, Vorobeva V, Kar S, Schmitt F, Schulte U, Schrecker M, Hite R, Fakler B, Jentsch T . Endosomal chloride/proton exchangers need inhibitory TMEM9 β-subunits for regulation and prevention of disease-causing overactivity . Nature Communications . 16 . 1-17 . 2025 . 40169677 . 10.1038/s41467-025-58546-3 . 11962092 .
• Schrecker M, Son Y, Planells-Cases R, Kar S, Vorobeva V, Schulte U, Faker B, Jentsch T, Hite R . Structural basis of ClC-3 transporter inhibition by TMEM9 and PtdIns(3,5)P2 . Nat Struct Mol Biol . 32 . 10 . 1972-1979 . 2025 . 40670814 . 10.1038/s41594-025-01617-2 . free .
• Borsani G, Rugarli EI, Taglialatela M, Wong C, Ballabio A . Characterization of a human and murine gene (CLCN3) sharing similarities to voltage-gated chloride channels and to a yeast integral membrane protein . Genomics . 27 . 1 . 131–41 . 1995 . 7665160 . 10.1006/geno.1995.1015 .
• Taine L, Coupry I, Boisseau P, Saura R, Lacombe D, Arveiler B . Refined localisation of the voltage-gated chloride channel, CLCN3, to 4q33 . Hum. Genet. . 102 . 2 . 178–81 . 1998 . 9521585 . 10.1007/s004390050673 . 22138203 .
• Shepard AR, Rae JL . Ion transporters and receptors in cDNA libraries from lens and cornea epithelia . Curr. Eye Res. . 17 . 7 . 708–19 . 1998 . 9678416 . 10.1080/02713689808951247 .
• Loo MA, Jensen TJ, Cui L, Hou Y, Chang XB, Riordan JR . Perturbation of Hsp90 interaction with nascent CFTR prevents its maturation and accelerates its degradation by the proteasome . EMBO J. . 17 . 23 . 6879–87 . 1998 . 9843494 . 1171036 . 10.1093/emboj/17.23.6879 .
• 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 .
• Hartley JL, Temple GF, Brasch MA . DNA cloning using in vitro site-specific recombination . Genome Res. . 10 . 11 . 1788–95 . 2000 . 11076863 . 310948 . 10.1101/gr.143000 .
• Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A . Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs . Genome Res. . 11 . 3 . 422–35 . 2001 . 11230166 . 311072 . 10.1101/gr.GR1547R .
• Huang P, Liu J, Di A, Robinson NC, Musch MW, Kaetzel MA, Nelson DJ . Regulation of human CLC-3 channels by multifunctional Ca2+/calmodulin-dependent protein kinase . J. Biol. Chem. . 276 . 23 . 20093–100 . 2001 . 11274166 . 10.1074/jbc.M009376200 . free .
• Lamb FS, Graeff RW, Clayton GH, Smith RL, Schutte BC, McCray PB . Ontogeny of CLCN3 chloride channel gene expression in human pulmonary epithelium . Am. J. Respir. Cell Mol. Biol. . 24 . 4 . 376–81 . 2001 . 11306429 . 10.1165/ajrcmb.24.4.4114 . free .
• Ogura T, Furukawa T, Toyozaki T, Yamada K, Zheng YJ, Katayama Y, Nakaya H, Inagaki N . ClC-3B, a novel ClC-3 splicing variant that interacts with EBP50 and facilitates expression of CFTR-regulated ORCC . FASEB J. . 16 . 8 . 863–5 . 2002 . 11967229 . 10.1096/fj.01-0845fje . free . 33470444 .
• Hermoso M, Satterwhite CM, Andrade YN, Hidalgo J, Wilson SM, Horowitz B, Hume JR . ClC-3 is a fundamental molecular component of volume-sensitive outwardly rectifying Cl- channels and volume regulation in HeLa cells and Xenopus laevis oocytes . J. Biol. Chem. . 277 . 42 . 40066–74 . 2002 . 12183454 . 10.1074/jbc.M205132200 . free .
• Gentzsch M, Cui L, Mengos A, Chang XB, Chen JH, Riordan JR . The PDZ-binding chloride channel ClC-3B localizes to the Golgi and associates with cystic fibrosis transmembrane conductance regulator-interacting PDZ proteins . J. Biol. Chem. . 278 . 8 . 6440–9 . 2003 . 12471024 . 10.1074/jbc.M211050200 . free .
• Jin NG, Kim JK, Yang DK, Cho SJ, Kim JM, Koh EJ, Jung HC, So I, Kim KW . Fundamental role of ClC-3 in volume-sensitive Cl- channel function and cell volume regulation in AGS cells . Am. J. Physiol. Gastrointest. Liver Physiol. . 285 . 5 . G938-48 . 2003 . 12842831 . 10.1152/ajpgi.00470.2002 . 326508 .
• Olsen ML, Schade S, Lyons SA, Amaral MD, Sontheimer H . Expression of voltage-gated chloride channels in human glioma cells . J. Neurosci. . 23 . 13 . 5572–82 . 2003 . 12843258 . 10.1523/JNEUROSCI.23-13-05572.2003. free . 6741216 .
• Salazar G, Love R, Styers ML, Werner E, Peden A, Rodriguez S, Gearing M, Wainer BH, Faundez V . AP-3-dependent mechanisms control the targeting of a chloride channel (ClC-3) in neuronal and non-neuronal cells . J. Biol. Chem. . 279 . 24 . 25430–9 . 2004 . 15073168 . 10.1074/jbc.M402331200 . free .
• Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A . From ORFeome to biology: a functional genomics pipeline . Genome Res. . 14 . 10B . 2136–44 . 2004 . 15489336 . 528930 . 10.1101/gr.2576704 .
• Zhou JG, Ren JL, Qiu QY, He H, Guan YY . Regulation of intracellular Cl- concentration through volume-regulated ClC-3 chloride channels in A10 vascular smooth muscle cells . J. Biol. Chem. . 280 . 8 . 7301–8 . 2005 . 15596438 . 10.1074/jbc.M412813200 . free .
• Yeung CH, Barfield JP, Cooper TG . Chloride channels in physiological volume regulation of human spermatozoa . Biol. Reprod. . 73 . 5 . 1057–63 . 2005 . 16033995 . 10.1095/biolreprod.105.044123 . free .
• Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, Bechtel S, Simpson J, Hofmann O, Hide W, Glatting KH, Huber W, Pepperkok R, Poustka A, Wiemann S . The LIFEdb database in 2006 . Nucleic Acids Res. . 34 . Database issue . D415-8 . 2006 . 16381901 . 1347501 . 10.1093/nar/gkj139 .

Notes and References

1. Web site: Entrez Gene: CLCN3 chloride channel 3.
2. Gentzsch M, Cui L, Mengos A, Chang XB, Chen JH, Riordan JR . The PDZ-binding chloride channel ClC-3B localizes to the Golgi and associates with cystic fibrosis transmembrane conductance regulator-interacting PDZ proteins . J. Biol. Chem. . 278 . 8 . 6440–9 . Feb 2003 . 12471024 . 10.1074/jbc.M211050200 . free .
3. Planells-Cases R, Vorobeva V, Kar S, Schmitt F, Schulte U, Schrecker M, Hite R, Fakler B, Jentsch T . Endosomal chloride/proton exchangers need inhibitory TMEM9 β-subunits for regulation and prevention of disease-causing overactivity . Nature Communications . 16 . 1-17 . 2025 . 40169677 . 10.1038/s41467-025-58546-3 . free. 11962092 .