CLCN3

CLCN3
Identifiers
Aliases	CLCN3 , CLC3, ClC-3, chloride voltage-gated channel 3, NEDSBA, NEDHYBA
External IDs	OMIM: 600580; MGI: 103555; HomoloGene: 20435; GeneCards: CLCN3; OMA:CLCN3 - orthologs
Gene location (Human) Chr. Chromosome 4 (human) [1] Band 4q33 Start 169,612,633 bp [1] End 169,723,673 bp [1]
Gene location (Mouse) Chr. Chromosome 8 (mouse) [2] Band 8 B3.1|8 30.9 cM Start 61,363,423 bp [2] End 61,436,334 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in mucosa of sigmoid colon endothelial cell Brodmann area 46 Epithelium of choroid plexus retinal pigment epithelium postcentral gyrus islet of Langerhans parotid gland right ventricle superior vestibular nucleus Top expressed in Rostral migratory stream mammillary body lateral septal nucleus ventromedial nucleus lateral geniculate nucleus lateral hypothalamus cingulate gyrus anterior amygdaloid area paraventricular nucleus of hypothalamus subiculum More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nucleotide binding volume-sensitive chloride channel activity PDZ domain binding protein homodimerization activity ion channel activity protein binding protein heterodimerization activity antiporter activity ATP binding chloride channel activity voltage-gated chloride channel activity solute:proton antiporter activity chloride ion binding Cellular component integral component of membrane endosome late endosome Golgi apparatus early endosome membrane membrane late endosome membrane synaptic vesicle vesicle membrane Golgi membrane plasma membrane transport vesicle membrane secretory granule cell surface early endosome specific granule phagocytic vesicle external side of plasma membrane cytoplasmic vesicle integral component of plasma membrane Biological process negative regulation of cell volume endosomal lumen acidification ion transport regulation of anion transmembrane transport chloride transport regulation of pH chloride transmembrane transport regulation of anion transport transmembrane transport transport synaptic vesicle lumen acidification Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1182 12725 Ensembl ENSG00000109572 ENSMUSG00000004319 UniProt P51790 P51791 RefSeq (mRNA) NM_001243372 NM_001243374 NM_001829 NM_173872 NM_007711 NM_173873 NM_173874 NM_173876 RefSeq (protein) NP_001230301 NP_001230303 NP_001820 NP_776297 NP_031737 NP_776298 NP_776299 NP_776301 Location (UCSC) Chr 4: 169.61 – 169.72 Mb Chr 8: 61.36 – 61.44 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

2Cl^-/H⁺ exchanger 3 is a protein that in humans is encoded by the CLCN3 gene. ^[5]

Interactions

CLCN3 has been shown to interact with PDZK1 and TMEM9.<ref name=pmid12471024>Gentzsch M, Cui L, Mengos A, Chang XB, Chen JH, Riordan JR (Feb 2003). "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. doi: 10.1074/jbc.M211050200 . PMID   12471024.<pmid40169677>Planells-Cases R, Vorobeva V, Kar S, Schmitt F, Schulte U, Schrecker M, Hite R, Fakler B, Jentsch T (2025). "Endosomal chloride/proton exchangers need inhibitory TMEM9 β-subunits for regulation and prevention of disease-causing overactivity". Nature Communications. 16: 1–17. doi: 10.1038/s41467-025-58546-3 . PMID   40169677.

See also

• Chloride channel

References

1. GRCh38: Ensembl release 89: ENSG00000109572 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000004319 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: CLCN3 chloride channel 3".

Further reading

• Planells-Cases R, Vorobeva V, Kar S, Schmitt F, Schulte U, Schrecker M, Hite R, Fakler B, Jentsch T (2025). "Endosomal chloride/proton exchangers need inhibitory TMEM9 β-subunits for regulation and prevention of disease-causing overactivity". Nature Communications. 16: 1–17. doi:10.1038/s41467-025-58546-3. PMID   40169677.

• Schrecker M, Son Y, Planells-Cases R, Kar S, Vorobeva V, Schulte U, Faker B, Jentsch T, Hite R (2025). "Structural basis of ClC-3 transporter inhibition by TMEM9 and PtdIns(3,5)P2". Nat Struct Mol Biol. 32 (10): 1972–1979. doi:10.1038/s41594-025-01617-2. PMID   40670814.
• Borsani G, Rugarli EI, Taglialatela M, Wong C, Ballabio A (1995). "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. doi:10.1006/geno.1995.1015. PMID   7665160.
• Taine L, Coupry I, Boisseau P, Saura R, Lacombe D, Arveiler B (1998). "Refined localisation of the voltage-gated chloride channel, CLCN3, to 4q33". Hum. Genet. 102 (2): 178–81. doi:10.1007/s004390050673. PMID   9521585. S2CID   22138203.
• Shepard AR, Rae JL (1998). "Ion transporters and receptors in cDNA libraries from lens and cornea epithelia". Curr. Eye Res. 17 (7): 708–19. doi:10.1080/02713689808951247. PMID   9678416.
• Loo MA, Jensen TJ, Cui L, Hou Y, Chang XB, Riordan JR (1998). "Perturbation of Hsp90 interaction with nascent CFTR prevents its maturation and accelerates its degradation by the proteasome". EMBO J. 17 (23): 6879–87. doi:10.1093/emboj/17.23.6879. PMC   1171036 . PMID   9843494.
• Lamb FS, Clayton GH, Liu BX, Smith RL, Barna TJ, Schutte BC (1999). "Expression of CLCN voltage-gated chloride channel genes in human blood vessels". J. Mol. Cell. Cardiol. 31 (3): 657–66. doi:10.1006/jmcc.1998.0901. PMID   10198195.
• Hartley JL, Temple GF, Brasch MA (2000). "DNA cloning using in vitro site-specific recombination". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC   310948 . PMID   11076863.
• 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 (2001). "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. doi:10.1101/gr.GR1547R. PMC   311072 . PMID   11230166.
• Huang P, Liu J, Di A, Robinson NC, Musch MW, Kaetzel MA, Nelson DJ (2001). "Regulation of human CLC-3 channels by multifunctional Ca2+/calmodulin-dependent protein kinase". J. Biol. Chem. 276 (23): 20093–100. doi: 10.1074/jbc.M009376200 . PMID   11274166.
• Lamb FS, Graeff RW, Clayton GH, Smith RL, Schutte BC, McCray PB (2001). "Ontogeny of CLCN3 chloride channel gene expression in human pulmonary epithelium". Am. J. Respir. Cell Mol. Biol. 24 (4): 376–81. doi: 10.1165/ajrcmb.24.4.4114 . PMID   11306429.
• Ogura T, Furukawa T, Toyozaki T, Yamada K, Zheng YJ, Katayama Y, Nakaya H, Inagaki N (2002). "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. doi: 10.1096/fj.01-0845fje . PMID   11967229. S2CID   33470444.
• Hermoso M, Satterwhite CM, Andrade YN, Hidalgo J, Wilson SM, Horowitz B, Hume JR (2002). "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. doi: 10.1074/jbc.M205132200 . PMID   12183454.
• Gentzsch M, Cui L, Mengos A, Chang XB, Chen JH, Riordan JR (2003). "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. doi: 10.1074/jbc.M211050200 . PMID   12471024.
• Jin NG, Kim JK, Yang DK, Cho SJ, Kim JM, Koh EJ, Jung HC, So I, Kim KW (2003). "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. doi:10.1152/ajpgi.00470.2002. PMID   12842831. S2CID   326508.
• Olsen ML, Schade S, Lyons SA, Amaral MD, Sontheimer H (2003). "Expression of voltage-gated chloride channels in human glioma cells". J. Neurosci. 23 (13): 5572–82. doi: 10.1523/JNEUROSCI.23-13-05572.2003 . PMC   6741216 . PMID   12843258.
• Salazar G, Love R, Styers ML, Werner E, Peden A, Rodriguez S, Gearing M, Wainer BH, Faundez V (2004). "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. doi: 10.1074/jbc.M402331200 . PMID   15073168.
• Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A (2004). "From ORFeome to biology: a functional genomics pipeline". Genome Res. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC   528930 . PMID   15489336.
• Zhou JG, Ren JL, Qiu QY, He H, Guan YY (2005). "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. doi: 10.1074/jbc.M412813200 . PMID   15596438.
• Yeung CH, Barfield JP, Cooper TG (2005). "Chloride channels in physiological volume regulation of human spermatozoa". Biol. Reprod. 73 (5): 1057–63. doi: 10.1095/biolreprod.105.044123 . PMID   16033995.
• 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 (2006). "The LIFEdb database in 2006". Nucleic Acids Res. 34 (Database issue): D415-8. doi:10.1093/nar/gkj139. PMC   1347501 . PMID   16381901.

External links

• CLCN3+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Human CLCN3 genome location and CLCN3 gene details page in the UCSC Genome Browser .

This article incorporates text from the United States National Library of Medicine, which is in the public domain.