CLCN3

CLCN3
Identifiers
Aliases	CLCN3, CLC3, ClC-3, chloride voltage-gated channel 3, NEDSBA, NEDHYBA
External IDs	OMIM: 600580; MGI: 103555; GeneCards: CLCN3
Gene location (Human)
Chr.	Chromosome 4 (human)
End	169,723,673 bp
Gene location (Mouse)
Chr.	Chromosome 8 (mouse)
End	61,436,334 bp
RNA expression pattern
	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
	; ; ; ;
	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
Databases	NCBI: entry; OMA: entry
	1182
	12725
	ENSG00000109572
	ENSMUSG00000004319
	P51790
	P51791
	NM_001243372; NM_001243374; NM_001829; NM_173872
	NM_007711; NM_173873; NM_173874; NM_173876
	NP_001230301; NP_001230303; NP_001820; NP_776297
	NP_031737; NP_776298; NP_776299; NP_776301
	Wikidata
View/Edit Human	View/Edit Mouse

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

Interactions

CLCN3 has been shown to interact with PDZK1 and TMEM9.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000109572 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000004319 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Entrez Gene: CLCN3 chloride channel 3".
↑ 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.
↑ 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. PMC 11962092. PMID 40169677.

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. PMC 11962092. 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.

This article on a gene on human chromosome 4 is a stub. You can help Wikipedia by adding missing information.

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000109572 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 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.

[entrez-5] "Entrez Gene: CLCN3 chloride channel 3".

[pmid12471024-6] 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.

[pmid40169677-7] 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. PMC 11962092. PMID 40169677.

CLCN3

Interactions

See also

References

Further reading

External links