CLCN2

CLCN2
Identifiers
Aliases	CLCN2 , CIC-2, CLC2, ECA2, ECA3, EGI11, EGI3, EGMA, EJM6, EJM8, LKPAT, clC-2, chloride voltage-gated channel 2, HALD2
External IDs	OMIM: 600570; MGI: 105061; HomoloGene: 3213; GeneCards: CLCN2; OMA:CLCN2 - orthologs
Gene location (Human) Chr. Chromosome 3 (human) [1] Band 3q27.1 Start 184,346,185 bp [1] End 184,361,650 bp [1]
Gene location (Mouse) Chr. Chromosome 16 (mouse) [2] Band 16 A3- B1|16 12.5 cM Start 20,521,714 bp [2] End 20,536,496 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in mucosa of transverse colon tibial nerve sural nerve right testis left testis right hemisphere of cerebellum C1 segment rectum gallbladder right ovary Top expressed in intestinal villus visual cortex duodenum primary visual cortex superior frontal gyrus jejunum large intestine colon renal capsule spermatocyte More reference expression data BioGPS More reference expression data
Gene ontology Molecular function voltage-gated ion channel activity chloride channel activity voltage-gated chloride channel activity protein binding Cellular component integral component of membrane plasma membrane membrane chloride channel complex integral component of plasma membrane Biological process cell differentiation involved in salivary gland development ion transmembrane transport chloride transport regulation of ion transmembrane transport ion transport retina development in camera-type eye transmembrane transport chloride transmembrane transport regulation of aldosterone biosynthetic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1181 12724 Ensembl ENSG00000114859 ENSMUSG00000022843 UniProt P51788 Q9R0A1 RefSeq (mRNA) NM_001171087 NM_001171088 NM_001171089 NM_004366 NM_009900 RefSeq (protein) NP_001164558 NP_001164559 NP_001164560 NP_004357 NP_034030 Location (UCSC) Chr 3: 184.35 – 184.36 Mb Chr 16: 20.52 – 20.54 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Chloride channel protein 2 is a protein that in humans is encoded by the CLCN2 gene. ^{[5] [6]} Mutations of this gene have been found to cause leukoencephalopathy ^[7] and Idiopathic generalised epilepsy (OMIM: 600699), ^[8] although the latter claim has been disputed. ^[9]

A gain of function mutation in the CLCN2 gene was found to cause primary aldosteronism, ^[10] a form of arterial hypertension due to excessive production of aldosterone by the neuroendocrine cells of the zona glomerulosa of the adrenal gland. The mutation was found to cause a chloride leak in these cells and increased the expression of aldosterone synthase. ^[11]

CLCN2 contains a transmembrane region that is involved in chloride ion transport as well two intracellular copies of the CBS domain.

See also

• Chloride channel

References

1. GRCh38: Ensembl release 89: ENSG00000114859 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000022843 – 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. Cid LP, Montrose-Rafizadeh C, Smith DI, Guggino WB, Cutting GR (March 1995). "Cloning of a putative human voltage-gated chloride channel (CIC-2) cDNA widely expressed in human tissues". Human Molecular Genetics. 4 (3): 407–413. doi:10.1093/hmg/4.3.407. PMID   7795595.
6. "Entrez Gene: CLCN2 chloride channel 2".
7. Depienne C, Bugiani M, Dupuits C, Galanaud D, Touitou V, Postma N, et al. (July 2013). "Brain white matter oedema due to ClC-2 chloride channel deficiency: an observational analytical study". The Lancet. Neurology. 12 (7): 659–668. doi:10.1016/S1474-4422(13)70053-X. hdl: 11858/00-001M-0000-0018-F3BD-9 . PMID   23707145. S2CID   16634353.
8. Combi R, Grioni D, Contri M, Redaelli S, Redaelli F, Bassi MT, et al. (April 2009). "Clinical and genetic familial study of a large cohort of Italian children with idiopathic epilepsy". Brain Research Bulletin. 79 (2): 89–96. doi:10.1016/j.brainresbull.2009.01.008. PMID   19200853. S2CID   3036929.
9. Niemeyer MI, Cid LP, Sepúlveda FV, Blanz J, Auberson M, Jentsch TJ (January 2010). "No evidence for a role of CLCN2 variants in idiopathic generalized epilepsy". Nature Genetics. 42 (1): 3. doi: 10.1038/ng0110-3 . PMID   20037607.
10. Fernandes-Rosa FL, Daniil G, Orozco IJ, Goppner C, Zein R, Jain V, et al. (March 2018). "A gain-of-function mutation in the CLCN2 chloride channel gene causes primary aldosteronism". Nature Genetics. 50 (3): 355–361. doi:10.1038/s41588-018-0053-8. ISSN   1546-1718. PMID   29403012.
11. Stowasser M, Wolley M, Wu A, Gordon RD, Schewe J, Stolting G, et al. (April 2019). "Pathogenesis of Familial Hyperaldosteronism Type II: New Concepts Involving Anion Channels" . Current Hypertension Reports. 21 (4): 31. doi:10.1007/s11906-019-0934-y. ISSN   1522-6417. PMID   30949771.

Further reading

• Lamb FS, Clayton GH, Liu BX, Smith RL, Barna TJ, Schutte BC (March 1999). "Expression of CLCN voltage-gated chloride channel genes in human blood vessels". Journal of Molecular and Cellular Cardiology. 31 (3): 657–666. doi:10.1006/jmcc.1998.0901. PMID   10198195.
• Sander T, Schulz H, Saar K, Gennaro E, Riggio MC, Bianchi A, et al. (June 2000). "Genome search for susceptibility loci of common idiopathic generalised epilepsies". Human Molecular Genetics. 9 (10): 1465–1472. doi: 10.1093/hmg/9.10.1465 . PMID   10888596.
• Lamb FS, Graeff RW, Clayton GH, Smith RL, Schutte BC, McCray PB (April 2001). "Ontogeny of CLCN3 chloride channel gene expression in human pulmonary epithelium". American Journal of Respiratory Cell and Molecular Biology. 24 (4): 376–381. doi: 10.1165/ajrcmb.24.4.4114 . PMID   11306429.
• Lipecka J, Bali M, Thomas A, Fanen P, Edelman A, Fritsch J (April 2002). "Distribution of ClC-2 chloride channel in rat and human epithelial tissues". American Journal of Physiology. Cell Physiology. 282 (4): C805 –C816. doi:10.1152/ajpcell.00291.2001. PMID   11880269.
• Nehrke K, Arreola J, Nguyen HV, Pilato J, Richardson L, Okunade G, et al. (June 2002). "Loss of hyperpolarization-activated Cl(-) current in salivary acinar cells from Clcn2 knockout mice". The Journal of Biological Chemistry. 277 (26): 23604–23611. doi: 10.1074/jbc.M202900200 . PMID   11976342.
• Dhani SU, Mohammad-Panah R, Ahmed N, Ackerley C, Ramjeesingh M, Bear CE (May 2003). "Evidence for a functional interaction between the ClC-2 chloride channel and the retrograde motor dynein complex". The Journal of Biological Chemistry. 278 (18): 16262–16270. doi: 10.1074/jbc.M209828200 . PMID   12601004.
• Olsen ML, Schade S, Lyons SA, Amaral MD, Sontheimer H (July 2003). "Expression of voltage-gated chloride channels in human glioma cells". The Journal of Neuroscience. 23 (13): 5572–5582. doi:10.1523/JNEUROSCI.23-13-05572.2003. PMC   6741216 . PMID   12843258.
• Cuppoletti J, Tewari KP, Sherry AM, Ferrante CJ, Malinowska DH (May 2004). "Sites of protein kinase A activation of the human ClC-2 Cl(-) channel". The Journal of Biological Chemistry. 279 (21): 21849–21856. doi: 10.1074/jbc.M312567200 . PMID   15010473.
• Niemeyer MI, Yusef YR, Cornejo I, Flores CA, Sepúlveda FV, Cid LP (September 2004). "Functional evaluation of human ClC-2 chloride channel mutations associated with idiopathic generalized epilepsies". Physiological Genomics. 19 (1): 74–83. doi:10.1152/physiolgenomics.00070.2004. hdl: 10533/175595 . PMID   15252188.
• Huber SM, Duranton C, Henke G, Van De Sand C, Heussler V, Shumilina E, et al. (October 2004). "Plasmodium induces swelling-activated ClC-2 anion channels in the host erythrocyte". The Journal of Biological Chemistry. 279 (40): 41444–41452. doi: 10.1074/jbc.M407618200 . PMID   15272009.
• Hori K, Takahashi Y, Horikawa N, Furukawa T, Tsukada K, Takeguchi N, et al. (September 2004). "Is the ClC-2 chloride channel involved in the Cl- secretory mechanism of gastric parietal cells?". FEBS Letters. 575 (1–3): 105–108. Bibcode:2004FEBSL.575..105H. doi: 10.1016/j.febslet.2004.08.044 . PMID   15388342. S2CID   13755479.
• Chu S, Blaisdell CJ, Bamford P, Ferro TJ (November 2004). "Interferon-gamma regulates ClC-2 chloride channel in lung epithelial cells". Biochemical and Biophysical Research Communications. 324 (1): 31–39. doi:10.1016/j.bbrc.2004.09.026. PMID   15464978.
• D'Agostino D, Bertelli M, Gallo S, Cecchin S, Albiero E, Garofalo PG, et al. (October 2004). "Mutations and polymorphisms of the CLCN2 gene in idiopathic epilepsy". Neurology. 63 (8): 1500–1502. doi:10.1212/01.wnl.0000142093.94998.1a. PMID   15505175. S2CID   46730230.
• Blaisdell CJ, Howard TD, Stern A, Bamford P, Bleecker ER, Stine OC (October 2004). "CLC-2 single nucleotide polymorphisms (SNPs) as potential modifiers of cystic fibrosis disease severity". BMC Medical Genetics. 5: 26. doi: 10.1186/1471-2350-5-26 . PMC   526769 . PMID   15507145.
• Heils A (2004). "CLCN2 and idiopathic generalized epilepsy". Advances in Neurology. 95: 265–271. PMID   15508929.
• Hinzpeter A, Lipecka J, Brouillard F, Baudoin-Legros M, Dadlez M, Edelman A, et al. (January 2006). "Association between Hsp90 and the ClC-2 chloride channel upregulates channel function". American Journal of Physiology. Cell Physiology. 290 (1): C45 –C56. CiteSeerX   10.1.1.533.5601 . doi:10.1152/ajpcell.00209.2005. PMID   16049054. S2CID   8655480.

External links

• CLCN2+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Human CLCN2 genome location and CLCN2 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.