8ta3

Structural highlights

Disease

CLCN2_HUMAN Leukoencephalopathy with mild cerebellar ataxia and white matter edema;Familial hyperaldosteronism type II;Juvenile myoclonic epilepsy. Disease susceptibility is associated with variants affecting the gene represented in this entry. Disease susceptibility may be associated with variants affecting the gene represented in this entry. Disease susceptibility is associated with variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry.

Function

CLCN2_HUMAN Voltage-gated chloride channel. Chloride channels have several functions including the regulation of cell volume, membrane potential stabilization, signal transduction and transepithelial transport. Involved in the regulation of aldosterone production. The opening of CLCN2 channels at hyperpolarized membrane potentials in the glomerulosa causes cell membrane depolarization, activation of voltage-gated Ca2+ channels and increased expression of aldosterone synthase, the rate-limiting enzyme for aldosterone biosynthesis (PubMed:29403011, PubMed:29403012).^{[1] [2] [3] [4]}

References

1. ↑ Niemeyer MI, Cid LP, Yusef YR, Briones R, Sepúlveda FV. Voltage-dependent and -independent titration of specific residues accounts for complex gating of a ClC chloride channel by extracellular protons. J Physiol. 2009 Apr 1;587(Pt 7):1387-400. PMID:19153159 doi:10.1113/jphysiol.2008.167353
2. ↑ Saint-Martin C, Gauvain G, Teodorescu G, Gourfinkel-An I, Fedirko E, Weber YG, Maljevic S, Ernst JP, Garcia-Olivares J, Fahlke C, Nabbout R, LeGuern E, Lerche H, Poncer JC, Depienne C. Two novel CLCN2 mutations accelerating chloride channel deactivation are associated with idiopathic generalized epilepsy. Hum Mutat. 2009 Mar;30(3):397-405. PMID:19191339 doi:10.1002/humu.20876
3. ↑ Scholl UI, Stölting G, Schewe J, Thiel A, Tan H, Nelson-Williams C, Vichot AA, Jin SC, Loring E, Untiet V, Yoo T, Choi J, Xu S, Wu A, Kirchner M, Mertins P, Rump LC, Onder AM, Gamble C, McKenney D, Lash RW, Jones DP, Chune G, Gagliardi P, Choi M, Gordon R, Stowasser M, Fahlke C, Lifton RP. CLCN2 chloride channel mutations in familial hyperaldosteronism type II. Nat Genet. 2018 Mar;50(3):349-354. PMID:29403011 doi:10.1038/s41588-018-0048-5
4. ↑ Fernandes-Rosa FL, Daniil G, Orozco IJ, Göppner C, El Zein R, Jain V, Boulkroun S, Jeunemaitre X, Amar L, Lefebvre H, Schwarzmayr T, Strom TM, Jentsch TJ, Zennaro MC. A gain-of-function mutation in the CLCN2 chloride channel gene causes primary aldosteronism. Nat Genet. 2018 Mar;50(3):355-361. PMID:29403012 doi:10.1038/s41588-018-0053-8