8fho

Structural highlights

Disease

S12A3_HUMAN Gitelman syndrome. The disease is caused by variants affecting the gene represented in this entry.

Function

S12A3_HUMAN Electroneutral sodium and chloride ion cotransporter. In kidney distal convoluted tubules, key mediator of sodium and chloride reabsorption (PubMed:21613606, PubMed:22009145). Receptor for the pro-inflammatory cytokine IL18. Contributes to IL18-induced cytokine production, including IFNG, IL6, IL18 and CCL2. May act either independently of IL18R1, or in a complex with IL18R1 (By similarity).[UniProtKB:P59158]^{[1] [2]} S12A2_DANRE Cation-chloride cotransporter which mediates the electroneutral transport of chloride, potassium and/or sodium ions across the membrane (PubMed:31367042). Plays a vital role in the regulation of ionic balance and cell volume (PubMed:31367042). Important for maintenance of endolymph volume in the otic vesicle, probably by regulating ion homeostasis (PubMed:19633174). Also plays a role in normal development of the swim bladder (PubMed:19633174).^{[3] [4]}

References

1. ↑ Cruz-Rangel S, Melo Z, Vazquez N, Meade P, Bobadilla NA, Pasantes-Morales H, Gamba G, Mercado A. Similar effects of all WNK3 variants on SLC12 cotransporters. Am J Physiol Cell Physiol. 2011 Sep;301(3):C601-8. doi:, 10.1152/ajpcell.00070.2011. Epub 2011 May 25. PMID:21613606 doi:http://dx.doi.org/10.1152/ajpcell.00070.2011
2. ↑ Glaudemans B, Yntema HG, San-Cristobal P, Schoots J, Pfundt R, Kamsteeg EJ, Bindels RJ, Knoers NV, Hoenderop JG, Hoefsloot LH. Novel NCC mutants and functional analysis in a new cohort of patients with Gitelman syndrome. Eur J Hum Genet. 2012 Mar;20(3):263-70. doi: 10.1038/ejhg.2011.189. Epub 2011 Oct , 19. PMID:22009145 doi:http://dx.doi.org/10.1038/ejhg.2011.189
3. ↑ Abbas L, Whitfield TT. Nkcc1 (Slc12a2) is required for the regulation of endolymph volume in the otic vesicle and swim bladder volume in the zebrafish larva. Development. 2009 Aug;136(16):2837-48. PMID:19633174 doi:10.1242/dev.034215
4. ↑ Chew TA, Orlando BJ, Zhang J, Latorraca NR, Wang A, Hollingsworth SA, Chen DH, Dror RO, Liao M, Feng L. Structure and mechanism of the cation-chloride cotransporter NKCC1. Nature. 2019 Jul 31. pii: 10.1038/s41586-019-1438-2. doi:, 10.1038/s41586-019-1438-2. PMID:31367042 doi:http://dx.doi.org/10.1038/s41586-019-1438-2