钠氯同向转运体
位於16號人類染色體的基因
钠氯同向转运体(sodium-chloride symporter、亦称为钠氯协同转运蛋白(Na+-Cl− cotransporter)、简称为NCC或NCCT，或敏感噻嗪类钠氯协同转运蛋白(thiazide-sensitive Na+-Cl− cotransporter)、或简称TSC，钠氯离子同向转运体)是在肾脏的一个协同转运蛋白(cotransporter)其具有再吸收钠及氯离子的功能，并从肾小管液进入肾的远曲小管细胞内。它是"电中性的阳离子结合氯离子的协同转运蛋白"之SLC12协同转运蛋白家族的一个成员。在人类中，它是由位于16q13的SLC12A3基因(溶质载体家族12成员的第3)所编码。[1]
| 溶质载体家族12(钠/氯转运体)、成员3 | |||
|---|---|---|---|
| 标识 | |||
| 代号 | SLC12A3; NCC; NCCT; TSC | ||
| 扩展标识 | 遗传学：600968 鼠基因：108114 同源基因：287 ChEMBL: 1876 GeneCards: SLC12A3 Gene | ||
| 直系同源体 | |||
| 物种 | 人类 | 小鼠 | |
| Entrez | 6559 | 20497 | |
| Ensembl | ENSG00000070915 | ENSMUSG00000031766 | |
| UniProt | P55017 | P59158 | |
| mRNA序列 | NM_000339 | NM_001205311 | |
| 蛋白序列 | NP_000330 | NP_001192240 | |
| 基因位置 |
Chr 16: 56.9 – 56.95 Mb |
Chr 8: 94.33 – 94.37 Mb | |
| PubMed查询 | [1] | [2] | |
分子生物学
编辑钠氯同向转运体或NCC是"电中性的阳离子结合氯离子的协同转运蛋白"之SLC12协同转运蛋白家族的一员，伴随着钾氯共转运蛋白(K+-Cl−协同转运蛋白或KCCs)、钠钾氯共转运蛋白(Na+-K+-Cl−协同转运蛋白或NKCCs)及孤儿成员CIP(协同转运蛋白相互作用蛋白)与CCC9。
功能
编辑病理
编辑吉特曼氏综合症
编辑高血压及血压
编辑假性醛固酮减少症II型
编辑参见
编辑注释
编辑- ^ Mastroianni N, De Fusco M, Zollo M, Arrigo G, Zuffardi O, Bettinelli A, Ballabio A, Casari G. Molecular cloning, expression pattern, and chromosomal localization of the human Na-Cl thiazide-sensitive cotransporter (SLC12A3). Genomics. August 1996, 35 (3): 486–93. PMID 8812482. doi:10.1006/geno.1996.0388.
延伸阅读
编辑- Kamdem LK, Hamilton L, Cheng C; et al. Genetic predictors of glucocorticoid-induced hypertension in children with acute lymphoblastic leukemia. Pharmacogenet. Genomics. 2008, 18 (6): 507–14. PMID 18496130. doi:10.1097/FPC.0b013e3282fc5801.
- Coto E, Arriba G, GarcÃa-Castro M; et al. Clinical and analytical findings in Gitelman's syndrome associated with homozygosity for the c.1925 G>A SLC12A3 mutation. Am. J. Nephrol. 2009, 30 (3): 218–21. PMID 19420906. doi:10.1159/000218104.
- Yasujima M, Tsutaya S. [Mutational analysis of a thiazide-sensitive Na-Cl cotransporter (SLC12A3) gene in a Japanese population—the Iwaki Health Promotion Project]. Rinsho Byori. 2009, 57 (4): 391–6. PMID 19489442.
- Shao L, Liu L, Miao Z; et al. A novel SLC12A3 splicing mutation skipping of two exons and preliminary screening for alternative splice variants in human kidney. Am. J. Nephrol. 2008, 28 (6): 900–7. PMID 18580052. doi:10.1159/000141932.
- van Rijn-Bikker PC, Mairuhu G, van Montfrans GA; et al. Genetic factors are relevant and independent determinants of antihypertensive drug effects in a multiracial population. Am. J. Hypertens. 2009, 22 (12): 1295–302. PMID 19779464. doi:10.1038/ajh.2009.192.
- Shao L, Ren H, Wang W; et al. Novel SLC12A3 mutations in Chinese patients with Gitelman's syndrome. Nephron Physiol. 2008, 108 (3): p29–36. PMID 18287808. doi:10.1159/000117815.
- Ji W, Foo JN, O'Roak BJ; et al. Rare independent mutations in renal salt handling genes contribute to blood pressure variation. Nat. Genet. 2008, 40 (5): 592–9. PMC 3766631
. PMID 18391953. doi:10.1038/ng.118. - Riveira-Munoz E, Devuyst O, Belge H; et al. Evaluating PVALB as a candidate gene for SLC12A3-negative cases of Gitelman's syndrome. Nephrol. Dial. Transplant. 2008, 23 (10): 3120–5. PMID 18469313. doi:10.1093/ndt/gfn229.
- Zhou B, Zhuang J, Gu D; et al. WNK4 enhances the degradation of NCC through a sortilin-mediated lysosomal pathway. J. Am. Soc. Nephrol. 2010, 21 (1): 82–92. PMC 2799281 . PMID 19875813. doi:10.1681/ASN.2008121275.
- Hsu YJ, Yang SS, Chu NF; et al. Heterozygous mutations of the sodium chloride cotransporter in Chinese children: prevalence and association with blood pressure. Nephrol. Dial. Transplant. 2009, 24 (4): 1170–5. PMID 19033254. doi:10.1093/ndt/gfn619.
- Nozu K, Iijima K, Nozu Y; et al. A deep intronic mutation in the SLC12A3 gene leads to Gitelman syndrome. Pediatr. Res. 2009, 66 (5): 590–3. PMID 19668106. doi:10.1203/PDR.0b013e3181b9b4d3.
- Ng DP, Nurbaya S, Choo S; et al. Genetic variation at the SLC12A3 locus is unlikely to explain risk for advanced diabetic nephropathy in Caucasians with type 2 diabetes. Nephrol. Dial. Transplant. 2008, 23 (7): 2260–4. PMID 18263927. doi:10.1093/ndt/gfm946.
- Aoi N, Nakayama T, Sato N; et al. Case-control study of the role of the Gitelman's syndrome gene in essential hypertension. Endocr. J. 2008, 55 (2): 305–10. PMID 18362449. doi:10.1507/endocrj.K07E-021.
- Qin L, Shao L, Ren H; et al. Identification of five novel variants in the thiazide-sensitive NaCl co-transporter gene in Chinese patients with Gitelman syndrome. Nephrology (Carlton). 2009, 14 (1): 52–8. PMID 19207868. doi:10.1111/j.1440-1797.2008.01042.x.
- Ridker PM, Paré G, Parker AN; et al. Polymorphism in the CETP gene region, HDL cholesterol, and risk of future myocardial infarction: Genomewide analysis among 18 245 initially healthy women from the Women's Genome Health Study. Circ Cardiovasc Genet. 2009, 2 (1): 26–33. PMC 2729193 . PMID 20031564. doi:10.1161/CIRCGENETICS.108.817304.
- Richardson C, Rafiqi FH, Karlsson HK; et al. Activation of the thiazide-sensitive Na+-Cl− cotransporter by the WNK-regulated kinases SPAK and OSR1. J. Cell. Sci. 2008, 121 (Pt 5): 675–84. PMID 18270262. doi:10.1242/jcs.025312.
- Wang XF, Lin RY, Wang SZ; et al. Association study of variants in two ion-channel genes (TSC and CLCNKB) and hypertension in two ethnic groups in Northwest China. Clin. Chim. Acta. 2008, 388 (1–2): 95–8. PMID 17997379. doi:10.1016/j.cca.2007.10.017.
- Miao Z, Gao Y, Bindels RJ; et al. Coexistence of normotensive primary aldosteronism in two patients with Gitelman's syndrome and novel thiazide-sensitive Na–Cl cotransporter mutations. Eur. J. Endocrinol. 2009, 161 (2): 275–83. PMID 19451210. doi:10.1530/EJE-09-0271.
- Zhan YY, Jiang X, Lin G; et al. [Association of thiazide-sensitive Na+-Cl* cotransporter gene polymorphisms with the risk of essential hypertension]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2007, 24 (6): 703–5. PMID 18067089.
