5k47

Structural highlights

Disease

[PKD2_HUMAN] Defects in PKD2 are the cause of polycystic kidney disease 2 (PKD2) [MIM:613095]. PKD2 is a disorder characterized by progressive formation and enlargement of cysts in both kidneys, typically leading to end-stage renal disease in adult life. Cysts also occurs in the liver and other organs. It represents approximately 15% of the cases of autosomal dominant polycystic kidney disease. PKD2 is clinically milder than PKD1 but it has a deleterious impact on overall life expectancy.^{[1] [2] [3] [4] [5] [6] [7] [8] [9]}

Function

[PKD2_HUMAN] Involved in fluid-flow mechanosensation by the primary cilium in renal epithelium (By similarity). PKD1 and PKD2 may function through a common signaling pathway that is necessary for normal tubulogenesis (By similarity). Acts as a regulator of cilium length, together with PKD1 (By similarity). The dynamic control of cilium length is essential in the regulation of mechanotransductive signaling. The cilium length response creates a negative feedback loop whereby fluid shear-mediated deflection of the primary cilium, which decreases intracellular cAMP, leads to cilium shortening and thus decreases flow-induced signaling (By similarity). Functions as a calcium permeable cation channel.

References

1. ↑ Veldhuisen B, Saris JJ, de Haij S, Hayashi T, Reynolds DM, Mochizuki T, Elles R, Fossdal R, Bogdanova N, van Dijk MA, Coto E, Ravine D, Norby S, Verellen-Dumoulin C, Breuning MH, Somlo S, Peters DJ. A spectrum of mutations in the second gene for autosomal dominant polycystic kidney disease (PKD2). Am J Hum Genet. 1997 Sep;61(3):547-55. PMID:9326320
2. ↑ Reynolds DM, Hayashi T, Cai Y, Veldhuisen B, Watnick TJ, Lens XM, Mochizuki T, Qian F, Maeda Y, Li L, Fossdal R, Coto E, Wu G, Breuning MH, Germino GG, Peters DJ, Somlo S. Aberrant splicing in the PKD2 gene as a cause of polycystic kidney disease. J Am Soc Nephrol. 1999 Nov;10(11):2342-51. PMID:10541293
3. ↑ Torra R, Viribay M, Telleria D, Badenas C, Watson M, Harris P, Darnell A, San Millan JL. Seven novel mutations of the PKD2 gene in families with autosomal dominant polycystic kidney disease. Kidney Int. 1999 Jul;56(1):28-33. PMID:10411676 doi:kid534
4. ↑ Watnick T, He N, Wang K, Liang Y, Parfrey P, Hefferton D, St George-Hyslop P, Germino G, Pei Y. Mutations of PKD1 in ADPKD2 cysts suggest a pathogenic effect of trans-heterozygous mutations. Nat Genet. 2000 Jun;25(2):143-4. PMID:10835625 doi:10.1038/75981
5. ↑ Reiterova J, Stekrova J, Peters DJ, Kapras J, Kohoutova M, Merta M, Zidovska J. Four novel mutations of the PKD2 gene in Czech families with autosomal dominant polycystic kidney disease. Hum Mutat. 2002 May;19(5):573. PMID:11968093 doi:10.1002/humu.9035
6. ↑ Magistroni R, He N, Wang K, Andrew R, Johnson A, Gabow P, Dicks E, Parfrey P, Torra R, San-Millan JL, Coto E, Van Dijk M, Breuning M, Peters D, Bogdanova N, Ligabue G, Albertazzi A, Hateboer N, Demetriou K, Pierides A, Deltas C, St George-Hyslop P, Ravine D, Pei Y. Genotype-renal function correlation in type 2 autosomal dominant polycystic kidney disease. J Am Soc Nephrol. 2003 May;14(5):1164-74. PMID:12707387
7. ↑ Stekrova J, Reiterova J, Merta M, Damborsky J, Zidovska J, Kebrdlova V, Kohoutova M. PKD2 mutations in a Czech population with autosomal dominant polycystic kidney disease. Nephrol Dial Transplant. 2004 May;19(5):1116-22. Epub 2004 Feb 19. PMID:14993477 doi:10.1093/ndt/gfh083
8. ↑ Peltola P, Lumiaho A, Miettinen R, Pihlajamaki J, Sandford R, Laakso M. Genetics and phenotypic characteristics of autosomal dominant polycystic kidney disease in Finns. J Mol Med (Berl). 2005 Aug;83(8):638-46. Epub 2005 Mar 17. PMID:15772804 doi:10.1007/s00109-005-0644-6
9. ↑ Hoefele J, Mayer K, Scholz M, Klein HG. Novel PKD1 and PKD2 mutations in autosomal dominant polycystic kidney disease (ADPKD). Nephrol Dial Transplant. 2011 Jul;26(7):2181-8. doi: 10.1093/ndt/gfq720. Epub, 2010 Nov 29. PMID:21115670 doi:10.1093/ndt/gfq720