This report describes polycystic kidney disease 2 (PKD2), which is a subtype of polycystic kidney disease; PKD2 exhibits autosomal dominant inheritance. The human gene implicated in this disease is polycystin-2 (also abbreviated PKD2), which is a calcium cation channel involved in calcium transport and calcium signaling in renal epithelial cells. There is a single orthologous gene in Drosophila, Dmel\Pkd2, for which loss-of-function alleles, RNAi targeting constructs, alleles caused by insertional mutagenesis have been generated. Dmel\Pkd2 is orthologous to two additional genes in human, PKD2L1 and PKD2L2.
The human PKD2 gene has not been introduced into flies (although the Hsap\PKD2L1 gene has).
Variant(s) implicated in human disease tested (as analogous mutation in fly gene): D627V in the fly Pkd2 gene (corresponds to D511V in the human PKD2 gene).
Homozygous loss-of-function alleles of Dmel\Pkd2 are viable, however, males are semi-sterile. The fly mutation analogous to the pathogenic D511V variant in the human gene reduces Pkd2 protein abundance and its localization to cilia; it results in a slightly reduced level of male sterility, thus appears to retain a low level of activity. This system has been used to test potential therapeutic compounds for polycystic kidney disease.
[updated Jun. 2017 by FlyBase; FBrf0222196]
Polycystic kidney disease usually presents with progressive, bilateral, multiple cyst formation in the kidneys; liver cysts and intracranial aneurysm frequently develop. Acute and chronic pain, nephrolithiasis, and hypertension are common complications. The most serious renal complication is end-stage renal disease, which occurs in approximately 50% of patients by the age of 60 years. The typical age of onset is in middle life, but the range is from infancy to 80 years (summary by Wu and Somlo, 2000; pubmed:10655152). [from MIM:173900; 2017.06.22]
[POLYCYSTIC KIDNEY DISEASE 2 WITH OR WITHOUT POLYCYSTIC LIVER DISEASE; PKD2](https://omim.org/entry/613095)
[POLYCYSTIN 2; PKD2](https://omim.org/entry/173910)
PKD2 is implicated in 15% of cases of autosomal dominant polycystic kidney disease. [Gene Reviews, Polycystic Kidney Disease, Autosomal Dominant; 2017.06.23]
Polycystic kidney disease-2 (PKD2) is caused by heterozygous mutation in the gene encoding polycystin-2 (PKD2). [from MIM:613095; 2017.06.22]
Polycystin-2 belongs to the superfamily of transient receptor potential (TRP) channels; it is a multi-pass membrane protein that functions as a calcium cation channel, and is involved in calcium transport and calcium signaling in renal epithelial cells. (Zhang et al., 2009; pubmed:19193631). The protein localizes to the primary cilia of kidney epithelium (Nauli, et al., 2003; pubmed:12514735). [from MIM:173910; 2017.06.22]
Many to one: 3 human to 1 Drosophila. The additional human genes are PKD2L1 and PKD2L2.
High- to moderate-scoring ortholog of human PKD2, PKD2L1 and PKD2L2 (1 Drosophila to 3 human). Dmel\Pkd2 shares 26% identity and 41% similarity with PKD2; the length of the aligned extent is shorter for PKD2L1 and PKD2L2.
