Genes homologous to the autosomal dominant polycystic kidney disease genes(PKD1 and PKD2)

Autosomal Dominant Polycystic Kidney Disease (ADPKD), a common inherited di sease leading to progressive renal failure, can be caused by a mutation in either the PKD1 or PKD2 gene. Both genes encode for putative transmembrane proteins, polycystin-1 and polycystin-2, which show significant homology to each other and are believed to interact at their carboxy termini. To ident ify genes that code for related proteins we searched for homologous sequenc es in several databases and identified one partial cDNA and two genomic seq uences with significant homology to both polycystin-1 and -2 Further analys is revealed one novel gene, PKD2L2, located on chromosome band 5q31, and tw o recently described genes, PKD2L and PKDREJ, located on chromosome bands 1 0q31 and 22q13.3, respectively. PKD2L2 and PKD2L, which encode proteins of 613 and 805 amino acids, are approximately 65% similar to polycystin-2 The third gene, PKDREJ, encodes a putative 2253 amino acid protein and shows ab out 35% similarity to both polycystin-1 and polycystin-2. For all the genes expression was found in testis. Additional expression of PKD2L was observe d in retina, brain, liver and spleen by RT-PCR. Analyses of five ADPKD fami lies without clear linkage to either the PKD1 or PKD2 locus showed no linka ge to any of the novel loci, excluding these genes as the cause of ADPKD in these families. Although these genes may not be involved in renal cystic d iseases, their striking homology to PKD2 and PKD1 implies similar roles and may contribute to elucidating the function of both polycystin-1 and polycy stin-2.