GENES INVOLVED IN POLYCYSTIC KIDNEY DISEASE Polycystic kidney disease is an autosomal dominant disorder. Worldwide, this disease accounts for 8-10% of end stage kidney disease and results in chronic renal failure in about 45% of the affected individuals by the age of 60. The patients with the disease develop cysts in both kidneys that gradually enlarge over the lifetime of the individual and ultimately lead to chronic renal failure and hypertension. At least two loci are known to exist for this disease. One locus was designated PKD4. By analysis of a genomic cosmid clone and cDNA, Lisowsky et al identified a new human gene on chromosome 16 (16p13.3) in the locus for polycystic kidney disease (PKD1). The gene contains at least one intron and is actively transcribed in tissues from kidney and brain. The predicted protein was homologous (42%) to the yeast scERV1 protein which is essential for oxidative phosphorylation, the maintenance of mitochondrial genomes, and the cell-division cycle. A second locus is present on chromosome 4q (4q21-23). In the May 31, 1996 issue of Science, Mochizuki et al describe identification of a second gene by positional cloning, whose nonsense mutation leads to this disease. The predicted protein consists of 968 amino acids and contains six transmembrane spans with both amino- and carboxyl termini residing in the cytoplasm. This protein shows amino acid similarity to the previously described PKD1 as well as the C elegans homolog of PKD1. The protein contains one potential calcium binding site and it is interesting that there is amino acid identity between this protein and the members of the family of voltage-activated calcium and sodium channels. REFERENCES: Kimberling, 1993 Autosomal dominant polycystic kidney disease: localization of the second gene to chromosome 4q13-q23. Genomics 18, 467-72 (1993) [94140341] (View Citation format,Abstract format,MEDLARS format,ASN.1 format,Save As..., or 30 MEDLINE neighbors ) Reeders, 1988 Regional localization of the autosomal dominant polycystic kidney disease locus. Genomics 3, 150-5 (1988) [89138432] (View Citation format,Abstract format,MEDLARS format,ASN.1 format,Save As..., or 30 MEDLINE neighbors ) Lisowsky, 1995 A new human gene located in the PKD1 region of chromosome 16 is a functional homologue to ERV1 of yeast. Genomics 29, 690-697 (1995) [96121380] (View Citation format,Abstract format,MEDLARS format,ASN.1 format,Save As..., 30 MEDLINE neighbors, 1 protein link, or 1 nucleotide link ) Germino, 1993 Positional cloning approach to the dominant polycystic kidney disease gene, PKD1. Kidney Int Suppl 39, S20-5 (1993) [93225364] (View Citation format,Abstract format,MEDLARS format,ASN.1 format,Save As..., or 30 MEDLINE neighbors ) Mchizuki T et al, 1996:PDK2, a gene for polycystic kideny disease that encodes an integral membrane protein. Science 272, 1339-1342, 1996