Polycystic kidney disease: the complete structure of the PKD1 gene and its protein. The International Polycystic Kidney Disease Consortium

Abstract

Mutations in the PKD1 gene are the most common cause of autosomal dominant polycystic kidney disease (ADPKD). Other PKD1-like loci on chromosome 16 are approximately 97% identical to PKD1. To determine the authentic PKD1 sequence, we obtained the genomic sequence of the PKD1 locus and assembled a PKD1 transcript from the sequence of 46 exons. The 14.5 kb PKD1 transcript encodes a 4304 amino acid protein that has a novel domain architecture. The amino-terminal half of the protein consists of a mosaic of previously described domains, including leucine-rich repeats flanked by characteristic cysteine-rich structures, LDL-A and C-type lectin domains, and 14 units of a novel 80 amino acid domain. The presence of these domains suggests that the PKD1 protein is involved in adhesive protein-protein and protein-carbohydrate interactions in the extracellular compartment. We propose a hypothesis that links the predicted properties of the protein with the diverse phenotypic features of ADPKD.