Molecular genetics of polycystic kidney disease

J Nephrol. Jan-Feb 1998;11(1):24-34.


Polycystic kidney disease (PKD) is a major, multigene disorder that is characterized by the growth of large, fluid-filled cysts from the nephrons and collecting ducts of affected kidneys. At least three different genes are thought to give rise to the autosomal dominant (ADPKD) form of PKD. Two of the genes (PKD1 and PKD2) have now been isolated and sequenced, and based on their predicted structures are thought to encode proteins (polycystin-1 and polycystin-2) that function together as part of a multi-component membrane-spanning complex involved in cell-cell or cell-matrix interactions. Most mutations identified in affected families appear to be inactivating for the PKD1 and PKD2 genes, and recent evidence has suggested that a two-hit mechanism, in which the normal PKD1 allele is also inactivated, may be required for cyst growth. The large number of genes showing abnormal expression in cystic kidneys in humans and rodent models suggests that cellular processes associated with signal transduction, transcriptional regulation, and cell-cycle control are involved in cyst formation and that the cellular defect in PKD directly affects the regulation of epithelial differentiation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Gene Expression
  • Humans
  • Membrane Proteins / genetics*
  • Mutation
  • Polycystic Kidney Diseases / genetics*
  • Proteins / genetics*
  • TRPP Cation Channels


  • Membrane Proteins
  • Proteins
  • TRPP Cation Channels
  • polycystic kidney disease 1 protein
  • polycystic kidney disease 2 protein