PKHD1 mutations in autosomal recessive polycystic kidney disease (ARPKD)

Hum Mutat. 2004 May;23(5):453-63. doi: 10.1002/humu.20029.


Autosomal recessive polycystic kidney disease (ARPKD) is an important cause of childhood renal- and liver-related morbidity and mortality. The clinical spectrum is widely variable. About 30 to 50% of affected individuals die in the neonatal period, while others survive into adulthood. ARPKD is caused by mutations in the PKHD1 (polycystic kidney and hepatic disease 1) gene on chromosome 6p12, which is among the largest human genes, with a minimum of 86 exons assembled into a variety of alternatively spliced transcripts. The longest continuous open reading frame is predicted to yield a 4,074-aa (447-kDa) multidomain integral membrane protein (fibrocystin/polyductin) of unknown function. This update compiles all known PKHD1 mutations and polymorphisms/sequence variants. Mutations were found to be scattered throughout the gene without evidence of clustering at specific sites. Most PKHD1 mutations are unique to single families ("private mutations") hampering genotype-phenotype correlations. Correlations have been drawn for the type of mutation rather than for the site of individual mutations. All patients carrying two truncating mutations displayed a severe phenotype with perinatal or neonatal demise, while patients surviving the neonatal period bear at least one missense mutation. However, some missense changes are obviously as devastating as truncating mutations. The present article intends 1) to provide an overview of PKHD1 mutations and polymorphisms/sequence variants identified so far, 2) to discuss potential genotype-phenotype correlations, and 3) to review them in the context of their clinical implications. A constantly updated list of mutations is available online ( and investigators are invited to submit their novel data to this PKHD1 mutation database.

Publication types

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

MeSH terms

  • DNA Mutational Analysis / trends
  • Genetic Variation
  • Genotype
  • Haplotypes
  • Humans
  • Molecular Sequence Data
  • Mutation*
  • Phenotype
  • Polycystic Kidney, Autosomal Recessive / diagnosis
  • Polycystic Kidney, Autosomal Recessive / genetics*
  • Polycystic Kidney, Autosomal Recessive / pathology
  • Polymorphism, Genetic
  • RNA Splicing
  • Receptors, Cell Surface / genetics*
  • Receptors, Cell Surface / metabolism


  • PKHD1 protein, human
  • Receptors, Cell Surface

Associated data

  • GENBANK/AF480064
  • GENBANK/AY074797
  • GENBANK/AY129465