The gene mutated in autosomal recessive polycystic kidney disease encodes a large, receptor-like protein

Nat Genet. 2002 Mar;30(3):259-69. doi: 10.1038/ng833. Epub 2002 Feb 4.


Autosomal recessive polycystic kidney disease (ARPKD) is characterized by dilation of collecting ducts and by biliary dysgenesis and is an important cause of renal- and liver-related morbidity and mortality. Genetic analysis of a rat with recessive polycystic kidney disease revealed an orthologous relationship between the rat locus and the ARPKD region in humans; a candidate gene was identified. A mutation was characterized in the rat and screening the 66 coding exons of the human ortholog (PKHD1) in 14 probands with ARPKD revealed 6 truncating and 12 missense mutations; 8 of the affected individuals were compound heterozygotes. The PKHD1 transcript, approximately 16 kb long, is expressed in adult and fetal kidney, liver and pancreas and is predicted to encode a large novel protein, fibrocystin, with multiple copies of a domain shared with plexins and transcription factors. Fibrocystin may be a receptor protein that acts in collecting-duct and biliary differentiation.

Publication types

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

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Animals
  • Cloning, Molecular
  • Female
  • Genetic Testing
  • Heterozygote
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Molecular Sequence Data
  • Mutation*
  • Polycystic Kidney, Autosomal Recessive / diagnosis
  • Polycystic Kidney, Autosomal Recessive / genetics*
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / genetics*
  • Sequence Homology, Amino Acid


  • PKHD1 protein, human
  • RNA, Messenger
  • Receptors, Cell Surface

Associated data

  • GENBANK/AL121946
  • GENBANK/AL355997
  • GENBANK/AL391221
  • GENBANK/AL590391
  • GENBANK/AY074797
  • RefSeq/XM_051857