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Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination.

Nephronophthisis (NPHP), an autosomal recessive cystic kidney disease, leads to chronic renal failure in children. The genes mutated in NPHP1 and NPHP4 have been identified, and a gene locus associated with infantile nephronophthisis (NPHP2) was mapped. The kidney phenotype of NPHP2 combines clinical features of NPHP and polycystic kidney disease (PKD). Here, we identify inversin (INVS) as the gene mutated in NPHP2 with and without situs inversus. We show molecular interaction of inversin with nephrocystin, the product of the gene mutated in NPHP1 and interaction of nephrocystin with beta-tubulin, a main component of primary cilia. We show that nephrocystin, inversin and beta-tubulin colocalize to primary cilia of renal tubular cells. Furthermore, we produce a PKD-like renal cystic phenotype and randomization of heart looping by knockdown of invs expression in zebrafish. The interaction and colocalization in cilia of inversin, nephrocystin and beta-tubulin connect pathogenetic aspects of NPHP to PKD, to primary cilia function and to left-right axis determination.

Pubmed ID: 12872123


  • Otto EA
  • Schermer B
  • Obara T
  • O'Toole JF
  • Hiller KS
  • Mueller AM
  • Ruf RG
  • Hoefele J
  • Beekmann F
  • Landau D
  • Foreman JW
  • Goodship JA
  • Strachan T
  • Kispert A
  • Wolf MT
  • Gagnadoux MF
  • Nivet H
  • Antignac C
  • Walz G
  • Drummond IA
  • Benzing T
  • Hildebrandt F


Nature genetics

Publication Data

August 18, 2003

Associated Grants

  • Agency: NIDDK NIH HHS, Id: R01 DK078209
  • Agency: NIDDK NIH HHS, Id: R21 DK069604

Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Base Sequence
  • Body Patterning
  • Child
  • Cilia
  • DNA
  • Female
  • Gene Targeting
  • Humans
  • Kidney Diseases, Cystic
  • Male
  • Membrane Proteins
  • Molecular Sequence Data
  • Mutation
  • Polycystic Kidney, Autosomal Recessive
  • Proteins
  • Situs Inversus
  • Transcription Factors
  • Tubulin
  • Zebrafish