2. Academic Validation
  3. ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3

ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3

  • Nat Genet. 2013 Aug;45(8):951-6. doi: 10.1038/ng.2681.
Sylvia Hoff 1,  Jan Halbritter,  Daniel Epting,  Valeska Frank,  Thanh-Minh T Nguyen,  Jeroen van Reeuwijk,  Christopher Boehlke,  Christoph Schell,  Takayuki Yasunaga,  Martin Helmstädter,  Miriam Mergen,  Emilie Filhol,  Karsten Boldt,  Nicola Horn,  Marius Ueffing,  Edgar A Otto,  Tobias Eisenberger,  Mariet W Elting,  Joanna A E van Wijk,  Detlef Bockenhauer,  Neil J Sebire,  Søren Rittig,  Mogens Vyberg,  Troels Ring,  Martin Pohl,  Lars Pape,  Thomas J Neuhaus,  Neveen A Soliman Elshakhs,  Sarah J Koon,  Peter C Harris,  Florian Grahammer,  Tobias B Huber,  E Wolfgang Kuehn,  Albrecht Kramer-Zucker,  Hanno J Bolz,  Ronald Roepman,  Sophie Saunier,  Gerd Walz,  Friedhelm Hildebrandt,  Carsten Bergmann,  Soeren S Lienkamp
Affiliations

Affiliation

  • 1 Department of Medicine, Renal Division, University of Freiburg Medical Center, Freiburg, Germany.
PMID: 23793029 DOI: 10.1038/ng.2681
Abstract

Nephronophthisis is an autosomal recessive cystic kidney disease that leads to renal failure in childhood or adolescence. Most NPHP gene products form molecular networks. Here we identify ANKS6 as a new NPHP family member that connects NEK8 (NPHP9) to INVS (NPHP2) and NPHP3. We show that ANKS6 localizes to the proximal cilium and confirm its role in renal development through knockdown experiments in zebrafish and Xenopus laevis. We also identify six families with ANKS6 mutations affected by nephronophthisis, including severe cardiovascular abnormalities, liver fibrosis and situs inversus. The oxygen sensor HIF1AN hydroxylates ANKS6 and INVS and alters the composition of the ANKS6-INVS-NPHP3 module. Knockdown of Hif1an in Xenopus results in a phenotype that resembles loss of Other NPHP proteins. Network analyses uncovered additional putative NPHP proteins and placed ANKS6 at the center of this NPHP module, explaining the overlapping disease manifestation caused by mutation in ANKS6, NEK8, INVS or NPHP3.

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