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

Sylvia Hoff, 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 BockenhauerNeil 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

Research output: Contribution to journalArticle

105 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)951-956
Number of pages6
JournalNature Genetics
Volume45
Issue number8
DOIs
StatePublished - Aug 2013

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Cardiovascular Abnormalities
Cystic Kidney Diseases
Situs Inversus
Mutation
Cilia
Xenopus laevis
Zebrafish
Xenopus
Liver Cirrhosis
Renal Insufficiency
Proteins
Oxygen
Phenotype
Kidney
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Hoff, S., Halbritter, J., Epting, D., Frank, V., Nguyen, T. M. T., Van Reeuwijk, J., ... Lienkamp, S. S. (2013). ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3. Nature Genetics, 45(8), 951-956. https://doi.org/10.1038/ng.2681

ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3. / Hoff, Sylvia; Halbritter, Jan; Epting, Daniel; Frank, Valeska; Nguyen, Thanh Minh T; Van Reeuwijk, Jeroen; Boehlke, Christopher; Schell, Christoph; Yasunaga, Takayuki; Helmstädter, Martin; Mergen, Miriam; Filhol, Emilie; Boldt, Karsten; Horn, Nicola; Ueffing, Marius; Otto, Edgar A.; Eisenberger, Tobias; Elting, Mariet W.; Van Wijk, Joanna A E; Bockenhauer, Detlef; Sebire, Neil J.; Rittig, Søren; Vyberg, Mogens; Ring, Troels; Pohl, Martin; Pape, Lars; Neuhaus, Thomas J.; Elshakhs, Neveen A Soliman; Koon, Sarah J.; Harris, Peter C; Grahammer, Florian; Huber, Tobias B.; Kuehn, E. Wolfgang; Zucker, Albrecht Kramer; Bolz, Hanno J.; Roepman, Ronald; Saunier, Sophie; Walz, Gerd; Hildebrandt, Friedhelm; Bergmann, Carsten; Lienkamp, Soeren S.

In: Nature Genetics, Vol. 45, No. 8, 08.2013, p. 951-956.

Research output: Contribution to journalArticle

Hoff, S, Halbritter, J, Epting, D, Frank, V, Nguyen, TMT, Van Reeuwijk, J, Boehlke, C, Schell, C, Yasunaga, T, Helmstädter, M, Mergen, M, Filhol, E, Boldt, K, Horn, N, Ueffing, M, Otto, EA, Eisenberger, T, Elting, MW, Van Wijk, JAE, Bockenhauer, D, Sebire, NJ, Rittig, S, Vyberg, M, Ring, T, Pohl, M, Pape, L, Neuhaus, TJ, Elshakhs, NAS, Koon, SJ, Harris, PC, Grahammer, F, Huber, TB, Kuehn, EW, Zucker, AK, Bolz, HJ, Roepman, R, Saunier, S, Walz, G, Hildebrandt, F, Bergmann, C & Lienkamp, SS 2013, 'ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3', Nature Genetics, vol. 45, no. 8, pp. 951-956. https://doi.org/10.1038/ng.2681
Hoff S, Halbritter J, Epting D, Frank V, Nguyen TMT, Van Reeuwijk J et al. ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3. Nature Genetics. 2013 Aug;45(8):951-956. https://doi.org/10.1038/ng.2681
Hoff, Sylvia ; Halbritter, Jan ; Epting, Daniel ; Frank, Valeska ; Nguyen, Thanh Minh T ; Van Reeuwijk, Jeroen ; Boehlke, Christopher ; Schell, Christoph ; Yasunaga, Takayuki ; Helmstädter, Martin ; Mergen, Miriam ; Filhol, Emilie ; Boldt, Karsten ; Horn, Nicola ; Ueffing, Marius ; Otto, Edgar A. ; Eisenberger, Tobias ; Elting, Mariet W. ; Van Wijk, Joanna A E ; Bockenhauer, Detlef ; Sebire, Neil J. ; Rittig, Søren ; Vyberg, Mogens ; Ring, Troels ; Pohl, Martin ; Pape, Lars ; Neuhaus, Thomas J. ; Elshakhs, Neveen A Soliman ; Koon, Sarah J. ; Harris, Peter C ; Grahammer, Florian ; Huber, Tobias B. ; Kuehn, E. Wolfgang ; Zucker, Albrecht Kramer ; Bolz, Hanno J. ; Roepman, Ronald ; Saunier, Sophie ; Walz, Gerd ; Hildebrandt, Friedhelm ; Bergmann, Carsten ; Lienkamp, Soeren S. / ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3. In: Nature Genetics. 2013 ; Vol. 45, No. 8. pp. 951-956.
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AU - Hoff, Sylvia

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AU - Nguyen, Thanh Minh T

AU - Van Reeuwijk, Jeroen

AU - Boehlke, Christopher

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AU - Yasunaga, Takayuki

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AU - Horn, Nicola

AU - Ueffing, Marius

AU - Otto, Edgar A.

AU - Eisenberger, Tobias

AU - Elting, Mariet W.

AU - Van Wijk, Joanna A E

AU - Bockenhauer, Detlef

AU - Sebire, Neil J.

AU - Rittig, Søren

AU - Vyberg, Mogens

AU - Ring, Troels

AU - Pohl, Martin

AU - Pape, Lars

AU - Neuhaus, Thomas J.

AU - Elshakhs, Neveen A Soliman

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AU - Harris, Peter C

AU - Grahammer, Florian

AU - Huber, Tobias B.

AU - Kuehn, E. Wolfgang

AU - Zucker, Albrecht Kramer

AU - Bolz, Hanno J.

AU - Roepman, Ronald

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