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 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

doi:10.1038/ng.2681

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 journal › Journal article › Research › peer-review

160 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 language	English
Journal	Nature Genetics
Volume	45
Issue number	8
Pages (from-to)	951-956
Number of pages	6
ISSN	1061-4036
DOIs	https://doi.org/10.1038/ng.2681
Publication status	Published - Aug 2013

Keywords

Animals
Cilia
Consanguinity
Exons
Gene Knockdown Techniques
Humans
Introns
Kidney Diseases, Cystic
Kinesin
Mice
Mutation
Nuclear Proteins
Phenotype
Polycystic Kidney Diseases
Protein Binding
Protein Interaction Maps
Protein Kinases
Protein Transport
Transcription Factors
Xenopus
Zebrafish
Zebrafish Proteins

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Hoff, S., Halbritter, J., Epting, D., Frank, V., Nguyen, T-M. T., van Reeuwijk, J., Boehlke, C., Schell, C., Yasunaga, T., Helmstädter, M., Mergen, M., Filhol, E., Boldt, K., Horn, N., Ueffing, M., Otto, E. A., Eisenberger, T., Elting, M. W., van Wijk, J. A. E., ... 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

@article{8ca99593de984fed914edfa085ecd734,

title = "ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3",

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.",

keywords = "Animals, Cilia, Consanguinity, Exons, Gene Knockdown Techniques, Humans, Introns, Kidney Diseases, Cystic, Kinesin, Mice, Mutation, Nuclear Proteins, Phenotype, Polycystic Kidney Diseases, Protein Binding, Protein Interaction Maps, Protein Kinases, Protein Transport, Transcription Factors, Xenopus, Zebrafish, Zebrafish Proteins",

author = "Sylvia Hoff and Jan Halbritter and Daniel Epting and Valeska Frank and Nguyen, {Thanh-Minh T} and {van Reeuwijk}, Jeroen and Christopher Boehlke and Christoph Schell and Takayuki Yasunaga and Martin Helmst{\"a}dter and Miriam Mergen and Emilie Filhol and Karsten Boldt and Nicola Horn and Marius Ueffing and Otto, {Edgar A} and Tobias Eisenberger and Elting, {Mariet W} and {van Wijk}, {Joanna A E} and Detlef Bockenhauer and Sebire, {Neil J} and S{\o}ren Rittig and Mogens Vyberg and Troels Ring and Martin Pohl and Lars Pape and Neuhaus, {Thomas J} and Elshakhs, {Neveen A Soliman} and Koon, {Sarah J} and Harris, {Peter C} and Florian Grahammer and Huber, {Tobias B} and Kuehn, {E Wolfgang} and Albrecht Kramer-Zucker and Bolz, {Hanno J} and Ronald Roepman and Sophie Saunier and Gerd Walz and Friedhelm Hildebrandt and Carsten Bergmann and Lienkamp, {Soeren S}",

year = "2013",

month = aug,

doi = "10.1038/ng.2681",

language = "English",

volume = "45",

pages = "951--956",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "8",

}

Hoff, S, Halbritter, J, Epting, D, Frank, V, Nguyen, T-MT, 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, Kramer-Zucker, A, 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

TY - JOUR

T1 - ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3

AU - Hoff, Sylvia

AU - Halbritter, Jan

AU - Epting, Daniel

AU - Frank, Valeska

AU - Nguyen, Thanh-Minh T

AU - van Reeuwijk, Jeroen

AU - Boehlke, Christopher

AU - Schell, Christoph

AU - Yasunaga, Takayuki

AU - Helmstädter, Martin

AU - Mergen, Miriam

AU - Filhol, Emilie

AU - Boldt, Karsten

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

AU - Koon, Sarah J

AU - Harris, Peter C

AU - Grahammer, Florian

AU - Huber, Tobias B

AU - Kuehn, E Wolfgang

AU - Kramer-Zucker, Albrecht

AU - Bolz, Hanno J

AU - Roepman, Ronald

AU - Saunier, Sophie

AU - Walz, Gerd

AU - Hildebrandt, Friedhelm

AU - Bergmann, Carsten

AU - Lienkamp, Soeren S

PY - 2013/8

Y1 - 2013/8

N2 - 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.

AB - 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.

KW - Animals

KW - Cilia

KW - Consanguinity

KW - Exons

KW - Gene Knockdown Techniques

KW - Humans

KW - Introns

KW - Kidney Diseases, Cystic

KW - Kinesin

KW - Mice

KW - Mutation

KW - Nuclear Proteins

KW - Phenotype

KW - Polycystic Kidney Diseases

KW - Protein Binding

KW - Protein Interaction Maps

KW - Protein Kinases

KW - Protein Transport

KW - Transcription Factors

KW - Xenopus

KW - Zebrafish

KW - Zebrafish Proteins

U2 - 10.1038/ng.2681

DO - 10.1038/ng.2681

M3 - Journal article

C2 - 23793029

SN - 1061-4036

VL - 45

SP - 951

EP - 956

JO - Nature Genetics

JF - Nature Genetics

IS - 8

ER -

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

Abstract

Keywords

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