PUBLICATION

The C175R mutation alters nuclear localization and transcriptional activity of the nephronophthisis NPHP7 gene product

Authors
Ramachandran, H., Yakulov, T.A., Engel, C., Müller, B., Walz, G.
ID
ZDB-PUB-150917-8
Date
2016
Source
European journal of human genetics : EJHG   24(5): 774-8 (Journal)
Registered Authors
Ramachandran, Hari
Keywords
none
MeSH Terms
  • Cell Nucleus/metabolism*
  • Zebrafish
  • Transcriptional Activation
  • Kidney Diseases, Cystic/genetics*
  • Kruppel-Like Transcription Factors/genetics*
  • Kruppel-Like Transcription Factors/metabolism
  • HEK293 Cells
  • Protein Binding
  • Active Transport, Cell Nucleus
  • Humans
  • Animals
  • Mutation, Missense*
(all 12)
PubMed
26374130 Full text @ Eur. J. Hum. Genet.
Abstract
Nephronophthisis (NPH) is a rare autosomal ciliopathy, but the leading cause for hereditary end-stage renal disease in children. Most NPH family members form large protein networks, which appear to participate in structural elements of the cilium and/or function to restrict access of molecules to the ciliary compartment. The zinc-finger protein GLIS2/NPHP7 represents an exception as it has been implicated in transcriptional regulation; only two families with GLIS2/NPHP7 mutations and typical NPH manifestations have been identified so far. We describe here that the recently identified GLIS2/NPHP7(C175R) point mutation abolished the nuclear localization of GLIS2/NPHP7. Forced nuclear import did not rescue the transcriptional defects of GLIS2/NPHP7(C175R), indicating additional defects as DNA-binding protein. We further observed that wild type, but not GLIS2/NPHP7(C175R), prevented the cyst formation caused by depletion of nphp7 in zebrafish embryos. Taken together, our findings indicate that the C175R mutation affects both localization and function of GLIS2/NPHP7, supporting a role of this mutation in NPH, but questioning the direct involvement of GLIS2/NPHP7 in ciliary functions.European Journal of Human Genetics advance online publication, 16 September 2015; doi:10.1038/ejhg.2015.199.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
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Citation
Ramachandran, H., Yakulov, T.A., Engel, C., Müller, B., Walz, G. (2016) The C175R mutation alters nuclear localization and transcriptional activity of the nephronophthisis NPHP7 gene product. European journal of human genetics : EJHG. 24(5):774-8.