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
-
- Active Transport, Cell Nucleus
- Animals
- Cell Nucleus/metabolism*
- HEK293 Cells
- Humans
- Kidney Diseases, Cystic/genetics*
- Kruppel-Like Transcription Factors/genetics*
- Kruppel-Like Transcription Factors/metabolism
- Mutation, Missense*
- Protein Binding
- Transcriptional Activation
- Zebrafish
- PubMed
- 26374130 Full text @ Eur. J. Hum. Genet.
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.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping