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

摘要: 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 structural elements of cilium and/or function restrict access molecules ciliary compartment. The zinc-finger GLIS2/NPHP7 represents an exception as it has been implicated transcriptional regulation; only two families with mutations and typical manifestations have identified so far. We describe here that recently GLIS2/NPHP7C175R point mutation abolished nuclear localization GLIS2/NPHP7. Forced import did not rescue defects GLIS2/NPHP7C175R, indicating additional DNA-binding protein. further observed wild type, prevented cyst formation caused by depletion nphp7 zebrafish embryos. Taken together, our findings indicate C175R affects both GLIS2/NPHP7, supporting role this NPH, questioning direct involvement functions.