NPHP4
Description
The NPHP4 (nephrocystin 4) is a protein-coding gene located on chromosome 1.
Nephrocystin-4 is a protein encoded by the NPHP4 gene in humans. It contains a proline-rich region and may play a role in renal tubular development and function. It interacts with nephrocystin, and mutations in the NPHP4 gene are linked to nephronophthisis type 4. Multiple alternative transcript variants have been described, but their full-length nature is not yet fully understood.
Nephrocystin-4 plays a role in organizing apical junctions, potentially as part of a functional module with NPHP1 and RPGRIP1L. While not essential for ciliogenesis itself, it's crucial for building functional cilia. It contributes to the organization of the subapical actin network in multiciliated epithelial cells, likely by recruiting INT to basal bodies of motile cilia, which then interacts with actin-modifying proteins like DAAM1. In collaboration with INVS, Nephrocystin-4 may down-regulate the canonical Wnt pathway and promote the Wnt-PCP pathway by controlling the expression and subcellular localization of disheveled proteins. It stabilizes JADE1 protein levels and facilitates its nuclear translocation, leading to a cooperative inhibition of canonical Wnt signaling. Nephrocystin-4 acts as a negative regulator of the hippo pathway by associating with LATS1 and influencing LATS1-dependent phosphorylation and localization of WWTR1/TAZ.
NPHP4 is also known as POC10, SLSN4.
