InterPro domain: IPR029775

All nephrocystin proteins (NPHPs) localise to primary cilia, which are critical regulators of several cell signalling pathways for embryonic development and tissue homeostasis.

Nephrocystin-4 (NPHP4) localises to the basal body [ 1 ] and is thought to be involved in basal body docking and organising ciliary trafficking [ 2 ]. It is a negative regulator of canonical Wnt signalling [ 3 , 4 ]. Mutations in NPHP4 cause Nephronophthisis 4, an autosomal-recessive cystic kidney disease that belongs to a broad spectrum of disorders collectively termed ciliopathies [ 5 ].

1. Characterization of the nephrocystin/nephrocystin-4 complex and subcellular localization of nephrocystin-4 to primary cilia and centrosomes. Hum. Mol. Genet. 14, 645-56
2. MKS and NPHP modules cooperate to establish basal body/transition zone membrane associations and ciliary gate function during ciliogenesis. J. Cell Biol. 192, 1023-41
3. Control of the Wnt pathways by nephrocystin-4 is required for morphogenesis of the zebrafish pronephros. Hum. Mol. Genet. 20, 2611-27
4. The ciliary protein nephrocystin-4 translocates the canonical Wnt regulator Jade-1 to the nucleus to negatively regulate β-catenin signaling. J. Biol. Chem. 287, 25370-80
5. The gene mutated in juvenile nephronophthisis type 4 encodes a novel protein that interacts with nephrocystin. Nat. Genet. 32, 300-5