NPHP3

NPHP3, also known as nephrocystin-3, is a human gene that encodes a ciliary protein involved in the function and maintenance of primary cilia in renal tubular cells and photoreceptors. The nephrocystin-3 protein localizes to the primary cilium and basal body, with enrichment at the ciliary transition zone, a region that regulates protein traffic into the cilium. As a member of the nephronophthisis (NPHP) protein family, nephrocystin-3 participates in the assembly and signaling functions of cilia and interacts with other ciliary proteins to support tubular morphogenesis and tissue architecture.

The protein contains coiled-coil domains that facilitate interactions within a network of ciliary components, including other NPHP proteins, and is thought to connect ciliary signaling with cellular polarity and trafficking processes. This network underpins the proper development and maintenance of renal tubules and other ciliated tissues.

Mutations in NPHP3 cause autosomal recessive nephronophthisis type 3, a renal tubulointerstitial disease that typically presents in childhood or adolescence with progressive kidney dysfunction. In some cases, the disease is part of syndromic ciliopathies such as Senior-Løken syndrome (kidney and retina) or other ciliopathy spectra that may include brain or liver involvement. The pathogenesis is linked to disrupted ciliary signaling and gate function, leading to tubular atrophy and fibrosis.

Animal models, including mice and zebrafish, have been used to study NPHP3 function, supporting its role in ciliary biology and ciliopathy-related phenotypes. Diagnosis often involves genetic testing for NPHP3 mutations in individuals with compatible renal and/or syndromic features. Treatment is supportive, focusing on kidney disease management, with transplantation as an option for end-stage disease.