NPHP3

Cilia effects upon perturbation of NPHP3

Cilia number / % ciliated:

Knockdown: Reduced, Overexpression: Increased

Loss-of-function effect:

Longer cilia

Overexpression effect:

No effect

Ciliogenesis screen results (3 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: No effect PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680
• Roosing et al. 2015 (siRNA) [siRNA]: No effect PMID:26595381

Phenotypes

Mouse phenotype:

preweaning lethality, incomplete penetrance, increased grip strength

Human ciliopathy phenotype:

nephronophthisis 3; NPHP3-related Meckel-like syndrome; renal-hepatic-pancreatic dysplasia 1; nephronophthisis; Nephronophthisis; renal-hepatic-pancreatic dysplasia; Senior-Loken syndrome; late-onset nephronophthisis; Joubert syndrome and related disorders

Ciliopathy associations

• COACH Syndrome
• Meckel-Gruber Syndrome
• Nephronophthisis
• Renal-hepatic-pancreatic Dysplasia
• Senior-Løken Syndrome

References: PMID:18371931, PMID:12872122, PMID:19303681, PMID:20007846, PMID:22819833, PMID:33323469, PMID:11261687, PMID:36253741, PMID:32341812, PMID:23438674, PMID:32714619

Subcellular localization

basal body, cilia, transition zone, ciliary tip

References: PMID:41005307, PMID:22328406, PMID:20169535, PMID:29395339

Functional category

• Ciliary assembly/disassembly
• Trafficking (BBSome, small GTPases, vesicular transport, ATPases)
• Actin & cytoskeleton regulation
• Signaling (Hedgehog, GPCRs, ion channels)
• Ciliary membrane
• Cardiac & muscle development
• Transition zone

Function

Mutations cause nephronophthisis type 3 (22328406). Interaction with Inversin is essential for NPHP3 localisation (20169535). Cooperates with Inversin and promotes ANKS6 phosphorylation by NEK8 in renal cilia. It may be involved in the regulation of noncanonical Wnt-pathway (29395339).