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

Subcellular localization

basal body, cilia, transition zone

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 re l cilia. It may be involved in the regulation of noncanonical Wnt-pathway (29395339).