INPP5E

Cilia effects upon perturbation of INPP5E

Cilia number / % ciliated:

Decreased cilia number

Loss-of-function effect:

Shorter cilia

Ciliogenesis screen results (5 screens)

• Kim2016: Not Reported
• Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-4.59) PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: Positive Regulator (Hh signaling, casTLE effect=-2.15) PMID:29459680
• Roosing et al. 2015 (siRNA) [siRNA]: No effect PMID:26595381
• Kim et al. 2010 (siRNA) [siRNA]: Shorter Cilia (Area per Cilia z=-3.87) PMID:20393562

Phenotypes

Mouse phenotype:

anophthalmia, abnormal craniofacial morphology, abnormal hindbrain morphology, preweaning lethality, complete penetrance, abnormal midbrain morphology, abnormal embryo size, edema, abnormal forebrain morphology, abnormal limb morphology, abnormal eye morphology

Mouse ciliopathy phenotype:

polydactyly, microphthalmia, eye hemorrhage, abnormal neural tube closure

Human ciliopathy phenotype:

Joubert syndrome 1; Joubert syndrome; Joubert syndrome and related disorders

Ciliopathy associations

• Joubert Syndrome

Subcellular localization

cilia, cytosol

Functional category

• Ciliary assembly/disassembly
• Trafficking (BBSome, small GTPases, vesicular transport, ATPases)
• Signaling (Hedgehog, GPCRs, ion channels)
• Ciliary membrane
• Transition zone

Function

Regulator of transition zone function. INPP5E may regulate Hedgehog sig ling via modulating the PI(4,5)P2- dependent recruitment of GPR161 to cilia. It is essential for maximal SMO accumulation at cilia after the Hh pathway (27998989). Controls ciliary growth factor, PI3K sig ling and stability (19668215). Mutations cause Joubert Syndrome and promotes premature destabilization of cilia (19668216). Suppressing inpp5e leads to shorter and fewer cilia in Kupffer’s vesicle. (39781470) Loss of INPP5E destabilizes ciliary axoneme and leads to resorption.(27998989) Inpp5e morphants have shortened and decreased cilia formation in zebrafish ducts. (23022135) INPP5E is required on ciliary membrane for regulating phosphoinositide levels, ciliogenesis, stability and signaling. (35463949) Down-regulation of Inpp5e led to reduced number and length of primary cilia in NIH3T3 cells. (34093381)

Model organism evidence