RPGRIP1L

Cilia effects upon perturbation of RPGRIP1L

Cilia number / % ciliated:

Unknown

Loss-of-function effect:

Longer cilia

Overexpression effect:

Unknown

Ciliogenesis screen results (2 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: No effect PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: Positive Regulator (Hh signaling, casTLE effect=-0.78) PMID:29459680

Phenotypes

Mouse phenotype:

hyperplasia, preweaning lethality, complete penetrance

Human ciliopathy phenotype:

Joubert syndrome; Joubert syndrome with hepatic defect; Meckel syndrome; Meckel syndrome, type 5; Joubert syndrome 7; Joubert syndrome and related disorders

Ciliopathy associations

• COACH Syndrome
• Joubert Syndrome
• Meckel-Gruber Syndrome

Subcellular localization

basal body, centrosome, cilia

Functional category

• Ciliary assembly/disassembly
• Actin & cytoskeleton regulation
• Signaling (Hedgehog, GPCRs, ion channels)
• Transition zone

Function

Mutations cause Joubert (17558407) and Meckel syndrome (17558409). It functions as cilium-specific scaffold that recruits a Nek4 sig ling network to regulate cilium assembly and stability. Interacts with RPGR (21685204). Loss of RPGRIP1L in human primary cell cultures and mice increases ciliary axonemal length (30728336). Interacts with MKS and NPHP proteins, and could potentially act as part of the gate for cytoplasmic proteins (30237221). Interacts with Psmd2, regulating the activity of the ciliary proteasome at the transition zone to control ciliary sig ling. This proteosomal function could be involved in the control of ciliary length (26150391). Rpgrip1l positively controls dishevelled levels. In the mouse and zebrafish, Rpgrip1l is required for positioning the basal body along the pla r polarity axis, morphants display pla r cell polarity defects (22927466).

Model organism evidence