RAB12

RAB12, member RAS oncogene family

Ensembl:
ENSG00000206418
UniProt:
Q6IQ22
OMIM:
616448

Cilia effects upon perturbation of RAB12

Cilia number / % ciliated:
Incrased cilia number
Loss-of-function effect:
Longer cilia
Overexpression effect:
Shorter cilia

Ciliogenesis screen results (4 screens)

  • Kim2016: Not Reported
  • Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-3.20) PMID:26167766
  • Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680
  • Roosing et al. 2015 (siRNA) [siRNA]: No effect PMID:26595381

Subcellular localization

cilia associated gene

Functional category

  • Ciliary assembly/disassembly
  • Trafficking (BBSome, small GTPases, vesicular transport, ATPases)
  • Cilia length regulation

Function

RAB12 negatively regulates primary ciliogenesis and centrosome organization. Overexpression of RAB12 (especially active Q100L) decreases the percentage of ciliated cells, shortens or truncates cilia, and causes centrosome enlargement and splitting. Loss of RAB12 (KO or mutant rescue) increases ciliation, restores normal cilia length, and rescues centrosome abnormalities, particularly in cells with pathogenic LRRK2 mutations. RAB12 overactivity suppresses cilia formation and alters centrosome homeostasis, while its loss promotes ciliogenesis and normal centrosomal structure(PMID: 39343966).

Model organism evidence

Mus musculus (3 references)

RAB12-LRRK2 Complex Suppresses Primary Ciliogenesis and Regulates Centrosome Homeostasis in Astrocytes.

As expected for a protein that regulates LRRK2 activity, Rab12 also influenced primary cilia formation.

PMIDs: 39071328, 37874635, 29125462