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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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RAB12
RAB12, member RAS oncogene family
Chromosome 18 · 18p11.22
NCBI Gene: 201475Ensembl: ENSG00000206418.5HGNC: HGNC:31332UniProt: A0A3B3ITT1
37PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingGDP bindingGTPase activityendosome to lysosome transportcorneal neovascularizationIncisional herniaplacental retentionatrial fibrillation
✦AI Summary

RAB12 is a small GTPase that regulates intracellular membrane trafficking by cycling between GDP-bound (inactive) and GTP-bound (active) conformations to recruit effector proteins for vesicle formation and transport 1. RAB12 plays key roles in protein transport from recycling endosomes to lysosomes and in autophagy regulation 2. It negatively regulates osteogenic differentiation of mesenchymal stem cells through the PCBP1/GLUT1 axis, controlling glucose metabolism in the bone microenvironment 3. Mechanistically, RAB12 functions as a robust substrate of LRRK2 kinase, with phosphorylation occurring at Ser106 4. The RAB12-LRRK2 complex suppresses primary ciliogenesis and regulates centrosome homeostasis in astrocytes by enhancing Rab10 phosphorylation and recruiting RILPL1 1. RAB12 also interacts with RILP family members to regulate mast cell secretory granule transport 5. Clinically, RAB12 is relevant to Parkinson's disease, where LRRK2 mutations elevate RAB12 phosphorylation levels. Phosphorylated RAB12 (pSer106) serves as an endogenous blood biomarker of G2019S LRRK2-driven disease, correlating with motor severity and responding to LRRK2 inhibition 4. Additionally, RAB12 under-prenylation contributes to choroideremia pathology by reducing autophagy and increasing mTORC1 signaling in retinal pigment epithelium 2.

Sources cited
1
RAB12 is a small GTPase that regulates intracellular membrane trafficking by cycling between GDP-bound (inactive) and GTP-bound (active) conformations to recruit effector proteins for vesicle formation and transport .
PMID: 39343966
2
RAB12 plays key roles in protein transport from recycling endosomes to lysosomes and in autophagy regulation .
PMID: 38920696
3
It negatively regulates osteogenic differentiation of mesenchymal stem cells through the PCBP1/GLUT1 axis, controlling glucose metabolism in the bone microenvironment .
PMID: 40147529
4
Mechanistically, RAB12 functions as a robust substrate of LRRK2 kinase, with phosphorylation occurring at Ser106 .
PMID: 39705401
5
RAB12 also interacts with RILP family members to regulate mast cell secretory granule transport .
PMID: 33986343
Disease Associationsⓘ20
corneal neovascularizationOpen Targets
0.32Weak
Incisional herniaOpen Targets
0.30Weak
placental retentionOpen Targets
0.24Weak
atrial fibrillationOpen Targets
0.24Weak
coronary artery diseaseOpen Targets
0.24Weak
cancerOpen Targets
0.23Weak
diabetes mellitusOpen Targets
0.23Weak
heart failureOpen Targets
0.23Weak
strokeOpen Targets
0.20Weak
Abnormal pupillary functionOpen Targets
0.20Weak
placenta praeviaOpen Targets
0.20Weak
psoriasisOpen Targets
0.16Weak
femoral neck fractureOpen Targets
0.16Weak
Abruptio PlacentaeOpen Targets
0.15Weak
hypopituitarismOpen Targets
0.15Weak
body weight gainOpen Targets
0.14Weak
cervical carcinomaOpen Targets
0.14Weak
muscle strainOpen Targets
0.14Weak
sprainOpen Targets
0.14Weak
lymphatic system diseaseOpen Targets
0.12Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
GDI1Protein interaction91%RILPL1Protein interaction83%GDI2Protein interaction81%RILPL2Protein interaction80%CHMProtein interaction77%DENND3Protein interaction65%
Tissue Expression6 tissues
Heart
100%
Brain
38%
Lung
30%
Ovary
25%
Liver
22%
Bone Marrow
14%
Gene Interaction Network
Click a node to explore
RAB12GDI1RILPL1GDI2RILPL2CHMDENND3
PROTEIN STRUCTURE
Preparing viewer…
PDB2IL1 · 2.10 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.18LoF Tolerant
pLIⓘ
0.02Tolerant
Observed/Expected LoF0.63 [0.36–1.18]
RankingsWhere RAB12 stands among ~20K protein-coding genes
  • #10,677of 20,598
    Most Researched37
  • #12,377of 17,882
    Most Constrained (LOEUF)1.18
Genes detectedRAB12
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
RAB12-LRRK2 complex suppresses primary ciliogenesis and regulates centrosome homeostasis in astrocytes.
PMID: 39343966
Nat Commun · 2024
1.00
2
The role of RAB12 in inhibiting osteogenic differentiation and driving metabolic dysregulation in osteoporosis.
PMID: 40147529
Life Sci · 2025
0.90
3
Lysosomal positioning regulates Rab10 phosphorylation at LRRK2
PMID: 36256825
Proc Natl Acad Sci U S A · 2022
0.80
4
In-depth mass-spectrometry reveals phospho-RAB12 as a blood biomarker of G2019S LRRK2-driven Parkinson's disease.
PMID: 39705401
Brain · 2025
0.70
5
Reduced Retinal Pigment Epithelial Autophagy Due to Loss of Rab12 Prenylation in a Human iPSC-RPE Model of Choroideremia.
PMID: 38920696
Cells · 2024
0.60