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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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RABGGTB
Rab geranylgeranyltransferase subunit beta
Chromosome 1 · 1p31.1
NCBI Gene: 5876Ensembl: ENSG00000137955.17HGNC: HGNC:9796UniProt: A8KAJ2
59PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingRab-protein geranylgeranyltransferase complexprotein geranylgeranylationendoplasmic reticulum to Golgi vesicle-mediated transportneurodegenerative diseaseneuroinflammatory disorderamyotrophic lateral sclerosisheart disease
✦AI Summary

RABGGTB is the catalytic β-subunit of geranylgeranyl transferase type 3 (GGTase-3), an enzyme complex that catalyzes the transfer of geranylgeranyl moieties to Rab GTPases and other protein substrates 1. This prenylation reaction is essential for membrane localization and proper cellular function of target proteins 2. RABGGTB-mediated geranylgeranylation of Rab7 regulates autophagosome-lysosome fusion, a critical process for protein degradation 3. The enzyme also modifies the v-SNARE protein YKT6, facilitating Golgi SNARE complex assembly necessary for vesicular transport 2. Additionally, GGTase-3 geranylgeranylates FBXL2, targeting it to cellular membranes where it functions in the SCF(FBXL2) E3 ubiquitin-ligase complex 4. Disrupted RABGGTB expression is implicated in multiple neuropsychiatric and neurodegenerative diseases. Schizophrenia shows decreased RABGGTB protein levels (8% reduction) in the dorsolateral prefrontal cortex 5. Multiple sclerosis patients demonstrate significant RABGGTB downregulation, particularly in females 6. ASD is associated with RABGGTB promoter hypomethylation and increased expression in the raphe nuclei 7. RABGGTB overexpression improves autophagy and reduces protein aggregation in ALS models 3. In pancreatic β-cells, GGTase-III containing RABGGTB is essential for glucose-stimulated insulin secretion 8. These findings establish RABGGTB as a critical regulator of membrane protein function with significant implications for neurological disease pathogenesis.

Sources cited
1
RABGGTB is the catalytic β-subunit of geranylgeranyl transferase type 3 (GGTase-3), an enzyme complex that catalyzes the transfer of geranylgeranyl moieties to Rab GTPases and other protein substrates .
PMID: 7991565
2
This prenylation reaction is essential for membrane localization and proper cellular function of target proteins .
PMID: 32128853
3
RABGGTB-mediated geranylgeranylation of Rab7 regulates autophagosome-lysosome fusion, a critical process for protein degradation .
PMID: 38042502
4
Additionally, GGTase-3 geranylgeranylates FBXL2, targeting it to cellular membranes where it functions in the SCF(FBXL2) E3 ubiquitin-ligase complex .
PMID: 31209342
5
Schizophrenia shows decreased RABGGTB protein levels (8% reduction) in the dorsolateral prefrontal cortex .
PMID: 32066669
6
Multiple sclerosis patients demonstrate significant RABGGTB downregulation, particularly in females .
PMID: 29574663
7
ASD is associated with RABGGTB promoter hypomethylation and increased expression in the raphe nuclei .
PMID: 40272067
8
In pancreatic β-cells, GGTase-III containing RABGGTB is essential for glucose-stimulated insulin secretion .
PMID: 40598917
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.53Moderate
neuroinflammatory disorderOpen Targets
0.36Weak
amyotrophic lateral sclerosisOpen Targets
0.08Suggestive
heart diseaseOpen Targets
0.05Suggestive
skin diseaseOpen Targets
0.03Suggestive
adolescent idiopathic scoliosisOpen Targets
0.02Suggestive
head injuryOpen Targets
0.02Suggestive
schizophreniaOpen Targets
0.02Suggestive
Parkinson diseaseOpen Targets
0.01Suggestive
chronic kidney diseaseOpen Targets
0.01Suggestive
ovarian carcinomaOpen Targets
0.01Suggestive
periodontitisOpen Targets
0.01Suggestive
dermatomyositisOpen Targets
0.00Suggestive
cancerOpen Targets
0.00Suggestive
hepatocellular carcinomaOpen Targets
0.00Suggestive
infectionOpen Targets
0.00Suggestive
neoplasmOpen Targets
0.00Suggestive
multiple myelomaOpen Targets
0.00Suggestive
multiple sclerosisOpen Targets
0.00Suggestive
acute quadriplegic myopathyOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
FBXL2Protein interaction100%PTP4A2Protein interaction96%RAB1AProtein interaction94%YKT6Protein interaction94%CHMProtein interaction86%RAB3AProtein interaction86%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
37%
Liver
34%
Heart
32%
Ovary
30%
Brain
24%
Gene Interaction Network
Click a node to explore
RABGGTBFBXL2PTP4A2RAB1AYKT6CHMRAB3A
PROTEIN STRUCTURE
Preparing viewer…
PDB6O60 · 2.50 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.69LoF Tolerant
pLIⓘ
0.02Tolerant
Observed/Expected LoF0.47 [0.33–0.69]
RankingsWhere RABGGTB stands among ~20K protein-coding genes
  • #7,808of 20,598
    Most Researched59
  • #5,179of 17,882
    Most Constrained (LOEUF)0.69
Genes detectedRABGGTB
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Protein expression of prenyltransferase subunits in postmortem schizophrenia dorsolateral prefrontal cortex.
PMID: 32066669
Transl Psychiatry · 2020
1.00
2
Genome-wide DNA methylation profiles in the raphe nuclei of patients with autism spectrum disorder.
PMID: 40272067
Psychiatry Clin Neurosci · 2025
0.90
3
RABGGTB plays a critical role in ALS pathogenesis.
PMID: 38042502
Brain Res Bull · 2024
0.80
4
Assessment of Protein Prenylation Pathway in Multiple Sclerosis Patients.
PMID: 29574663
J Mol Neurosci · 2018
0.70
5
Exploring genetic and epigenetic markers for predicting or monitoring response to cognitive-behavioral therapy in obsessive-compulsive disorder: A systematic review.
PMID: 40324706
Neurosci Biobehav Rev · 2025
0.60