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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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RAB18
RAB18, member RAS oncogene family
Chromosome 10 Β· 10p12.1
NCBI Gene: 22931Ensembl: ENSG00000099246.19HGNC: HGNC:14244UniProt: B7Z4P9
130PubMed Papers
21Diseases
0Drugs
9Pathogenic Variants
FUNCTIONAL ROLE
Transporter
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
endoplasmic reticulum tubular network organizationlipid droplet organizationendoplasmic reticulum tubular networkendoplasmic reticulum membraneMicro syndromeWarburg micro syndromeneurodegenerative diseasecerebral atherosclerosis
✦AI Summary

RAB18 is a conserved small GTPase that functions as a key regulator of intracellular membrane trafficking by cycling between inactive GDP-bound and active GTP-bound states to recruit downstream effectors 1. RAB18 localizes to multiple organelles, particularly the endoplasmic reticulum (ER) and lipid droplets 2. Primary functions include: (1) mediating ER-lipid droplet contact sites through ZFYVE1 localization, essential for lipid droplet biogenesis and maturation 13; (2) maintaining ER structure 4; and (3) regulating cholesterol biosynthesis through interactions with sterol-modifying proteins EBP and ORP2 5. RAB18 plays critical roles in eye and brain development 6. Loss-of-function RAB18 mutations cause Warburg Micro syndrome, an autosomal recessive disorder characterized by developmental abnormalities 25. Conversely, RAB18 overexpression promotes gastric cancer proliferation and chemoresistance through mitochondrial regulation 7, and exacerbates non-alcoholic fatty liver disease by regulating lipid droplet proteins PLIN2 and PPARΞ³ 8. RAB18 also functions in lipophagy inhibition and copper-induced cell death pathways 9. These opposing roles in development versus disease highlight RAB18's context-dependent importance in metabolic homeostasis and cellular stress responses.

Sources cited
1
RAB18 mediates ZFYVE1 localization to lipid droplets and forms ER-lipid droplet contacts; Rab proteins cycle between GDP and GTP-bound states
PMID: 30970241
2
Rab proteins regulate membrane trafficking and vesicle dynamics; RAB18 maintains ER structure
PMID: 24891604
3
RAB18 plays a key role in eye and brain development and neurodegeneration
PMID: 21473985
4
RAB18 is conserved across eukaryotes, localizes to ER and lipid droplets; absence causes Warburg-Micro syndrome; involved in organelle tethering and autophagy
PMID: 30830238
5
RAB18 and its effector NRZ regulate ER-lipid droplet contact sites essential for lipid droplet biogenesis and maturation
PMID: 31075519
6
RAB18 interacts with sterol-modifying proteins EBP and ORP2; RAB18 deficiency impairs cholesterol biosynthesis; loss causes Warburg Micro syndrome
PMID: 37774976
7
RAB18 overexpression promotes gastric cancer proliferation, chemoresistance, and migration through mitochondrial regulation
PMID: 30464528
8
RAB18 overexpression exacerbates NAFLD by regulating PLIN2 and PPARΞ³ expression; increases lipid accumulation and liver injury
PMID: 39030773
9
RAB18 inhibits lipophagy and regulates cuproptosis in hepatic stellate cells through phase separation and mitochondrial-associated membrane formation
PMID: 40213908
Disease Associationsβ“˜21
Micro syndromeOpen Targets
0.82Strong
Warburg micro syndromeOpen Targets
0.59Moderate
neurodegenerative diseaseOpen Targets
0.50Moderate
cerebral atherosclerosisOpen Targets
0.30Weak
malunion fractureOpen Targets
0.28Weak
adolescent idiopathic scoliosisOpen Targets
0.27Weak
genetic disorderOpen Targets
0.19Weak
spinal cord injuryOpen Targets
0.17Weak
acquired thrombocytopeniaOpen Targets
0.16Weak
skull disorderOpen Targets
0.16Weak
Abnormality of the skeletal systemOpen Targets
0.16Weak
renal carcinomaOpen Targets
0.15Weak
spinal stenosisOpen Targets
0.15Weak
Abnormal mastoid morphologyOpen Targets
0.14Weak
middle ear disorderOpen Targets
0.14Weak
vertebral disorderOpen Targets
0.14Weak
vertebral joint diseaseOpen Targets
0.14Weak
vertebral column disorderOpen Targets
0.13Weak
Back painOpen Targets
0.13Weak
non-suppurative otitis mediaOpen Targets
0.13Weak
Warburg micro syndrome 3UniProt
Pathogenic Variants9
NM_021252.5(RAB18):c.125-23A>GLikely pathogenic
Warburg micro syndrome 3
β˜…β˜†β˜†β˜†2025
NM_021252.5(RAB18):c.276_277del (p.Asp94fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 94
NM_021252.5(RAB18):c.460del (p.Thr154fs)Likely pathogenic
Warburg micro syndrome 3
β˜…β˜†β˜†β˜†2021β†’ Residue 154
NM_021252.5(RAB18):c.272C>T (p.Thr91Ile)Likely pathogenic
Warburg micro syndrome 3
β˜…β˜†β˜†β˜†2021β†’ Residue 91
NM_021252.5(RAB18):c.549del (p.Gly184fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2020β†’ Residue 184
NM_021252.5(RAB18):c.619T>C (p.Ter207Gln)Pathogenic
Warburg micro syndrome 3
β˜…β˜†β˜†β˜†β†’ Residue 207
NM_021252.5(RAB18):c.284C>G (p.Thr95Arg)Pathogenic
Warburg micro syndrome 3
β˜†β˜†β˜†β˜†2013β†’ Residue 95
NM_021252.5(RAB18):c.274AGA[1] (p.Arg93del)Pathogenic
Warburg micro syndrome 3
β˜†β˜†β˜†β˜†2011β†’ Residue 93
NM_021252.5(RAB18):c.71T>A (p.Leu24Gln)Pathogenic
Warburg micro syndrome 3
β˜†β˜†β˜†β˜†2011β†’ Residue 24
View on ClinVar β†—
Related Genes
STX18Protein interaction100%RINT1Protein interaction100%ZW10Protein interaction88%RAB3GAP2Protein interaction82%TBC1D20Protein interaction79%GDI1Protein interaction75%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
86%
Heart
76%
Liver
39%
Ovary
32%
Lung
29%
Gene Interaction Network
Click a node to explore
RAB18STX18RINT1ZW10RAB3GAP2TBC1D20GDI1
PROTEIN STRUCTURE
Preparing viewer…
PDB1X3S Β· 1.32 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.54Moderately Constrained
pLIβ“˜
0.95Intolerant
Observed/Expected LoF0.27 [0.15–0.54]
RankingsWhere RAB18 stands among ~20K protein-coding genes
  • #3,606of 20,598
    Most Researched130 Β· top quartile
  • #2,932of 5,498
    Most Pathogenic Variants9
  • #3,379of 17,882
    Most Constrained (LOEUF)0.54 Β· top quartile
Genes detectedRAB18
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Rab18: new insights into the function of an essential protein.
PMID: 30830238
Cell Mol Life Sci Β· 2019
1.00
2
Lipid droplet biogenesis.
PMID: 31075519
Curr Opin Cell Biol Β· 2019
0.90
3
The role of NSP6 in the biogenesis of the SARS-CoV-2 replication organelle.
PMID: 35551511
Nature Β· 2022
0.80
4
Comparative proximity biotinylation implicates the small GTPase RAB18 in sterol mobilization and biosynthesis.
PMID: 37774976
J Biol Chem Β· 2023
0.70
5
Diallyl Trisulfide From Garlic Regulates RAB18 Phase Separation to Inhibit Lipophagy and Induce Cuproptosis in Hepatic Stellate Cells for Antifibrotic Effects.
PMID: 40213908
Adv Sci (Weinh) Β· 2025
0.60