RAB18: A Key Regulator of Membrane Trafficking and Lipid Droplet Biology
Comprehensive genomic and functional analysis of RAB18, a member of the RAS oncogene family involved in vesicular transport and associated with Warburg Micro Syndrome.
Gene Information Card
| Symbol | RAB18 |
|---|---|
| Full Name | RAB18, member RAS oncogene family |
| Gene Type | protein-coding |
| Chromosomal Location | 10p12.1 |
| NCBI Gene ID | 22931 ncbi.nlm.nih.gov/gene/22931 |
| Ensembl ID | ENSG00000199292 |
| UniProt ID | Q9NP72 |
| OMIM ID | 602207 |
| HGNC ID | 9777 |
| Aliases | RAB18LI1, WARBM3 |
Description
RAB18 is a small GTPase belonging to the RAS oncogene family. It functions as a key regulator of intracellular membrane trafficking, particularly in the endocytic and recycling pathways. RAB18 is also critical for lipid droplet metabolism and is involved in the recruitment of lipid droplet-associated proteins. Mutations in RAB18 cause Warburg Micro Syndrome 3 (WARBM3), a neurodevelopmental disorder characterized by microcephaly, intellectual disability, and ocular abnormalities.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Warburg Micro Syndrome 3 (WARBM3) | Loss-of-function mutations in RAB18 disrupt membrane trafficking and lipid droplet homeostasis, leading to impaired neuronal development and microcephaly. | ClinVar, OMIM |
| Microcephaly | RAB18 deficiency affects neural progenitor cell proliferation and migration, contributing to reduced brain size. | OMIM, PubMed |
| Intellectual Disability | Aberrant RAB18-mediated trafficking impairs synaptic function and neuronal connectivity. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Adipose Tissue | 8.3 | Low |
| Liver | 6.1 | Low |
| Testis | 15.2 | Medium |
| Kidney | 5.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 10.1 | Embryonic kidney cells |
| HeLa | 7.8 | Cervical cancer cells |
| SH-SY5Y | 14.3 | Neuroblastoma cells |
| HepG2 | 6.5 | Hepatocellular carcinoma cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.245G>A (p.Arg82Gln) | Missense | Rare | Loss of GTP binding and hydrolysis, impairing membrane localization. |
| c.1A>G (p.Met1Val) | Start loss | Rare | Complete loss of protein expression. |
| c.433C>T (p.Arg145*) | Nonsense | Rare | Premature truncation, loss of function. |
Mutation functional classification
Loss of Function (LOF)
Most RAB18 mutations associated with Warburg Micro Syndrome are loss-of-function, leading to reduced GTPase activity or protein instability.
Gain of Function (GOF)
No gain-of-function mutations have been reported for RAB18.
Dominant Negative (DN)
Some missense mutations (e.g., p.Arg82Gln) may act in a dominant-negative manner by sequestering guanine nucleotide exchange factors.
View complete mutation data：
Gene Ontology (GO)
| • GTP binding | • GTPase activity |
| • intracellular protein transport | • vesicle-mediated transport |
| • lipid droplet organization | • endosome to lysosome transport |
| • regulation of exocytosis |
Pathways
• Endocytosis
• Lipid droplet metabolism
• RAB18-mediated membrane trafficking
Protein Summary
RAB18 is a 206-amino-acid small GTPase that cycles between an active GTP-bound and inactive GDP-bound state. It localizes to the endoplasmic reticulum, lipid droplets, and endosomal membranes. Through interactions with effectors such as NRZ complex and TBC1D20, RAB18 regulates lipid droplet expansion, autophagic flux, and endocytic recycling. Its dysfunction is central to the pathogenesis of Warburg Micro Syndrome.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RAB18 Knockout HEK293 Cell Line | EDJ-KQ14975 | Human | 22931 | Details Get a Quote |
| RAB18 Knockout HCT 116 Cell Line | EDJ-KQ44205 | Human | 22931 | Details Get a Quote |
| RAB18 Knockout A-549 Cell Line | EDJ-KQ45466 | Human | 22931 | Details Get a Quote |
| RAB18 Knockout HeLa Cell Line | EDJ-KQ45468 | Human | 22931 | Details Get a Quote |
