RAB18

Chr 10AR

RAB18, member RAS oncogene family

Also known as: RAB18LI1, WARBM3

NCBI Gene: 22931ENSG00000099246UniProt: Q9NP72

The protein encoded by this gene is a member of a family of Ras-related small GTPases that regulate membrane trafficking in organelles and transport vesicles. Knockdown studies is zebrafish suggest that this protein may have a role in eye and brain development. Mutations in this gene are associated with Warburg micro syndrome type 3. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2012]

Primary Disease Associations & Inheritance

Warburg micro syndrome 3MIM #614222
AR
232
ClinVar variants
23
Pathogenic / LP
0.91
pLI score· haploinsufficient
0
Active trials
Clinical Summary— RAB18
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.91). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
23 Pathogenic / Likely Pathogenic· 112 VUS of 232 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.39LOEUF
pLI 0.910
Z-score 2.96
OE 0.08 (0.03–0.39)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.39Z-score
OE missense 0.63 (0.51–0.77)
68 obs / 108.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.08 (0.03–0.39)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.63 (0.51–0.77)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.06
0≤1.21.6
LoF obs/exp: 1 / 12.2Missense obs/exp: 68 / 108.8Syn Z: -0.30

ClinVar Variant Classifications

232 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic5
VUS112
Likely Benign39
Benign38
Conflicting4
18
Pathogenic
5
Likely Pathogenic
112
VUS
39
Likely Benign
38
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
2
14
0
18
Likely Pathogenic
2
1
2
0
5
VUS
3
34
74
1
112
Likely Benign
0
3
23
13
39
Benign
0
1
37
0
38
Conflicting
—4
Total74115014216

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

RAB18 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

RAB18-related Warburg micro syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Warburg micro syndrome 3

MIM #614222

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Diallyl Trisulfide From Garlic Regulates RAB18 Phase Separation to Inhibit Lipophagy and Induce Cuproptosis in Hepatic Stellate Cells for Antifibrotic Effects.
Tian H et al.·Adv Sci (Weinh)
2025
2'3'-cGAMP interactome identifies 2'3'-cGAMP/Rab18/FosB signaling in cell migration control independent of innate immunity.
Deng Y et al.·Sci Adv
2024
Rab18 Drift in Lipid Droplet and Endoplasmic Reticulum Interactions of Adipocytes under Obesogenic Conditions.
López-Alcalá J et al.·Int J Mol Sci
2023
The Warburg Micro Syndrome-associated Rab3GAP-Rab18 module promotes autolysosome maturation through the Vps34 Complex I.
Takáts S et al.·FEBS J
2021
RAB18, a protein associated with Warburg Micro syndrome, controls neuronal migration in the developing cerebral cortex.
Wu Q et al.·Mol Brain
2016
The association of RAB18 gene polymorphism (rs3765133) with cerebellar volume in healthy adults.
Cheng CY et al.·Cerebellum
2014
Rab18 Collaborates with Rab7 to Modulate Lysosomal and Autophagy Activities in the Nervous System: an Overlapping Mechanism for Warburg Micro Syndrome and Charcot-Marie-Tooth Neuropathy Type 2B.
Nian FS et al.·Mol Neurobiol
2019Functional
The Long Noncoding RNA ΒFaar Promotes White Adipose Tissue Browning and Prevents Diet-Induced Obesity.
Yang Y et al.·Adv Sci (Weinh)
2025
Mutation spectrum in RAB3GAP1, RAB3GAP2, and RAB18 and genotype-phenotype correlations in warburg micro syndrome and Martsolf syndrome.
Handley MT et al.·Hum Mutat
2013
Loss-of-function mutations in RAB18 cause Warburg micro syndrome.
Bem D et al.·Am J Hum Genet
2011
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools