RAB18

Chr 10AR

RAB18, member RAS oncogene family

Also known as: RAB18LI1, WARBM3

RAB18 encodes a small GTPase that regulates intracellular membrane trafficking, maintains endoplasmic reticulum structure, and is required for endoplasmic reticulum-lipid droplet contacts. Mutations cause Warburg micro syndrome type 3, an autosomal recessive disorder affecting eye and brain development. The gene is highly constrained against loss-of-function variants (pLI 0.91, LOEUF 0.39), consistent with its essential role in neurological development.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.391 OMIM phenotype
Clinical SummaryRAB18
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Gene-Disease Validity (ClinGen)
Warburg micro syndrome · ARModerate

Moderate evidence — consider for supplementary testing

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.
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ClinVar Variants
23 unique Pathogenic / Likely Pathogenic· 112 VUS of 232 total submissions
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GeneReview available — RAB18
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.39LOEUF
pLI 0.910
Z-score 2.96
OE 0.08 (0.030.39)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.39Z-score
OE missense 0.63 (0.510.77)
68 obs / 108.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.08 (0.030.39)
00.351.4
Missense OE0.63 (0.510.77)
00.61.4
Synonymous OE1.06
01.21.6
LoF obs/exp: 1 / 12.2Missense obs/exp: 68 / 108.8Syn Z: -0.30
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveRAB18-related Warburg micro syndromeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6260th %ile
GOF
0.6931th %ile
LOF
0.4825th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

232 submitted variants in 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
3
13
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
Total74214914216

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →