RAB30

Chr 11

RAB30, member RAS oncogene family

NCBI Gene: 27314ENSG00000137502UniProt: Q15771OMIM: 605693

RAB30 encodes a small GTPase that regulates intracellular membrane trafficking and maintains Golgi apparatus structural integrity. Mutations cause autosomal recessive developmental delay with seizures and microcephaly, typically presenting in infancy. This gene is highly constrained against loss-of-function variants, indicating intolerance to protein-disrupting mutations.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.38
Clinical Summary— RAB30
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.92). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
15 unique Pathogenic / Likely Pathogenic· 19 VUS of 41 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.38LOEUF
pLI 0.921
Z-score 3.02
OE 0.08 (0.03–0.38)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.94Z-score
OE missense 0.48 (0.39–0.61)
54 obs / 111.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.08 (0.03–0.38)
0≤0.351.4
Missense OE0.48 (0.39–0.61)
0≤0.61.4
Synonymous OE0.86
0≤1.21.6
LoF obs/exp: 1 / 12.5Missense obs/exp: 54 / 111.6Syn Z: 0.69
DN
0.6744th %ile
GOF
0.7125th %ile
LOF
0.4135th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function, dominant-negative and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median
LOFLOEUF 0.38

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

41 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15
VUS19
15
Pathogenic
19
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
15
0
15
Likely Pathogenic
0
0
0
0
0
VUS
0
15
4
0
19
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total01519034

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

View in ClinVar →

Protein Context — Lollipop Plot

RAB30 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients