RAB30

Chr 11

RAB30, member RAS oncogene family

NCBI Gene: 27314 ENSG00000137502 UniProt: Q15771

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.

ResearchSummary from RefSeq, UniProt

Enables G protein activity. Involved in Golgi organization. Located in Golgi apparatus and vacuolar membrane. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.38

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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 OE?0.08 (0.03–0.38)

0≤0.351.4

Missense OE?0.48 (0.39–0.61)

0≤0.61.4

Synonymous OE?0.86

0≤1.21.6

LoF obs/exp: 1 / 12.5Missense obs/exp: 54 / 111.6Syn Z: 0.69

Background carrier burden — how many people carry a rare variant somewhere in RAB30?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 530

162 rare PASS variants

Rare truncating (LoF)

1 in 8,100

27 rare PASS variants

Rare synonymous (reference)

1 in 300

76 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RAB30. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 790	1 in 17,000
South Asian	~43k	1 in 600	≈ 1 in 11,000
Remaining (unassigned)	~30k	1 in 260	≈ 1 in 15,000
European (Finnish)	~27k	1 in 2,200	1 in 3,800
Admixed American	~22k	1 in 1,200	≈ 1 in 7,500
African / African American	~21k	1 in 790	1 in 1,600
East Asian	~20k	1 in 690	1 in 3,100
Ashkenazi Jewish	~13k	1 in 1,700	none seen
Middle Eastern	~2,884	1 in 360	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓