RAB1B

Chr 11

RAB1B, member RAS oncogene family

NCBI Gene: 81876 ENSG00000174903 UniProt: Q9H0U4 OMIM: 612565

RAB1B encodes a small GTPase that regulates vesicular transport between the endoplasmic reticulum and Golgi apparatus and plays a role in autophagy initiation. Mutations cause autosomal recessive intellectual disability with seizures and brain malformations, typically presenting in infancy or early childhood. This gene is highly constrained against loss-of-function variants, indicating its critical importance for normal cellular function.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

Members of the RAB protein family, such as RAB1B, are low molecular mass monomeric GTPases localized on the cytoplasmic surfaces of distinct membrane-bound organelles. RAB1B functions in the early secretory pathway and is essential for vesicle transport between the endoplasmic reticulum (ER) and Golgi (Chen et al., 1997 [PubMed 9030196]; Alvarez et al., 2003 [PubMed 12802079]).[supplied by OMIM, Jan 2009]

GeneReviews OMIM 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

0.42

LOEUF

Mechanism· predicted

📖

GeneReview available — RAB1B

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.42LOEUF

pLI 0.884

Z-score 2.86

OE 0.09 (0.03–0.42)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.74Z-score

OE missense 0.57 (0.47–0.69)

72 obs / 127.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.09 (0.03–0.42)

0≤0.351.4

Missense OE?0.57 (0.47–0.69)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 1 / 11.4Missense obs/exp: 72 / 127.1Syn Z: 0.28

Background carrier burden — how many people carry a rare variant somewhere in RAB1B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 760

166 rare PASS variants

Rare truncating (LoF)

1 in 27,000

15 rare PASS variants

Rare synonymous (reference)

1 in 300

105 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RAB1B. 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 820	1 in 28,000
South Asian	~43k	1 in 830	≈ 1 in 21,000
Remaining (unassigned)	~30k	1 in 940	none seen
European (Finnish)	~27k	1 in 1,100	none seen
Admixed American	~22k	1 in 380	none seen
African / African American	~21k	1 in 430	none seen
East Asian	~20k	1 in 330	≈ 1 in 6,600
Ashkenazi Jewish	~13k	none seen	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 570	≈ 1 in 2,900

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 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓