RAB3IL1

Chr 11

RAB3A interacting protein like 1

Also known as: GRAB

NCBI Gene: 5866 ENSG00000167994 UniProt: Q8TBN0

The protein functions as a guanine nucleotide exchange factor that activates RAB3A and potentially RAB8A/RAB8B GTPases, which regulate synaptic vesicle exocytosis and other cellular trafficking processes. Mutations cause autosomal recessive Warburg micro syndrome, a severe neurodevelopmental disorder characterized by microcephaly, intellectual disability, congenital cataracts, microcornea, microphthalmia, and hypogonadism with onset in infancy.

ResearchSummary from RefSeq, UniProt

This gene encodes a guanine nucleotide exchange factor for the ras-related protein Rab3A. The encoded protein binds Rab3a and the inositol hexakisphosphate kinase InsP6K1. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 7. [provided by RefSeq, Nov 2012]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.78

LOEUF

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

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.78LOEUF

pLI 0.000

Z-score 2.30

OE 0.45 (0.27–0.78)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.48Z-score

OE missense 0.91 (0.81–1.02)

206 obs / 226.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.45 (0.27–0.78)

0≤0.351.4

Missense OE?0.91 (0.81–1.02)

0≤0.61.4

Synonymous OE?0.85

0≤1.21.6

LoF obs/exp: 9 / 20.1Missense obs/exp: 206 / 226.4Syn Z: 1.17

Background carrier burden — how many people carry a rare variant somewhere in RAB3IL1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 68

642 rare PASS variants

Rare truncating (LoF)

1 in 1,100

95 rare PASS variants

Rare synonymous (reference)

1 in 130

269 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RAB3IL1. 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 110	1 in 860
South Asian	~43k	1 in 70	1 in 750
Remaining (unassigned)	~30k	1 in 69	1 in 2,100
European (Finnish)	~27k	1 in 290	1 in 1,800
Admixed American	~22k	1 in 65	1 in 440
African / African American	~21k	1 in 53	1 in 1,500
East Asian	~20k	1 in 84	1 in 1,800
Ashkenazi Jewish	~13k	1 in 430	none seen
Middle Eastern	~2,884	1 in 94	≈ 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): 9 of 10 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 10.? see exons ↓