ARL5B

Chr 10

ARF like GTPase 5B

Also known as: ARL8

NCBI Gene: 221079 ENSG00000165997 UniProt: Q96KC2 OMIM: 608909

ARL5B encodes a regulatory GTPase that binds and exchanges GTP and GDP, belonging to the ADP-ribosylation factor-like protein family within the RAS superfamily. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy, characterized by severe intellectual disability, seizures, and brain abnormalities. The gene shows tolerance to loss-of-function variants in the general population.

OMIM ResearchSummary from RefSeq, UniProt

ARL5B (ARL8) belongs to a family of proteins that are structurally similar to ADP-ribosylation factors (ARFs; see MIM 103180). ARLs and ARFs are part of the RAS superfamily of regulatory GTPases.[supplied by OMIM, Nov 2010]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

—

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

gnomad: Error: gnomAD API error: 400

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in ARL5B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 1,000

178 rare PASS variants

Rare truncating (LoF)

1 in 26,000

22 rare PASS variants

Rare synonymous (reference)

1 in 1,000

94 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ARL5B. 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 1,100	1 in 33,000
South Asian	~43k	1 in 430	≈ 1 in 11,000
Remaining (unassigned)	~30k	1 in 2,000	≈ 1 in 30,000
European (Finnish)	~27k	1 in 2,200	≈ 1 in 13,000
Admixed American	~22k	1 in 450	none seen
African / African American	~21k	1 in 900	none seen
East Asian	~20k	1 in 670	≈ 1 in 6,600
Ashkenazi Jewish	~13k	none seen	≈ 1 in 13,000
Middle Eastern	~2,884	≈ 1 in 1,400	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.