ARL8B
Chr 3ARF like GTPase 8B
Also known as: ARL10C, Gie1
ARL8B encodes a small GTPase that regulates lysosomal positioning, transport, and fusion, playing critical roles in immune cell cytotoxicity, antigen presentation, and synaptic function. Mutations cause autosomal recessive immunodeficiency with defective cytolytic granule exocytosis and impaired natural killer cell function. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.649), suggesting some tolerance to protein-truncating mutations.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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.
ClinVar Variant Classifications
111 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | — | — | — | — | 73 |
Likely Pathogenic | — | — | — | — | 5 |
VUS | — | — | — | — | 23 |
Likely Benign | — | — | — | — | 1 |
Benign | — | — | — | — | 0 |
| Total | — | 102 | |||
Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ARL8B · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools