ARRB2
Chr 17arrestin beta 2
Also known as: ARB2, ARR2, BARR2
Arrestin beta 2 regulates G-protein coupled receptor signaling by mediating receptor desensitization, internalization, and serves as a signaling scaffold for MAPK and other pathways in the central nervous system and peripheral tissues. Mutations cause neurodevelopmental disorder with epilepsy, cataracts, and feeding difficulties, inherited in an autosomal recessive pattern. The gene shows significant constraint against loss-of-function variants (LOEUF 0.444), indicating intolerance to complete protein loss.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function, gain-of-function and dominant-negative). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). 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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
105 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 21 | 0 | 21 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 43 | 9 | 0 | 52 |
Likely Benign | 0 | 2 | 1 | 0 | 3 |
Benign | 0 | 0 | 0 | 2 | 2 |
| Total | 0 | 45 | 32 | 2 | 79 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ARRB2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
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