ARRB1

Chr 11

arrestin beta 1

Also known as: ARB1, ARR1

NCBI Gene: 408 ENSG00000137486 UniProt: P49407 OMIM: 107940

ARRB1 encodes arrestin beta-1, which regulates G-protein coupled receptor signaling by mediating receptor desensitization, internalization, and activation of downstream signaling pathways including MAPK and AKT. Mutations cause autosomal dominant Bardet-Biedl syndrome with features including retinal dystrophy, obesity, polydactyly, and intellectual disability. The gene is highly constrained against loss-of-function variants (pLI 0.99), indicating that haploinsufficiency is likely not tolerated.

OMIM ResearchSummary from RefSeq, UniProt

Members of arrestin/beta-arrestin protein family are thought to participate in agonist-mediated desensitization of G-protein-coupled receptors and cause specific dampening of cellular responses to stimuli such as hormones, neurotransmitters, or sensory signals. Arrestin beta 1 is a cytosolic protein and acts as a cofactor in the beta-adrenergic receptor kinase (BARK) mediated desensitization of beta-adrenergic receptors. Besides the central nervous system, it is expressed at high levels in peripheral blood leukocytes, and thus the BARK/beta-arrestin system is believed to play a major role in regulating receptor-mediated immune functions. Alternatively spliced transcripts encoding different isoforms of arrestin beta 1 have been described. [provided by RefSeq, Jan 2011]

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

0.26

LOEUF· LoF intol.

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.26LOEUF

pLI 0.994

Z-score 4.16

OE 0.08 (0.03–0.26)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.36Z-score

OE missense 0.59 (0.52–0.68)

157 obs / 264.9 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.08 (0.03–0.26)

0≤0.351.4

Missense OE?0.59 (0.52–0.68)

0≤0.61.4

Synonymous OE?0.90

0≤1.21.6

LoF obs/exp: 2 / 24.0Missense obs/exp: 157 / 264.9Syn Z: 0.83

Background carrier burden — how many people carry a rare variant somewhere in ARRB1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

460 rare PASS variants

Rare truncating (LoF)

1 in 5,800

43 rare PASS variants

Rare synonymous (reference)

1 in 120

214 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ARRB1. 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 130	1 in 5,700
South Asian	~43k	1 in 220	≈ 1 in 14,000
Remaining (unassigned)	~30k	1 in 130	≈ 1 in 15,000
European (Finnish)	~27k	1 in 280	1 in 3,800
Admixed American	~22k	1 in 170	none seen
African / African American	~21k	1 in 130	≈ 1 in 4,500
East Asian	~20k	1 in 160	≈ 1 in 5,700
Ashkenazi Jewish	~13k	1 in 1,000	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 170	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.

Exome coverage (gnomAD): 14 of 16 coding exons well covered in gnomAD exomes; exons 1, 15 marginal. Genomes: all 16.? see exons ↓