ARRB1

Chr 11

arrestin beta 1

Also known as: ARB1, ARR1

NCBI Gene: 408ENSG00000137486UniProt: P49407

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]

68
ClinVar variants
8
Pathogenic / LP
0.99
pLI score· haploinsufficient
0
Active trials
Clinical Summary— ARRB1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 43 VUS of 68 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.08 (0.03–0.26)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.59 (0.52–0.68)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.90
0≤1.21.6
LoF obs/exp: 2 / 24.0Missense obs/exp: 157 / 264.9Syn Z: 0.83

ClinVar Variant Classifications

68 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
VUS43
Likely Benign3
8
Pathogenic
43
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
0
0
0
0
0
VUS
0
41
2
0
43
Likely Benign
0
2
0
1
3
Benign
0
0
0
0
0
Total04310154

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ARRB1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
ARRESTIN, BETA, 1; ARRB1
MIM #107940 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Lianweng formula restores intestinal barrier function in ulcerative colitis through the β-arrestin 1/NF-κB signaling axis.
Lv J et al.·Phytomedicine
2025
Pharmacogenomics of GLP-1 receptor agonists: a genome-wide analysis of observational data and large randomised controlled trials.
Dawed AY et al.·Lancet Diabetes Endocrinol
2023
The extracellular matrix protein type I collagen and fibronectin are regulated by β-arrestin-1/endothelin axis in human ovarian fibroblasts.
Masi I et al.·J Exp Clin Cancer Res
2025
ARRB1-Promoted NOTCH1 Degradation Is Suppressed by OncomiR miR-223 in T-cell Acute Lymphoblastic Leukemia.
Shu Y et al.·Cancer Res
2020
A Tiered Approach to Exome Sequencing Analysis in Early-Onset Primary Ovarian Insufficiency.
McGlacken-Byrne SM et al.·J Clin Endocrinol Metab
2025
Mechanisms and Opportunities of the Arrestin Beta Signaling Pathway in Liver Diseases.
Zhou W et al.·DNA Cell Biol
2025Review
Tobacco use is associated with low peripheral beta-arrestin 1 levels in major depression: A preliminary report.
Mesdom P et al.·Drug Alcohol Depend
2022
EHMT2 Suppresses ARRB1 Transcription and Activates the Hedgehog Signaling to Promote Malignant Phenotype and Stem Cell Property in Oral Squamous Cell Carcinoma.
Niu L et al.·Mol Biotechnol
2025
Transcriptome-Wide Analysis and Experimental Validation from FFPE Tissue Identifies Stage-Specific Gene Expression Profiles Differentiating Adenoma, Carcinoma In-Situ and Adenocarcinoma in Colorectal Cancer Progression.
Alhosani F et al.·Int J Mol Sci
2025
β-Arrestins Regulate Stem Cell-Like Phenotype and Response to Chemotherapy in Bladder Cancer.
Kallifatidis G et al.·Mol Cancer Ther
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Intercellular transfer of circ_0017636 via exosomal vehicles overcomes glioblastoma chemoresistance through ARRB1-mediated signaling restoration.
Li Q et al.·Cell Signal
2026
The role and mechanism of ARRB1 in simulated space radiation and microgravity-induced lung carcinogenesis.
Xu Y et al.·NPJ Microgravity
2025🔓 Open AccessFunctional
Integrating Pharmacogenomic Insights in GLP-1 Receptor Agonist Therapy: Direct GLP1R and ARRB1 Variants and Indirect CYP2D6 Influences in Personalized Obesity Management.
Jayathilaka NS et al.·Clin Pharmacol Drug Dev
2025
Armillariella tabescens polysaccharides alleviate ER stress in 5-FU-induced intestinal epithelial injury and mucositis via ARRB1 modulation.
Gui Z et al.·Am J Physiol Gastrointest Liver Physiol
2025
P300-Mediated ARRB1 Lactylation Promotes Mitochondrial Dysfunction and Neuronal Apoptosis in Subarachnoid Hemorrhage Via Upregulating S100A9.
Mi K et al.·Neurochem Res
2025
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools