ARRB2

Chr 17

arrestin beta 2

Also known as: ARB2, ARR2, BARR2

NCBI Gene: 409ENSG00000141480UniProt: P32121

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 2, like arrestin beta 1, was shown to inhibit beta-adrenergic receptor function in vitro. It is expressed at high levels in the central nervous system and may play a role in the regulation of synaptic receptors. Besides the brain, a cDNA for arrestin beta 2 was isolated from thyroid gland, and thus it may also be involved in hormone-specific desensitization of TSH receptors. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2012]

78
ClinVar variants
22
Pathogenic / LP
0.51
pLI score
0
Active trials
Clinical Summary— ARRB2
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.51) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
22 Pathogenic / Likely Pathogenic· 51 VUS of 78 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.44LOEUF
pLI 0.507
Z-score 3.56
OE 0.21 (0.11–0.44)
Moderately constrained

More LoF-intolerant than ~75% 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.
2.38Z-score
OE missense 0.58 (0.51–0.67)
150 obs / 257.7 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.0.21 (0.11–0.44)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.58 (0.51–0.67)
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.0.89
0≤1.21.6
LoF obs/exp: 5 / 23.7Missense obs/exp: 150 / 257.7Syn Z: 0.88

ClinVar Variant Classifications

78 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic1
VUS51
Likely Benign3
Benign2
21
Pathogenic
1
Likely Pathogenic
51
VUS
3
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
21
0
21
Likely Pathogenic
0
0
1
0
1
VUS
0
42
9
0
51
Likely Benign
0
2
1
0
3
Benign
0
0
0
2
2
Total04432278

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
ARRESTIN, BETA, 2; ARRB2
MIM #107941 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Dysregulated Smooth Muscle Cell BMPR2-ARRB2 Axis Causes Pulmonary Hypertension.
Wang L et al.·Circ Res
2023
PRL-mediated STAT5B/ARRB2 pathway promotes the progression of prostate cancer through the activation of MAPK signaling.
Yang T et al.·Cell Death Dis
2024
Association of polymorphisms in ARRB2 and clinical response to methadone for pain in advanced cancer.
Ozberk D et al.·Pharmacogenomics
2022
β-Arrestin 2 as a Prognostic Indicator and Immunomodulatory Factor in Multiple Myeloma.
Mathews P et al.·Cells
2025
A Common Variant of ARRB2 Promoter Region Associated with the Prognosis of Heart Failure.
Ren H et al.·Hum Hered
2023
Combining Single-Cell RNA Sequencing and Mendelian Randomization to Explore Novel Drug Targets for Parkinson's Disease.
Wu X et al.·Mol Neurobiol
2025
The Comprehensive Analysis of Hub Gene ARRB2 in Prostate Cancer.
Zhou B et al.·Dis Markers
2022
Comprehensive analyses for the coagulation and macrophage-related genes to reveal their joint roles in the prognosis and immunotherapy of lung adenocarcinoma patients.
Li Z et al.·Front Immunol
2023Cohort
REG3A promotes gemcitabine resistance in pancreatic cancer via the GPR54/ARRB2/ERK1/2 ligand-directed signaling pathway.
Liu J et al.·Biochem Pharmacol
2025
The human reticulocyte transcriptome.
Goh SH et al.·Physiol Genomics
2007
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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