ADRB2

Chr 5

adrenoceptor beta 2

Also known as: ADRB2R, ADRBR, ARB2, B2AR, BAR, BETA2AR

NCBI Gene: 154 ENSG00000169252 UniProt: P07550

This gene encodes beta-2-adrenergic receptor which is a member of the G protein-coupled receptor superfamily. This receptor is directly associated with one of its ultimate effectors, the class C L-type calcium channel Ca(V)1.2. This receptor-channel complex also contains a G protein, an adenylyl cyclase, cAMP-dependent kinase, and the counterbalancing phosphatase, PP2A. The assembly of the signaling complex provides a mechanism that ensures specific and rapid signaling by this G protein-coupled receptor. This receptor is also a transcription regulator of the alpha-synuclein gene, and together, both genes are believed to be associated with risk of Parkinson's Disease. This gene is intronless. Different polymorphic forms, point mutations, and/or downregulation of this gene are associated with nocturnal asthma, obesity, type 2 diabetes and cardiovascular disease. [provided by RefSeq, Oct 2019]

ClinVar variants

Pathogenic / LP

0.53

pLI score

Active trials

Clinical Summary— ADRB2

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.53) — some intolerance to loss-of-function variants.

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ClinVar Variants

11 Pathogenic / Likely Pathogenic· 14 VUS of 56 total submissions

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Clinical Trials

7 active or recruiting trials — potential therapeutic options may be available

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.

0.59LOEUF

pLI 0.525

Z-score 2.46

OE 0.19 (0.08–0.59)

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.

1.35Z-score

OE missense 0.75 (0.67–0.85)

180 obs / 238.5 exp

Tolerant

Mild missense constraint

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.0.19 (0.08–0.59)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.75 (0.67–0.85)

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.1.03

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	11	0	11
Likely Pathogenic	0	0	0	0
VUS	11	3	0	14
Likely Benign	1	1	6	8
Benign	3	13	7	23
Total	15	28	13	56

ADRB2

Population Genetics & Constraint

ClinVar Variant Classifications

Classification Summary

Curated Variants Distribution

Protein Context — Lollipop Plot

OMIM — Genotype-Phenotype Relationships

Gene Overview

ClinGen Curation

Disease Associations

External Resources

Variant Interpretation

Population Databases

Gene Resources