ADRB2

Summary

ADRB2 (adrenoceptor beta 2, HGNC:286) is a protein-coding gene on chromosome 5q32, encoding Beta-2 adrenergic receptor (P07550). G protein-coupled receptor for catecholamines that couples to both G(s) and G(i) proteins, activating bifurcated signaling pathways.

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.

Source: NCBI Gene 154 — RefSeq curated summary.

At a glance

• Gene–disease (curated): inherited susceptibility to asthma (Limited, GenCC)
• GWAS associations: 8
• Clinical variants (ClinVar): 47 total
• Regional missense constraint (gnomAD): 1 of 3 regions constrained (≈3% of expected missense variation)
• GTEx eGene: eQTL in 14 tissues, sQTL in 0 (q < 0.05)
• Drug target: yes — 52 curated mechanism-of-action drugs, 11 via a complex or family; 166 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
• Approved drugs (ChEMBL mechanism of action): 32 — Albuterol, Arformoterol Tartrate, Bitolterol Mesylate, +29 more
• Approved drugs acting on a complex or family including it: 11 — Carteolol Hydrochloride, Carvedilol, Dipivefrin Hydrochloride, +8 more (Adrenergic receptor beta; Adrenergic receptor)
• Pharmacogenomics (PharmGKB): 1 CPIC/DPWG dosing guideline (e.g. carvedilol;labetalol;nadolol;pindolol;propranolol;sotalol)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.90 (unconstrained)
• MANE Select transcript: NM_000024
• Interaction hub: 2,554 STRING partners (top 4% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:286
Approved symbol	ADRB2
Name	adrenoceptor beta 2
Location	5q32
Locus type	gene with protein product
Status	Approved
Aliases	ADRBR, BAR, B2AR, ARB2
Ensembl gene	ENSG00000169252
Ensembl biotype	protein_coding
OMIM	109690
Entrez	154

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

MANE Select: ENST00000305988

ENST00000305988

RefSeq mRNA: 1 — MANE Select: NM_000024 NM_000024

CCDS: CCDS4292

Canonical transcript exons

ENST00000305988 — 1 exons

Exon	Start	End
ENSE00001154479	148826611	148828623

Expression profiles

Bgee: expression breadth ubiquitous, 242 present calls, max score 94.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.9587 / max 1688.7395, expressed in 1252 samples.

Highest expression (Bgee): cartilage tissue, granulocyte, upper leg skin, gingival epithelium, cervix squamous epithelium.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ADRB2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 14 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

14 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Heart Atrial Appendage	eqtl	6.1e-11	+0.35	5:148740443:T:C
Cells EBV-transformed lymphocytes	eqtl	3.0e-08	-0.41	5:148826178:G:A
Cells Cultured fibroblasts	eqtl	4.3e-08	+0.23	5:149014071:T:C
Whole Blood	eqtl	5.1e-04	-0.14	5:148820990:G:A
Skin Not Sun Exposed Suprapubic	eqtl	8.1e-04	+0.13	5:148913123:T:C
Nerve Tibial	eqtl	9.0e-04	+0.54	5:148852647:C:T
Thyroid	eqtl	1.2e-03	+0.16	5:149036293:A:C
Adipose Subcutaneous	eqtl	1.2e-03	+0.12	5:148837993:C:T
Testis	eqtl	2.4e-03	+1.12	5:148820311:A:C
Brain Frontal Cortex BA9	eqtl	1.1e-02	-0.65	5:148933039:G:C
Artery Tibial	eqtl	1.7e-02	-0.17	5:149138758:AC:A
Esophagus Muscularis	eqtl	2.2e-02	+0.14	5:148948046:T:C
Brain Caudate basal ganglia	eqtl	2.5e-02	-0.62	5:148080541:G:T
Artery Aorta	eqtl	3.1e-02	+0.20	5:149036293:A:C

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
59320	17.5788	1250
59322	0.1440	18
59323	0.1372	32
59321	0.0987	40

Top tissues by expression

showing 100 of 282 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cartilage tissue	UBERON:0002418	94.21	gold quality
granulocyte	CL:0000094	94.18	gold quality
upper leg skin	UBERON:0004262	93.09	gold quality
gingival epithelium	UBERON:0001949	91.02	gold quality
cervix squamous epithelium	UBERON:0006922	90.31	gold quality
gingiva	UBERON:0001828	90.09	gold quality
squamous epithelium	UBERON:0006914	90.01	gold quality
palpebral conjunctiva	UBERON:0001812	89.84	gold quality
esophagus squamous epithelium	UBERON:0006920	89.01	gold quality
skin of abdomen	UBERON:0001416	88.82	gold quality
lower lobe of lung	UBERON:0008949	88.80	gold quality
epithelium of esophagus	UBERON:0001976	87.35	gold quality
skin of leg	UBERON:0001511	87.23	gold quality
omental fat pad	UBERON:0010414	86.80	gold quality
peritoneum	UBERON:0002358	86.71	gold quality
adipose tissue of abdominal region	UBERON:0007808	86.61	gold quality
right lung	UBERON:0002167	86.57	gold quality
zone of skin	UBERON:0000014	86.25	gold quality
subcutaneous adipose tissue	UBERON:0002190	85.86	gold quality
cervix epithelium	UBERON:0004801	85.40	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	85.39	gold quality
biceps brachii	UBERON:0001507	85.33	gold quality
adipose tissue	UBERON:0001013	85.17	gold quality
upper lobe of left lung	UBERON:0008952	85.11	gold quality
upper lobe of lung	UBERON:0008948	85.07	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	84.86	gold quality
connective tissue	UBERON:0002384	84.79	gold quality
leukocyte	CL:0000738	83.82	gold quality
lung	UBERON:0002048	83.39	gold quality
blood	UBERON:0000178	83.02	gold quality
monocyte	CL:0000576	82.97	gold quality
mononuclear cell	CL:0000842	82.94	gold quality
bone marrow	UBERON:0002371	82.54	gold quality
tongue squamous epithelium	UBERON:0006919	81.92	silver quality
nipple	UBERON:0002030	81.86	gold quality
skeletal muscle tissue	UBERON:0001134	81.77	gold quality
tibialis anterior	UBERON:0001385	81.59	gold quality
deltoid	UBERON:0001476	81.26	silver quality
vagina	UBERON:0000996	81.10	gold quality
hindlimb stylopod muscle	UBERON:0004252	80.96	gold quality
muscle tissue	UBERON:0002385	80.89	gold quality
skin of hip	UBERON:0001554	80.64	gold quality
esophagus mucosa	UBERON:0002469	80.64	gold quality
oviduct epithelium	UBERON:0004804	80.61	gold quality
oral cavity	UBERON:0000167	80.56	gold quality
muscle of leg	UBERON:0001383	80.30	gold quality
muscle organ	UBERON:0001630	79.99	gold quality
bone marrow cell	CL:0002092	79.90	gold quality
penis	UBERON:0000989	79.85	gold quality
gastrocnemius	UBERON:0001388	79.82	gold quality
calcaneal tendon	UBERON:0003701	79.42	gold quality
right lobe of liver	UBERON:0001114	79.34	gold quality
esophagus	UBERON:0001043	77.88	gold quality
lower esophagus mucosa	UBERON:0035834	77.30	gold quality
spleen	UBERON:0002106	77.00	gold quality
vastus lateralis	UBERON:0001379	76.97	silver quality
visceral pleura	UBERON:0002401	76.96	gold quality
mouth mucosa	UBERON:0003729	76.96	gold quality
trabecular bone tissue	UBERON:0002483	76.67	gold quality
heart left ventricle	UBERON:0002084	76.63	gold quality
right atrium auricular region	UBERON:0006631	76.60	gold quality
quadriceps femoris	UBERON:0001377	76.52	silver quality
cardiac atrium	UBERON:0002081	76.43	gold quality
cardiac ventricle	UBERON:0002082	76.31	gold quality
uterine cervix	UBERON:0000002	76.25	gold quality
pharyngeal mucosa	UBERON:0000355	76.20	gold quality
thoracic mammary gland	UBERON:0005200	76.15	gold quality
mammary gland	UBERON:0001911	76.09	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	75.87	gold quality
liver	UBERON:0002107	75.80	gold quality
heart	UBERON:0000948	75.41	gold quality
minor salivary gland	UBERON:0001830	75.38	gold quality
tendon	UBERON:0000043	75.03	gold quality
lower esophagus muscularis layer	UBERON:0035833	74.95	gold quality
lower esophagus	UBERON:0013473	74.93	gold quality
ectocervix	UBERON:0012249	74.91	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	74.90	gold quality
saliva-secreting gland	UBERON:0001044	74.51	gold quality
mucosa of stomach	UBERON:0001199	74.40	gold quality
pleura	UBERON:0000977	74.37	gold quality
layer of synovial tissue	UBERON:0007616	74.33	gold quality
buccal mucosa cell	CL:0002336	74.28	gold quality
ventricular zone	UBERON:0003053	74.20	gold quality
tibia	UBERON:0000979	74.13	gold quality
fallopian tube	UBERON:0003889	74.13	gold quality
prostate gland	UBERON:0002367	73.82	gold quality
nasal cavity mucosa	UBERON:0001826	73.81	gold quality
left ventricle myocardium	UBERON:0006566	73.67	gold quality
apex of heart	UBERON:0002098	73.50	gold quality
tonsil	UBERON:0002372	73.35	gold quality
urethra	UBERON:0000057	73.06	gold quality
mammalian vulva	UBERON:0000997	72.82	gold quality
parietal pleura	UBERON:0002400	72.82	gold quality
gall bladder	UBERON:0002110	72.77	gold quality
nasal cavity epithelium	UBERON:0005384	72.73	silver quality
body of tongue	UBERON:0011876	72.55	silver quality
tibial nerve	UBERON:0001323	71.76	gold quality
right coronary artery	UBERON:0001625	71.61	gold quality
endothelial cell	CL:0000115	71.52	silver quality
body of stomach	UBERON:0001161	71.36	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Lung	tissue	18.4
Adipose tissue	tissue	18.3
Esophagus	tissue	14.2
Liver	tissue	13.3
Cervix	tissue	12.7
Vagina	tissue	12.2
Bone marrow	tissue	11.8
Cerebellum	tissue	11.1
Hippocampus	tissue	11.0
Skeletal muscle	tissue	10.9
Breast	tissue	9.9
Placenta	tissue	9.3
Locus coeruleus	tissue	8.6
Prostate	tissue	8.5
Tongue	tissue	8.1
Spleen	tissue	7.4
Stomach 1	tissue	7.1
Skin 1	tissue	6.4
Urinary bladder	tissue	6.4
Heart muscle	tissue	6.3
Nucleus accumbens	tissue	5.6
Tonsil	tissue	5.6
Postcentral gyrus	tissue	4.9
Salivary gland	tissue	3.9
Fallopian tube	tissue	3.9
Lymph node	tissue	3.8
Choroid plexus	tissue	3.7
Substantia nigra	tissue	3.6
Smooth muscle	tissue	3.5
Gallbladder	tissue	3.5
Spinal cord	tissue	3.4
Medulla oblongata	tissue	3.3
Corpus callosum	tissue	3.3
Putamen	tissue	3.1
Periaqueductal gray	tissue	3.1
Septum	tissue	3.1
Cerebral cortex	tissue	3.0
Basal ganglia	tissue	3.0
Amygdala	tissue	3.0
Hypothalamus	tissue	3.0
Appendix	tissue	3.0
Insular cortex	tissue	3.0
Pons	tissue	2.8
Ventral forebrain	tissue	2.8
Rectum	tissue	2.7
Midbrain	tissue	2.7
Thalamus	tissue	2.6
Hippocampal formation	tissue	2.6
Prefrontal cortex	tissue	2.5
Superior colliculi	tissue	2.5
Thymus	tissue	2.5
Entorhinal cortex	tissue	2.5
Retrosplenial and cingulate cortex	tissue	2.5
Retrosplenial cortex	tissue	2.5
Temporal cortex	tissue	2.4
Motor cortex	tissue	2.3
Occipital cortex	tissue	2.3
Colon	tissue	2.2
Endometrium 1	tissue	2.2
Olfactory bulb	tissue	2.1

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Cerebellar white matter (15.4), Nucleus rhomboideus (14.8), Cervical spinal cord, ventral horn (13.2), Kolliker-Fuse nucleus (13.0), Lateral parabrachial nucleus (12.9).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, BCL3, CEBPA, EZH2, FOXC1, HIC1

miRNA regulators (miRDB)

Targeting ADRB2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 92 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4500	99.99	72.72	2367
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-4458	99.96	71.64	1650
HSA-LET-7D-5P	99.96	71.76	1632

Functional genomics

gnomAD constraint: pLI 0.00102, LOEUF 0.901, missense Z 2.01 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000305988 splits into 3 regions with different missense tolerance; 1 is missense-constrained (≈3% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
5:148,826,832–148,827,752	315 / 399.8	0.79	no
5:148,827,753–148,827,799	4 / 18.2	0.22	yes (p 8.6e-04)
5:148,827,800–148,828,070	106 / 109.2	0.97	no

Literature-anchored findings (GeneRIF, showing 40)

• the allelic frequency of beta2-adrenergic receptor gene mutation in codons 16 and 27 did not differ between obese subjects and non-obese (PMID:11718682)
• The distribution of the SNP genotype AA, GA and GG at position 1023 in the severe hypertension group was significantly different from that in normal group. (PMID:11798846)
• sequestration caused by Akt and insulin (PMID:11809767)
• The beta2-adrenoceptor (ADRB2) plays a pivotal role in signalling in relation to hypertension and obesity. Polymorphisms of the ADRB2 gene have been shown to be potentially related to essential hypertension and other non-cardiovascular disease phenotypes. (PMID:11821707)
• Regulation of beta2-adrenergic receptors on CD4 and CD8 positive lymphocytes by cytokines in vitro (PMID:11884023)
• 27Glu polymorphism of the beta2-adrenergic receptor gene interacts with physical activity influencing obesity risk among female subjects (PMID:12030897)
• the beta2-adrenergic receptor is associated with the propensity to gain weight from childhood to young adulthood in males (PMID:12080445)
• variation in asthma (review article) (PMID:12083965)
• beta1-adrenoceptor and beta2-adrenoceptor couple to Gs-proteins to activate adenylyl cyclase (PMID:12106601)
• role of heterodimerization with beta 1-adrenergic receptor regulates beta 2-adrenergic receptor internalization and ERK signaling efficacy (PMID:12140284)
• polymorphic in cystic fibrosis (PMID:12142723)
• polymorphic in cystic fibrosis (PMID:12142724)
• assessment of binding and activation properties of Cys mutants (PMID:12167654)
• linkage analysis of ADRB2 polymorphisms does not support the role of this gene as a major causative gene for the detected linkage of human chromosome 5 with hypertension (PMID:12215468)
• Results indicate that the proportion of homo- and heterodimers between the closely related beta(1)- and beta(2)-adrenergic receptors is determined by their relative levels of expression. (PMID:12244098)
• beta(2)AR activation of ERK1/2 does not require PKA phosphorylation of the beta(2)AR, receptor internalization or switching from activation of G(s) to G(i) but clearly requires activation of a Src family member that may be downstream of PKA. (PMID:12391272)
• identified the Zn2+ binding site responsible for the positive effect of Zn2+ ions on agonist binding to the 2AR (PMID:12409304)
• Data report a novel positioning of Src, mediating signals from insulin to phosphatidylinositol 3-kinase and to beta(2)-adrenergic receptor trafficking. (PMID:12429837)
• data demonstrate that homozygosity for Arg16, which in vitro is associated with decreased down-regulation of the beta(2)AR, protects from preterm delivery (PMID:12439523)
• Effects of Arg16 Gly polymorphism on forearm blood flow responses to isoproterenol dependent on differences in endothelial generation of nitric oxide. Regional blood flow responses to isoproterenol greater in Gly16 than in Arg16 homozygotes. (PMID:12527744)
• No evidence of excess allele sharing identity by descent in sib pairs, revealing a lack of linkage between 2q14-q23 or 5q32 (chromosome region harboring the gene. encoding beta 2 adrenergic receptor) and hypertension in our study sample. (PMID:12569260)
• The Glu27 allele of the beta2-adrenergic receptor was associated with a lower risk of incident coronary events in an elderly population (PMID:12682000)
• Polymorphisms not significantly different in NIDDM compared with normal values. (PMID:12716862)
• lipolytic catecholamine resistance of sc adipocytes in polycystic ovary syndrome is probably due to a combination of decreased amounts of beta(2)-adrenergic receptors, the regulatory II beta-component of protein kinase A, and hormone-sensitive lipase (PMID:12727985)
• b2-AR 27Glu polymorphism has a protective effect against metabolic disorders in obese families from southern Poland. (PMID:12824951)
• lipolysis and fat oxidation promoted by a peak oxygen consumption test appear to be blunted in polymorphic Glu27Glu beta2 adrenergic receptor obese females (PMID:12832031)
• agonist-induced desensitization of cardiac beta2ARs is more pronounced in wild type than Thr164Ile polymorphism subjects. (PMID:12869379)
• Females with polymorphism and higher carbohydrate intake had higher obesity risk. High carbohydrate intake was associated with higher insulin levels among women with Gln27Glu polymorphism. (PMID:12888635)
• The association of genetic polymorphisms of ADRB2 with blood pressure-related and obesity-related phenotypes. (PMID:12900437)
• findings show that signaling via the erythrocyte beta2-adrenergic receptor and heterotrimeric guanine nucleotide-binding protein (Galphas) regulated the entry of the human malaria parasite Plasmodium falciparum (PMID:14500986)
• the Arg(16) and Gln(27) variants of the beta(2)-adrenergic receptor gene contribute to metabolic syndrome susceptibility in men. (PMID:14557466)
• down-regulation of beta(2)-AR protein with labor may constitute a contributory mechanism by which uterine quiescence is removed at term. (PMID:14557486)
• Beta2-adrenergic receptor variants are associated with spirometric values and bronchodilator responsiveness, but different regions of the gene provide evidence for association with these phenotypes. (PMID:14610472)
• variation in the beta(2)AR gene is associated in the pathogenesis of asthma and acts as a disease modifier in nocturnal asthma (PMID:14657864)
• Arg16/Gly polymorphism is associated with differences in acute pressor responses to sympathoexcitation (PMID:14665698)
• Increased sensitivity to catecholamine-induced lipolysis of Gly allele promotes higher free fatty acids concentrations in portal system, which could enhance higher levels of fasting insulin. (PMID:14693408)
• Insulin and beta-adrenergic agonists stimulate a rapid phosphorylation and sequestration of the beta2-adrenergic receptors (beta2ARs). (PMID:14709719)
• the beta2-AR genotype, both independently and interacting with habitual PA levels, is significantly associated with a-vDO2 during exercise in postmenopausal women (PMID:14715679)
• internalization of beta(1)AR is both arrestin- and dynamin-dependent and follows the same clathrin-mediated endocytic pathway as beta(2)AR (PMID:14734649)
• 3D structure of human beta2 adrenergic receptor predicts ligand-binding sites for epinephrine and norepinephrine. (PMID:14981238)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	adrb2b	ENSDARG00000054510
danio_rerio	adrb2a	ENSDARG00000088124
mus_musculus	Adrb2	ENSMUSG00000045730
rattus_norvegicus	Adrb2	ENSRNOG00000019217
caenorhabditis_elegans	ser-5	WBGENE00008890

Paralogs (18): ADRB1 (ENSG00000043591), ADRA1A (ENSG00000120907), DRD2 (ENSG00000149295), ADRA2A (ENSG00000150594), GPR101 (ENSG00000165370), ADRA1B (ENSG00000170214), ADRA1D (ENSG00000171873), OR5T3 (ENSG00000172489), OR56A1 (ENSG00000180934), OR5T1 (ENSG00000181698), OR5T2 (ENSG00000181718), OR56A4 (ENSG00000183389), ADRA2C (ENSG00000184160), OR56A3 (ENSG00000184478), OR13F1 (ENSG00000186881), OR56A5 (ENSG00000188691), ADRB3 (ENSG00000188778), ADRA2B (ENSG00000274286)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:87938) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 36 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal liver morphology	1
small liver	1
abnormal spleen morphology	1
enlarged spleen	1
decreased body weight	1
abnormal retina morphology	1
abnormal osteoclast physiology	1
abnormal heart rate	1
abnormal skin morphology	1
increased circulating insulin level	1
abnormal eye morphology	1
abnormal kidney morphology	1
increased systemic arterial blood pressure	1
enlarged kidney	1
abnormal insulin secretion	1
abnormal auditory brainstem response	1
decreased mean systemic arterial blood pressure	1
abnormal bone resorption	1
abnormal osteoclast morphology	1
decreased bone resorption	1
abnormal osteoblast physiology	1
abnormal retina ganglion layer morphology	1
abnormal Muller cell morphology	1
decreased circulating glucose level	1
increased bone mass	1

+11 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pan troglodytes	P60021	100.0%	Diamond
Pongo pygmaeus	P61752	100.0%	Diamond
Gorilla gorilla gorilla	Q76MS7	100.0%	Diamond
Macaca mulatta	O77680	99.8%	Diamond
Pongo abelii	Q5RF57	99.1%	Diamond
Capra hircus	Q9XT57	98.8%	Diamond
Ovis aries	Q9XT58	98.8%	Diamond
Meriones unguiculatus	O70430	98.6%	Diamond
Felis catus	Q9TST6	98.6%	Diamond
Sus scrofa	P11483	98.1%	Diamond
Bos taurus	P41984	98.1%	Diamond
Canis lupus familiaris	O77621	97.6%	Diamond
Cavia porcellus	P35382	96.8%	Diamond
Mesocricetus auratus	P04274	95.7%	Diamond
Tscherskia triton	Q4KWL2	95.7%	Diamond
Oryctolagus cuniculus	O02824	95.5%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
FBXO38-DT	ncRNA	102546294
HTR4	protein-coding	3360
SPINK9	protein-coding	643394
FBXO38	protein-coding	81545
SPINK7	protein-coding	84651
SH3TC2-DT	ncRNA	255187
MIR584	ncRNA	693169
SH3TC2	protein-coding	79628

Protein

Protein identifiers

Beta-2 adrenergic receptor — P07550 (reviewed: P07550)

Alternative names: Beta-2 adrenoreceptor

All UniProt accessions (2): P07550, X5DQM5

UniProt curated annotations — full annotation on UniProt →

Function. G protein-coupled receptor for catecholamines that couples to both G(s) and G(i) proteins, activating bifurcated signaling pathways. ADRB2 binds epinephrine (Epi) with an approximately 30-fold greater affinity than norepinephrine (NE). In the heart, Epi- and NE-activated ADRB2 induces rapid and slow cardiomyocyte contraction rate, respectively. Both NE and Epi promote coupling to G(s)/PKA pathway to regulate myocyte contraction rate. Epi also promotes ADRB2 coupling to G(i) proteins to exert cardioprotective effects especially in the conditions of hypoxia and oxidative stress through the G(i)/PI3K/Akt signaling pathway. ADRB2-G(s) signaling delivers proapoptotic signals in cardiomyocytes although G(i)-mediated survival effect appears to predominate. ADRB2 also transduces signals independently of PKA to regulate cellular pH by modulating Na(+)/H(+) exchanger SLC9A3 function.

Subunit / interactions. Binds NHERF1 and GPRASP1. Interacts with ARRB1 and ARRB2. Interacts with SRC. Interacts with USP20 and USP33. Interacts with VHL; the interaction, which is increased on hydroxylation of ADRB2, ubiquitinates ADRB2 leading to its degradation. Interacts with EGLN3; the interaction hydroxylates ADRB2 facilitating VHL-E3 ligase-mediated ubiquitination. Interacts (via PDZ-binding motif) with SNX27 (via PDZ domain); the interaction is required when endocytosed to prevent degradation in lysosomes and promote recycling to the plasma membrane. Interacts with CNIH4. Interacts with ARRDC3. Interacts with NEDD4. Interacts with MARCHF2.

Subcellular location. Cell membrane. Golgi apparatus.

Post-translational modifications. Palmitoylated. Mainly palmitoylated at Cys-341. Palmitoylation may reduce accessibility of phosphorylation sites by anchoring the receptor to the plasma membrane. Agonist stimulation promotes depalmitoylation and further allows Ser-345 and Ser-346 phosphorylation. Also undergoes transient, ligand-induced palmitoylation at Cys-265 probably by ZDHHC9, ZDHHC14 and ZDHHC18 within the Golgi. Palmitoylation at Cys-265 requires phosphorylation by PKA and receptor internalization and stabilizes the receptor. Could be depalmitoylated by LYPLA1 at the plasma membrane. Phosphorylated by PKA and BARK/GRK2 upon agonist stimulation, which mediates homologous desensitization of the receptor. PKA-mediated phosphorylation seems to facilitate phosphorylation by BARK/GRK2. Distinct temporal phosphorylation on Ser-355 and Ser-356 by BARK/GRK2 plays a critical role for dictating receptor cellular events and signaling properties induced by Epi or NE in cardiomyocytes. Phosphorylation of Tyr-141 is induced by insulin and leads to supersensitization of the receptor. Polyubiquitinated. Agonist-induced ubiquitination leads to sort internalized receptors to the lysosomes for degradation. Deubiquitination by USP20 and USP33, leads to ADRB2 recycling and resensitization after prolonged agonist stimulation. USP20 and USP33 are constitutively associated and are dissociated immediately after agonist stimulation. Ubiquitination by the VHL-E3 ligase complex is oxygen-dependent. Hydroxylation by EGLN3 occurs only under normoxia and increases the interaction with VHL and the subsequent ubiquitination and degradation of ADRB2.

Polymorphism. The Gly-16 allele is overrepresented in individuals affected by nocturnal asthma as compared to controls, and appears to be an important genetic factor in the expression of this asthmatic phenotype.

Similarity. Belongs to the G protein-coupled receptor 1 family. Adrenergic receptor subfamily. ADRB2 sub-subfamily.

RefSeq proteins (1): NP_000015* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000332	ADRB2_rcpt	Family
IPR002233	ADR_fam	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (99 total): helix 17, binding site 12, mutagenesis site 12, modified residue 10, sequence variant 9, topological domain 8, transmembrane region 7, strand 7, sequence conflict 4, turn 3, lipid moiety-binding region 2, glycosylation site 2, disulfide bond 2, chain 1, region of interest 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

showing 30 of 150 structures by resolution:

PDB	Title	Method	Resolution (Å)
1GQ4	STRUCTURAL DETERMINANTS OF THE NHERF INTERACTION WITH BETA2AR AND PDGFR	X-RAY DIFFRACTION	1.9
2RH1	High resolution crystal structure of human B2-adrenergic G protein-coupled receptor.	X-RAY DIFFRACTION	2.4
6PS2	XFEL beta2 AR structure by ligand exchange from Timolol to Alprenolol.	X-RAY DIFFRACTION	2.4
9WG6	D1R-Gs in complexed with Dopamine/LY3154207/BMSA1/UNC9815	ELECTRON MICROSCOPY	2.44
9RKF	Dark structure of beta-2 Adrenergic receptor with photoazolol in Dark state recorded at …	X-RAY DIFFRACTION	2.45
9RKG	Mixed model refinement of beta-2 Adrenergic receptor with photoazolol in dark state and …	X-RAY DIFFRACTION	2.45
5D5A	In meso in situ serial X-ray crystallography structure of the Beta2-adrenergic receptor …	X-RAY DIFFRACTION	2.48
6PS3	XFEL beta2 AR structure by ligand exchange from Timolol to Carvedilol.	X-RAY DIFFRACTION	2.5
9Q3L	CryoEM structure of beta2-adrenergic receptor dimer mediated by a biased allosteric …	ELECTRON MICROSCOPY	2.5
9RKH	Dark structure of beta-2 Adrenergic receptor with photoazolol in Dark state recorded at …	X-RAY DIFFRACTION	2.5
9WG0	D1R-Gs in complexed with SKF81297/LY3154207/BMSA1/UNC10062	ELECTRON MICROSCOPY	2.59
6PS4	XFEL beta2 AR structure by ligand exchange from Timolol to ICI-118551.	X-RAY DIFFRACTION	2.6
9RKI	Mixed model refinement of beta-2 Adrenergic receptor with photoazolol in dark state and …	X-RAY DIFFRACTION	2.6
9WEU	D1R-Gs in complexed with SKF81297/LY3154207/BMSA1	ELECTRON MICROSCOPY	2.65
9U4Y	cryo-EM structure of Xenopus laevis GnRHR bound with mammal GnRH	ELECTRON MICROSCOPY	2.67
6PS6	XFEL beta2 AR structure by ligand exchange from Timolol to Timolol.	X-RAY DIFFRACTION	2.7
5X7D	Structure of beta2 adrenoceptor bound to carazolol and an intracellular allosteric …	X-RAY DIFFRACTION	2.7
9I54	Dopamine 1 receptor:GaS complex bound to 24	ELECTRON MICROSCOPY	2.72
4LDE	Structure of beta2 adrenoceptor bound to BI167107 and an engineered nanobody	X-RAY DIFFRACTION	2.79
3D4S	Cholesterol bound form of human beta2 adrenergic receptor.	X-RAY DIFFRACTION	2.8
6PRZ	XFEL beta2 AR structure by ligand exchange from Alprenolol to Alprenolol.	X-RAY DIFFRACTION	2.8
9I52	Dopamine 1 receptor:GaS complex bound to 19B	ELECTRON MICROSCOPY	2.8
3NY8	Crystal structure of the human beta2 adrenergic receptor in complex with the inverse …	X-RAY DIFFRACTION	2.84
3NY9	Crystal structure of the human beta2 adrenergic receptor in complex with a novel inverse …	X-RAY DIFFRACTION	2.84
9U9V	beta2-adrenergic receptor in complex with methamphetamine	ELECTRON MICROSCOPY	2.85
8ZWG	cryoEM structure of JR14a bound C3aR-Gi complex	ELECTRON MICROSCOPY	2.87
9LW5	Cryo-EM structure of dopamine bound mut-beta2-Adrenergic Receptor …	ELECTRON MICROSCOPY	2.87
6PS5	XFEL beta2 AR structure by ligand exchange from Timolol to Propranolol.	X-RAY DIFFRACTION	2.9
8GG0	CryoEM structure of beta-2-adrenergic receptor in complex with GTP-bound Gs heterotrimer …	ELECTRON MICROSCOPY	2.9
9BUY	Structure of the LM189-Bound beta2AR-Gi Complex	ELECTRON MICROSCOPY	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P07550-F1	79.74	0.60

Antibody-complex structures (SAbDab)

24 antibodies co-crystallized with this protein: 2R4R, 2R4S, 3KJ6, 3P0G, 3SN6, 4LDE, 4LDL, 4LDO, 4QKX, 5JQH, 6MXT, 6N48, 6NI3, 7BZ2, 7DHI, 7DHR, 7XK9, 7XKA, 8UHB, 8W1V, 8ZBE, 8ZCJ, 9U4Y, 9U9V

Human Protein Atlas

Protein class: Transporters, G-protein coupled receptors, GPCRs excl olfactory receptors, Predicted membrane proteins, GPCRHMM predicted membrane proteins, FDA approved drug targets, Small molecule drugs, Human disease related genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane; basal body; cytokinetic bridge; microtubules; mitotic spindle; primary cilium

Antibody reliability (HPA): IF supported

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (12)

Position	Role
113	(R)-adrenaline
113	(S)-carazolol
113	(S)-timolol
118	(S)-timolol
203	(S)-carazolol
293	(R)-adrenaline
293	(S)-timolol
312	(R)-adrenaline
312	(S)-carazolol
312	(S)-timolol
316	(R)-adrenaline
316	(S)-timolol

Post-translational modifications (12)

Type	Positions
Phosphotyrosine	141
Phosphoserine	246, 261, 262, 345, 346, 355, 356
4-hydroxyproline	382, 395
S-palmitoyl cysteine	265, 341

Disulfide bonds (2)

Type	Positions
Disulfide bond	106–191, 184–190

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	6, 15

Mutagenesis-validated functional residues (12)

Position	Phenotype
79	affects binding of catecholamines, and produces an uncoupling between the receptor and stimulatory g proteins.
141	abolishes insulin-induced tyrosine phosphorylation and insulin-induced receptor supersensitization.
174	increased noradrenaline affinity.
265	loss of ligand-induced palmitoylation.
300	increased noradrenaline affinity.
341	loss of basal palmitoylation.
341	uncoupled receptor.
345–346	delayed agonist-promoted desensitization.
350	does not affect insulin-induced tyrosine phosphorylation or insulin-induced receptor supersensitization.
354	does not affect insulin-induced tyrosine phosphorylation or insulin-induced receptor supersensitization.
366	does not affect insulin-induced tyrosine phosphorylation or insulin-induced receptor supersensitization.
413	loss of interaction with nherf1 after isoprenaline stimulation. inhibition of slc9a3 activity after isoprenaline stimulation. no change in …

Function

Pathways and Gene Ontology

Reactome pathways

5 curated (TAS) of 16; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

16 pathways:

ID	Pathway	Evidence
R-HSA-390696	Adrenoceptors	curated
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis	curated
R-HSA-8856828	Clathrin-mediated endocytosis	curated
R-HSA-418555	G alpha (s) signalling events	curated
R-HSA-5689880	Ub-specific processing proteases	curated
R-HSA-375280	Amine ligand-binding receptors	—
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)	—
R-HSA-5688426	Deubiquitination	—
R-HSA-388396	GPCR downstream signalling	—
R-HSA-500792	GPCR ligand binding	—
R-HSA-199991	Membrane Trafficking	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-597592	Post-translational protein modification	—
R-HSA-162582	Signal Transduction	—
R-HSA-372790	Signaling by GPCR	—
R-HSA-5653656	Vesicle-mediated transport	—

MSigDB gene sets: 515 (showing top): BIOCARTA_GCR_PATHWAY, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_AUTOPHAGY, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_LYSOSOMAL_TRANSPORT, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_RESPONSE_TO_COLD, GOBP_CIRCULATORY_SYSTEM_PROCESS, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOCC_SECRETORY_GRANULE, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_NEGATIVE_REGULATION_OF_MUSCLE_CONTRACTION, GOBP_RESPONSE_TO_DIETARY_EXCESS, MODULE_64, GOBP_ENDOSOME_TO_LYSOSOME_TRANSPORT

GO Biological Process (26): norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure (GO:0002025), receptor-mediated endocytosis (GO:0006898), regulation of smooth muscle contraction (GO:0006940), cell surface receptor signaling pathway (GO:0007166), adenylate cyclase-modulating G protein-coupled receptor signaling pathway (GO:0007188), endosome to lysosome transport (GO:0008333), positive regulation of cardiac muscle cell apoptotic process (GO:0010666), negative regulation of cardiac muscle cell apoptotic process (GO:0010667), positive regulation of MAPK cascade (GO:0043410), negative regulation of G protein-coupled receptor signaling pathway (GO:0045744), positive regulation of mini excitatory postsynaptic potential (GO:0061885), adrenergic receptor signaling pathway (GO:0071875), adenylate cyclase-activating adrenergic receptor signaling pathway (GO:0071880), adenylate cyclase-inhibiting adrenergic receptor signaling pathway (GO:0071881), AMPA selective glutamate receptor signaling pathway (GO:0098990), positive regulation of cardiac muscle cell contraction (GO:0106134), positive regulation of cold-induced thermogenesis (GO:0120162), positive regulation of glutamate receptor signaling pathway (GO:1900451), positive regulation of autophagosome maturation (GO:1901098), positive regulation of lipophagy (GO:1904504), cellular response to amyloid-beta (GO:1904646), response to psychosocial stress (GO:1990911), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), blood vessel diameter maintenance (GO:0097746)

GO Molecular Function (13): amyloid-beta binding (GO:0001540), beta2-adrenergic receptor activity (GO:0004941), adenylate cyclase binding (GO:0008179), potassium channel regulator activity (GO:0015459), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), protein-containing complex binding (GO:0044877), norepinephrine binding (GO:0051380), G protein-coupled receptor activity (GO:0004930), adrenergic receptor activity (GO:0004935), beta-adrenergic receptor activity (GO:0004939), protein binding (GO:0005515), enzyme binding (GO:0019899)

GO Cellular Component (12): nucleus (GO:0005634), lysosome (GO:0005764), endosome (GO:0005768), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), endosome membrane (GO:0010008), membrane (GO:0016020), apical plasma membrane (GO:0016324), clathrin-coated endocytic vesicle membrane (GO:0030669), signaling receptor complex (GO:0043235), neuronal dense core vesicle (GO:0098992), early endosome (GO:0005769)

Reactome top-level categories

12 top-level categories:

Category	Pathways
Signaling by GPCR	2
Amine ligand-binding receptors	1
GPCR downstream signalling	1
Deubiquitination	1
Clathrin-mediated endocytosis	1
Membrane Trafficking	1
Vesicle-mediated transport	1
Signal Transduction	1
GPCR ligand binding	1
Class A/1 (Rhodopsin-like receptors)	1
Post-translational protein modification	1
Metabolism of proteins	1

GO top-level categories

showing 60 of 76 GO namespaces:

Category	Terms
G protein-coupled receptor signaling pathway	4
adrenergic receptor signaling pathway	3
vesicle-mediated transport	2
cardiac muscle cell apoptotic process	2
regulation of cardiac muscle cell apoptotic process	2
adrenergic receptor activity	2
positive regulation of macroautophagy	2
protein binding	2
binding	2
intracellular membrane-bounded organelle	2
endomembrane system	2
endosome	2
regulation of systemic arterial blood pressure by norepinephrine-epinephrine	1
negative regulation of systemic arterial blood pressure	1
vasodilation	1
endocytosis	1
regulation of muscle contraction	1
smooth muscle contraction	1
signal transduction	1
adenylate cyclase activity	1
lysosomal transport	1
positive regulation of striated muscle cell apoptotic process	1
negative regulation of striated muscle cell apoptotic process	1
MAPK cascade	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
regulation of G protein-coupled receptor signaling pathway	1
negative regulation of signal transduction	1
regulation of mini excitatory postsynaptic potential	1
mini excitatory postsynaptic potential	1
positive regulation of excitatory postsynaptic potential	1
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	1
AMPA glutamate receptor activity	1
ionotropic glutamate receptor signaling pathway	1
cardiac muscle cell contraction	1
regulation of cardiac muscle cell contraction	1
positive regulation of actin filament-based movement	1
positive regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
glutamate receptor signaling pathway	1
positive regulation of signal transduction	1
regulation of glutamate receptor signaling pathway	1
positive regulation of organelle organization	1
positive regulation of protein-containing complex disassembly	1
autophagosome maturation	1
regulation of autophagosome maturation	1
lipophagy	1
regulation of lipophagy	1
peptide binding	1
beta-adrenergic receptor activity	1
enzyme binding	1
potassium channel activity	1
ion channel regulator activity	1
identical protein binding	1
protein dimerization activity	1
cation binding	1
catecholamine binding	1
transmembrane signaling receptor activity	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 20 of 51 annotations. The rest are phylogenetic / computational / electronic (IEA).

20 experimentally-supported GO terms:

GO term	NS	Evidence
AMPA selective glutamate receptor signaling pathway	BP	genetic interaction
adenylate cyclase-activating adrenergic receptor signaling pathway	BP	direct assay
adrenergic receptor signaling pathway	BP	direct assay
cellular response to amyloid-beta	BP	genetic interaction
negative regulation of G protein-coupled receptor signaling pathway	BP	direct assay
positive regulation of MAPK cascade	BP	direct assay
positive regulation of autophagosome maturation	BP	direct assay
positive regulation of glutamate receptor signaling pathway	BP	genetic interaction
positive regulation of lipophagy	BP	direct assay
receptor-mediated endocytosis	BP	direct assay
Golgi apparatus	CC	direct assay
plasma membrane	CC	direct assay
signaling receptor complex	CC	direct assay
amyloid-beta binding	MF	direct assay
beta2-adrenergic receptor activity	MF	direct assay
identical protein binding	MF	physical interaction
norepinephrine binding	MF	direct assay
potassium channel regulator activity	MF	direct assay
protein homodimerization activity	MF	physical interaction
protein-containing complex binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 2,554 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADRB2	ARRB1	P49407	925
ADRB2	ARRB2	P32121	894
ADRB2	GRK2	P25098	841
ADRB2	SAG	P10523	828
ADRB2	PRKACA	P17612	806
ADRB2	PRKACG	P22612	806
ADRB2	PRKACB	P22694	806
ADRB2	ADCY9	O60503	761
ADRB2	GRK5	P34947	727
ADRB2	TPM3	P06753	719
ADRB2	GRK6	P43250	642
ADRB2	AKT1	P31749	641
ADRB2	RAPGEF3	O95398	625
ADRB2	PDE4A	P27815	622
ADRB2	SRC	P12931	620

IntAct

Human interaction partners of ADRB2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 176 partners by confidence:

Partner	Interaction type	MIscore	Records
MAGI3	direct interaction	0.720	10
ARRDC3	colocalization	0.680	6
ADORA1	physical association	0.610	5
ARRB2	physical association	0.610	5
GNAS	association	0.610	5
SRC	direct interaction	0.610	3
NHERF1	direct interaction	0.560	7
ATP5IF1	physical association	0.560	3
BRPF3	physical association	0.560	3
BRWD1	physical association	0.560	3
CCDC158	physical association	0.560	3
E2F8	physical association	0.560	3
EEF1DP3	physical association	0.560	3
ELL2	physical association	0.560	3
EZH2	physical association	0.560	3
GUSBP1	physical association	0.560	3
PARP11	physical association	0.560	3
RNF138	physical association	0.560	3
RNF208	physical association	0.560	3
SNW1	physical association	0.560	3
TEX35	physical association	0.560	3
TMEM61	physical association	0.560	3
HNRNPK	physical association	0.510	2
MGLL	physical association	0.510	2
EIF2B1	physical association	0.460	2
MBP	proximity	0.450	2
PRNP	proximity	0.450	2
PATJ	direct interaction	0.440	7
GRIP2	direct interaction	0.440	5
GRIP1	direct interaction	0.440	4

BioGRID (426 interactions; top human partners by supporting records): ARRDC3 (Affinity Capture-Western; 8 records), SLC9A3R1 (Co-crystal Structure; 5 records), ARRB2 (Affinity Capture-Western; 4 records), GNAS (Affinity Capture-Western; 4 records), GNB1 (Proximity Label-MS; 4 records), GNB2L1 (Affinity Capture-MS; 4 records), GRK6 (Reconstituted Complex; 4 records), ADRBK1 (Reconstituted Complex; 3 records), AKAP12 (Reconstituted Complex; 3 records), AMFR (Affinity Capture-MS; 3 records), CLTC (Affinity Capture-Western; 3 records), DRD4 (Affinity Capture-Western; 3 records), EGLN3 (Affinity Capture-Western; 3 records), GPR37 (Two-hybrid; 3 records), HNRNPK (Affinity Capture-Western; 3 records)

SIGNOR signaling

showing 34 of 54 signaling interactions:

A	Effect	B	Mechanism
AKT	down-regulates	ADRB2	phosphorylation
(R)-adrenaline	up-regulates	ADRB2	“chemical activation”
“albuterol sulfate”	up-regulates	ADRB2	“chemical activation”
AKT1	down-regulates	ADRB2	phosphorylation
ADRB2	“up-regulates activity”	GNAS	binding
ADRB2	“up-regulates activity”	GNAL	binding
ADRB2	“up-regulates activity”	GNAQ	binding
ADRB2	“up-regulates activity”	GNA14	binding
L-isoprenaline	“up-regulates activity”	ADRB2	“chemical activation”
(R)-salbutamol	“up-regulates activity”	ADRB2	“chemical activation”
EGLN3	“up-regulates quantity by stabilization”	ADRB2	hydroxylation
ADRB2	“up-regulates activity”	GNAI1	binding
ADRB2	“up-regulates activity”	GNA15	binding
PRKCD	“down-regulates activity”	ADRB2	phosphorylation
GRK5	unknown	ADRB2	phosphorylation
INSR	“down-regulates activity”	ADRB2	phosphorylation
ARRB2	“down-regulates activity”	ADRB2	binding
metaproterenol	“up-regulates activity”	ADRB2	“chemical activation”
olodaterol	“up-regulates activity”	ADRB2	“chemical activation”
vilanterol	“up-regulates activity”	ADRB2	“chemical activation”
2-(hydroxymethyl)-4-(1-hydroxy-2-{[6-(4-phenylbutoxy)hexyl]amino}ethyl)phenol	“up-regulates activity”	ADRB2	“chemical activation”
N-[2-hydroxy-5-(1-hydroxy-2-{[1-(4-methoxyphenyl)propan-2-yl]amino}ethyl)phenyl]formamide	“up-regulates activity”	ADRB2	“chemical activation”
8-hydroxy-5-[1-hydroxy-2-(propan-2-ylamino)butyl]-1H-quinolin-2-one	“up-regulates activity”	ADRB2	“chemical activation”
“Cy3-bifunctional dye zwitterion”	“up-regulates activity”	ADRB2	“chemical activation”
clenbuterol	“up-regulates activity”	ADRB2	“chemical activation”
procaterol	“up-regulates activity”	ADRB2	“chemical activation”
fenoterol	“up-regulates activity”	ADRB2	“chemical activation”
terbutaline	“up-regulates activity”	ADRB2	“chemical activation”
adrenaline	“up-regulates activity”	ADRB2	“chemical activation”
arformoterol	“up-regulates activity”	ADRB2	“chemical activation”
propranolol	“down-regulates activity”	ADRB2	“chemical inhibition”
atenolol	“down-regulates activity”	ADRB2	“chemical inhibition”
isoprenaline	“up-regulates activity”	ADRB2	“chemical activation”
SLC9A3R1	“up-regulates activity”	ADRB2	binding

Protein complexes (CORUM) (23)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

23 complexes by size:

Complex	Subunits	Members
★ ADRB2-AKAP5-KCNMA1 complex	3	ADRB2, AKAP5, KCNMA1
★ ADRB2-CFTR-NHERF1 complex	3	ADRB2, CFTR, NHERF1
★ ADRB2-OXTR complex	2	ADRB2, OXTR
★ ADRA1D-ADRB2 complex	2	ADRA1D, ADRB2
★ ADRB2-RAB8A complex	2	ADRB2, RAB8A
★ ADRA2C-ADRB2 complex	2	ADRA2C, ADRB2
★ ADRB1-ADRB2 complex	2	ADRB1, ADRB2
★ ADRB2-OPRD1 complex	2	ADRB2, OPRD1
★ ADRB2-ARRDC3 complex	2	ADRB2, ARRDC3
★ ADRB2-ARRDC4 complex	2	ADRB2, ARRDC4
★ ADRB2-CNIH4 complex	2	ADRB2, CNIH4
★ ADRB2-USP20 complex	2	ADRB2, USP20
★ ADRB2-USP33 complex	2	ADRB2, USP33
★ ADRB2-MARCHF2 complex	2	ADRB2, MARCHF2
★ ADRB2-EIF2S2 complex	2	ADRB2, EIF2S2
★ ADRB2-AGTR1 complex	2	ADRB2, AGTR1
★ ADRB2-HTR4D complex	2	ADRB2, HTR4
★ ADRB2-SSTR5 complex	2	ADRB2, SSTR5
★ ADRB2-RAB11A complex	2	ADRB2, RAB11A
★ ADRB2-KCNMA1 complex	2	ADRB2, KCNMA1
★ ADRB2-PTGER1 complex	2	ADRB2, PTGER1
★ ADRB2-GIPR complex	2	ADRB2, GIPR
★ Beta-2 adrenergic receptor	1	ADRB2

Ligand–receptor pairs (CellPhoneDB) (6)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

6 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
PNMT;SLC18A1	receptor	Signaling by Adrenaline
DBH;SLC18A1	receptor	Signaling by Noradrenaline
PNMT	receptor	Signaling by Epinephrine
PNMT;SLC18A2	receptor	Signaling by Adrenaline
DBH;SLC6A2	receptor	Signaling by Noradrenaline
DBH;SLC18A2	receptor	Signaling by Noradrenaline

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 176 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Long-term potentiation	6	22.5×	5e-05
Ras activation upon Ca2+ influx through NMDA receptor	5	22.5×	3e-04
Unblocking of NMDA receptors, glutamate binding and activation	5	21.4×	3e-04
Negative regulation of NMDA receptor-mediated neuronal transmission	5	21.4×	3e-04
Assembly and cell surface presentation of NMDA receptors	10	20.0×	2e-08
Dopamine Neurotransmitter Release Cycle	5	19.6×	4e-04
Neurexins and neuroligins	11	17.1×	2e-08
Protein-protein interactions at synapses	7	14.6×	8e-05

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	9	31.9×	7e-09
protein localization to synapse	6	28.0×	2e-05
receptor clustering	7	26.6×	3e-06
regulation of postsynaptic membrane neurotransmitter receptor levels	6	18.1×	2e-04
excitatory postsynaptic potential	5	13.5×	3e-03
protein targeting	5	11.2×	6e-03
receptor internalization	5	9.9×	9e-03
protein-containing complex assembly	9	6.2×	2e-03

Disease & clinical

Genetic variants

Variant evidence for ADRB2: 47 ClinVar records (0 pathogenic / likely pathogenic); 1 PharmGKB dosing guideline; 8 GWAS associations.

ClinVar

47 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	12
Benign	22

AlphaMissense

1,067 missense substitutions predicted likely pathogenic (of 2,740 scored), across 248 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M215	9	0.948	0.998
D79	8	0.998	0.999
N51	8	0.997	1.000
D113	8	0.996	0.998
F282	8	0.992	1.000
F290	8	0.988	0.999
D130	8	0.987	0.997
S120	8	0.984	1.000
F208	8	0.984	0.999
N322	8	0.984	0.999
F332	8	0.972	0.999
N318	8	0.971	0.998
F289	8	0.961	0.999
F336	8	0.952	0.997
F71	8	0.948	0.993
F193	8	0.938	0.994
N312	8	0.906	0.993
M82	8	0.904	0.991
F139	8	0.886	0.989
S329	8	0.868	0.993

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Prostate Adenocarcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	6.64e-07
Liver Hepatocellular Carcinoma (validation)	favorable	0.000863

Disease associations

OMIM: gene MIM:109690 | disease phenotypes:

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
inherited susceptibility to asthma	Limited	Autosomal dominant

Mondo (1): inherited susceptibility to asthma (MONDO:0010940)

GWAS associations

8 associations:

Study	Trait	p-value
GCST007431_56	Lung function (FEV1/FVC)	2e-27
GCST007432_28	FEV1	6e-18
GCST007430_58	Peak expiratory flow	2e-16
GCST004632_114	Lymphocyte percentage of white cells	4e-13
GCST011766_6	Chronic obstructive pulmonary disease	9e-13
GCST90002382_184	Eosinophil percentage of white cells	1e-9
GCST007692_123	Chronic obstructive pulmonary disease	3e-7
GCST005777_1	Systolic blood pressure	9e-6

EFO canonical traits (from GWAS)

6 canonical traits:

EFO ID	Trait name
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0006335	systolic blood pressure
EFO:0009718	peak expiratory flow
EFO:0004713	FEV/FVC ratio
EFO:0004314	forced expiratory volume
EFO:0007991	eosinophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL2094118 (PROTEIN FAMILY), CHEMBL2096974 (SELECTIVITY GROUP), CHEMBL210 (SINGLE PROTEIN), CHEMBL2111388 (SELECTIVITY GROUP), CHEMBL2331074 (PROTEIN FAMILY)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the ADRB2 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

52 curated-mechanism drugs:

Drug	Modality	Max phase
ALBUTEROL	Small molecule	4
ARFORMOTEROL TARTRATE	Small molecule	4
BITOLTEROL MESYLATE	Small molecule	4
CELIPROLOL	Small molecule	4
DILEVALOL HYDROCHLORIDE	Small molecule	4
DOBUTAMINE HYDROCHLORIDE	Small molecule	4
ESMOLOL HYDROCHLORIDE	Small molecule	4
FENOTEROL	Small molecule	4
FORMOTEROL FUMARATE	Small molecule	4
INDACATEROL MALEATE	Small molecule	4
ISOETHARINE MESYLATE	Small molecule	4
LEVALBUTEROL TARTRATE	Small molecule	4
LEVOBUNOLOL HYDROCHLORIDE	Small molecule	4
METAPROTERENOL SULFATE	Small molecule	4
METIPRANOLOL HYDROCHLORIDE	Small molecule	4
NADOLOL	Small molecule	4
NEBIVOLOL HYDROCHLORIDE	Small molecule	4
OLODATEROL HYDROCHLORIDE	Small molecule	4
OXPRENOLOL HYDROCHLORIDE	Small molecule	4
PENBUTOLOL SULFATE	Small molecule	4
PINDOLOL	Small molecule	4
PIRBUTEROL ACETATE	Small molecule	4
PRONETALOL	Small molecule	4
PROPAFENONE HYDROCHLORIDE	Small molecule	4
PROPRANOLOL HYDROCHLORIDE	Small molecule	4
PROTOKYLOL HYDROCHLORIDE	Small molecule	4
RITODRINE HYDROCHLORIDE	Small molecule	4
SALMETEROL XINAFOATE	Small molecule	4
SOTALOL HYDROCHLORIDE	Small molecule	4
TERBUTALINE SULFATE	Small molecule	4
TIMOLOL	Small molecule	4
VILANTEROL TRIFENATATE	Small molecule	4
BAMBUTEROL	Small molecule	3
PROCATEROL	Small molecule	3
ABEDITEROL	Small molecule	2
AZD3199	Unknown	2
BATEFENTEROL	Small molecule	2
BEDORADRINE SULFATE	Small molecule	2
BUCINDOLOL	Small molecule	2
CARMOTEROL	Small molecule	2
CLENBUTEROL	Small molecule	2
LY377604	Small molecule	2
MILVETEROL	Small molecule	2
NAVAFENTEROL	Small molecule	2
PF-00610355	Small molecule	2
REPROTEROL	Small molecule	2
RIMITEROL	Small molecule	2
TULOBUTEROL	Small molecule	2
VILANTEROL .ALPHA.-PHENYL CINNAMATE	Small molecule	2
GSK159802	Unknown	1
ISOXSUPRINE HYDROCHLORIDE	Small molecule	1
LAS190792	Small molecule	1

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes ADRB2 — the drug acts on the assembly or class, not necessarily on this subunit alone.

11 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
CARTEOLOL HYDROCHLORIDE	Adrenergic receptor beta	3	4
CARVEDILOL	Adrenergic receptor beta	3	4
DIPIVEFRIN HYDROCHLORIDE	Adrenergic receptor	9	4
DROXIDOPA	Adrenergic receptor	9	4
EPHEDRINE SULFATE	Adrenergic receptor	9	4
EPINEPHRINE	Adrenergic receptor	9	4
HYDROXYAMPHETAMINE HYDROBROMIDE	Adrenergic receptor	9	4
ISOPROTERENOL SULFATE	Adrenergic receptor beta	3	4
LABETALOL HYDROCHLORIDE	Adrenergic receptor	9	4
MEPHENTERMINE SULFATE	Adrenergic receptor	9	4
NOREPINEPHRINE BITARTRATE	Adrenergic receptor	9	4

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 392,521 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

showing 60 of 166 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL714	ALBUTEROL	4	67,715
CHEMBL1363	ARFORMOTEROL	4	35,304
CHEMBL27810	CELIPROLOL	4	9,214
CHEMBL926	DOBUTAMINE	4	17,217
CHEMBL768	ESMOLOL	4	15,192
CHEMBL32800	FENOTEROL	4	22,782
CHEMBL1256786	FORMOTEROL	4	483
CHEMBL1095777	INDACATEROL	4	2,827
CHEMBL1201213	ISOETHARINE	4	11,613
CHEMBL1201153	ISOETHARINE MESYLATE	4	858
CHEMBL1201237	LEVOBUNOLOL	4	10,688
CHEMBL776	METAPROTERENOL	4	22,154
CHEMBL521606	NADOLOL	4	74
CHEMBL434394	NEBIVOLOL	4	9,764
CHEMBL605846	OLODATEROL	4	1,488
CHEMBL546	OXPRENOLOL	4	14,901
CHEMBL500	PINDOLOL	4	28,862
CHEMBL631	PROPAFENONE	4	12,817
CHEMBL27	PROPRANOLOL	4	86,565
CHEMBL1671	PROPRANOLOL HYDROCHLORIDE	4	22,003
CHEMBL83063	RITODRINE	4
CHEMBL1263	SALMETEROL	4
CHEMBL1082607	SALMETEROL XINAFOATE	4
CHEMBL471	SOTALOL	4
CHEMBL1700	SOTALOL HYDROCHLORIDE	4
CHEMBL1760	TERBUTALINE	4
CHEMBL499	TIMOLOL	4
CHEMBL642	ACEBUTOLOL	4
CHEMBL752	ADENOSINE PHOSPHATE	4
CHEMBL629	AMITRIPTYLINE	4
CHEMBL1491	AMLODIPINE	4
CHEMBL1113	AMOXAPINE	4
CHEMBL1112	ARIPIPRAZOLE	4
CHEMBL24	ATENOLOL	4
CHEMBL297302	BENPERIDOL	4
CHEMBL1691	BETAXOLOL HYDROCHLORIDE	4
CHEMBL645	BISOPROLOL	4
CHEMBL2105760	BREXPIPRAZOLE	4
CHEMBL493	BROMOCRIPTINE	4
CHEMBL1014	CANDESARTAN CILEXETIL	4
CHEMBL839	CARTEOLOL	4
CHEMBL723	CARVEDILOL	4
CHEMBL790	CHLORHEXIDINE	4
CHEMBL1626	CLEMASTINE	4
CHEMBL415	CLOMIPRAMINE	4
CHEMBL104	CLOTRIMAZOLE	4
CHEMBL42	CLOZAPINE	4
CHEMBL1346	DARIFENACIN	4
CHEMBL1172	DESLORATADINE	4
CHEMBL384467	DEXAMETHASONE	4
CHEMBL1732	DIHYDROERGOTAMINE	4
CHEMBL1200517	DIHYDROERGOTAMINE MESYLATE	4
CHEMBL1200833	DIPIVEFRIN HYDROCHLORIDE	4
CHEMBL219916	DOMPERIDONE	4
CHEMBL59	DOPAMINE	4
CHEMBL707	DOXAZOSIN	4
CHEMBL502182	ELAGOLIX SODIUM	4
CHEMBL679	EPINEPHRINE	4
CHEMBL1256958	EPINEPHRINE BITARTRATE	4
CHEMBL442	ERGOTAMINE	4

PharmGKB: 1 entry (CPIC guideline: yes)

PharmGKB clinical annotations

23 annotations by evidence level (1 strongest → 4):

Variant	Association	Level	Drugs	Phenotypes
rs1042713	Efficacy	2A	salmeterol	Asthma
rs1042713	Efficacy	3	corticosteroids	Asthma
rs1042713	Efficacy	3	corticosteroids;selective beta-2-adrenoreceptor agonists	Asthma
rs1042713	PD	3	salbutamol
rs1042713	Efficacy	3	salbutamol	Asthma
rs1042713	Toxicity	3	risperidone	Schizophrenia
rs1042713	Efficacy	3	methacholine	Asthma
rs1042713	Efficacy	3	tiotropium	Asthma
rs1042713	Other	3	isoproterenol
rs1042713	Efficacy	3	Ace Inhibitors;Plain;Angiotensin II Antagonists;Beta Blocking Agents;digoxin;diuretics;spironolactone	Heart Failure
rs1042713	Dosage	3	ephedrine;phenylephrine
rs1042713	Efficacy	3	propranolol	Liver Cirrhosis
rs1042713	Efficacy	3	atenolol;metoprolol	Tachycardia
rs1042714	Efficacy	3	enalapril	Hypertrophy;Left Ventricular
rs1042714	Efficacy	3	carvedilol	Heart Failure
rs1042714	Efficacy	3	terbutaline
rs1042714	Toxicity	3	atenolol;metoprolol	Hypertension
rs1042714	Efficacy	3	atenolol;metoprolol	Tachycardia
rs1042718	Toxicity	3	fentanyl;propofol;remifentanil;sevoflurane	Hypotensive disorder
rs1042718	Other	3	fentanyl
rs1800888	Other	3	salbutamol
rs1042713	Efficacy	4	benazepril	Essential hypertension
rs1042713	Efficacy	4	Beta Blocking Agents	Cardiomyopathy;Dilated;Heart Failure

PharmGKB variants

5 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1042713	ADRB2	2A	11.75	15	salmeterol;salbutamol;corticosteroids;corticosteroids;selective beta-2-adrenoreceptor agonists;methacholine;benazepril;risperidone;isoproterenol;tiotropium;ephedrine;phenylephrine
rs1042714	ADRB2	3	5.25	5	enalapril;carvedilol;atenolol;metoprolol;terbutaline
rs1800888	ADRB2	3	0.00	1	salbutamol
rs11959113	ADRB2	3	2.25	1	fentanyl
rs1042718	ADRB2	3	3.00	2	fentanyl;fentanyl;propofol;remifentanil;sevoflurane

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

42 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs1042714	atenolol, metoprolol	Toxicity	Genotype GG is associated with increased risk of Hypertriglyceridemia due to atenolol or metoprolol in people with Hypertension as compared to genotypes CC + CG.	PMID:16027735
rs1042714	metoprolol	Toxicity	Genotype CC is associated with decreased total cholesterol due to metoprolol in people with Hypertension.	PMID:17671401
rs1042714	metoprolol	Toxicity	Genotype CG is associated with increased triglycerides due to metoprolol in people with Hypertension.	PMID:17671401
rs1042713	methacholine	Efficacy	Genotype AA is associated with decreased response to methacholine in people with Asthma as compared to genotype GG.	PMID:23384627
rs1042713	corticosteroids	Efficacy	Genotype AA is associated with increased risk of uncontrolled asthma when treated with corticosteroids in children with Asthma as compared to genotype GG.	PMID:24279851
rs1042713	corticosteroids, salmeterol	Efficacy	Genotype AA is associated with increased risk of exacerbations when treated with corticosteroids and salmeterol in children with Asthma as compared to genotype GG.	PMID:24279851
rs1042713	tiotropium	Efficacy	Genotype AA is associated with increased response to tiotropium in people with Asthma as compared to genotypes AG + GG.	PMID:19183167
rs2053044	ramipril	Efficacy	Genotypes AA + AG is associated with increased response to ramipril in people with Hypertension as compared to genotype GG.	PMID:26111150
rs1042713	phenylephrine	Dosage	Genotype AA is associated with increased dose of phenylephrine in women as compared to genotype GG.	PMID:25730298
rs1042713	corticosteroids, selective beta-2-adrenoreceptor agonists	Efficacy	Allele A is associated with decreased response to corticosteroids and selective beta-2-adrenoreceptor agonists in children with Asthma as compared to genotype GG.	PMID:26774659
rs1042713	propranolol	Efficacy	Genotype GG is associated with increased response to propranolol in people with Liver Cirrhosis as compared to genotype AA.	PMID:26109805
rs1042718	fentanyl, propofol, remifentanil, sevoflurane	Toxicity	Genotype AA is associated with increased severity of Hypotension when treated with fentanyl, propofol, remifentanil or sevoflurane as compared to genotype CC.	PMID:26771271
rs1042714	Drugs For Obstructive Airway Diseases	Efficacy	Genotype GG is associated with increased exacerbation of asthma when treated with Drugs For Obstructive Airway Diseases in children with Asthma as compared to genotypes CG + GG.	PMID:30334910
rs1042714	atenolol, metoprolol	Efficacy	Genotype CC is associated with increased response to atenolol or metoprolol in people with Tachycardia as compared to genotypes CG + GG.	PMID:31090079
rs1042713	atenolol, metoprolol	Efficacy	Genotype AA is associated with increased response to atenolol or metoprolol in people with Tachycardia as compared to genotypes AG + GG.	PMID:31090079
rs1042713	salmeterol	Efficacy	Allele G is associated with increased response to salmeterol in children Asthma as compared to allele A.	PMID:30425908
rs1042713	salbutamol	PD	Genotype AA is associated with decreased response to salbutamol in healthy individuals as compared to genotypes AG + GG.	PMID:15687340
rs1042713	Beta Blocking Agents	Efficacy	Allele A is associated with increased response to Beta Blocking Agents in children with Cardiomyopathy, Dilated as compared to allele G.	PMID:25406899
rs1042713	Beta Blocking Agents	Efficacy	Genotype GG is associated with decreased risk of Death when treated with Beta Blocking Agents in people with Acute coronary syndrome as compared to genotypes AA + AG.	PMID:22703928
rs1042713	Beta Blocking Agents	Efficacy	Genotypes AG + GG is associated with increased risk of heart transplantation or Death in people not taking Beta Blocking Agents in people with Heart Failure as compared to genotype AA.	PMID:30374408
rs1042713		Other	Allele G is associated with decreased activity of ADRB2 of peripheral lymphocytes as compared to allele A.	PMID:30374408
rs1042713	dexmedetomidine	Efficacy	Genotype AA is associated with increased response to dexmedetomidine in people with surgery as compared to genotypes AG + GG.	PMID:37693312
rs1042714	salbutamol	Efficacy	Genotype GG is associated with decreased clinical benefit to salbutamol in people with Asthma as compared to genotypes CC + CG.	PMID:40834135
rs1042717	salbutamol	Efficacy	Genotype AA is associated with decreased clinical benefit to salbutamol in people with Asthma as compared to genotypes AG + GG.	PMID:40834135
rs1042713	mepolizumab	Efficacy	Allele G is associated with increased clinical benefit to mepolizumab in people with Asthma as compared to allele A.	PMID:40985517
rs1042713	corticosteroids	Efficacy	Genotype AA is associated with increased dose of corticosteroids in children with Asthma as compared to genotypes AG + GG.	PMID:42666756
rs1042714	carvedilol	Efficacy	Genotype CC is associated with decreased likelihood of improved left ventricular ejection fraction when treated with carvedilol in people with Heart Failure as compared to genotypes CG + GG.	PMID:12835612
rs1042713	salmeterol	Efficacy	Genotype AA is associated with decreased response to salmeterol in people with Asthma as compared to genotype GG.	PMID:16322642
rs1042714	carvedilol	Efficacy	Allele C is associated with increased reduction in resting blood pressure when treated with carvedilol in healthy individuals as compared to allele G.	PMID:21599570
rs1042713	risperidone	Toxicity	Allele G is associated with increased likelihood of Sexual adverse events when treated with risperidone in people with Schizophrenia as compared to allele A.	PMID:22212732
rs2400707	hydrochlorothiazide	Efficacy	Genotypes AA + AG are associated with increased reduction in whole day ambulatory blood pressure when treated with hydrochlorothiazide in people with Essential hypertension as compared to genotype GG.	PMID:16172412
rs1800888	terbutaline	Efficacy	Genotype CT is associated with decreased response to terbutaline in healthy individuals as compared to genotype CC.	PMID:11222464
rs1042714	terbutaline	Metabolism/PK	Genotype GG is associated with increased response to terbutaline in healthy individuals as compared to genotypes CC + CG.	PMID:12563174
rs1042713	salmeterol	Efficacy	Genotype AA is associated with decreased response to salmeterol in children with Asthma.	PMID:23126384
rs1042713	salmeterol	Efficacy	Genotype AA is associated with increased risk of asthma exacerbations when exposed to salmeterol in children with Asthma as compared to genotype GG.	PMID:16772309
rs1042713	salbutamol, salmeterol	Efficacy	Genotype AA is associated with increased risk of asthma exacerbations when exposed to salbutamol or salmeterol in children with Asthma as compared to genotype GG.	PMID:19800676
rs1042713	benazepril	Efficacy	Genotypes AG + GG are associated with increased response to benazepril in people with Essential hypertension as compared to genotype AA.	PMID:15554460
rs1042714	enalapril	Efficacy	Genotypes CG + GG are associated with increased response to enalapril in people with Hypertrophy, Left Ventricular as compared to genotype CC.	PMID:17178264
rs1042714	atenolol	Efficacy	Genotypes CG + GG are not associated with response to atenolol in people with Hypertrophy, Left Ventricular as compared to genotype CC.	PMID:17178264
rs1042714	atenolol, enalapril	Efficacy	Genotypes CG + GG are associated with increased response to atenolol and enalapril in people with Hypertrophy, Left Ventricular as compared to genotype CC.	PMID:17178264
rs1042714	carvedilol	Efficacy	Genotype GG is associated with increased response to carvedilol in people with Heart Failure as compared to genotypes CC + CG.	PMID:20352314
rs1042713	“““Ace Inhibitors, Plain””, ““Angiotensin II Antagonists””, ““Beta Blocking Agents””, ““digoxin””, ““diuretics””, ““spironolactone”””	Other	Genotype GG is associated with increased risk of emergency department and hospital utliization when treated with Ace Inhibitors, Plain, Angiotensin II Antagonists, Beta Blocking Agents, digoxin, diuretics or spironolactone in people with Heart Failure as compared to genotypes AA + AG.	PMID:22543981

PharmGKB dosing guidelines

CPIC / DPWG genotype-guided dosing for this gene (drug × pharmacogene).

1 dosing guidelines:

Guideline	Source	Drug	Dosing?	Recommendation?
Annotation of CPIC Guideline for carvedilol, labetalol, nadolol, pindo	CPIC	carvedilol;labetalol;nadolol;pindolol;propranolol;sotalol

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: gpcr — Adrenoceptors

Most potent curated ligand interactions (68 total), top 25:

Ligand	Action	Affinity	Parameter
[125I]ICYP	Partial agonist	11.4	pKd
carvedilol	Partial agonist	10.6	pKi
7-methylcyanopindolol	Antagonist	10.4	pKi
salmeterol	Partial agonist	10.4	pEC50
bucindolol	Partial agonist	10.3	pKi
carazolol	Partial agonist	10.3	pEC50
[3H]dihydroalprenolol	Antagonist	10.1	pKd
bunolol	Antagonist	10.1	pKi
BI-167107	Partial agonist	10.0	pEC50
cyanopindolol	Partial agonist	10.0	pEC50
ICI118551	Antagonist	10.0	pA2
timolol	Antagonist	10.0	pKi
bupranolol	Antagonist	9.9	pKi
3HCGP12177	Partial agonist	9.8	pKd
carteolol	Antagonist	9.8	pKi
CGP12177	Partial agonist	9.7	pEC50
fenoterol	Agonist	9.6	pEC50
alprenolol	Partial agonist	9.5	pKd
pindolol	Partial agonist	9.5	pKi
oxprenolol	Partial agonist	9.4	pKi
vilanterol	Agonist	9.4	pKi
propranolol	Antagonist	9.3	pKi
indacaterol	Agonist	9.3	pEC50
salbutamol	Partial agonist	8.7	pEC50
olodaterol	Agonist	8.7	pKi

Binding affinities (BindingDB)

1921 measured of 2181 human assays (2370 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
[O-methyl-11C]2-{4-[4-(7-methoxynaphthalen-1-yl)piperazin-1-yl]butyl}-4-methyl-2H-[1,2,4]triazine-3,5-dione	EC50	0.01 nM
CHEMBL4871517	KI	0.0126 nM
CHEMBL4863525	KI	0.0158 nM
(R)-N-benzyl-2-(3-(2-(2-hydroxy-2-(4-hydroxy-3-(hydroxymethyl)phenyl)ethylamino)-2-methylpropyl)phenyl)acetamide	EC50	0.02 nM
N-(2-methoxybenzyl)-5-((R)-2-((R)-2-hydroxy-2-(4-hydroxy-3-(hydroxymethyl)phenyl)ethylamino)propyl)-1H-indole-2-carboxamide	EC50	0.02 nM
(R)-N-(2-chloro-4-hydroxybenzyl)-2-(3-(2-(2-hydroxy-2-(4-hydroxy-3-(methylsulfonamido)phenyl)ethylamino)-2-methylpropyl)phenyl)acetamide	EC50	0.02 nM
N-benzyl-5-((R)-2-((R)-2-hydroxy-2-(4-hydroxy-3-(hydroxymethyl)phenyl)ethylamino)propyl)-N-methyl-1H-indole-2-carboxamide	EC50	0.022 nM
(R)-N-benzyl-2-(3-(2-(2-hydroxy-2-(4-hydroxy-3-(methylsulfonamido)phenyl)ethylamino)-2-methylpropyl)phenyl)acetamide	EC50	0.023 nM
N-(3,4-dichlorobenzyl)-2-(3-((R)-2-((R)-2-hydroxy-2-(4-hydroxy-3-(hydroxymethyl)phenyl)ethylamino)propyl)phenyl)acetamide	EC50	0.024 nM
CHEMBL4874819	KI	0.0251 nM
N-benzyl-2-(3-((R)-2-((R)-2-hydroxy-2-(4-hydroxy-3-(methylsulfonamido)phenyl)ethylamino)propyl)phenyl)acetamide	EC50	0.027 nM
2-(8-Bromo-2,3,6,7-tetrahydro-benzo[1,2-b;4,5-b’]difuran-4-yl)-ethylamine	EC50	0.029 nM
N-(cyclohexylmethyl)-2-(3-((R)-2-((R)-2-hydroxy-2-(4-hydroxy-3-(methylsulfonamido)phenyl)ethylamino)propyl)phenyl)acetamide	EC50	0.03 nM
5-{(R)-2-[(R)-2-hydroxy-2-(4-hydroxy-3-hydroxymethyl-phenyl)-ethylamino]-propyl}-1H-indole-2-carboxylic acid (4H-1lambda*4*-thiazol-2-ylmethyl)-amide	EC50	0.031 nM
Berlafenone	KD	0.035 nM
5-((R)-2-((R)-2-hydroxy-2-(4-hydroxy-3-(hydroxymethyl)phenyl)ethylamino)propyl)-N-(pyridin-2-ylmethyl)-1H-indole-2-carboxamide	EC50	0.038 nM
N-(2-(methylthio)benzyl)-5-((R)-2-((R)-2-hydroxy-2-(4-hydroxy-3-(hydroxymethyl)phenyl)ethylamino)propyl)-1H-indole-2-carboxamide	EC50	0.038 nM
CHEMBL4857743	KI	0.0398 nM
2-(3-((R)-2-((R)-2-hydroxy-2-(4-hydroxy-3-(methylsulfonamido)phenyl)ethylamino)propyl)phenyl)-N-(2-methoxybenzyl)acetamide	EC50	0.04 nM
2-(3-((R)-2-((R)-2-hydroxy-2-(4-hydroxy-3-(methylsulfonamido)phenyl)ethylamino)propyl)phenyl)-N-(3-phenylpropyl)acetamide	EC50	0.04 nM
2-(3-((R)-2-((R)-2-hydroxy-2-(4-hydroxy-3-(methylsulfonamido)phenyl)ethylamino)propyl)phenyl)-N-phenethylacetamide	EC50	0.04 nM
CHEMBL4469364	EC50	0.0407 nM
(R)-N-(4-hydroxy-2,6-dimethylbenzyl)-2-(3-(2-(2-hydroxy-2-(4-hydroxy-3-(methylsulfonamido)phenyl)ethylamino)-2-methylpropyl)phenyl)acetamide	EC50	0.045 nM
N-benzyl-5-((R)-2-((R)-2-hydroxy-2-(4-hydroxy-3-(hydroxymethyl)phenyl)ethylamino)propyl)-1H-indole-2-carboxamide	EC50	0.049 nM
CHEMBL4649233	EC50	0.049 nM
MJ-9184-1,(+/-)	EC50	0.05 nM
N-(2-ethoxybenzyl)-2-(3-((R)-2-((R)-2-hydroxy-2-(4-hydroxy-3-(methylsulfonamido)phenyl)ethylamino)propyl)phenyl)acetamide	EC50	0.05 nM
CHEMBL4866806	KI	0.0501 nM
N-(cyclobutylmethyl)-5-((R)-2-((R)-2-hydroxy-2-(4-hydroxy-3-(hydroxymethyl)phenyl)ethylamino)propyl)-1H-indole-2-carboxamide	EC50	0.051 nM
N-(2,6-difluorobenzyl)-5-((R)-2-((R)-2-hydroxy-2-(4-hydroxy-3-(hydroxymethyl)phenyl)ethylamino)propyl)-1H-indole-2-carboxamide	EC50	0.053 nM
5-((R)-2-((R)-2-hydroxy-2-(4-hydroxy-3-(hydroxymethyl)phenyl)ethylamino)propyl)-N-((R)-1-phenylethyl)-1H-indole-2-carboxamide	EC50	0.058 nM
N-(2,6-dimethoxybenzyl)-5-((R)-2-((R)-2-hydroxy-2-(4-hydroxy-3-(hydroxymethyl)phenyl)ethylamino)propyl)-1H-indole-2-carboxamide	EC50	0.058 nM
N-adamantan-1-yl-2-(3-{(R)-2-[(R)-2-hydroxy-2-(4-hydroxy-3-hydroxymethyl-phenyl)-ethylamino]-propyl}-phenyl)-acetamide	EC50	0.06 nM
N-(3,4-dimethylbenzyl)-2-(3-((R)-2-((R)-2-hydroxy-2-(4-hydroxy-3-(methylsulfonamido)phenyl)ethylamino)propyl)phenyl)acetamide	EC50	0.06 nM
(R)-N-(3,4-dichlorobenzyl)-2-(3-(2-(2-hydroxy-2-(4-hydroxy-3-(methylsulfonamido)phenyl)ethylamino)-2-methylpropyl)phenyl)acetamide	EC50	0.07 nM
CHEMBL4537644	EC50	0.0759 nM
(R)-N-(3,5-dichloro-4-hydroxybenzyl)-2-(3-(2-(2-hydroxy-2-(4-hydroxy-3-(methylsulfonamido)phenyl)ethylamino)-2-methylpropyl)phenyl)acetamide	EC50	0.09 nM
N-benzyl-2-(3-((R)-2-((R)-2-hydroxy-2-(4-hydroxy-3-(hydroxymethyl)phenyl)ethylamino)propyl)phenyl)acetamide	EC50	0.096 nM
(R)-N-benzyl-2-(3-(2-(2-hydroxy-2-(4-hydroxy-3-(hydroxymethyl)phenyl)ethylamino)ethyl)phenyl)acetamide	EC50	0.096 nM
CHEMBL3426706	EC50	0.1 nM
2-((1-(3-(9H-carbazol-4-yloxy)-2-hydroxypropyl)piperidin-4-yl)methyl)-5-methoxy-1H-benzo[de]isoquinoline-1,3(2H)-dione	KI	0.1 nM
CHEMBL4854418	KI	0.1 nM
CHEMBL4871702	KI	0.1 nM
5-{(R)-2-[(R)-2-hydroxy-2-(4-hydroxy-3-hydroxymethyl-phenyl)-ethylamino]-propyl}-1H-indole-2-carboxylic acid 4-sulfamoyl-benzylamide	EC50	0.122 nM
CHEMBL3426697	EC50	0.126 nM
CHEMBL1940833	EC50	0.126 nM
CHEMBL4639822	EC50	0.129 nM
(R)-1-((R)-3-Chloro-phenyl)-2-[2-(7-methoxy-1H-indol-3-yl)-1-methyl-ethylamino]-ethanol	EC50	0.13 nM
(R)-1-(3-Chloro-phenyl)-2-[2-(7-methoxy-1H-indol-3-yl)-1-methyl-ethylamino]-ethanol	EC50	0.13 nM
(R)-N-(3,5-dichloro-2-hydroxybenzyl)-2-(3-(2-(2-hydroxy-2-(4-hydroxy-3-(methylsulfonamido)phenyl)ethylamino)-2-methylpropyl)phenyl)acetamide	EC50	0.13 nM

ChEMBL bioactivities

3382 potent at pChembl≥5 of 3627 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.97	EC50	0.01072	nM	CHEMBL4847536
10.94	EC50	0.01148	nM	CHEMBL5570917
10.92	Ki	0.012	nM	CHEMBL2012522
10.90	Ki	0.01259	nM	CHEMBL4871517
10.90	EC50	0.01259	nM	CHEMBL4871708
10.90	Ki	0.01259	nM	CHEMBL5550055
10.90	Ki	0.01259	nM	CHEMBL5517637
10.90	Ki	0.01259	nM	CHEMBL6067690
10.89	EC50	0.01288	nM	CHEMBL4873082
10.88	EC50	0.01318	nM	CHEMBL5574011
10.88	EC50	0.01318	nM	CHEMBL5571865
10.87	EC50	0.01349	nM	CHEMBL4848793
10.83	EC50	0.01479	nM	CHEMBL4854569
10.80	Ki	0.01585	nM	CHEMBL4863525
10.80	Ki	0.01585	nM	CHEMBL5505762
10.80	Ki	0.01585	nM	CHEMBL5555464
10.80	Ki	0.01585	nM	CHEMBL5559271
10.80	EC50	0.01585	nM	CHEMBL5571445
10.79	EC50	0.01622	nM	CHEMBL4634131
10.78	EC50	0.0166	nM	CHEMBL4865710
10.76	EC50	0.01738	nM	CHEMBL4848018
10.75	EC50	0.01778	nM	CHEMBL4848704
10.75	EC50	0.01778	nM	CHEMBL4862449
10.74	Kd	0.0182	nM	CHEMBL4092412
10.74	EC50	0.0182	nM	CHEMBL4860454
10.74	EC50	0.0182	nM	CHEMBL4868938
10.74	EC50	0.0182	nM	CHEMBL4854261
10.71	EC50	0.0195	nM	CHEMBL4855974
10.70	EC50	0.02	nM	CHEMBL230486
10.70	EC50	0.02	nM	CHEMBL236039
10.70	EC50	0.02	nM	OLODATEROL
10.70	Ki	0.01995	nM	CHEMBL5184455
10.70	Ki	0.01995	nM	CHEMBL5558368
10.70	Ki	0.01995	nM	CHEMBL5558825
10.70	EC50	0.02	nM	CHEMBL1242943
10.68	EC50	0.021	nM	CHEMBL4445289
10.68	EC50	0.02089	nM	CHEMBL4445289
10.67	EC50	0.02138	nM	CHEMBL4872480
10.67	EC50	0.02138	nM	CHEMBL4863282
10.66	EC50	0.022	nM	CHEMBL236041
10.65	EC50	0.02239	nM	CHEMBL4857267
10.65	EC50	0.02239	nM	CHEMBL4868585
10.65	EC50	0.02239	nM	CHEMBL5573592
10.65	EC50	0.02239	nM	CHEMBL5574770
10.64	EC50	0.023	nM	CHEMBL1243189
10.63	EC50	0.02344	nM	CHEMBL4868684
10.62	EC50	0.02399	nM	CHEMBL4635163
10.62	EC50	0.02399	nM	CHEMBL5565495
10.62	EC50	0.024	nM	CHEMBL230490
10.61	EC50	0.02455	nM	CHEMBL4846631

PubChem BioAssay actives

2182 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
5-[(2R)-2-[[(2R)-2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl]amino]propyl]-N-(pyridin-2-ylmethyl)-1H-indole-2-carboxamide	302101: Agonist activity at human recombinant adrenergic beta-2 receptor expressed in CHO cells assessed as elevation in cAMP levels	ec50	<0.0001	uM
5-[(2R)-2-[[(2R)-2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl]amino]propyl]-N-(1,3-thiazol-2-ylmethyl)-1H-indole-2-carboxamide	302101: Agonist activity at human recombinant adrenergic beta-2 receptor expressed in CHO cells assessed as elevation in cAMP levels	ec50	<0.0001	uM
N-[(3,4-dichlorophenyl)methyl]-2-[3-[(2R)-2-[[(2R)-2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl]amino]propyl]phenyl]acetamide	510454: Agonist activity at human recombinant beta2 adrenergic receptor expressed in CHO cells assessed as elevation in cAMP level after 1 hr by flashplate method	ec50	<0.0001	uM
N-benzyl-2-[3-[(2R)-2-[[(2R)-2-hydroxy-2-[4-hydroxy-3-(methanesulfonamido)phenyl]ethyl]amino]propyl]phenyl]acetamide	510454: Agonist activity at human recombinant beta2 adrenergic receptor expressed in CHO cells assessed as elevation in cAMP level after 1 hr by flashplate method	ec50	<0.0001	uM
N-benzyl-2-[3-[2-[[(2R)-2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl]amino]-2-methylpropyl]phenyl]acetamide	290780: Agonist activity at human recombinant beta-2 adrenoceptor expressed in CHO cells assessed as elevation of cAMP	ec50	<0.0001	uM
2-[3-[(2R)-2-[[(2R)-2-hydroxy-2-[4-hydroxy-3-(methanesulfonamido)phenyl]ethyl]amino]propyl]phenyl]-N-(2-phenylethyl)acetamide	510454: Agonist activity at human recombinant beta2 adrenergic receptor expressed in CHO cells assessed as elevation in cAMP level after 1 hr by flashplate method	ec50	<0.0001	uM
N-[(2-ethoxyphenyl)methyl]-2-[3-[(2R)-2-[[(2R)-2-hydroxy-2-[4-hydroxy-3-(methanesulfonamido)phenyl]ethyl]amino]propyl]phenyl]acetamide	510454: Agonist activity at human recombinant beta2 adrenergic receptor expressed in CHO cells assessed as elevation in cAMP level after 1 hr by flashplate method	ec50	<0.0001	uM
N-benzyl-2-[3-[2-[[(2R)-2-hydroxy-2-[4-hydroxy-3-(methanesulfonamido)phenyl]ethyl]amino]-2-methylpropyl]phenyl]acetamide	510454: Agonist activity at human recombinant beta2 adrenergic receptor expressed in CHO cells assessed as elevation in cAMP level after 1 hr by flashplate method	ec50	<0.0001	uM
N-(cyclohexylmethyl)-2-[3-[(2R)-2-[[(2R)-2-hydroxy-2-[4-hydroxy-3-(methanesulfonamido)phenyl]ethyl]amino]propyl]phenyl]acetamide	510454: Agonist activity at human recombinant beta2 adrenergic receptor expressed in CHO cells assessed as elevation in cAMP level after 1 hr by flashplate method	ec50	<0.0001	uM
2-[3-[(2R)-2-[[(2R)-2-hydroxy-2-[4-hydroxy-3-(methanesulfonamido)phenyl]ethyl]amino]propyl]phenyl]-N-(3-phenylpropyl)acetamide	510454: Agonist activity at human recombinant beta2 adrenergic receptor expressed in CHO cells assessed as elevation in cAMP level after 1 hr by flashplate method	ec50	<0.0001	uM
2-[3-[(2R)-2-[[(2R)-2-hydroxy-2-[4-hydroxy-3-(methanesulfonamido)phenyl]ethyl]amino]propyl]phenyl]-N-[(2-methoxyphenyl)methyl]acetamide	510454: Agonist activity at human recombinant beta2 adrenergic receptor expressed in CHO cells assessed as elevation in cAMP level after 1 hr by flashplate method	ec50	<0.0001	uM
Olodaterol	1760531: Agonist activity at beta2 adrenoceptor (unknown origin)	ec50	<0.0001	uM
N-[(2-chloro-4-hydroxyphenyl)methyl]-2-[3-[2-[[(2R)-2-hydroxy-2-[4-hydroxy-3-(methanesulfonamido)phenyl]ethyl]amino]-2-methylpropyl]phenyl]acetamide	510454: Agonist activity at human recombinant beta2 adrenergic receptor expressed in CHO cells assessed as elevation in cAMP level after 1 hr by flashplate method	ec50	<0.0001	uM
N-[(4-hydroxy-2,6-dimethylphenyl)methyl]-2-[3-[2-[[(2R)-2-hydroxy-2-[4-hydroxy-3-(methanesulfonamido)phenyl]ethyl]amino]-2-methylpropyl]phenyl]acetamide	510454: Agonist activity at human recombinant beta2 adrenergic receptor expressed in CHO cells assessed as elevation in cAMP level after 1 hr by flashplate method	ec50	<0.0001	uM
Olodaterol Hydrochloride	1650066: Agonist activity at human beta2 adrenoreceptor overexpressed in human HEK293 cells assessed as cAMP accumulation incubated for 60 mins by HTRF assay	ec50	<0.0001	uM
(1-benzylpiperidin-4-yl)methyl (2S)-2-hydroxy-2-[3-[[4-[3-[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]propylcarbamoyl]phenyl]methoxy]phenyl]-2-phenylacetate	2065077: Displacement of [125I]-Cyanopindolol from human beta2 adrenoceptor assessed as inhibition constant incubated for 1 hrs by Microbeta scintillation counter	ki	<0.0001	uM
(1-benzylpiperidin-4-yl)methyl (2R)-2-hydroxy-2-[3-[[4-[3-[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]propylcarbamoyl]phenyl]methoxy]phenyl]-2-phenylacetate	2065077: Displacement of [125I]-Cyanopindolol from human beta2 adrenoceptor assessed as inhibition constant incubated for 1 hrs by Microbeta scintillation counter	ki	<0.0001	uM
(1-cyclobutylpiperidin-4-yl)methyl (2S)-2-hydroxy-2-[3-[3-[[4-[[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]methyl]benzoyl]amino]propoxy]phenyl]-2-phenylacetate	2065077: Displacement of [125I]-Cyanopindolol from human beta2 adrenoceptor assessed as inhibition constant incubated for 1 hrs by Microbeta scintillation counter	ki	<0.0001	uM
(1-methylpiperidin-4-yl)methyl (2S)-2-hydroxy-2-[3-[3-[[4-[[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]methyl]benzoyl]amino]propoxy]phenyl]-2-phenylacetate	2065077: Displacement of [125I]-Cyanopindolol from human beta2 adrenoceptor assessed as inhibition constant incubated for 1 hrs by Microbeta scintillation counter	ki	<0.0001	uM
(1-benzylpiperidin-4-yl)methyl 1-[[5-[4-[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]butylcarbamoyl]thiophen-2-yl]methylamino]-2,3-dihydroindene-1-carboxylate	2065077: Displacement of [125I]-Cyanopindolol from human beta2 adrenoceptor assessed as inhibition constant incubated for 1 hrs by Microbeta scintillation counter	ki	<0.0001	uM
6-hydroxy-8-[1-hydroxy-2-[(2-methyl-4-phenylbutan-2-yl)amino]ethyl]-4H-1,4-benzoxazin-3-one	1650066: Agonist activity at human beta2 adrenoreceptor overexpressed in human HEK293 cells assessed as cAMP accumulation incubated for 60 mins by HTRF assay	ec50	<0.0001	uM
4-[3-(tert-butylamino)-2-hydroxypropoxy]-1H-indole-2-carbonitrile	1626022: Displacement of [3H]DHA from inactive/G protein-uncoupled human beta2-AR expressed in CHO cell membranes by liquid scintillation counting	kd	<0.0001	uM
8-hydroxy-5-[(1R)-1-hydroxy-2-[(2-methyl-4-phenylbutan-2-yl)amino]ethyl]-1H-quinolin-2-one	1543325: Agonist activity at human beta2 adrenergic receptor expressed in HEK293 cells assessed as increase in cAMP accumulation after 60 mins by HTRF assay	ec50	<0.0001	uM
8-hydroxy-5-[1-hydroxy-2-[(2-methyl-4-phenylbutan-2-yl)amino]ethyl]-1H-quinolin-2-one	1543325: Agonist activity at human beta2 adrenergic receptor expressed in HEK293 cells assessed as increase in cAMP accumulation after 60 mins by HTRF assay	ec50	<0.0001	uM
8-hydroxy-5-[1-hydroxy-2-[3-(3-hydroxyphenyl)propylamino]ethyl]-1H-quinolin-2-one	1543325: Agonist activity at human beta2 adrenergic receptor expressed in HEK293 cells assessed as increase in cAMP accumulation after 60 mins by HTRF assay	ec50	<0.0001	uM
8-hydroxy-5-[1-hydroxy-2-[3-(2-methoxyphenyl)propylamino]ethyl]-1H-quinolin-2-one	1543325: Agonist activity at human beta2 adrenergic receptor expressed in HEK293 cells assessed as increase in cAMP accumulation after 60 mins by HTRF assay	ec50	<0.0001	uM
8-hydroxy-5-[1-hydroxy-2-[3-(2-hydroxyphenyl)propylamino]ethyl]-1H-quinolin-2-one	1543325: Agonist activity at human beta2 adrenergic receptor expressed in HEK293 cells assessed as increase in cAMP accumulation after 60 mins by HTRF assay	ec50	<0.0001	uM
8-hydroxy-5-[1-hydroxy-2-[3-(3-methoxyphenyl)propylamino]ethyl]-1H-quinolin-2-one	1543325: Agonist activity at human beta2 adrenergic receptor expressed in HEK293 cells assessed as increase in cAMP accumulation after 60 mins by HTRF assay	ec50	<0.0001	uM
6-hydroxy-8-[(1R)-1-hydroxy-2-[[4-(3-hydroxyphenyl)-2-methylbutan-2-yl]amino]ethyl]-4H-1,4-benzoxazin-3-one;hydrochloride	1650066: Agonist activity at human beta2 adrenoreceptor overexpressed in human HEK293 cells assessed as cAMP accumulation incubated for 60 mins by HTRF assay	ec50	<0.0001	uM
6-hydroxy-8-[1-hydroxy-2-[[4-(3-hydroxyphenyl)-2-methylbutan-2-yl]amino]ethyl]-4H-1,4-benzoxazin-3-one;hydrochloride	1650066: Agonist activity at human beta2 adrenoreceptor overexpressed in human HEK293 cells assessed as cAMP accumulation incubated for 60 mins by HTRF assay	ec50	<0.0001	uM
6-hydroxy-8-[(1R)-1-hydroxy-2-[[4-(2-methoxyphenyl)-2-methylbutan-2-yl]amino]ethyl]-4H-1,4-benzoxazin-3-one;hydrochloride	1650066: Agonist activity at human beta2 adrenoreceptor overexpressed in human HEK293 cells assessed as cAMP accumulation incubated for 60 mins by HTRF assay	ec50	<0.0001	uM
6-hydroxy-8-[(1R)-1-hydroxy-2-[[4-(3-methoxyphenyl)-2-methylbutan-2-yl]amino]ethyl]-4H-1,4-benzoxazin-3-one;hydrochloride	1650066: Agonist activity at human beta2 adrenoreceptor overexpressed in human HEK293 cells assessed as cAMP accumulation incubated for 60 mins by HTRF assay	ec50	<0.0001	uM
6-hydroxy-8-[1-hydroxy-2-[[4-(2-methoxyphenyl)-2-methylbutan-2-yl]amino]ethyl]-4H-1,4-benzoxazin-3-one;hydrochloride	1650066: Agonist activity at human beta2 adrenoreceptor overexpressed in human HEK293 cells assessed as cAMP accumulation incubated for 60 mins by HTRF assay	ec50	<0.0001	uM
6-hydroxy-8-[1-hydroxy-2-[[4-(4-hydroxyphenyl)-2-methylbutan-2-yl]amino]ethyl]-4H-1,4-benzoxazin-3-one;hydrochloride	1650066: Agonist activity at human beta2 adrenoreceptor overexpressed in human HEK293 cells assessed as cAMP accumulation incubated for 60 mins by HTRF assay	ec50	<0.0001	uM
6-hydroxy-8-[(1R)-1-hydroxy-2-[[4-(4-methoxyphenyl)-2-methylbutan-2-yl]amino]ethyl]-4H-1,4-benzoxazin-3-one;hydrochloride	1650066: Agonist activity at human beta2 adrenoreceptor overexpressed in human HEK293 cells assessed as cAMP accumulation incubated for 60 mins by HTRF assay	ec50	<0.0001	uM
6-hydroxy-8-[1-hydroxy-2-[[4-(3-methoxyphenyl)-2-methylbutan-2-yl]amino]ethyl]-4H-1,4-benzoxazin-3-one;hydrochloride	1650066: Agonist activity at human beta2 adrenoreceptor overexpressed in human HEK293 cells assessed as cAMP accumulation incubated for 60 mins by HTRF assay	ec50	<0.0001	uM
6-hydroxy-8-[(1R)-1-hydroxy-2-[(2-methyl-4-phenylbutan-2-yl)amino]ethyl]-4H-1,4-benzoxazin-3-one;hydrochloride	1650066: Agonist activity at human beta2 adrenoreceptor overexpressed in human HEK293 cells assessed as cAMP accumulation incubated for 60 mins by HTRF assay	ec50	<0.0001	uM
6-hydroxy-8-[1-hydroxy-2-[[4-(4-methoxyphenyl)-2-methylbutan-2-yl]amino]ethyl]-4H-1,4-benzoxazin-3-one;hydrochloride	1650066: Agonist activity at human beta2 adrenoreceptor overexpressed in human HEK293 cells assessed as cAMP accumulation incubated for 60 mins by HTRF assay	ec50	<0.0001	uM
6-hydroxy-8-[(1R)-1-hydroxy-2-[[4-(4-hydroxyphenyl)-2-methylbutan-2-yl]amino]ethyl]-4H-1,4-benzoxazin-3-one;hydrochloride	1650066: Agonist activity at human beta2 adrenoreceptor overexpressed in human HEK293 cells assessed as cAMP accumulation incubated for 60 mins by HTRF assay	ec50	<0.0001	uM
butanedioic acid;6-[4-[2-[[(2S)-3-(9H-carbazol-4-yloxy)-2-hydroxypropyl]amino]-2-methylpropyl]phenoxy]pyridine-3-carboxamide	652454: Displacement of [125I]Iodocyanopindolol from human adrenergic beta2 receptor expressed in insect sf9 cells by scintillation counting	ki	<0.0001	uM
5-[2-[3-(3-fluorophenyl)propylamino]-1-hydroxyethyl]-8-hydroxy-1H-quinolin-2-one;hydrochloride	1783430: Agonist activity at human beta2 adrenoreceptor overexpressed in HEK293 cells assessed as cAMP accumulation	ec50	<0.0001	uM
8-hydroxy-5-[1-hydroxy-2-[[2-methyl-4-(3-methylphenyl)butan-2-yl]amino]ethyl]-1H-quinolin-2-one;hydrochloride	1783430: Agonist activity at human beta2 adrenoreceptor overexpressed in HEK293 cells assessed as cAMP accumulation	ec50	<0.0001	uM
8-hydroxy-5-[1-hydroxy-2-[[4-(3-hydroxyphenyl)-2-methylbutan-2-yl]amino]ethyl]-1H-quinolin-2-one;hydrochloride	1783430: Agonist activity at human beta2 adrenoreceptor overexpressed in HEK293 cells assessed as cAMP accumulation	ec50	<0.0001	uM
8-hydroxy-5-[1-hydroxy-2-[4-(4-methoxyphenyl)butan-2-ylamino]ethyl]-1H-quinolin-2-one;hydrochloride	1783430: Agonist activity at human beta2 adrenoreceptor overexpressed in HEK293 cells assessed as cAMP accumulation	ec50	<0.0001	uM
8-hydroxy-5-[(1R)-1-hydroxy-2-[[(2R)-4-(2-methoxyphenyl)butan-2-yl]amino]ethyl]-1H-quinolin-2-one;hydrochloride	1783430: Agonist activity at human beta2 adrenoreceptor overexpressed in HEK293 cells assessed as cAMP accumulation	ec50	<0.0001	uM
5-[2-[4-(4-chlorophenyl)butan-2-ylamino]-1-hydroxyethyl]-8-hydroxy-1H-quinolin-2-one;hydrochloride	1783430: Agonist activity at human beta2 adrenoreceptor overexpressed in HEK293 cells assessed as cAMP accumulation	ec50	<0.0001	uM
5-[2-[[4-(3-chlorophenyl)-2-methylbutan-2-yl]amino]-1-hydroxyethyl]-8-hydroxy-1H-quinolin-2-one;hydrochloride	1783430: Agonist activity at human beta2 adrenoreceptor overexpressed in HEK293 cells assessed as cAMP accumulation	ec50	<0.0001	uM
5-[2-[4-(2-chlorophenyl)butan-2-ylamino]-1-hydroxyethyl]-8-hydroxy-1H-quinolin-2-one;hydrochloride	1783430: Agonist activity at human beta2 adrenoreceptor overexpressed in HEK293 cells assessed as cAMP accumulation	ec50	<0.0001	uM
8-hydroxy-5-[1-hydroxy-2-[4-(2-methoxyphenyl)butan-2-ylamino]ethyl]-1H-quinolin-2-one;hydrochloride	1783430: Agonist activity at human beta2 adrenoreceptor overexpressed in HEK293 cells assessed as cAMP accumulation	ec50	<0.0001	uM
8-hydroxy-5-[1-hydroxy-2-[[4-(2-methoxyphenyl)-2-methylbutan-2-yl]amino]ethyl]-1H-quinolin-2-one;hydrochloride	1783430: Agonist activity at human beta2 adrenoreceptor overexpressed in HEK293 cells assessed as cAMP accumulation	ec50	<0.0001	uM

CTD chemical–gene interactions

192 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Terbutaline	increases phosphorylation, decreases expression, affects response to substance, decreases activity, affects binding (+10 more)	23
Carvedilol	decreases abundance, decreases reaction, increases activity, increases uptake, affects reaction (+7 more)	15
ICI 118551	increases phosphorylation, decreases response to substance, affects cotreatment, decreases abundance, decreases activity (+7 more)	14
Isoproterenol	increases abundance, increases phosphorylation, increases chemical synthesis, increases expression, increases uptake (+6 more)	14
Cyclic AMP	increases reaction, increases activity, decreases activity, decreases reaction, affects binding (+5 more)	11
Propranolol	increases phosphorylation, decreases activity, decreases reaction, increases activity, increases abundance (+6 more)	11
Albuterol	affects binding, increases abundance, increases phosphorylation, decreases response to substance, increases activity (+3 more)	10
Epinephrine	increases abundance, increases phosphorylation, increases reaction, increases localization, decreases reaction (+2 more)	7
Valproic Acid	affects expression, affects cotreatment, increases expression	7
Salmeterol Xinafoate	increases phosphorylation, decreases reaction, decreases expression, affects binding, increases expression (+2 more)	6
Formoterol Fumarate	decreases reaction, increases expression, increases reaction, affects expression, affects binding (+3 more)	5
Fenoterol	affects binding, increases activity, decreases abundance, increases abundance, increases phosphorylation (+1 more)	5
Particulate Matter	increases phosphorylation, increases methylation, decreases expression, decreases reaction, decreases phosphorylation (+3 more)	5
Atenolol	increases phosphorylation, decreases activity, decreases abundance, decreases reaction, increases activity (+3 more)	4
CGP 12177	decreases activity, decreases abundance, affects binding, decreases reaction	3
Alprenolol	decreases reaction, affects binding, increases abundance, increases phosphorylation, affects cotreatment (+1 more)	3
Cisplatin	affects cotreatment, increases expression	3
Dactinomycin	affects cotreatment, increases expression, decreases reaction, affects expression	3
Colforsin	affects cotreatment, increases reaction, increases activity, affects reaction, increases phosphorylation (+4 more)	3
Metoprolol	decreases reaction, affects response to substance, affects binding, decreases abundance, decreases activity	3
Norepinephrine	affects binding, increases activity, increases abundance, decreases reaction	3
Metaproterenol	decreases expression, increases phosphorylation, affects expression, affects binding, increases activity (+1 more)	3
Pindolol	decreases activity, decreases abundance, decreases reaction, decreases expression, affects binding (+2 more)	3
Potassium	increases activity, affects cotreatment, affects reaction, increases transport, increases abundance (+2 more)	3
Tretinoin	decreases expression, increases expression	3
Cyclosporine	decreases expression, increases expression	3
Aflatoxin B1	affects expression, decreases methylation, increases expression	3
trichostatin A	affects expression, increases expression	2
sodium arsenite	decreases expression	2
broxaterol	affects binding, increases activity, increases abundance, decreases reaction	2

ChEMBL screening assays

1026 unique, capped per target: 596 binding, 423 functional, 7 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3254788	Binding	Inhibition of beta-adrenergic receptor (unknown origin)	Linked Aryl Aryloxypropanolamines as a new class of lipid catabolis agents. — *J Med Chem*
CHEMBL646912	Functional	In vitro agonistic activity against cAMP accumulation level in CHO cells expressing human beta-AR receptor	4-Aminopiperidine ureas as potent selective agonists of the human beta(3)-adrenergic receptor. — *Bioorg Med Chem Lett*
CHEMBL4051050	ADMET	Agonist activity at recombinant human beta2 adrenergic receptor expressed in CHO cells assessed as accumulation of cyclic AMP after 30 mins	Discovery of Novel Indazole Derivatives as Orally Available β3-Adrenergic Receptor Agonists Lacking Off-Target-Based Cardiovascular Side Effects. — *J Med Chem*

Cellosaurus cell lines

23 cell lines: 8 transformed cell line, 8 cancer cell line, 5 spontaneously immortalized cell line, 1 telomerase immortalized cell line, 1 hybrid cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_6631	Gbeta2AR13	Transformed cell line	Female
CVCL_9869	HEK-293B2	Transformed cell line	Female
CVCL_B1BR	Abcam A-431 ADRB2 KO	Cancer cell line	Female
CVCL_B8B1	Abcam HCT 116 ADRB2 KO	Cancer cell line	Male
CVCL_B8S7	Abcam MCF-7 ADRB2 KO	Cancer cell line	Female
CVCL_B9D3	Abcam A-549 ADRB2 KO	Cancer cell line	Male
CVCL_C0S5	ACTOne ADRB2	Transformed cell line	Female
CVCL_C3K0	N/Tert-1 ADRB2	Telomerase immortalized cell line	Male
CVCL_D7JS	Ubigene A-549 ADRB2 KO	Cancer cell line	Male
CVCL_D9XA	Ubigene HeLa ADRB2 KO	Cancer cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for ADRB2 across ~30M SureChEMBL compounds — explore on Sugi Predict.