ADRB1

Summary

ADRB1 (adrenoceptor beta 1, HGNC:285) is a protein-coding gene on chromosome 10q25.3, encoding Beta-1 adrenergic receptor (P08588). G protein-coupled receptor for catecholamines that couples to G(s) proteins to activate adenylate cyclase and cAMP-dependent pathway.

The adrenergic receptors (subtypes alpha 1, alpha 2, beta 1, and beta 2) are a prototypic family of guanine nucleotide binding regulatory protein-coupled receptors that mediate the physiological effects of the hormone epinephrine and the neurotransmitter norepinephrine. Beta-1 adrenoceptors are predominately located in the heart. Specific polymorphisms in this gene have been shown to affect the resting heart rate and can be involved in heart failure.

Source: NCBI Gene 153 — RefSeq curated summary.

At a glance

• Gene–disease (curated): short sleep, familial natural, 2 (Limited, GenCC)
• GWAS associations: 57
• Clinical variants (ClinVar): 74 total — 1 pathogenic
• Phenotypes (HPO): 2
• Druggable target: yes — 154 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000684

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:285
Approved symbol	ADRB1
Name	adrenoceptor beta 1
Location	10q25.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000043591
Ensembl biotype	protein_coding
OMIM	109630
Entrez	153

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000369295

RefSeq mRNA: 1 — MANE Select: NM_000684 NM_000684

CCDS: CCDS7586

Canonical transcript exons

ENST00000369295 — 1 exons

Exon	Start	End
ENSE00001449426	114043866	114046904

Expression profiles

Bgee: expression breadth ubiquitous, 205 present calls, max score 97.28.

FANTOM5 (CAGE): breadth broad, TPM avg 5.8674 / max 852.7263, expressed in 588 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
107148	3.9371	495
107147	0.9851	319
107150	0.6932	183
107149	0.2521	118

Top tissues by expression

279 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
heart right ventricle	UBERON:0002080	97.28	gold quality
parotid gland	UBERON:0001831	96.39	gold quality
bronchial epithelial cell	CL:0002328	93.58	gold quality
lower lobe of lung	UBERON:0008949	92.36	gold quality
endothelial cell	CL:0000115	91.25	gold quality
placenta	UBERON:0001987	90.98	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.82	gold quality
apex of heart	UBERON:0002098	89.28	gold quality
adult organism	UBERON:0007023	87.75	gold quality
postcentral gyrus	UBERON:0002581	87.28	gold quality
buccal mucosa cell	CL:0002336	86.76	silver quality
parietal lobe	UBERON:0001872	86.62	gold quality
cardiac ventricle	UBERON:0002082	86.61	gold quality
colonic epithelium	UBERON:0000397	86.53	gold quality
entorhinal cortex	UBERON:0002728	86.39	gold quality
heart left ventricle	UBERON:0002084	86.27	gold quality
superior frontal gyrus	UBERON:0002661	85.33	gold quality
primary visual cortex	UBERON:0002436	85.11	gold quality
middle temporal gyrus	UBERON:0002771	84.68	gold quality
epithelium of bronchus	UBERON:0002031	84.45	gold quality
myocardium	UBERON:0002349	83.78	gold quality
occipital lobe	UBERON:0002021	83.72	gold quality
right atrium auricular region	UBERON:0006631	83.71	gold quality
cardiac atrium	UBERON:0002081	83.55	gold quality
bronchus	UBERON:0002185	83.50	gold quality
mucosa of paranasal sinus	UBERON:0005030	82.27	gold quality
heart	UBERON:0000948	81.98	gold quality
left ventricle myocardium	UBERON:0006566	79.80	gold quality
upper lobe of lung	UBERON:0008948	79.51	gold quality
right lung	UBERON:0002167	79.13	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.23
E-GEOD-124858	no	1.28

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BMAL1, CREM, EGR1, MYC, NCOA1, NR3C1, RARA, RXRA, SP1, ZHX2

miRNA regulators (miRDB)

117 targeting ADRB1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
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-4768-5P	100.00	69.49	2861
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
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

Literature-anchored findings (GeneRIF, showing 40)

• A polymorphism in the beta1 adrenergic receptor is associated with resting heart rate (PMID:11854867)
• Gly389Arg ADRB1 variant is associated with greater body weight and BMI in Caucasian women due to a greater fat mass (PMID:12032746)
• The agonist-specific component of beta1AR downregulation requires internalization correlating more closely with receptor degradation, while the cAMP-specific component does not require internalization and is associated with downregulation of beta1AR mRNA. (PMID:12069593)
• beta1-adrenoceptor and beta2-adrenoceptor couple to Gs-proteins to activate adenylyl cyclase (PMID:12106601)
• role of heterodimerization with beta 2-adrenergic receptor regulates beta 2-adrenergic receptor internalization and ERK signaling efficacy (PMID:12140284)
• Suppressive effect of the Gly389 allele of the beta1-adrenergic receptor gene on the occurrence of ventricular tachycardia in dilated cardiomyopathy. (PMID:12197595)
• 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)
• Glycosylation regulates receptor surface expression and dimerization (PMID:12270132)
• These results suggest a model whereby the physical interaction between the beta1-AR and CNrasGEF facilitates the transduction of Gsalpha-induced cAMP signal into the activation of Ras. (PMID:12391161)
• An interaction between beta(1)AR and alpha(2A)AR is regulated by glycosylation and may play a key role in cross-talk and mutual regulation between these receptors. (PMID:12529373)
• An association was not found between B1AR polymorphism and major depression, but there was a tendency for a relation between CC homozygosity and a better and even faster response to antidepressant treatment in patients with major depression. (PMID:12815745)
• The partial agonist activity of bucindolol is dependent on the activation state of the human beta-1 adrenergic receptor (PMID:12847069)
• Data show that the beta(1)-adrenergic receptor Arg389 variant predisposes to heart failure through hyperactive signaling programs, depressed receptor coupling and ventricular dysfunction, and influences the therapeutic response to beta-receptor blockade. (PMID:14502278)
• 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)
• PKA-mediated phosphorylation of G protein-coupled receptors might result in motif-dependent desensitization or resensitization. (PMID:14990580)
• The ADRB1/R389G polymorphism tended to be associated with hypertensive status in male subjects (p=0.0117, p(c)=0.0702). (PMID:15055253)
• Single-nucleotide polymorphisms (SNPs) in the beta1-adrenergic receptor (ADRB1) allelic frequencies were analyzed in Alzheimer’s disease. The combination of G protein beta3 subunit and ADRB1 polymorphisms produces AD susceptibility. (PMID:15212839)
• The Ser49Gly functional polymorphism in the beta(1) adrenergic receptor might explain some of the population variance in extraversion and related personality traits. (PMID:15312808)
• the lack of agonist-mediated ubiquitination of beta1AR may prevent its extensive trafficking to lysosomes (PMID:15331590)
• Substitution of the C-terminal cytoplasmic tail of the beta2-adrenergic receptor on the beta1-adrenergic receptor enabled the chimeric G protein-coupled receptor to be functionally and spatially regulated by insulin. (PMID:15388645)
• evidence for an interaction between the beta1- and beta2-adrenergic receptors was observed in men for longitudinal change in body mass index and women showed suggestive evidence for an interaction between the beta1- and beta3-adrenergic receptors (PMID:15833937)
• beta1AR or the beta2AR polymorphisms do not affect patient response to beta-blockade treatment for stable congestive heart failure (PMID:15861037)
• the Arg389Arg and Ser49Gly polymorphisms may have roles in left ventricular remodeling changes in response to beta-blocker therapy (PMID:15864115)
• Beta(1)-adrenergic receptor mRNA expressions in myocardium were significantly lower in patients with heart failure than those in control subjects. (PMID:15932670)
• In this small pilot series, a single nucleotide polymorphism at codon 389 in the beta1-AR seems to correlate with a response to betaxolol therapy in normal, nonglaucomatous volunteers. (PMID:16325708)
• the amphipathic character of helix 8 and side chain projections of Asp382 and Arg384 within the hydrophilic interface might serve as a tethering site for the G protein (PMID:16500896)
• Val-120, Ile-185, Asp-212, and Lys-253 are critically involved in conformational changes occurring during receptor activation (PMID:16648137)
• Homozygousbeta1AR Arg389Gly predicts cardiac troponin release in subarachnoid hemorrhage. Combining homozygous B1AR Arg389Gly & homozygous deletion of B2AR increases the odds of reduced left ventricular ejection fraction. (PMID:16728691)
• These findings indicate that Lys324 lies in a groove between helices 3 and 6, and its mutagenesis generates a mutant receptor with very low binding affinity for the GDP-bound isoform of G(s). (PMID:16760361)
• beta1-adrenergic receptors are upregulated and troponin I is dephosphorylated in end-stage heart failure patients supported by ventricular assist devices (PMID:16765375)
• Certain polymorphisms of the ADRB1 and ADRB2 genes influence the pathophysiology of open-angle glaucoma in Japanese patients. (PMID:16785856)
• beta(1)AR-389 variation alters signaling in multiple models and affects the beta-blocker therapeutic response in heart failure (PMID:16844790)
• These results suggest that the dynamic association of 14-3-3 proteins to both beta(1)AR and Kv11.1 channels is involved in the adrenergic modulation of this critical regulator of cardiac repolarization and refractoriness. (PMID:16914520)
• AKAP79 provides cyclic AMP-dependent protein kinase to phosphorylate the beta1-adrenergic receptor and thereby dictate the recycling and resensitization itineraries of the beta1-adrenergic receptor (PMID:16940053)
• Our results suggest that CRM 1-dependent NES-mediated mechanisms influence the degradation and agonist-mediated down-regulation of the beta1-AR mRNAs. (PMID:16997396)
• In this relatively small study, double homozygosity for Arg389 and Ser49 of the human beta1-adrenergic receptor associated with the risk of symptoms in LQT1. (PMID:17023080)
• Golgin-160 interacts with beta1AR (PMID:17118120)
• Genetic polymorphisms in the B1AR gene have the potential to explain some of the observed ethnic variability in drug response and to improve clinical practice (Review) (PMID:17329986)
• results suggest that the Arg389Gly polymorphism does not have any clinically important impact on the pathogenesis of obesity in Danish white subjects; this variant is most likely not to be a major contributor to the development of hypertension (PMID:17335470)
• Pulse wave velocity and nitroglycerin-induced hyperemia were both closely associated with the Ser49Gly polymorphism. (PMID:17345787)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	adrb1	ENSDARG00000007490
mus_musculus	Adrb1	ENSMUSG00000035283
rattus_norvegicus	Adrb1	ENSRNOG00000017002
caenorhabditis_elegans	ser-5	WBGENE00008890

Paralogs (18): ADRA1A (ENSG00000120907), DRD2 (ENSG00000149295), ADRA2A (ENSG00000150594), GPR101 (ENSG00000165370), ADRB2 (ENSG00000169252), 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)

Protein

Protein identifiers

Beta-1 adrenergic receptor — P08588 (reviewed: P08588)

Alternative names: Beta-1 adrenoreceptor

All UniProt accessions (1): P08588

UniProt curated annotations — full annotation on UniProt →

Function. G protein-coupled receptor for catecholamines that couples to G(s) proteins to activate adenylate cyclase and cAMP-dependent pathway. Binds epinephrine and norepinephrine with approximately equal affinity. Mediates the activation of Ras via binding with cAMP-dependent RAPGEF2. As part of the sympathetic nervous system, plays a role in the physiologic regulation of cardiac functions such as stimulation of cardiomyocyte contraction. Also delivers proapoptotic signals in cardiomyocytes. Involved in the regulation of sleep/wake behaviors.

Subunit / interactions. Interacts (via PDZ-binding motif) with RAPGEF2 (via PDZ domain); the interaction is direct and is required for Ras activation upon ligand stimulation. Interacts (via PDZ-binding motif) with GOPC, MAGI3 and DLG4; interaction mediates ADRB1 trafficking and signaling in a cell-specific manner.

Subcellular location. Cell membrane.

Post-translational modifications. Homologous desensitization of the receptor is mediated by its phosphorylation by beta-adrenergic receptor kinase.

Domain organisation. The PDZ domain-binding motif mediates competitive interactions with GOPC, MAGI3 and DLG4 and plays a role in subcellular location of the receptor.

Polymorphism. Genetic variations in ADRB1 are associated with inter-individual variability in the resting heart rate. This quantitative trait has been significantly correlated with cardiovascular morbidity and mortality [MIM:607276]. Genetic variations in ADRB1 are associated with the familial natural short sleep 2 (FNSS2) phenotype, an autosomal dominant trait [MIM:618591]. Individuals with this trait require less sleep in any 24-hour period than is typical for their age group.

Similarity. Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRB1 sub-subfamily.

RefSeq proteins (1): NP_000675* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000507	ADRB1_rcpt	Family
IPR002233	ADR_fam	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (69 total): helix 15, mutagenesis site 11, topological domain 8, sequence variant 8, transmembrane region 7, binding site 6, modified residue 3, region of interest 2, compositionally biased region 2, disulfide bond 2, chain 1, short sequence motif 1, lipid moiety-binding region 1, glycosylation site 1, turn 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
7BVQ	X-RAY DIFFRACTION	2.5
7BU7	X-RAY DIFFRACTION	2.6
7BU6	X-RAY DIFFRACTION	2.7
7BTS	X-RAY DIFFRACTION	3.13
9L84	ELECTRON MICROSCOPY	3.22
8S2T	ELECTRON MICROSCOPY	3.3
2LSQ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08588-F1	77.01	0.52

Antibody-complex structures (SAbDab): 4 — 7BTS, 7BU6, 7BU7, 8S2T

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 (6): 138; 138; 344; 344; 363; 363

Post-translational modifications (4): 312, 412, 428, 392

Disulfide bonds (2): 131–216, 209–215

Glycosylation sites (1): 15

Mutagenesis-validated functional residues (11):

Position	Phenotype
199	decreased noradrenaline affinity.
347	decreased noradrenaline affinity.
359	decreased noradrenaline affinity.
474	loss of interaction with gopc.
474	loss of interaction with gopc; when associated with a-477.
475	loss of interaction with gopc. loss of interaction with rapgef2. abolishes agonist-induced ras activation.
475	loss of interaction with rapgef2.
475	partial loss of interaction with gopc.
476	partial loss of interaction with gopc.
477	loss of interaction with gopc.
477	loss of interaction with rapgef2. abolishes agonist-induced ras activation.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-390696	Adrenoceptors
R-HSA-418555	G alpha (s) signalling events
R-HSA-162582	Signal Transduction
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-375280	Amine ligand-binding receptors
R-HSA-388396	GPCR downstream signalling
R-HSA-500792	GPCR ligand binding

MSigDB gene sets: 238 (showing top): GOBP_CIRCADIAN_RHYTHM, BENPORATH_ES_WITH_H3K27ME3, GOBP_BEHAVIOR, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_RESPONSE_TO_COLD, GOBP_CIRCULATORY_SYSTEM_PROCESS, XU_GH1_AUTOCRINE_TARGETS_UP, GOCC_SECRETORY_GRANULE, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_RESPONSE_TO_DIETARY_EXCESS, GCANCTGNY_MYOD_Q6, GOBP_GROWTH, GOBP_REGULATION_OF_SYSTEMIC_ARTERIAL_BLOOD_PRESSURE, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, SP1_Q2_01

GO Biological Process (19): positive regulation of heart rate by epinephrine-norepinephrine (GO:0001996), positive regulation of the force of heart contraction by epinephrine-norepinephrine (GO:0001997), diet induced thermogenesis (GO:0002024), norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure (GO:0002025), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), response to cold (GO:0009409), positive regulation of cardiac muscle cell apoptotic process (GO:0010666), heat generation (GO:0031649), negative regulation of multicellular organism growth (GO:0040015), fear response (GO:0042596), positive regulation of MAPK cascade (GO:0043410), regulation of circadian sleep/wake cycle, sleep (GO:0045187), brown fat cell differentiation (GO:0050873), adenylate cyclase-activating adrenergic receptor signaling pathway (GO:0071880), positive regulation of cold-induced thermogenesis (GO:0120162), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), positive regulation of heart contraction (GO:0045823), regulation of postsynaptic membrane potential (GO:0060078)

GO Molecular Function (9): beta-adrenergic receptor activity (GO:0004939), beta1-adrenergic receptor activity (GO:0004940), PDZ domain binding (GO:0030165), alpha-2A adrenergic receptor binding (GO:0031694), protein heterodimerization activity (GO:0046982), obsolete G protein-coupled neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential (GO:0099579), G protein-coupled receptor activity (GO:0004930), adrenergic receptor activity (GO:0004935), protein binding (GO:0005515)

GO Cellular Component (6): early endosome (GO:0005769), plasma membrane (GO:0005886), Schaffer collateral - CA1 synapse (GO:0098685), neuronal dense core vesicle (GO:0098992), endosome (GO:0005768), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Signaling by GPCR	2
Amine ligand-binding receptors	1
GPCR downstream signalling	1
Signal Transduction	1
GPCR ligand binding	1
Class A/1 (Rhodopsin-like receptors)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of blood pressure by epinephrine-norepinephrine	2
adrenergic receptor signaling pathway	2
positive regulation of heart rate	1
positive regulation of the force of heart contraction by chemical signal	1
response to dietary excess	1
adaptive thermogenesis	1
regulation of systemic arterial blood pressure by norepinephrine-epinephrine	1
negative regulation of systemic arterial blood pressure	1
vasodilation	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
response to stress	1
response to temperature stimulus	1
cardiac muscle cell apoptotic process	1
positive regulation of striated muscle cell apoptotic process	1
regulation of cardiac muscle cell apoptotic process	1
temperature homeostasis	1
multicellular organism growth	1
regulation of multicellular organism growth	1
negative regulation of developmental growth	1
negative regulation of multicellular organismal process	1
multicellular organismal response to stress	1
MAPK cascade	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
regulation of circadian sleep/wake cycle	1
circadian sleep/wake cycle, sleep	1
fat cell differentiation	1
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1
positive regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
signal transduction	1
regulation of heart contraction	1

Protein interactions and networks

STRING

1524 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADRB1	ARRB1	P49407	929
ADRB1	DLG4	P78352	907
ADRB1	CAMK2D	Q13557	764
ADRB1	ARRB2	P32121	750
ADRB1	REN	P00797	747
ADRB1	GRK5	P34947	736
ADRB1	GOPC	Q9HD26	734
ADRB1	SAG	P10523	719
ADRB1	PRKACG	P22612	719
ADRB1	TPM3	P06753	703
ADRB1	ADCY5	O95622	676
ADRB1	RHO	P08100	650
ADRB1	GNAS	Q5JWF2	645
ADRB1	GNAQ	P50148	633
ADRB1	SLC6A3	Q01959	625

IntAct

162 interactions, top by confidence:

A	B	Type	Score
MAGI2	ADRB1	psi-mi:“MI:0407”(direct interaction)	0.830
ADRB1	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.830
MAGI2	ADRB1	psi-mi:“MI:0914”(association)	0.830
ADRB1	MAGI2	psi-mi:“MI:0403”(colocalization)	0.830
MAGI2	ADRB1	psi-mi:“MI:0915”(physical association)	0.830
ADRB1	MAGI3	psi-mi:“MI:0407”(direct interaction)	0.740
MAGI3	ADRB1	psi-mi:“MI:0407”(direct interaction)	0.740
ADRB1	MAGI3	psi-mi:“MI:0915”(physical association)	0.740
MAGI3	ADRB1	psi-mi:“MI:0403”(colocalization)	0.740
Dlg4	ADRB1	psi-mi:“MI:0407”(direct interaction)	0.620
ADRB1	MAGI1	psi-mi:“MI:0407”(direct interaction)	0.620
MAGI1	ADRB1	psi-mi:“MI:0407”(direct interaction)	0.620
ADRB1	ADORA1	psi-mi:“MI:0915”(physical association)	0.610
ADORA1	ADRB2	psi-mi:“MI:0914”(association)	0.610
ADRB1	GPER1	psi-mi:“MI:0915”(physical association)	0.570

BioGRID (16): GIPC1 (Two-hybrid), GIPC1 (Affinity Capture-Western), USP20 (Affinity Capture-Western), ARRB1 (Reconstituted Complex), ADRB1 (Affinity Capture-Western), ADRB1 (Reconstituted Complex), ADRB1 (Two-hybrid), ADRB1 (Two-hybrid), ADRB1 (Affinity Capture-Western), ADRB1 (Affinity Capture-Western), MAGI2 (Affinity Capture-Western), ARRB1 (Affinity Capture-Western), ARRB2 (Affinity Capture-Western), ADRB1 (Protein-peptide), GPRASP1 (Reconstituted Complex)

ESM2 similar proteins: O02662, O02666, O43603, O70432, O95665, P08588, P13945, P18090, P18825, P18871, P21917, P22086, P25100, P25962, P26255, P30729, P31387, P34971, P35365, P46626, P47899, P50406, P51436, P79148, P97714, Q01337, Q28524, Q28927, Q28998, Q5IS65, Q60474, Q60476, Q60483, Q6TLJ0, Q7TQN7, Q7TQP2, Q80UC6, Q8IZ08, Q91V45, Q924U1

Diamond homologs: G3M4F8, O02662, O02666, O02824, O08892, O42574, O70431, O70432, O77680, P04274, P07550, P07700, P08588, P10608, P13945, P15823, P17124, P18090, P18130, P18762, P18841, P19327, P21728, P21918, P23944, P25021, P25100, P25102, P25115, P25962, P26255, P28222, P28334, P28564, P31388, P34971, P35348, P35368, P35404, P35406

SIGNOR signaling

20 interactions.

A	Effect	B	Mechanism
GOPC	down-regulates	ADRB1	relocalization
ADRB1	“up-regulates activity”	GNAS	binding
ADRB1	“up-regulates activity”	GNAL	binding
ADRB1	“up-regulates activity”	GNA14	binding
L-isoprenaline	“up-regulates activity”	ADRB1	“chemical activation”
ARRB2	“down-regulates activity”	ADRB1	binding
N-[2-hydroxy-5-(1-hydroxy-2-{[1-(4-methoxyphenyl)propan-2-yl]amino}ethyl)phenyl]formamide	“up-regulates activity”	ADRB1	“chemical activation”
“Cy3-bifunctional dye zwitterion”	“up-regulates activity”	ADRB1	“chemical activation”
denopamine	“up-regulates activity”	ADRB1	“chemical activation”
clenbuterol	“up-regulates activity”	ADRB1	“chemical activation”
procaterol	“up-regulates activity”	ADRB1	“chemical activation”
(R)-salbutamol	“up-regulates activity”	ADRB1	“chemical activation”
fenoterol	“up-regulates activity”	ADRB1	“chemical activation”
terbutaline	“up-regulates activity”	ADRB1	“chemical activation”
metaproterenol	“up-regulates activity”	ADRB1	“chemical activation”
adrenaline	“up-regulates activity”	ADRB1	“chemical activation”
arformoterol	“up-regulates activity”	ADRB1	“chemical activation”
practolol	“down-regulates activity”	ADRB1	“chemical inhibition”
metoprolol	“down-regulates activity”	ADRB1	“chemical inhibition”
isoprenaline	“up-regulates activity”	ADRB1	“chemical activation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 90 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
Dopamine Neurotransmitter Release Cycle	5	43.5×	5e-06
Protein-protein interactions at synapses	7	32.6×	2e-07
Assembly and cell surface presentation of NMDA receptors	7	31.2×	2e-07
Neurexins and neuroligins	9	31.1×	2e-09
Neuronal System	7	5.4×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	8	55.3×	7e-10
regulation of postsynaptic membrane neurotransmitter receptor levels	5	29.5×	8e-05
bicellular tight junction assembly	5	19.7×	4e-04
protein-containing complex assembly	9	12.2×	1e-05
protein localization to plasma membrane	8	10.3×	1e-04
cell-cell adhesion	7	8.5×	7e-04
protein transport	12	6.3×	7e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	57
Likely benign	6
Benign	9

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
691285	NM_000684.3(ADRB1):c.560C>T (p.Ala187Val)	Pathogenic

SpliceAI

8 predictions. Top by Δscore:

Variant	Effect	Δscore
10:114045723:A:T	donor_gain	0.4800
10:114046751:T:G	acceptor_gain	0.3900
10:114045722:G:GT	donor_gain	0.2900
10:114045157:T:TA	acceptor_gain	0.2700
10:114044431:T:TA	acceptor_gain	0.2200
10:114045560:GGT:G	donor_gain	0.2100
10:114045561:GTG:G	donor_gain	0.2100
10:114045562:TGT:T	donor_gain	0.2100

AlphaMissense

3017 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:114044443:A:C	D104A	1.000
10:114044443:A:T	D104V	1.000
10:114044504:G:C	W124C	1.000
10:114044504:G:T	W124C	1.000
10:114044524:G:A	C131Y	1.000
10:114044779:G:A	C216Y	1.000
10:114044785:T:G	F218C	1.000
10:114044829:T:C	F233L	1.000
10:114044831:C:A	F233L	1.000
10:114044831:C:G	F233L	1.000
10:114045123:G:C	G331R	1.000
10:114045129:T:C	F333L	1.000
10:114045131:C:A	F333L	1.000
10:114045131:C:G	F333L	1.000
10:114045150:T:C	F340L	1.000
10:114045152:C:A	F340L	1.000
10:114045152:C:G	F340L	1.000
10:114045153:T:C	F341L	1.000
10:114045155:C:A	F341L	1.000
10:114045155:C:G	F341L	1.000
10:114045239:C:A	N369K	1.000
10:114045239:C:G	N369K	1.000
10:114044355:G:C	G75R	0.999
10:114044360:T:A	N76K	0.999
10:114044360:T:G	N76K	0.999
10:114044431:T:A	L100Q	0.999
10:114044431:T:C	L100P	0.999
10:114044442:G:C	D104H	0.999
10:114044443:A:G	D104G	0.999
10:114044444:C:A	D104E	0.999

dbSNP variants (sampled 300 via entrez): RS1000906238 (10:114046198 C>G), RS1001063424 (10:114043194 G>C), RS1001255106 (10:114045702 A>G), RS1001693111 (10:114047079 A>G), RS1001731719 (10:114045431 CGAT>C), RS1002068782 (10:114044171 C>A,G), RS1003154736 (10:114047080 G>C), RS1003633613 (10:114047261 A>C), RS1004156981 (10:114043027 G>A,T), RS1004167974 (10:114044060 C>A,T), RS1004192312 (10:114043865 C>G,T), RS1004495662 (10:114043077 G>A), RS1004528418 (10:114042735 T>G), RS1005017684 (10:114046655 A>G), RS1005175047 (10:114045368 G>C,T)

Disease associations

OMIM: gene MIM:109630 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
short sleep, familial natural, 2	Limited	Autosomal dominant

Mondo (2): pulmonary disease, chronic obstructive, susceptibility to (MONDO:0100167), (MONDO:0020786)

Orphanet (0):

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0033063	Shortened sleep phase

GWAS associations

57 associations (top):

Study	Trait	p-value
GCST001236_10	Blood pressure	2.000000e-09
GCST001380_2	Gaucher disease severity	2.000000e-06
GCST001758_10	Birth weight	4.000000e-09
GCST004280_62	Diastolic blood pressure	5.000000e-07
GCST004776_56	Systolic blood pressure	6.000000e-06
GCST004777_22	Diastolic blood pressure	8.000000e-06
GCST005146_8	Birth weight	5.000000e-18
GCST006021_28	Systolic blood pressure	1.000000e-10
GCST006166_94	Diastolic blood pressure x alcohol consumption interaction (2df test)	8.000000e-23
GCST006167_85	Mean arterial pressure x alcohol consumption interaction (2df test)	2.000000e-10
GCST006169_16	Diastolic blood pressure x alcohol consumption (light vs heavy) interaction (2df test)	9.000000e-09
GCST006170_23	Systolic blood pressure x alcohol consumption (light vs heavy) interaction (2df test)	2.000000e-09
GCST006172_41	Mean arterial pressure x alcohol consumption (light vs heavy) interaction (2df test)	1.000000e-10
GCST006187_27	Diastolic blood pressure (cigarette smoking interaction)	1.000000e-21
GCST006187_28	Diastolic blood pressure (cigarette smoking interaction)	3.000000e-22
GCST006188_6	Systolic blood pressure (cigarette smoking interaction)	2.000000e-14
GCST006188_7	Systolic blood pressure (cigarette smoking interaction)	1.000000e-22
GCST006190_47	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	5.000000e-12
GCST006190_71	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	3.000000e-06
GCST006192_33	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	2.000000e-06
GCST006192_67	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	5.000000e-11
GCST006193_30	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	5.000000e-12
GCST006193_70	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	2.000000e-06
GCST006195_11	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	3.000000e-06
GCST006195_60	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	8.000000e-11
GCST006231_43	Mean arterial pressure	2.000000e-09
GCST006258_17	Diastolic blood pressure	9.000000e-15
GCST006259_1	Systolic blood pressure	5.000000e-13
GCST006434_96	Systolic blood pressure x alcohol consumption interaction (2df test)	2.000000e-20
GCST006666_21	Lipid traits (pleiotropy) (HIPO component 1)	4.000000e-08

EFO canonical traits (19, from GWAS)

EFO ID	Trait name
EFO:0006340	mean arterial pressure
EFO:0004344	birth weight
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure
EFO:0004329	alcohol drinking
EFO:0006527	smoking status measurement
EFO:0004530	triglyceride measurement
EFO:0004574	total cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0009928	Diuretic use measurement
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0005939	parental genotype effect measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004462	PR interval
EFO:0004327	electrocardiography
EFO:0007984	platelet component distribution width
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL2094118 (PROTEIN FAMILY), CHEMBL2096974 (SELECTIVITY GROUP), CHEMBL2097169 (SELECTIVITY GROUP), CHEMBL213 (SINGLE PROTEIN), CHEMBL2331074 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

154 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 555,280 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1200323	LABETALOL HYDROCHLORIDE	4	2,621
CHEMBL1215	PHENYLEPHRINE	4	37,782
CHEMBL1437	NOREPINEPHRINE	4	108,675
CHEMBL1671	PROPRANOLOL HYDROCHLORIDE	4	21,811
CHEMBL1700	SOTALOL HYDROCHLORIDE	4	3,968
CHEMBL27	PROPRANOLOL	4	85,886
CHEMBL434	ISOPROTERENOL	4	40,234
CHEMBL471	SOTALOL	4	21,777
CHEMBL6995	PRACTOLOL	4	4,261
CHEMBL1008	BEPRIDIL	4	11,776
CHEMBL1014	CANDESARTAN CILEXETIL	4	11,194
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1095777	INDACATEROL	4	2,735
CHEMBL1112	ARIPIPRAZOLE	4	24,205
CHEMBL1173055	RUCAPARIB	4	7,009
CHEMBL1175	DULOXETINE	4	28,527
CHEMBL1198857	VILANTEROL	4	2,552
CHEMBL1200438	TIOCONAZOLE	4	15,162
CHEMBL1201129	DECITABINE	4	58,183
CHEMBL1201237	LEVOBUNOLOL	4	10,597
CHEMBL1201284	CINACALCET	4
CHEMBL1201303	PYRVINIUM	4
CHEMBL1201304	INDOCYANINE GREEN ACID FORM	4
CHEMBL1201319	METARAMINOL	4
CHEMBL1201356	METHYLERGONOVINE	4
CHEMBL1256786	FORMOTEROL	4
CHEMBL1263	SALMETEROL	4
CHEMBL12713	SERTINDOLE	4
CHEMBL13	METOPROLOL	4
CHEMBL1336	SORAFENIB	4

PharmGKB: 1 entry (VIP=true, CPIC=true)

PharmGKB clinical annotations

14 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1801252	Efficacy	3	timolol
rs1801252	Toxicity	3	Beta Blocking Agents	Major Adverse Cardiac Events (MACE)
rs1801252	Efficacy	3	metoprolol	Hypertension
rs1801252	Efficacy	3	carvedilol
rs1801253	Toxicity	3	muraglitazar	Diabetes Mellitus;Edema;Hyperlipidemias
rs1801253	Efficacy	4	Beta Blocking Agents	Cardiomyopathy;Dilated;Heart Failure
rs1801253	Efficacy	3	dobutamine
rs1801253	Dosage	3	catecholamines	Coronary Artery Disease
rs1801253	Efficacy	3	metoprolol
rs1801253	Dosage	3	carvedilol	Heart Failure
rs1801253	Efficacy	3	bucindolol	Heart Failure
rs1801253	Efficacy	3	Ace Inhibitors;Plain;Angiotensin II Antagonists;Beta Blocking Agents;digoxin;diuretics;spironolactone	Heart Failure
rs1801253	Efficacy	4	atenolol	Atrial Fibrillation;Essential hypertension;Tachycardia
rs1801253	Efficacy	4	carvedilol	Heart Failure

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1801252	ADRB1	3	3.50	4	carvedilol;timolol;Beta Blocking Agents;metoprolol
rs1801253	ADRB1	3	7.00	10	muraglitazar;carvedilol;bucindolol;dobutamine;catecholamines;Ace Inhibitors;Plain;Angiotensin II Antagonists;Beta Blocking Agents;digoxin;diuretics;spironolactone;Beta Blocking Agents;metoprolol;atenolol

PharmGKB dosing guidelines

1 guidelines.

Source	Drug	Guideline	Dosing?	Recommendation?
CPIC	acebutolol;atenolol;betaxolol;bisoprolol;carvedilol;esmolol;labetalol;metoprolol;nadolol;nebivolol;pindolol;propranolol;sotalol	Annotation of CPIC Guideline for acebutolol, atenolol, betaxolol, bisoprolol, carvedilol, esmolol, labetalol, metoprolol, nadolol, nebivolol, pindolol, propranolol, sotalol and ADRA2C, ADRB1, GRK4, GRK5

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Adrenoceptors

Most potent curated ligand interactions (59 total), top 25:

Ligand	Action	Affinity	Parameter
[125I]ICYP	Antagonist	11.3	pKd
cyanopindolol	Antagonist	10.5	pKd
7-methylcyanopindolol	Antagonist	10.4	pKd
carazolol	Antagonist	10.2	pKd
carvedilol	Antagonist	9.8	pKi
CGP 20712A	Antagonist	9.6	pKi
3HCGP 12177	Partial agonist	9.4	pKd
CGP 12177	Partial agonist	9.4	pKi
bupranolol	Antagonist	9.4	pKi
bucindolol	Antagonist	9.3	pKi
pindolol	Partial agonist	9.3	pKi
BI-167107	Agonist	9.22	pEC50
nebivolol	Antagonist	9.2	pKi
betaxolol	Antagonist	9.12	pKi
NDD-825	Antagonist	9.0	pKi
timolol	Antagonist	9.0	pKi
ICI-89406	Partial agonist	8.8	pKi
(-)-propranolol	Antagonist	8.7	pKi
NDD-713	Antagonist	8.5	pKi
LK 204-545	Antagonist	8.5	pKi
NIP	Antagonist	8.4	pKi
SR59230A	Antagonist	8.4	pKi
bunolol	Antagonist	8.4	pKi
labetalol	Antagonist	8.2	pKi
cicloprolol	Antagonist	8.0	pKi

Binding affinities (BindingDB)

39 measured of 49 human assays (81 total across all organisms); most potent 39 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
roxindole	KI	0.11 nM
3,3-diethyl-1-[(4R,7R)-6-methyl-6,11-diazatetracyclo[7.6.1.0^{2,7}.0^{12,16}]hexadeca-1(15),2,9,12(16),13-pentaen-4-yl]urea	KI	0.15 nM
2-Chlor-11-(2-dimethylaminoaethoxy)-dibenzo(b,f)-thiepin	KI	0.5 nM
4-[3-(tert-butylamino)-2-hydroxypropoxy]-2,3-dihydro-1H-1,3-benzodiazol-2-one hydrochloride	KD	0.62 nM
ICI 89,406	KD	1.24 nM
[3-(9H-carbazol-4-yloxy)-2-hydroxypropyl][2-(2-methoxyphenoxy)ethyl]amine	KD	1.76 nM
5-[2-(4-Benzo[d]isothiazol-3-yl-piperazin-1-yl)-ethyl]-6-chloro-1,3-dihydro-indol-2-one	KI	1.9 nM
Permax	KI	1.91 nM
tert-butyl[3-(2-chloro-5-methylphenoxy)-2-hydroxypropyl]amine	KD	3.1 nM
Terguride	KI	3.47 nM
S18616	KI	3.98 nM
tert-butyl(2-hydroxy-3-{[4-(morpholin-4-yl)-1,2,5-thiadiazol-3-yl]oxy}propyl)amine	KD	5.35 nM
Bromocriptine+ (GTP+)	KI	12.9 nM
Bisoprolol fumarate	KD	15 nM
CAS_174689-39-5	KI	16.4 nM
NSC_54746	KI	19.9 nM
1-(4-{3-[4-(6-Fluoro-benzo[d]isoxazol-3-yl)-piperidin-1-yl]-propoxy}-3-methoxy-phenyl)-ethanone	KI	33 nM
Fluorocarazolol,(S)	KI	34 nM
cid_3396	KI	56 nM
N-(2-{[(2R)-2-hydroxy-3-(4-hydroxyphenoxy)propyl]amino}ethyl)morpholine-4-carboxamide	KD	60 nM
Propanolol,(+/-)	KI	272 nM
4-[2-(dipropylamino)ethyl]-1,3-dihydro-2H-indol-2-one	KI	288 nM
N-{3-acetyl-4-[2-hydroxy-3-(propan-2-ylamino)propoxy]phenyl}butanamide	KD	347 nM
1-(naphthalen-2-yl)-2-(propan-2-ylamino)ethan-1-ol	KD	363 nM
2-[4-(2-{[(2R)-2-hydroxy-3-phenoxypropyl]amino}ethoxy)phenoxy]acetic acid	KD	427 nM
NSC_4850	KI	447 nM
CAS_85760-74-3	IC50	462 nM	US-9359372: Hexahydrodibenzo[a,g]quinolizine compound, preparation method thereof, pharmaceutical composition and use thereof
Pramipexole	KI	692 nM
SR 147778	KI	1000 nM
1-[2-[4-[5-chloro-1-(4-fluorophenyl)-indol-3-yl]-1-piperidyl]ethyl]imidazolidin-2-one	KI	1050 nM
NSC_71149	KI	1310 nM
B-HT 920	KI	1700 nM
NSC_3083544	KI	1710 nM
7-{4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy}-3,4-dihydroquinolin-2(1H)-one	EC50	1880 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof
CAS_1893-33-0	KI	2770 nM
(6,7-Dihydroxy-1,2,3,4-tetrahydro-naphthalen-2-yl)-dimethyl-ammonium	KI	3800 nM
salmeterol xinafoate	KD	4170 nM
cid_2685	KI	7360 nM
Levalbuterol	KD	21900 nM

ChEMBL bioactivities

2185 potent at pChembl≥5 of 2377 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.64	Ki	0.023	nM	CHEMBL2012522
10.40	IC50	0.04	nM	CHEMBL2011218
10.30	IC50	0.05	nM	CHEMBL2011226
10.30	IC50	0.05	nM	CHEMBL2011227
10.12	Kd	0.075	nM	CHEMBL4860528
10.12	Kd	0.075	nM	CHEMBL5207281
10.12	Kd	0.075	nM	CHEMBL5206565
10.12	Kd	0.075	nM	CHEMBL5201074
10.10	IC50	0.08	nM	CHEMBL2011216
10.08	EC50	0.084	nM	ISOPROTERENOL
10.00	IC50	0.1	nM	CHEMBL2011215
10.00	IC50	0.1	nM	CHEMBL2011224
10.00	Ki	0.1	nM	CHEMBL1084707
9.99	Ki	0.103	nM	CARVEDILOL
9.98	EC50	0.1047	nM	CHEMBL5574456
9.96	IC50	0.11	nM	CHEMBL2011213
9.92	EC50	0.1202	nM	CHEMBL5572781
9.89	EC50	0.13	nM	CHEMBL416012
9.89	EC50	0.1288	nM	CHEMBL5575873
9.89	EC50	0.13	nM	CHEMBL26183
9.86	EC50	0.138	nM	CHEMBL5567636
9.85	IC50	0.14	nM	CHEMBL2011235
9.82	EC50	0.1514	nM	CHEMBL5563982
9.77	EC50	0.1698	nM	CHEMBL5550060
9.75	EC50	0.1778	nM	CHEMBL5565088
9.75	IC50	0.178	nM	CARVEDILOL
9.74	Ki	0.182	nM	AROTINOLOL
9.70	IC50	0.2	nM	CHEMBL2011214
9.63	EC50	0.2344	nM	CHEMBL5573953
9.61	EC50	0.2455	nM	CHEMBL5569415
9.61	EC50	0.2455	nM	CHEMBL5595588
9.60	IC50	0.25	nM	CHEMBL2011217
9.60	Ki	0.25	nM	CHEMBL36060
9.59	EC50	0.257	nM	CHEMBL5562809
9.52	IC50	0.3	nM	CHEMBL2011225
9.51	EC50	0.309	nM	CHEMBL5574770
9.49	EC50	0.3236	nM	CHEMBL5570271
9.48	Kd	0.3311	nM	CHEMBL3392321
9.48	Kd	0.3311	nM	CGP-20712A
9.46	IC50	0.35	nM	CHEMBL2011228
9.42	Kd	0.38	nM	(S)-TOLIPROLOL
9.40	EC50	0.3981	nM	CHEMBL5564275
9.36	Ki	0.434	nM	CHEMBL117405
9.29	EC50	0.5129	nM	CHEMBL5592612
9.29	EC50	0.5129	nM	CHEMBL5568704
9.28	Ki	0.52	nM	PINDOLOL
9.27	Ki	0.532	nM	PINDOLOL
9.24	EC50	0.57	nM	CHEMBL1257913
9.22	EC50	0.6026	nM	CHEMBL4868585
9.22	EC50	0.6	nM	CHEMBL579394

PubChem BioAssay actives

2074 with measured affinity, of 5938 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
butanedioic acid;6-[4-[2-[[(2S)-3-(9H-carbazol-4-yloxy)-2-hydroxypropyl]amino]-2-methylpropyl]phenoxy]pyridine-3-carboxamide	652453: Displacement of [125I]Iodocyanopindolol from human adrenergic beta1 receptor expressed in insect sf9 cells by scintillation counting	ki	<0.0001	uM
1-[2-[[(2S)-3-(2-cyanophenoxy)-2-hydroxypropyl]amino]ethyl]-3-[3-(2-fluoroethoxy)phenyl]urea	652407: Displacement of 3H-CGP-12177 from adrenergic beta1 receptor by cell based assay	ic50	<0.0001	uM
(1R)-1-(3-chlorophenyl)-2-[[(2R)-1-(7-methoxy-1H-indol-3-yl)propan-2-yl]amino]ethanol	40110: Agonistic activity against human Beta-1 adrenergic receptor by measuring cAMP accumulation in CHO cells expressing beta3-AR	ec50	0.0001	uM
1-[2-[[(2S)-3-(2-cyanophenoxy)-2-hydroxypropyl]amino]ethyl]-3-(4-methoxyphenyl)urea	652407: Displacement of 3H-CGP-12177 from adrenergic beta1 receptor by cell based assay	ic50	0.0001	uM
1-[2-[[(2S)-3-(2-cyanophenoxy)-2-hydroxypropyl]amino]ethyl]-3-[4-(2-fluoroethoxy)phenyl]urea	652407: Displacement of 3H-CGP-12177 from adrenergic beta1 receptor by cell based assay	ic50	0.0001	uM
1-[N’-[3-(2-amino-4-methyl-1,3-thiazol-5-yl)propyl]carbamimidoyl]-3-pentylurea	1895233: Displacement of [3H]CGP12177 from human beta-1 adrenergic receptor stably expressed in HEK293T cell membrane incubated for 2 hrs by scintillation counting analysis	kd	0.0001	uM
1-[(1R)-1-phenylethyl]-3-[N’-[3-(1H-1,2,4-triazol-5-yl)propyl]carbamimidoyl]urea;dihydrochloride	1895233: Displacement of [3H]CGP12177 from human beta-1 adrenergic receptor stably expressed in HEK293T cell membrane incubated for 2 hrs by scintillation counting analysis	kd	0.0001	uM
1-[N’-[3-(5-amino-1,3,4-thiadiazol-2-yl)propyl]carbamimidoyl]-3-pentylurea;bis(2,2,2-trifluoroacetic acid)	1895233: Displacement of [3H]CGP12177 from human beta-1 adrenergic receptor stably expressed in HEK293T cell membrane incubated for 2 hrs by scintillation counting analysis	kd	0.0001	uM
1-[N’-[3-(5-amino-1,3,4-thiadiazol-2-yl)propyl]carbamimidoyl]-3-benzylurea;bis(2,2,2-trifluoroacetic acid)	1895233: Displacement of [3H]CGP12177 from human beta-1 adrenergic receptor stably expressed in HEK293T cell membrane incubated for 2 hrs by scintillation counting analysis	kd	0.0001	uM
methyl (2R)-2-amino-3-[4-[(2S)-3-(2,3-dihydro-1,4-benzodioxin-3-ylmethylamino)-2-hydroxypropoxy]phenyl]propanoate	2002280: Antagonist activity at human beta1-adrenergic receptor expressed in CHO-K1 cells co-expressing CRE-SPAP reporter gene assessed as inhibition of fenoterol-induced CRE-SPAP production by measuring rightward shift of the fenoterol concentration response curve measured after 5 hrs incubation	kd	0.0001	uM
5-hydroxy-8-[1-hydroxy-2-[3-(3-hydroxyphenyl)propylamino]ethyl]-4H-1,4-benzoxazin-3-one;hydrochloride	2089646: Agonist activity at human beta1 adrenoceptor expressed in HEK293 cells assessed as induction of accumulation of cAMP by HTRF assay	ec50	0.0001	uM
5-hydroxy-8-[1-hydroxy-2-[3-(4-hydroxyphenyl)propylamino]ethyl]-4H-1,4-benzoxazin-3-one;hydrochloride	2089646: Agonist activity at human beta1 adrenoceptor expressed in HEK293 cells assessed as induction of accumulation of cAMP by HTRF assay	ec50	0.0001	uM
8-[2-[3-(3,5-difluorophenyl)propylamino]-1-hydroxyethyl]-5-hydroxy-4H-1,4-benzoxazin-3-one;hydrochloride	2089646: Agonist activity at human beta1 adrenoceptor expressed in HEK293 cells assessed as induction of accumulation of cAMP by HTRF assay	ec50	0.0001	uM
5-hydroxy-8-[1-hydroxy-2-[3-(2-hydroxyphenyl)propylamino]ethyl]-4H-1,4-benzoxazin-3-one;hydrochloride	2089646: Agonist activity at human beta1 adrenoceptor expressed in HEK293 cells assessed as induction of accumulation of cAMP by HTRF assay	ec50	0.0001	uM
Isoproterenol	246460: Agonistic activity was assessed by measuring cAMP accumulation in CHO cell lines expressing cloned human Beta-1 adrenergic receptor	ec50	0.0001	uM
2-[[1-[3-(9H-carbazol-4-yloxy)-2-hydroxypropyl]piperidin-4-yl]methyl]-5-methoxybenzo[de]isoquinoline-1,3-dione	484592: Displacement of [125I]cyanopindolol from human adrenergic beta-1 receptor expressed in CHOK1 cells	ki	0.0001	uM
N-[2-[[(2S)-3-(2-cyanophenoxy)-2-hydroxypropyl]amino]ethyl]-2-(4-fluorophenyl)acetamide	652407: Displacement of 3H-CGP-12177 from adrenergic beta1 receptor by cell based assay	ic50	0.0001	uM
1-[2-[[(2S)-3-(2-cyanophenoxy)-2-hydroxypropyl]amino]ethyl]-3-[6-(2-fluoroethoxy)-3-pyridinyl]urea	652407: Displacement of 3H-CGP-12177 from adrenergic beta1 receptor by cell based assay	ic50	0.0001	uM
1-[2-[[(2S)-3-(2-cyanophenoxy)-2-hydroxypropyl]amino]ethyl]-3-(6-iodo-3-pyridinyl)urea	652407: Displacement of 3H-CGP-12177 from adrenergic beta1 receptor by cell based assay	ic50	0.0001	uM
1-[2-[[(2S)-3-(2-cyanophenoxy)-2-hydroxypropyl]amino]ethyl]-3-(4-fluorophenyl)urea	652407: Displacement of 3H-CGP-12177 from adrenergic beta1 receptor by cell based assay	ic50	0.0001	uM
1-(6-bromo-3-pyridinyl)-3-[2-[[(2S)-3-(2-cyanophenoxy)-2-hydroxypropyl]amino]ethyl]urea	652407: Displacement of 3H-CGP-12177 from adrenergic beta1 receptor by cell based assay	ic50	0.0001	uM
(1R)-1-(3-chlorophenyl)-2-[1-(7-methoxy-1H-indol-3-yl)propan-2-ylamino]ethanol	1095332: Agonist activity at Homo sapiens (human) beta1 adrenoreceptor	ec50	0.0001	uM
5-hydroxy-8-[1-hydroxy-2-[3-(3-methylphenyl)propylamino]ethyl]-4H-1,4-benzoxazin-3-one;hydrochloride	2089646: Agonist activity at human beta1 adrenoceptor expressed in HEK293 cells assessed as induction of accumulation of cAMP by HTRF assay	ec50	0.0002	uM
8-[2-[3-(3-fluorophenyl)propylamino]-1-hydroxyethyl]-5-hydroxy-4H-1,4-benzoxazin-3-one;hydrochloride	2089646: Agonist activity at human beta1 adrenoceptor expressed in HEK293 cells assessed as induction of accumulation of cAMP by HTRF assay	ec50	0.0002	uM
8-[2-[3-(4-chlorophenyl)propylamino]-1-hydroxyethyl]-5-hydroxy-4H-1,4-benzoxazin-3-one;hydrochloride	2089646: Agonist activity at human beta1 adrenoceptor expressed in HEK293 cells assessed as induction of accumulation of cAMP by HTRF assay	ec50	0.0002	uM
8-[2-[3-(4-fluorophenyl)propylamino]-1-hydroxyethyl]-5-hydroxy-4H-1,4-benzoxazin-3-one;hydrochloride	2089646: Agonist activity at human beta1 adrenoceptor expressed in HEK293 cells assessed as induction of accumulation of cAMP by HTRF assay	ec50	0.0002	uM
5-hydroxy-8-[1-hydroxy-2-[3-(2-methoxyphenyl)propylamino]ethyl]-4H-1,4-benzoxazin-3-one;hydrochloride	2089646: Agonist activity at human beta1 adrenoceptor expressed in HEK293 cells assessed as induction of accumulation of cAMP by HTRF assay	ec50	0.0002	uM
8-[2-[3-(2-fluorophenyl)propylamino]-1-hydroxyethyl]-5-hydroxy-4H-1,4-benzoxazin-3-one;hydrochloride	2089646: Agonist activity at human beta1 adrenoceptor expressed in HEK293 cells assessed as induction of accumulation of cAMP by HTRF assay	ec50	0.0002	uM
5-[2-[3-(tert-butylamino)-2-hydroxypropyl]sulfanyl-1,3-thiazol-4-yl]thiophene-2-carboxamide	2033266: Inhibition of beta-1 adrenoceptor (unknown origin)	ki	0.0002	uM
1-[2-[[(2S)-3-(2-cyanophenoxy)-2-hydroxypropyl]amino]ethyl]-3-(2-fluorophenyl)urea	652407: Displacement of 3H-CGP-12177 from adrenergic beta1 receptor by cell based assay	ic50	0.0002	uM
1-[2-[[3-(2-cyanophenoxy)-2-hydroxypropyl]amino]ethyl]-3-phenylurea;hydrate	739711: Antagonist activity at human beta1 adrenoceptor expressed in CHOK1 cells assessed as inhibition of cimaterol-induced [3H]cAMP accumulation incubated for 15 mins prior to cimaterol induction measured after 5 hrs	kd	0.0003	uM
5-hydroxy-8-[1-hydroxy-2-(3-phenylpropylamino)ethyl]-4H-1,4-benzoxazin-3-one;hydrochloride	2089646: Agonist activity at human beta1 adrenoceptor expressed in HEK293 cells assessed as induction of accumulation of cAMP by HTRF assay	ec50	0.0003	uM
5-hydroxy-8-[1-hydroxy-2-(4-phenylbutylamino)ethyl]-4H-1,4-benzoxazin-3-one;hydrochloride	2089646: Agonist activity at human beta1 adrenoceptor expressed in HEK293 cells assessed as induction of accumulation of cAMP by HTRF assay	ec50	0.0003	uM
5-hydroxy-8-[1-hydroxy-2-[3-(2-methylphenyl)propylamino]ethyl]-4H-1,4-benzoxazin-3-one;hydrochloride	2089646: Agonist activity at human beta1 adrenoceptor expressed in HEK293 cells assessed as induction of accumulation of cAMP by HTRF assay	ec50	0.0003	uM
2-hydroxy-5-[2-[[2-hydroxy-3-[4-[1-methyl-4-(trifluoromethyl)imidazol-2-yl]phenoxy]propyl]amino]ethoxy]benzamide	739711: Antagonist activity at human beta1 adrenoceptor expressed in CHOK1 cells assessed as inhibition of cimaterol-induced [3H]cAMP accumulation incubated for 15 mins prior to cimaterol induction measured after 5 hrs	kd	0.0003	uM
4-[(2S)-3-(tert-butylamino)-2-hydroxypropoxy]-1,3-dihydrobenzimidazol-2-one	220776: Inhibition of I-iodocyanopindolol binding to human beta 1 adrenergic receptors	ki	0.0003	uM
1-[2-[[(2S)-3-(2-cyanophenoxy)-2-hydroxypropyl]amino]ethyl]-3-(6-fluoro-3-pyridinyl)urea	652407: Displacement of 3H-CGP-12177 from adrenergic beta1 receptor by cell based assay	ic50	0.0003	uM
1-[2-[[(2S)-3-(2-cyanophenoxy)-2-hydroxypropyl]amino]ethyl]-3-[4-(3-fluoropropoxy)phenyl]urea	652407: Displacement of 3H-CGP-12177 from adrenergic beta1 receptor by cell based assay	ic50	0.0003	uM
1-(5-bromopyrazin-2-yl)-3-[2-[[(2S)-3-(2-cyanophenoxy)-2-hydroxypropyl]amino]ethyl]urea	652407: Displacement of 3H-CGP-12177 from adrenergic beta1 receptor by cell based assay	ic50	0.0003	uM
(2S)-1-(3-methylphenoxy)-3-(propan-2-ylamino)propan-2-ol	366093: Binding affinity to beta-1 adrenergic receptor	kd	0.0004	uM
5-hydroxy-8-[1-hydroxy-2-[3-(3-methoxyphenyl)propylamino]ethyl]-4H-1,4-benzoxazin-3-one;hydrochloride	2089646: Agonist activity at human beta1 adrenoceptor expressed in HEK293 cells assessed as induction of accumulation of cAMP by HTRF assay	ec50	0.0004	uM
5-hydroxy-8-[1-hydroxy-2-[3-[3-(trifluoromethyl)phenyl]propylamino]ethyl]-4H-1,4-benzoxazin-3-one;hydrochloride	2089646: Agonist activity at human beta1 adrenoceptor expressed in HEK293 cells assessed as induction of accumulation of cAMP by HTRF assay	ec50	0.0005	uM
5-hydroxy-8-[1-hydroxy-2-[3-(4-methoxyphenyl)propylamino]ethyl]-4H-1,4-benzoxazin-3-one;hydrochloride	2089646: Agonist activity at human beta1 adrenoceptor expressed in HEK293 cells assessed as induction of accumulation of cAMP by HTRF assay	ec50	0.0005	uM
Pindolol	301362: Binding affinity at human adrenergic beta-1 receptor	ki	0.0005	uM
5-[(1R)-2-[[4-(3-chlorophenyl)-2-methylbutan-2-yl]amino]-1-hydroxyethyl]-8-hydroxy-1H-quinolin-2-one;hydrochloride	1783429: Agonist activity at human beta1 adrenoreceptor overexpressed in HEK293 cells assessed as cAMP accumulation	ec50	0.0006	uM
3-[2-hydroxy-3-[[1-(5-phenylthieno[2,3-d]pyrimidin-4-yl)piperidin-4-yl]amino]propoxy]phenol	517619: Agonist activity at human recombinant adrenergic beta-1 receptor expressed in CHO cells assessed as cyclic AMP formation by HTRF assay	ec50	0.0006	uM
4-[3-(tert-butylamino)-2-hydroxypropoxy]-1,3-dihydrobenzimidazol-2-one	1798580: 3H-CGP 12177 Whole Cell Binding Assay from Article 10.1038/sj.bjp.0706048: “The selectivity of beta-adrenoceptor antagonists at the human beta1, beta2 and beta3 adrenoceptors.”	kd	0.0006	uM
5-hydroxy-8-[1-hydroxy-2-[[2-methyl-1-(2-methylphenyl)propan-2-yl]amino]ethyl]-4H-1,4-benzoxazin-3-one	438906: Agonist activity at human adrenergic beta 1 expressed in CHO-K1 cells assessed as intracellular cAMP accumulation	ec50	0.0006	uM
5-hydroxy-8-[1-hydroxy-2-[3-(4-methylphenyl)propylamino]ethyl]-4H-1,4-benzoxazin-3-one;hydrochloride	2089646: Agonist activity at human beta1 adrenoceptor expressed in HEK293 cells assessed as induction of accumulation of cAMP by HTRF assay	ec50	0.0007	uM
4-hydroxy-7-[(1R)-1-hydroxy-2-[[(1R,2R)-2-(2-phenylethyl)cyclopentyl]amino]ethyl]-3H-1,3-benzothiazol-2-one	1185818: Displacement of [125I]iodo-(+/-)-cyanopindolol from human adrenergic beta1 receptor expressed in CHO cells after 3 hrs by radio-ligand binding assay	ki	0.0008	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Carvedilol	affects cotreatment, affects binding, decreases abundance, increases activity, affects response to substance (+7 more)	18
Metoprolol	affects response to substance, affects cotreatment, affects binding, decreases activity, decreases abundance (+2 more)	13
Atenolol	affects response to substance, affects binding, increases expression, increases phosphorylation, increases abundance (+6 more)	11
Propranolol	increases uptake, affects binding, decreases abundance, decreases reaction, increases phosphorylation (+6 more)	11
Cyclic AMP	decreases abundance, affects cotreatment, increases abundance, affects abundance, affects reaction (+5 more)	8
Dobutamine	affects response to substance, affects cotreatment, increases reaction, affects binding, increases uptake (+3 more)	8
Isoproterenol	affects binding, increases abundance, increases phosphorylation, affects response to substance, decreases reaction (+3 more)	7
Bisoprolol	affects binding, decreases activity, decreases abundance, decreases reaction, increases abundance	7
CGP 12177	decreases activity, decreases abundance, affects cotreatment, affects binding, decreases reaction (+2 more)	5
CGP 20712A	affects binding, decreases abundance, decreases reaction, increases abundance, increases activity (+3 more)	5
Valproic Acid	affects expression, increases expression, increases methylation	5
Alprenolol	decreases reaction, increases phosphorylation, increases reaction, decreases activity, decreases abundance (+6 more)	4
Norepinephrine	affects binding, increases activity, increases abundance, decreases reaction, increases reaction	4
Pindolol	decreases abundance, decreases reaction, increases abundance, increases expression, affects reaction (+3 more)	4
Bupranolol	affects cotreatment, increases abundance, affects binding, decreases reaction, decreases activity	3
Epinephrine	affects reaction, affects binding, increases abundance, decreases reaction, increases activity	3
Estradiol	decreases reaction, increases expression	3
Terbutaline	affects binding, decreases activity, increases activity, decreases reaction	3
broxaterol	affects binding, decreases activity, increases activity, decreases reaction	2
cyanopindolol	decreases reaction, affects binding	2
Nebivolol	affects binding, decreases reaction, increases activity	2
Albuterol	affects binding, decreases reaction	2
Colforsin	affects cotreatment, increases abundance, increases reaction, increases activity, affects reaction (+3 more)	2
Labetalol	affects cotreatment, decreases reaction, increases abundance, increases activity, decreases activity	2
Nickel	decreases expression	2
Nicotine	increases expression, increases phosphorylation, decreases response to substance, affects binding, decreases activity (+1 more)	2
Timolol	affects binding, decreases activity, decreases reaction, increases abundance	2
Betaxolol	affects binding, decreases activity	2
Iodocyanopindolol	affects binding, decreases reaction	2
aristolochic acid I	decreases expression	1

ChEMBL screening assays

809 unique, capped per target: 509 binding, 290 functional, 10 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
CHEMBL4051048	ADMET	Agonist activity at recombinant human beta1 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

7 cell lines: 4 spontaneously immortalized cell line, 2 transformed cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1J6	Abcam HeLa ADRB1 KO	Cancer cell line	Female
CVCL_C0S4	ACTOne ADRB1	Transformed cell line	Female
CVCL_H393	CHO-K1/ADRB1/Galpha15	Spontaneously immortalized cell line	Female
CVCL_KU78	cAMP Hunter CHO-K1 ADRB1 Gs	Spontaneously immortalized cell line	Female
CVCL_KW29	PathHunter CHO-K1 ADRB1 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_W457	HEK-293B1	Transformed cell line	Female
CVCL_ZK41	GeneBLAzer ADRB1-CRE-bla CHO-K1	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.