ADRB3

Summary

ADRB3 (adrenoceptor beta 3, HGNC:288) is a protein-coding gene on chromosome 8p11.23, encoding Beta-3 adrenergic receptor (P13945). G protein-coupled receptor for catecholamines that couples to both G(s) and G(i) proteins, leading to either activation or inhibition of adenylate cyclase and cAMP-dependent pathway, respectively.

The protein encoded by this gene belongs to the family of beta adrenergic receptors, which mediate catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor is located mainly in the adipose tissue and is involved in the regulation of lipolysis and thermogenesis. Obesity and bodyweight-related disorders are correlated with certain polymorphisms in three subtypes of beta-adrenoceptor, among them, the ADRB3 gene.

Source: NCBI Gene 155 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 69 total
• Phenotypes (HPO): 6
• Druggable target: yes — 91 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000025

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:288
Approved symbol	ADRB3
Name	adrenoceptor beta 3
Location	8p11.23
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000188778
Ensembl biotype	protein_coding
OMIM	109691
Entrez	155

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 retained_intron

ENST00000345060, ENST00000520341

RefSeq mRNA: 1 — MANE Select: NM_000025 NM_000025

CCDS: CCDS6099

Canonical transcript exons

ENST00000345060 — 2 exons

Exon	Start	End
ENSE00001364618	37965265	37966599
ENSE00001406417	37962990	37964239

Expression profiles

Bgee: expression breadth broad, 67 present calls, max score 81.49.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2326 / max 126.5461, expressed in 45 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92723	0.1870	41
92721	0.0210	3
92724	0.0113	4
92722	0.0075	2
92725	0.0058	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
diaphragm	UBERON:0001103	81.49	gold quality
right ovary	UBERON:0002118	79.75	gold quality
left ovary	UBERON:0002119	79.09	gold quality
ovary	UBERON:0000992	76.19	gold quality
left ventricle myocardium	UBERON:0006566	74.09	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	73.66	gold quality
left uterine tube	UBERON:0001303	72.91	gold quality
cardiac muscle of right atrium	UBERON:0003379	72.52	gold quality
lower esophagus muscularis layer	UBERON:0035833	71.88	gold quality
lower esophagus	UBERON:0013473	71.73	gold quality
superficial temporal artery	UBERON:0001614	70.00	gold quality
triceps brachii	UBERON:0001509	69.44	gold quality
CA1 field of hippocampus	UBERON:0003881	69.36	gold quality
gluteal muscle	UBERON:0002000	69.29	gold quality
tongue squamous epithelium	UBERON:0006919	68.60	gold quality
placenta	UBERON:0001987	67.57	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	67.27	gold quality
endothelial cell	CL:0000115	67.18	gold quality
urinary bladder	UBERON:0001255	67.07	gold quality
myocardium	UBERON:0002349	66.98	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	66.89	gold quality
vena cava	UBERON:0004087	65.92	gold quality
secondary oocyte	CL:0000655	65.23	gold quality
vastus lateralis	UBERON:0001379	64.98	gold quality
quadriceps femoris	UBERON:0001377	64.62	gold quality
parotid gland	UBERON:0001831	64.50	gold quality
epithelial cell of pancreas	CL:0000083	64.36	gold quality
layer of synovial tissue	UBERON:0007616	64.06	gold quality
cardia of stomach	UBERON:0001162	63.75	gold quality
gall bladder	UBERON:0002110	63.73	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.79

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, FOXO1, SHOX2, SP1, TRPV4

miRNA regulators (miRDB)

90 targeting ADRB3, 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-4481	100.00	66.42	1669
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-6870-5P	99.99	68.55	2115
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-4745-5P	99.98	65.95	1028
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-570-3P	99.96	72.41	4910

Literature-anchored findings (GeneRIF, showing 40)

• lipid mobilizing factor induces lipolysis through binding to a beta3-adrenoceptor (PMID:11875710)
• the cAMP response of W64R-beta3AR can be enhanced under the particular condition that adenylyl cyclase type III was coexpressed (PMID:11949887)
• obese postmenopausal women who carry the Trp64Arg variant in the beta(3)-adrenoceptor had similar changes in body composition and energy expenditure to noncarriers of the variant in response to prolonged caloric restriction (PMID:12037740)
• polymorphism found to be associated with exercise-mediated improvement in glucose tolerance and leptin resistance in healthy Japanese men (PMID:12062855)
• The frequency of Trp64Arg mutation of beta(3)-AR gene was higher in the male subjects with MS than those with simple obesity and non-obese controls (PMID:12133431)
• genetic variants in the gene appear not to have a major role as modifier genes in familial combined hyperlipidemia (PMID:12370850)
• findings suggest that the Trp64Arg variant in the beta3-adrenergic receptor gene may be associated with reducing LDL particle size, probably due to insulin resistance (PMID:12647276)
• beta3-adrenergic receptors play a role in proliferation and migration of cultured human retinal endothelial cells. (PMID:12670949)
• results suggest that the Arginine-64 beta(3)-adrenoceptor allele contributes significantly to the genetic variability in both resting metabolic rate and thermic effect of feeding (PMID:12690078)
• Amino acid substistution is not associated with insulin resistance phenotype. (PMID:12739018)
• Arg64/arg64 beta(3)-AR polymorphism may contribute to increased triglycerides and very low-density lipoprotein cholesterol in rheumatoid arthritis patients, independently of chloroquine treatment. (PMID:12739037)
• b3-AR 64Arg polymorphisms have a protective effect against metabolic disorders in obese families from southern Poland. (PMID:12824951)
• ADRB3 polymorphism is not associated with a risk of endometrial neoplasms. (PMID:12962933)
• genotypes of aldehyde dehydrogenase 2 and beta3-adrenergic receptor were strongly associated with elevated alanine aminotransferase level which increased with the accumulation of components of metabolic syndrome (PMID:14506613)
• The Trp(64)Arg mutation of ADRB3 has little or no influence on either body weight or body mass index in the general Japanese population. (PMID:14671190)
• altitude-related lifestyle of a population has had little influence on the frequency of Trp64Arg polymorphism and obesity in Bolivian natives (PMID:14713387)
• beta3-AR genotype does not appear to be associated with any maximal or submaximal exercise CV hemodynamic responses in postmenopausal women. (PMID:14715679)
• the Trp64Arg variant of the beta3-adrenergic receptor gene may have a role in the central adiposity gain in a metabolic syndrome (PMID:14739355)
• beta(3) adrenergic receptor (ADRB3) R64 allele was associated with increased body weight and body mass index in men but not in women (PMID:14742851)
• polymorphic in metabolic syndrome phenotype in brazil (PMID:14747257)
• The Trp64Arg polymorphism of the beta(3)-receptor does not predispose to preeclampsia, and it is it not associated with obesity and carbohydrate intolerance in a population of young pregnant women. (PMID:15042014)
• hetero-oligomerization between beta(2)AR and beta(3)AR forms a beta-adrenergic signaling unit that possesses unique functional properties (PMID:15123695)
• body fat response to exercise training in older adults is associated with the combined effects of the Glu12/Glu9 alpha2b-adrenergic receptor, Trp64Arg beta3-adrenergic receptor, and Gln27Glu beta2-adrenergic receptor gene variants (PMID:15166301)
• Beta3-adrenoceptors are expressed in the endothelium of human coronary resistance arteries and mediate adrenergic vasodilatation through both NO and vessel hyperpolarization. (PMID:15302798)
• the ADRB3 Trp64Arg variant is not related to the development of gestational diabetes mellitus and has no effect on obesity during pregnancy in a Taiwanese population (PMID:15334374)
• the ADRB2 Arg(16)-Gly genotype influences total cholesterol and LDL-C levels in an age-specific manner, that it may interact with beta(3)-adrenergic receptor Trp(64)-Arg genotypes (PMID:15334382)
• results suggest that the combination of cholecystokinin 1 receptor (CCK1R) and the beta3-adrenergic receptor (beta3-AR) polymorphisms is a contributing factor for midlife weight gain in men (PMID:15340101)
• Polymorphisms in beta3-adrenergic receptor is associated with Type 2 Diabetes Mellitus (PMID:15355441)
• the Trp64Arg beta3-AR gene polymorphism may contribute to insulin resistance associated with reduced fetal growth. (PMID:15472194)
• The beta(3)-AR Trp64Arg polymorphism might have an impact on the mechanisms involved in leptin release from adipose tissue. (PMID:15536594)
• beta3-adrenoceptor (beta3-AR) stimulation regulates the activity of cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. (PMID:15563584)
• predominant role for beta(3)-AR in the regulation of human myometrium contractility, especially at the end of pregnancy (PMID:15585565)
• study does not confirm the influence of Trp64Arg mutation in heterozygous carriers on insulin resistance (PMID:15641247)
• the Arg allele of the Trp64Arg polymorphism in the beta3-adrenergic receptor gene may contribute to the susceptibility to endometrial cancer among obese/overweight individuals (PMID:15743038)
• Both newly detected TSC C1784T and ADRB3 T727C are gene polymorphisms susceptible to the antihypertensive effect of thiazides in patients with essential hypertension (PMID:15824464)
• 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 (PMID:15833937)
• Beta(3)-adrenoceptor mRNA expressions were significantly higher in patients with heart failure than those in controls. (PMID:15932670)
• beta3-adrenergic receptor Trp64Arg polymorphism is linked to BP elevation (PMID:15956122)
• beta3 adrenoceptor activation exerts inhibitory effect on human fibroblast DNA synthesis as a result of the activation of nitric oxide-cyclic GMP pathway and the inhibition of adenylate cyclase activity. (PMID:16301818)
• results suggest no association between Trp64Arg polymorphism of the beta3-AR gene and the incidence of overweight and type 2 diabetes mellitus in Polish population (PMID:16320158)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	adrb3b	ENSDARG00000052919
danio_rerio	adrb3a	ENSDARG00000053646
mus_musculus	Adrb3	ENSMUSG00000031489
rattus_norvegicus	Adrb3	ENSRNOG00000012674
caenorhabditis_elegans	ser-5	WBGENE00008890

Paralogs (18): ADRB1 (ENSG00000043591), 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), ADRA2B (ENSG00000274286)

Protein

Protein identifiers

Beta-3 adrenergic receptor — P13945 (reviewed: P13945)

Alternative names: Beta-3 adrenoreceptor

All UniProt accessions (2): A8KAG8, P13945

UniProt curated annotations — full annotation on UniProt →

Function. G protein-coupled receptor for catecholamines that couples to both G(s) and G(i) proteins, leading to either activation or inhibition of adenylate cyclase and cAMP-dependent pathway, respectively. The rank order of potency for physiological agonists is norepinephrine > epinephrine. Involved in the regulation of thermogenesis and lipolysis in brown and white adipose tissue, after coupling to G(s) proteins and stimulation of the cAMP-PKA axis. Also activates lipolytic process by coupling to G(i) proteins and consequent initiation of the ERK1/2 MAP kinase cascade. Participates in relaxation of the blood vessels and the urinary bladder. Also mediates negative inotropic effects in cardiomyocytes through activation of an NO synthase pathway and subsequent increase in cGMP levels, possibly involving G(i/o) protein-mediated coupling.

Subunit / interactions. Interacts with ARRDC3.

Subcellular location. Cell membrane.

Tissue specificity. Expressed mainly in adipose tissues.

Polymorphism. The variant Arg-64 seems to be associated with weight gain (obesity) and is also associated with susceptibility to non-insulin-dependent diabetes mellitus (NIDDM).

Similarity. Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRB3 sub-subfamily.

RefSeq proteins (1): NP_000016* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000681	ADRB3_rcpt	Family
IPR002233	ADR_fam	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (39 total): helix 13, topological domain 8, transmembrane region 7, sequence variant 4, glycosylation site 2, disulfide bond 2, chain 1, lipid moiety-binding region 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9IJE	ELECTRON MICROSCOPY	2.34
9IJD	ELECTRON MICROSCOPY	2.76

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P13945-F1	79.41	0.59

Antibody-complex structures (SAbDab): 2 — 9IJD, 9IJE

Functional residue map

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

Post-translational modifications (1): 361

Disulfide bonds (2): 110–196, 189–195

Glycosylation sites (2): 8, 26

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: 242 (showing top): BENPORATH_ES_WITH_H3K27ME3, GOBP_BEHAVIOR, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_RESPONSE_TO_COLD, GOBP_CIRCULATORY_SYSTEM_PROCESS, STAEGE_EWING_FAMILY_TUMOR, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_NEGATIVE_REGULATION_OF_MUSCLE_CONTRACTION, GOBP_RESPONSE_TO_DIETARY_EXCESS, GOBP_GROWTH, GOBP_REGULATION_OF_SYSTEMIC_ARTERIAL_BLOOD_PRESSURE, GOBP_REGULATION_OF_SMOOTH_MUSCLE_CONTRACTION, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_DEVELOPMENTAL_GROWTH

GO Biological Process (25): diet induced thermogenesis (GO:0002024), norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure (GO:0002025), carbohydrate metabolic process (GO:0005975), generation of precursor metabolites and energy (GO:0006091), energy reserve metabolic process (GO:0006112), G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger (GO:0007187), adenylate cyclase-modulating G protein-coupled receptor signaling pathway (GO:0007188), adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193), response to cold (GO:0009409), heat generation (GO:0031649), negative regulation of multicellular organism growth (GO:0040015), eating behavior (GO:0042755), positive regulation of MAPK cascade (GO:0043410), negative regulation of smooth muscle contraction (GO:0045986), brown fat cell differentiation (GO:0050873), positive regulation of lipid catabolic process (GO:0050996), negative regulation of cardiac muscle contraction (GO:0055118), positive regulation of ERK1 and ERK2 cascade (GO:0070374), adenylate cyclase-activating adrenergic receptor signaling pathway (GO:0071880), adenylate cyclase-inhibiting adrenergic receptor signaling pathway (GO:0071881), positive regulation of cold-induced thermogenesis (GO:0120162), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), adrenergic receptor signaling pathway (GO:0071875)

GO Molecular Function (10): G protein activity (GO:0003925), beta-adrenergic receptor activity (GO:0004939), beta3-adrenergic receptor activity (GO:0015052), beta-3 adrenergic receptor binding (GO:0031699), protein homodimerization activity (GO:0042803), epinephrine binding (GO:0051379), norepinephrine binding (GO:0051380), G protein-coupled receptor activity (GO:0004930), adrenergic receptor activity (GO:0004935), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), signaling receptor complex (GO:0043235), 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
G protein-coupled receptor signaling pathway	3
adrenergic receptor signaling pathway	3
cation binding	2
catecholamine binding	2
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
primary metabolic process	1
metabolic process	1
energy derivation by oxidation of organic compounds	1
adenylate cyclase activity	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase inhibitor activity	1
response to stress	1
response to temperature stimulus	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
feeding behavior	1
MAPK cascade	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
smooth muscle contraction	1
regulation of smooth muscle contraction	1
negative regulation of muscle contraction	1
fat cell differentiation	1
positive regulation of catabolic process	1
lipid catabolic process	1
positive regulation of lipid metabolic process	1
regulation of lipid catabolic process	1
negative regulation of heart contraction	1
negative regulation of striated muscle contraction	1
regulation of cardiac muscle contraction	1
cardiac muscle contraction	1
positive regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1

Protein interactions and networks

STRING

1278 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADRB3	UCP1	P25874	937
ADRB3	LIPE	Q05469	826
ADRB3	FGF21	Q9NSA1	762
ADRB3	ADIPOQ	Q15848	757
ADRB3	UCP2	P55851	748
ADRB3	PRDM16	Q9HAZ2	733
ADRB3	PPARA	Q07869	732
ADRB3	PPARGC1A	Q9UBK2	722
ADRB3	CIDEA	O60543	722
ADRB3	SRC	P12931	720
ADRB3	UCP3	P55916	704
ADRB3	PPARG	P37231	681
ADRB3	DIO2	Q92813	677
ADRB3	INS	P01308	670
ADRB3	LEP	P41159	668

IntAct

15 interactions, top by confidence:

A	B	Type	Score
SH3GL2	ADRB3	psi-mi:“MI:0915”(physical association)	0.400
SH3GL1	ADRB3	psi-mi:“MI:0915”(physical association)	0.400
ADRB3	SH3GL3	psi-mi:“MI:0915”(physical association)	0.400
RAMP1	ADRB3	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	ADRB3	psi-mi:“MI:0915”(physical association)	0.400
ADRB3	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	ADRB3	psi-mi:“MI:0915”(physical association)	0.400
CFTR	ADRB3	psi-mi:“MI:0915”(physical association)	0.370
ADRB3	Cav3	psi-mi:“MI:2364”(proximity)	0.270
Nos3	ADRB3	psi-mi:“MI:2364”(proximity)	0.270
ADRB3	Nos1	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (4): ADRB3 (Affinity Capture-Western), SRC (Affinity Capture-Western), ADRB3 (Reconstituted Complex), ADRB3 (PCA)

ESM2 similar proteins: A0A6I8PUB9, O00155, O00270, O08726, O14842, O43603, O60755, O88626, O88634, O88853, O88854, P0C5I1, P13945, P46092, P50406, Q15722, Q28524, Q3T181, Q3ZC80, Q5IS65, Q60483, Q6XKD3, Q76JU8, Q76JU9, Q76JV1, Q80UC6, Q862A8, Q862A9, Q8HYC3, Q8K3T4, Q8MJV2, Q8MJV3, Q8TDU6, Q8TDU9, Q920E0, Q924U0, Q95252, Q969F8, Q96G91, Q96P69

Diamond homologs: E7EM37, O01670, O02662, O02666, O02824, O18935, O19012, O19014, O19025, O19032, O19054, O19091, O42574, O77621, O77680, O77700, O77713, O77715, O77721, O77723, O77830, P04274, P07550, P07700, P10608, P11615, P13945, P15823, P17124, P18090, P18130, P18762, P18841, P18901, P21728, P21918, P23944, P25021, P25100, P25102

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
ADRB3	“up-regulates activity”	GNAS	binding
ADRB3	“up-regulates activity”	GNAL	binding
L-isoprenaline	“up-regulates activity”	ADRB3	“chemical activation”
N-[2-hydroxy-5-(1-hydroxy-2-{[1-(4-methoxyphenyl)propan-2-yl]amino}ethyl)phenyl]formamide	“up-regulates activity”	ADRB3	“chemical activation”
NYYJKMXNVNFOFQ-MHZLTWQESA-N	“up-regulates activity”	ADRB3	“chemical activation”
fenoterol	“up-regulates activity”	ADRB3	“chemical activation”
terbutaline	“up-regulates activity”	ADRB3	“chemical activation”
metaproterenol	“up-regulates activity”	ADRB3	“chemical activation”
adrenaline	“up-regulates activity”	ADRB3	“chemical activation”
isoprenaline	“up-regulates activity”	ADRB3	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	57
Likely benign	4
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

217 predictions. Top by Δscore:

Variant	Effect	Δscore
8:37964437:CAGG:C	donor_gain	0.9100
8:37965263:AC:A	donor_gain	0.9100
8:37965264:CC:C	donor_gain	0.9100
8:37965264:CCCGT:C	donor_gain	0.8800
8:37965259:ACCT:A	donor_loss	0.8700
8:37965260:CCTA:C	donor_loss	0.8700
8:37965261:CTACC:C	donor_loss	0.8700
8:37965262:TACC:T	donor_loss	0.8700
8:37965263:A:T	donor_loss	0.8700
8:37965264:C:CA	donor_loss	0.8700
8:37965256:GTTAC:G	donor_loss	0.8600
8:37965258:TAC:T	donor_loss	0.8500
8:37965263:A:AC	donor_gain	0.8500
8:37965264:C:CC	donor_gain	0.8500
8:37965257:TTAC:T	donor_loss	0.8400
8:37964236:AGCCC:A	acceptor_loss	0.8300
8:37964238:CC:C	acceptor_gain	0.8300
8:37964239:CC:C	acceptor_gain	0.8300
8:37964240:C:CG	acceptor_loss	0.8300
8:37964241:T:A	acceptor_loss	0.8300
8:37964427:T:C	donor_gain	0.8200
8:37965262:TACCC:T	donor_gain	0.8200
8:37964451:A:AC	donor_gain	0.8100
8:37964452:C:CC	donor_gain	0.8100
8:37964436:A:AC	donor_gain	0.7600
8:37964437:C:CC	donor_gain	0.7600
8:37964240:C:CC	acceptor_gain	0.7500
8:37964395:CCA:C	donor_gain	0.7300
8:37965256:G:GC	donor_gain	0.7300
8:37964452:CAA:C	acceptor_gain	0.7200

AlphaMissense

2551 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:37965567:G:C	F301L	0.992
8:37965567:G:T	F301L	0.992
8:37965569:A:G	F301L	0.992
8:37965831:G:C	F213L	0.991
8:37965831:G:T	F213L	0.991
8:37965833:A:G	F213L	0.991
8:37965546:G:C	F308L	0.988
8:37965546:G:T	F308L	0.988
8:37965548:A:G	F308L	0.988
8:37966098:G:C	S124R	0.982
8:37966098:G:T	S124R	0.982
8:37966100:T:G	S124R	0.982
8:37965543:A:C	F309L	0.981
8:37965543:A:T	F309L	0.981
8:37965545:A:G	F309L	0.981
8:37965550:G:C	P307R	0.977
8:37965550:G:T	P307H	0.977
8:37965560:A:G	C304R	0.975
8:37965877:A:C	F198C	0.974
8:37965558:G:C	C304W	0.973
8:37965414:A:C	F352L	0.971
8:37965414:A:T	F352L	0.971
8:37965416:A:G	F352L	0.971
8:37965559:C:T	C304Y	0.970
8:37966161:C:A	W103C	0.970
8:37966161:C:G	W103C	0.970
8:37966305:G:C	N55K	0.970
8:37966305:G:T	N55K	0.970
8:37965415:A:C	F352C	0.968
8:37965444:G:C	N342K	0.964

dbSNP variants (sampled 300 via entrez): RS1000149764 (8:37965295 G>A,C,T), RS1000416960 (8:37965110 G>A), RS1002283138 (8:37964546 T>A,C,G), RS1003024920 (8:37968553 A>G), RS1003452936 (8:37964685 G>A,C), RS1003467733 (8:37967664 C>T), RS1004014766 (8:37964407 AG>A), RS1004317593 (8:37964659 C>A,G), RS1005274583 (8:37964779 A>T), RS1005866573 (8:37965763 C>A,G), RS1005965069 (8:37967027 G>T), RS1006668088 (8:37968534 T>C), RS1006929480 (8:37962511 A>T), RS1006999593 (8:37968161 A>G), RS1008192667 (8:37964068 G>A)

Disease associations

OMIM: gene MIM:109691 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): obesity disorder (MONDO:0011122)

Orphanet (2): Obesity due to melanocortin 4 receptor deficiency (Orphanet:71529), NON RARE IN EUROPE: Non rare obesity (Orphanet:521399)

HPO phenotypes

6 total (6 of 6 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0001513	Obesity
HP:0010982	Polygenic inheritance
HP:0012340	Decreased resting energy expenditure
HP:0031819	Increased waist to hip ratio

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL2094118 (PROTEIN FAMILY), CHEMBL2097169 (SELECTIVITY GROUP), CHEMBL2111388 (SELECTIVITY GROUP), CHEMBL2331074 (PROTEIN FAMILY), CHEMBL246 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

91 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 740,402 (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
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1064	SIMVASTATIN	4	123,163
CHEMBL1112	ARIPIPRAZOLE	4	24,205
CHEMBL118	CELECOXIB	4	112,844
CHEMBL1201237	LEVOBUNOLOL	4	10,597
CHEMBL1256786	FORMOTEROL	4	480
CHEMBL1262	OXICONAZOLE	4	48
CHEMBL1263	SALMETEROL	4	40,383
CHEMBL1423	PIMOZIDE	4	17,310
CHEMBL1479	DANAZOL	4	16,256
CHEMBL1480	FELODIPINE	4
CHEMBL1491	AMLODIPINE	4
CHEMBL1516474	TEGASEROD MALEATE	4
CHEMBL163	RITONAVIR	4
CHEMBL17157	TERFENADINE	4
CHEMBL1732	DIHYDROERGOTAMINE	4
CHEMBL2010601	IVACAFTOR	4
CHEMBL2095212	MIRABEGRON	4
CHEMBL2107826	VIBEGRON	4
CHEMBL269732	TACROLIMUS ANHYDROUS	4

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs4994	Toxicity	3	olanzapine	Schizophrenia;Weight gain

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4994	ADRB3	3	2.00	1	olanzapine

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Adrenoceptors

Most potent curated ligand interactions (34 total), top 25:

Ligand	Action	Affinity	Parameter
L 755507	Full agonist	10.1	pEC50
[125I]ICYP	Partial agonist	9.8	pKd
L742791	Agonist	8.8	pEC50
mirabegron	Agonist	8.8	pEC50
[3H]L748337	Antagonist	8.7	pKd
solabegron	Agonist	8.7	pEC50
L-748328	Antagonist	8.6	pKi
tertatolol	Antagonist	8.6	pKi
L-748337	Partial agonist	8.4	pEC50
SR59230A	Antagonist	8.4	pKi
carazolol	Partial agonist	8.4	pKi
carvedilol	Antagonist	8.3	pKi
vibegron	Agonist	7.96	pEC50
CGP 12177	Partial agonist	7.3	pKi
bupranolol	Antagonist	7.3	pKi
(-)-noradrenaline	Full agonist	7.2	pEC50
propranolol	Antagonist	7.2	pKi
SB251023	Agonist	7.14	pEC50
pindolol	Partial agonist	7.1	pKi
[3H]CGP12177	Partial agonist	7.0	pKd
BRL 37344	Full agonist	7.0	pKi
nebivolol	Antagonist	7.0	pKi
bunolol	Antagonist	6.8	pKi
ICI 118551	Antagonist	6.6	pKi
(-)-adrenaline	Full agonist	6.5	pEC50

Binding affinities (BindingDB)

19 measured of 25 human assays (38 total across all organisms); most potent 19 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
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
tert-butyl[3-(2-chloro-5-methylphenoxy)-2-hydroxypropyl]amine	KD	3.1 nM
tert-butyl(2-hydroxy-3-{[4-(morpholin-4-yl)-1,2,5-thiadiazol-3-yl]oxy}propyl)amine	KD	5.35 nM
Bisoprolol fumarate	KD	15 nM
CAS_174689-39-5	KI	16.4 nM
KUR-1246	KI	25.7 nM
N-(2-{[(2R)-2-hydroxy-3-(4-hydroxyphenoxy)propyl]amino}ethyl)morpholine-4-carboxamide	KD	60 nM
Propanolol,(+/-)	KI	272 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_71149	KI	1310 nM
NSC_3083544	KI	1710 nM
salmeterol xinafoate	KD	4170 nM
cid_2685	KI	7360 nM
N-{5-[2-(Adamantan-1-ylamino)-1-hydroxy-ethyl]-2-hydroxy-phenyl}-methanesulfonamide	KI	11000 nM
Levalbuterol	KD	21900 nM

ChEMBL bioactivities

2244 potent at pChembl≥5 of 2377 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.80	EC50	0.016	nM	RAFABEGRON
10.70	EC50	0.02	nM	CHEMBL1257555
10.54	EC50	0.029	nM	CHEMBL446806
10.50	EC50	0.03162	nM	CHEMBL446806
10.46	EC50	0.035	nM	CHEMBL529659
10.46	EC50	0.035	nM	CHEMBL470857
10.40	EC50	0.04	nM	CHEMBL3128199
10.40	EC50	0.04	nM	CHEMBL1257675
10.39	EC50	0.041	nM	CHEMBL453322
10.38	EC50	0.042	nM	CHEMBL509156
10.36	EC50	0.044	nM	CHEMBL550871
10.23	EC50	0.059	nM	CHEMBL459646
10.22	EC50	0.06	nM	CHEMBL303537
10.21	EC50	0.062	nM	CHEMBL282190
10.21	EC50	0.062	nM	CHEMBL518168
10.21	EC50	0.062	nM	CHEMBL452696
10.21	EC50	0.062	nM	RAFABEGRON
10.20	EC50	0.0631	nM	CHEMBL245873
10.20	EC50	0.0631	nM	CHEMBL452134
10.19	EC50	0.064	nM	CHEMBL507506
10.18	EC50	0.066	nM	CHEMBL487682
10.18	EC50	0.066	nM	CHEMBL473702
10.16	EC50	0.069	nM	CHEMBL453056
10.10	EC50	0.08	nM	CHEMBL490733
10.04	EC50	0.091	nM	CHEMBL486051
10.02	EC50	0.095	nM	CHEMBL284782
10.00	EC50	0.1	nM	CHEMBL205224
10.00	EC50	0.1	nM	CHEMBL207943
10.00	EC50	0.099	nM	CHEMBL452798
10.00	EC50	0.1	nM	CHEMBL551532
9.96	EC50	0.11	nM	CHEMBL282190
9.90	EC50	0.1259	nM	CHEMBL469395
9.90	EC50	0.1259	nM	CHEMBL491726
9.89	EC50	0.13	nM	CHEMBL3128200
9.89	EC50	0.13	nM	CHEMBL445481
9.85	EC50	0.14	nM	CHEMBL451760
9.85	EC50	0.14	nM	CHEMBL510100
9.85	EC50	0.14	nM	CHEMBL491726
9.85	EC50	0.14	nM	CHEMBL455773
9.85	EC50	0.14	nM	CHEMBL1257797
9.82	EC50	0.15	nM	CHEMBL3128198
9.82	EC50	0.15	nM	CHEMBL3128194
9.82	EC50	0.15	nM	CHEMBL26183
9.80	EC50	0.16	nM	CHEMBL459862
9.80	EC50	0.16	nM	CHEMBL551272
9.74	EC50	0.18	nM	CHEMBL3128189
9.74	EC50	0.18	nM	CHEMBL488430
9.72	EC50	0.19	nM	CHEMBL488223
9.72	EC50	0.19	nM	CHEMBL487443
9.72	EC50	0.19	nM	CHEMBL491891

PubChem BioAssay actives

2136 with measured affinity, of 5026 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
2-cyclohexyloxy-4-[4-[(2R)-2-[[(2R)-2-hydroxy-2-phenylethyl]amino]propyl]phenyl]benzoic acid	344247: Agonist activity at human recombinant beta3 adrenergic receptor expressed in CHO cells assessed as cAMP accumulation by enzyme immuno assay	ec50	<0.0001	uM
4-[4-[2-[[(2R)-2-(6-amino-3-pyridinyl)-2-hydroxyethyl]amino]ethyl]phenyl]-2-cyclohexyloxybenzoic acid	344247: Agonist activity at human recombinant beta3 adrenergic receptor expressed in CHO cells assessed as cAMP accumulation by enzyme immuno assay	ec50	<0.0001	uM
4-[4-[(2R)-2-[[(2R)-2-hydroxy-2-phenylethyl]amino]propyl]phenyl]-2-(2-methylpropoxy)benzoic acid	344247: Agonist activity at human recombinant beta3 adrenergic receptor expressed in CHO cells assessed as cAMP accumulation by enzyme immuno assay	ec50	<0.0001	uM
2-(hydroxymethyl)-4-[2-hydroxy-3-[[1-(5-phenylthieno[2,3-d]pyrimidin-4-yl)piperidin-4-yl]amino]propoxy]phenol	517626: Agonist activity at human recombinant adrenergic beta3 receptor expressed in CHO cells assessed as cyclic AMP formation by HTRF assay	ec50	<0.0001	uM
4-[2-hydroxy-3-[[1-(5-phenylthieno[2,3-d]pyrimidin-4-yl)piperidin-4-yl]amino]propoxy]-2-(methoxymethyl)phenol	517626: Agonist activity at human recombinant adrenergic beta3 receptor expressed in CHO cells assessed as cyclic AMP formation by HTRF assay	ec50	<0.0001	uM
4-[4-[2-[[(2R)-2-(4-amino-3-pyridinyl)-2-hydroxyethyl]amino]ethyl]phenyl]-2-cyclohexyloxy-N-methylsulfonylbenzamide;dihydrochloride	349762: Agonist activity at human recombinant beta3 adrenergic receptor expressed in CHO cells assessed as cAMP accumulation by enzyme immunoassay	ec50	<0.0001	uM
4-[4-[2-[[(2R)-2-(4-amino-3-pyridinyl)-2-hydroxyethyl]amino]ethyl]phenyl]-2-cyclohexyloxybenzoic acid	349762: Agonist activity at human recombinant beta3 adrenergic receptor expressed in CHO cells assessed as cAMP accumulation by enzyme immunoassay	ec50	<0.0001	uM
4-[4-[2-[[(1R,2S)-1-hydroxy-1-(3-hydroxyphenyl)propan-2-yl]amino]ethyl]phenyl]-N-methylsulfonyl-2-propan-2-yloxybenzamide	429597: Agonist activity at human recombinant adrenergic beta3 receptor expressed in CHO cells assessed as stimulation of cAMP level after 1 hr by enzyme immunoassay	ec50	<0.0001	uM
2-[[3-[(2R)-2-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]-1H-indol-7-yl]oxy]acetic acid	41938: Agonistic activity against human Beta-3 adrenergic receptor as cAMP accumulation in CHO cells expressing beta3-AR	ec50	<0.0001	uM
(4R)-2-amino-N-[4-[[(2S,5R)-5-[(R)-(3-fluorophenyl)-hydroxymethyl]pyrrolidin-2-yl]methyl]phenyl]-5,6-dihydro-4H-cyclopenta[d][1,3]thiazole-4-carboxamide	1074825: Agonist activity at human beta-3 adrenergic receptor expressed in CHO cells assessed as increase in intracellular cAMP accumulation after 30 mins by time-resolved fluorescence assay	ec50	<0.0001	uM
4-[4-[2-[[(1R,2S)-1-hydroxy-1-(4-hydroxyphenyl)propan-2-yl]amino]ethyl]phenyl]-2-propan-2-yloxybenzoic acid	344247: Agonist activity at human recombinant beta3 adrenergic receptor expressed in CHO cells assessed as cAMP accumulation by enzyme immuno assay	ec50	0.0001	uM
4-[4-[2-[[(1R,2S)-1-hydroxy-1-phenylpropan-2-yl]amino]ethyl]phenyl]-2-(2-methylpropyl)benzoic acid	344247: Agonist activity at human recombinant beta3 adrenergic receptor expressed in CHO cells assessed as cAMP accumulation by enzyme immuno assay	ec50	0.0001	uM
(1R)-1-(3-chlorophenyl)-2-[[(2R)-1-(7-methoxy-1H-indol-3-yl)propan-2-yl]amino]ethanol	41938: Agonistic activity against human Beta-3 adrenergic receptor as cAMP accumulation in CHO cells expressing beta3-AR	ec50	0.0001	uM
3-[3-[2-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]ethylamino]phenyl]pyridine-4-carboxylic acid	264374: Activity at human beta-3 adrenergic receptor expressed in CHO cells by stimulation of cAMP production	ec50	0.0001	uM
4-[4-[2-[[(2R)-2-(6-amino-3-pyridinyl)-2-hydroxyethyl]amino]ethyl]phenyl]-2-(2-methylpropyl)benzoic acid	344247: Agonist activity at human recombinant beta3 adrenergic receptor expressed in CHO cells assessed as cAMP accumulation by enzyme immuno assay	ec50	0.0001	uM
4-[4-[2-[[(2R)-2-(6-amino-3-pyridinyl)-2-hydroxyethyl]amino]ethoxy]phenyl]-2-(2-methylpropyl)benzoic acid	344247: Agonist activity at human recombinant beta3 adrenergic receptor expressed in CHO cells assessed as cAMP accumulation by enzyme immuno assay	ec50	0.0001	uM
2-[3-[[(2R)-2-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]amino]phenyl]thiophene-3-carboxylic acid	308437: Agonist activity at human beta-3 adrenergic receptor expressed in CHO cells assessed as cAMP accumulation	ec50	0.0001	uM
4-[4-[(2R)-2-[[(2R)-2-hydroxy-2-phenylethyl]amino]propyl]phenyl]-2-propan-2-yloxybenzoic acid	344247: Agonist activity at human recombinant beta3 adrenergic receptor expressed in CHO cells assessed as cAMP accumulation by enzyme immuno assay	ec50	0.0001	uM
4-[4-[2-[[(2R)-2-hydroxy-2-(3-hydroxyphenyl)ethyl]amino]ethyl]phenyl]-2-propan-2-yloxybenzoic acid	344247: Agonist activity at human recombinant beta3 adrenergic receptor expressed in CHO cells assessed as cAMP accumulation by enzyme immuno assay	ec50	0.0001	uM
2-ethyl-4-[2-hydroxy-3-[[1-(5-phenylthieno[2,3-d]pyrimidin-4-yl)piperidin-4-yl]amino]propoxy]phenol	517626: Agonist activity at human recombinant adrenergic beta3 receptor expressed in CHO cells assessed as cyclic AMP formation by HTRF assay	ec50	0.0001	uM
2-cyclohexyloxy-4-[4-[2-[[(2R)-2-hydroxy-2-phenylethyl]amino]ethyl]phenyl]-N-methylsulfonylbenzamide;hydrochloride	349762: Agonist activity at human recombinant beta3 adrenergic receptor expressed in CHO cells assessed as cAMP accumulation by enzyme immunoassay	ec50	0.0001	uM
2-(cyclohexylamino)-4-[4-[2-[[(2R)-2-hydroxy-2-phenylethyl]amino]ethyl]phenyl]-N-methylsulfonylbenzamide;dihydrochloride	349762: Agonist activity at human recombinant beta3 adrenergic receptor expressed in CHO cells assessed as cAMP accumulation by enzyme immunoassay	ec50	0.0001	uM
2-cyclohexyloxy-4-[4-[2-[[(2R)-2-hydroxy-2-pyridin-3-ylethyl]amino]ethyl]phenyl]-N-methylsulfonylbenzamide;dihydrochloride	349762: Agonist activity at human recombinant beta3 adrenergic receptor expressed in CHO cells assessed as cAMP accumulation by enzyme immunoassay	ec50	0.0001	uM
2-(cyclohexylamino)-4-[4-[2-[[(2R)-2-hydroxy-2-pyridin-3-ylethyl]amino]ethyl]phenyl]-N-methylsulfonylbenzamide;trihydrochloride	349762: Agonist activity at human recombinant beta3 adrenergic receptor expressed in CHO cells assessed as cAMP accumulation by enzyme immunoassay	ec50	0.0001	uM
4-[4-[2-[[(2R)-2-(4-aminophenyl)-2-hydroxyethyl]amino]ethyl]phenyl]-2-cyclohexyloxy-N-methylsulfonylbenzamide;dihydrochloride	349762: Agonist activity at human recombinant beta3 adrenergic receptor expressed in CHO cells assessed as cAMP accumulation by enzyme immunoassay	ec50	0.0001	uM
2-[[2-[2-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]ethyl]-1H-indol-7-yl]oxy]acetic acid	41664: Binding affinity towards human Beta-3 adrenergic receptor	ec50	0.0001	uM
4-[4-[(2R)-2-[[(2R)-2-hydroxy-2-pyridin-3-ylethyl]amino]propyl]phenyl]-2-propan-2-yloxybenzoic acid	344247: Agonist activity at human recombinant beta3 adrenergic receptor expressed in CHO cells assessed as cAMP accumulation by enzyme immuno assay	ec50	0.0001	uM
4-[4-[(2R)-2-[[(2R)-2-hydroxy-2-pyridin-3-ylethyl]amino]propyl]phenyl]-2-propoxybenzoic acid	344247: Agonist activity at human recombinant beta3 adrenergic receptor expressed in CHO cells assessed as cAMP accumulation by enzyme immuno assay	ec50	0.0001	uM
2-cyclohexyloxy-4-[4-[(2R)-2-[[(2R)-2-hydroxy-2-pyridin-3-ylethyl]amino]propyl]phenyl]benzoic acid	344247: Agonist activity at human recombinant beta3 adrenergic receptor expressed in CHO cells assessed as cAMP accumulation by enzyme immuno assay	ec50	0.0001	uM
4-[4-[2-[[(2R)-2-(4-amino-3-pyridinyl)-2-hydroxyethyl]amino]ethyl]phenyl]-N-methylsulfonyl-2-propan-2-yloxybenzamide	349762: Agonist activity at human recombinant beta3 adrenergic receptor expressed in CHO cells assessed as cAMP accumulation by enzyme immunoassay	ec50	0.0001	uM
4-[4-[2-[[(2R)-2-(4-amino-3-pyridinyl)-2-hydroxyethyl]amino]ethyl]phenyl]-N-methylsulfonyl-2-propan-2-ylsulfanylbenzamide	349762: Agonist activity at human recombinant beta3 adrenergic receptor expressed in CHO cells assessed as cAMP accumulation by enzyme immunoassay	ec50	0.0001	uM
4-[4-[2-[[(2R)-2-(4-amino-3-pyridinyl)-2-hydroxyethyl]amino]ethyl]phenyl]-2-(2-methylpropyl)benzoic acid	349762: Agonist activity at human recombinant beta3 adrenergic receptor expressed in CHO cells assessed as cAMP accumulation by enzyme immunoassay	ec50	0.0001	uM
4-[4-[(2R)-2-[[(2R)-2-hydroxy-2-phenylethyl]amino]propyl]phenyl]-2-(2-methylpropyl)-N-methylsulfonylbenzamide	429597: Agonist activity at human recombinant adrenergic beta3 receptor expressed in CHO cells assessed as stimulation of cAMP level after 1 hr by enzyme immunoassay	ec50	0.0001	uM
2-[[3-[2-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]-1H-indol-7-yl]oxy]acetic acid	1095329: Agonist activity at Homo sapiens (human) beta3 adrenoreceptor	ec50	0.0001	uM
(4R)-2-amino-N-[4-[[(2S,5R)-5-[(R)-(4-fluorophenyl)-hydroxymethyl]pyrrolidin-2-yl]methyl]phenyl]-5,6-dihydro-4H-cyclopenta[d][1,3]thiazole-4-carboxamide	1074825: Agonist activity at human beta-3 adrenergic receptor expressed in CHO cells assessed as increase in intracellular cAMP accumulation after 30 mins by time-resolved fluorescence assay	ec50	0.0001	uM
(4R)-2-amino-N-[4-[[(2S,5R)-5-[(R)-hydroxy(phenyl)methyl]pyrrolidin-2-yl]methyl]phenyl]-5,6-dihydro-4H-cyclopenta[d][1,3]thiazole-4-carboxamide	1074825: Agonist activity at human beta-3 adrenergic receptor expressed in CHO cells assessed as increase in intracellular cAMP accumulation after 30 mins by time-resolved fluorescence assay	ec50	0.0001	uM
(4R)-2-amino-N-[4-[[(2S,5R)-5-[(R)-(3-chlorophenyl)-hydroxymethyl]pyrrolidin-2-yl]methyl]phenyl]-5,6-dihydro-4H-cyclopenta[d][1,3]thiazole-4-carboxamide	1074825: Agonist activity at human beta-3 adrenergic receptor expressed in CHO cells assessed as increase in intracellular cAMP accumulation after 30 mins by time-resolved fluorescence assay	ec50	0.0001	uM
2-[4-[(2R)-2-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]phenoxy]acetic acid	41938: Agonistic activity against human Beta-3 adrenergic receptor as cAMP accumulation in CHO cells expressing beta3-AR	ec50	0.0001	uM
3-[3-[[(2R)-2-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]amino]phenyl]benzoic acid	264374: Activity at human beta-3 adrenergic receptor expressed in CHO cells by stimulation of cAMP production	ec50	0.0001	uM
[3-[(2R)-2-[[(2R)-2-hydroxy-2-[3-(thiophen-2-ylsulfonylamino)phenyl]ethyl]amino]propyl]-1H-indol-7-yl] methanesulfonate	1095329: Agonist activity at Homo sapiens (human) beta3 adrenoreceptor	ec50	0.0002	uM
4-[3-[[(2R)-2-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]amino]phenyl]benzene-1,3-dicarboxylic acid	264374: Activity at human beta-3 adrenergic receptor expressed in CHO cells by stimulation of cAMP production	ec50	0.0002	uM
4-[4-[2-[[(2R)-2-(6-acetamido-3-pyridinyl)-2-hydroxyethyl]amino]ethyl]phenyl]-2-cyclohexyloxy-N-methylsulfonylbenzamide	429597: Agonist activity at human recombinant adrenergic beta3 receptor expressed in CHO cells assessed as stimulation of cAMP level after 1 hr by enzyme immunoassay	ec50	0.0002	uM
4-[4-[2-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]ethylamino]phenyl]-2-propoxybenzoic acid	344247: Agonist activity at human recombinant beta3 adrenergic receptor expressed in CHO cells assessed as cAMP accumulation by enzyme immuno assay	ec50	0.0002	uM
4-[4-[2-[[(2R)-2-(6-amino-3-pyridinyl)-2-hydroxyethyl]amino]ethyl]phenyl]-2-propan-2-yloxybenzoic acid	344247: Agonist activity at human recombinant beta3 adrenergic receptor expressed in CHO cells assessed as cAMP accumulation by enzyme immuno assay	ec50	0.0002	uM
4-[4-[(2R)-2-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]phenyl]benzoic acid	344247: Agonist activity at human recombinant beta3 adrenergic receptor expressed in CHO cells assessed as cAMP accumulation by enzyme immuno assay	ec50	0.0002	uM
4-[4-[(2R)-2-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]phenyl]-2-propan-2-yloxybenzoic acid	344247: Agonist activity at human recombinant beta3 adrenergic receptor expressed in CHO cells assessed as cAMP accumulation by enzyme immuno assay	ec50	0.0002	uM
4-[4-[2-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]ethoxy]phenyl]-2-propoxybenzoic acid	344247: Agonist activity at human recombinant beta3 adrenergic receptor expressed in CHO cells assessed as cAMP accumulation by enzyme immuno assay	ec50	0.0002	uM
2-cyclohexyloxy-4-[4-[2-[[(2R)-2-hydroxy-2-phenylethyl]amino]ethoxy]phenyl]benzoic acid	344247: Agonist activity at human recombinant beta3 adrenergic receptor expressed in CHO cells assessed as cAMP accumulation by enzyme immuno assay	ec50	0.0002	uM
4-[4-[2-[[(2R)-2-hydroxy-2-pyridin-3-ylethyl]amino]ethyl]phenyl]-N-methylsulfonyl-2-propan-2-ylsulfanylbenzamide;dihydrochloride	349762: Agonist activity at human recombinant beta3 adrenergic receptor expressed in CHO cells assessed as cAMP accumulation by enzyme immunoassay	ec50	0.0002	uM
4-[4-[2-[[(2R)-2-hydroxy-2-pyridin-3-ylethyl]amino]ethyl]phenyl]-N-methylsulfonyl-2-(propan-2-ylamino)benzamide;trihydrochloride	349762: Agonist activity at human recombinant beta3 adrenergic receptor expressed in CHO cells assessed as cAMP accumulation by enzyme immunoassay	ec50	0.0002	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
CGP 12177	increases abundance, decreases reaction, affects binding, increases activity	5
Isoproterenol	affects binding, increases activity, increases abundance, decreases reaction	4
3-(2-ethylphenoxy)-1-(1,2,3,4-tetrahydronaphth-1-ylamino)-2-propanol oxalate	affects binding, decreases activity, decreases reaction, increases abundance, increases activity	3
Norepinephrine	increases activity, increases abundance, decreases reaction, affects binding	3
ICI 118551	increases activity, decreases reaction, affects binding, decreases activity, decreases abundance	2
broxaterol	affects binding, increases activity, increases abundance, decreases reaction	2
cyanopindolol	affects binding, decreases reaction	2
CGP 20712A	affects binding, decreases activity, decreases abundance, increases activity, decreases reaction	2
BRL 37344	decreases reaction, affects binding, increases activity, increases abundance	2
L 748,337	decreases reaction, increases activity, affects binding, decreases activity	2
Cyclic AMP	decreases activity, affects binding, decreases reaction, increases abundance, increases activity (+2 more)	2
Epinephrine	increases activity, increases abundance, decreases reaction, affects binding	2
Pindolol	increases abundance, decreases reaction, affects binding, increases activity	2
Terbutaline	affects binding, increases activity, increases abundance, decreases reaction	2
bisphenol A	affects cotreatment, increases methylation	1
kojic acid	decreases expression	1
arsenite	increases methylation	1
amibegron	increases response to substance, affects binding, increases activity, decreases reaction	1
SR 59104A	affects binding, increases activity	1
SR 59119A	affects binding, decreases reaction, increases abundance, increases activity	1
N-(4-(2-((2-hydroxy-2-(3-pyridinyl)ethyl)amino)ethyl)phenyl)-4-(4-(4-(trifluoromethyl)phenyl)thiazol-2-yl)benzenesulfonamide	increases activity, affects binding	1
solabegron	affects binding, increases activity	1
N-(3-hydroxy-1-(naphthalen-1-yl)-1,8,11-trioxa-5-azatridecan-13-yl)-6-(2-(2-(4,4-difluoro-4,4a-dihydro-5-(thiophen-2-yl)-4-bora-3a,4a-diaza-s-indacene-3-yl)vinyl)phenoxyacetamido)hexanamide	affects binding, decreases reaction	1
Salmeterol Xinafoate	decreases reaction, affects binding, decreases activity, decreases abundance	1
Formoterol Fumarate	affects binding, increases activity, increases abundance, decreases reaction	1
Rosiglitazone	decreases expression	1
Carvedilol	affects binding, decreases reaction	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1
Albuterol	increases abundance, decreases reaction, affects binding, increases activity	1

ChEMBL screening assays

508 unique, capped per target: 282 functional, 224 binding, 2 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
CHEMBL4406616	ADMET	Displacement of [3H]-CGP12177 from recombinant human beta3 adrenergic receptor expressed in HEK Flp-In cell membranes measured after 90 mins by microbeta scintillation counting method	Discovery, Optimization, and Characterization of ML417: A Novel and Highly Selective D3 Dopamine Receptor Agonist. — J Med Chem

Cellosaurus cell lines

5 cell lines: 2 cancer cell line, 2 transformed cell line, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1RI	Abcam U-87MG ADRB3 KO	Cancer cell line	Male
CVCL_H363	293/ADRB3/CRE-Luc	Transformed cell line	Female
CVCL_KV91	cAMP Hunter DLD1 ADRB3 Gs	Cancer cell line	Male
CVCL_YK00	HEK293 ADRB3 HiTSeeker	Transformed cell line	Female
CVCL_ZK43	GeneBLAzer ADRB3-CRE-bla CHO-K1	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00076362	PHASE4	COMPLETED	Pediatric Hypothalamic Obesity
NCT00079547	PHASE4	COMPLETED	The Safety and Effectiveness of Low and High Carbohydrate Diets
NCT00115063	PHASE4	TERMINATED	LOSS- Louisiana Obese Subjects Study
NCT00134303	PHASE4	COMPLETED	Trial Comparing Metformin Versus Placebo in Non Alcoholic Steatohepatitis (NASH) Patients Receiving Bariatric Surgery for Obesity
NCT00143936	PHASE4	COMPLETED	The Safety and Efficacy of Low and High Carbohydrate Diets
NCT00143962	PHASE4	COMPLETED	Comparison of Two Approaches to Weight Loss Follow-Up Study
NCT00152360	PHASE4	COMPLETED	The Effect of Xenical on Weight and Risk Factors
NCT00176306	PHASE4	COMPLETED	Levofloxacin Pharmacokinetics (PK) in the Severely Obese
NCT00203450	PHASE4	COMPLETED	Zonegran for the Treatment of Weight Gain Associated With Psychotropic Medication Use: A Placebo-Controlled Trial
NCT00205504	PHASE4	COMPLETED	Oral Contraceptives in the Metabolic Syndrome
NCT00229229	PHASE4	TERMINATED	Comparison of 4 Diets in the Management of Overweight Patients With Vascular Disease
NCT00234988	PHASE4	COMPLETED	A Phase IV, Multi-Center, Open-Label Trial of Sibutramine in Combination With a Hypocaloric Diet in Obese and Overweight Thai Subjects.
NCT00264589	PHASE4	COMPLETED	Exercise Training and Cardiovascular Function in Obesity and in Type 2 Diabetes
NCT00288873	PHASE4	COMPLETED	Characterization of Hyperparathyroidism and Vitamin D Deficiency in Obesity
NCT00298857	PHASE4	TERMINATED	A Pharmacokinetic Study to Compare the Dosing of Valproic Acid in Subjects With Different Body Weights
NCT00315146	PHASE4	COMPLETED	Optimizing Body Composition for Function in Older Adults
NCT00319202	PHASE4	TERMINATED	Clinical Trial to Assess the Effects of Candesartan on the Carbohydrate Metabolism of Obese Subjects
NCT00327912	PHASE4	UNKNOWN	Laparoscopic Roux-en-Y Gastric Bypass Versus Laparoscopic Biliopancreatic Diversion (BPD)- Duodenal Switch for Superobesity
NCT00352287	PHASE4	COMPLETED	Study to Determine the Effects of Human Growth Hormone and Pioglitazone in Overweight, Prediabetic Adults
NCT00353054	PHASE4	COMPLETED	Effect of Calcium/Vitamin D Supplementation on Body Weight and Fat Loss.
NCT00390637	PHASE4	COMPLETED	Diet, Obesity and Genes (DiOGenes)
NCT00415688	PHASE4	COMPLETED	Lifestyle Modification for Obesity-Related Type 2 Diabetes
NCT00433641	PHASE4	COMPLETED	Weight Loss in Response to Sibutramine (MERIDIA) is Influenced by the Inherited Genes
NCT00440375	PHASE4	COMPLETED	Effects of Rosiglitazone on Bone in Postmenopausal Diabetic Women
NCT00453557	PHASE4	COMPLETED	Mechanism of Growth Hormone Effects on Adipose Tissue
NCT00456885	PHASE4	COMPLETED	The Effect of Exenatide on Weight and Hunger in Obese, Healthy Women
NCT00463112	PHASE4	COMPLETED	Effect of Diet Plus Sibutramine on Hormonal and Metabolic Features in Overweight and Obese Women With PCOS
NCT00512187	PHASE4	COMPLETED	Moderate Weight Loss Makes Obese Patients With Severe Chronic Plaque Psoriasis Responsive to Sub-Optimal Dose of Cyclosporine: an Investigator Blinded, Controlled, Randomized Clinical Trial
NCT00516919	PHASE4	COMPLETED	Study of Behavioral Weight Loss Therapy for Obesity and Binge Eating in Monolingual Hispanic Persons
NCT00522470	PHASE4	COMPLETED	Effects of Rosiglitazone on Serum Ghrelin and Peptide YY Levels
NCT00537810	PHASE4	COMPLETED	Treatment of Binge Eating in Obese Patients in Primary Care
NCT00538486	PHASE4	COMPLETED	A Randomized, Double-Blind, Active Control Trial Comparing Effects of Telmisartan, Candesartan and Amlodipine, Alone or Plus Metformin, on Non-Diabetic, Obese Hypertensive Patients
NCT00584389	PHASE4	TERMINATED	The Effect of Rimonabant on Energy Expenditure, Fat Metabolism and Body Composition
NCT00585182	PHASE4	COMPLETED	Study to Evaluate Weight-based Enoxaparin Dosing in Obese Medical Patients at Risk for DVT
NCT00632840	PHASE4	COMPLETED	Pharmacological Regulation of Fat Transport in Metabolic Syndrome
NCT00636142	PHASE4	COMPLETED	Effects of Infliximab on Insulin Sensitivity and Beta Cell Function in Insulin Resistant Human Obesity
NCT00675987	PHASE4	COMPLETED	A Randomized Clinical Trial To Study Losartan On Endothelial Dysfunction and Insulin Resistance In Obese Patients
NCT00694811	PHASE4	COMPLETED	Effects of Re-Feeding Duration on Weight Maintenance After Weight Loss With Very-Low-Energy Diets (VLEDs)
NCT00699413	PHASE4	TERMINATED	Supplements for Controlling Resistance to Insulin
NCT00729963	PHASE4	COMPLETED	Sibutramine Versus Continuous Positive Airway Pressure (CPAP)in Obstructive Sleep Apnea (OSA) Patients