ADRA2B

Summary

ADRA2B (adrenoceptor alpha 2B, HGNC:282) is a protein-coding gene on chromosome 2q11.2, encoding Alpha-2B adrenergic receptor (P18089). Alpha-2 adrenergic receptors are G protein-coupled receptors for catecholamines that activate G(i/o) protein pathway, thereby promoting adenylyl cyclase inhibition, ERK1/2 stimulation, and voltage-gated calcium channels suppression.

This intronless gene encodes a seven-pass transmembrane protein. This protein is a member of a subfamily of G protein-coupled receptors that regulate neurotransmitter release from sympathetic nerves and from adrenergic neurons in the central nervous system.

Source: NCBI Gene 151 — RefSeq curated summary.

At a glance

• Gene–disease (curated): benign adult familial myoclonic epilepsy (Supportive, GenCC) — +3 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 110 total — 8 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 8
• Druggable target: yes — 316 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000682

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:282
Approved symbol	ADRA2B
Name	adrenoceptor alpha 2B
Location	2q11.2
Locus type	gene with protein product
Status	Approved
Aliases	ADRARL1
Ensembl gene	ENSG00000274286
Ensembl biotype	protein_coding
OMIM	104260
Entrez	151

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000620793

RefSeq mRNA: 1 — MANE Select: NM_000682 NM_000682

CCDS: CCDS56129

Canonical transcript exons

ENST00000620793 — 1 exons

Exon	Start	End
ENSE00003744297	96112876	96116571

Expression profiles

Bgee: expression breadth ubiquitous, 147 present calls, max score 85.18.

FANTOM5 (CAGE): breadth broad, TPM avg 1.8198 / max 132.1735, expressed in 347 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
29701	0.6831	120
29703	0.6576	223
29702	0.4791	172

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	85.18	gold quality
tendon of biceps brachii	UBERON:0008188	85.06	silver quality
gastrocnemius	UBERON:0001388	76.19	gold quality
heart left ventricle	UBERON:0002084	75.38	gold quality
muscle of leg	UBERON:0001383	75.34	gold quality
buccal mucosa cell	CL:0002336	74.95	gold quality
cardiac ventricle	UBERON:0002082	74.76	gold quality
right lobe of liver	UBERON:0001114	72.15	gold quality
spleen	UBERON:0002106	72.08	gold quality
type B pancreatic cell	CL:0000169	71.91	gold quality
lower esophagus muscularis layer	UBERON:0035833	71.71	gold quality
lower esophagus	UBERON:0013473	71.62	gold quality
metanephros cortex	UBERON:0010533	71.53	gold quality
cervix squamous epithelium	UBERON:0006922	71.51	gold quality
omental fat pad	UBERON:0010414	71.17	gold quality
peritoneum	UBERON:0002358	71.12	gold quality
adipose tissue of abdominal region	UBERON:0007808	70.79	gold quality
muscle organ	UBERON:0001630	70.53	gold quality
subcutaneous adipose tissue	UBERON:0002190	70.07	gold quality
hindlimb stylopod muscle	UBERON:0004252	69.60	gold quality
triceps brachii	UBERON:0001509	69.05	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	69.02	gold quality
heart	UBERON:0000948	68.97	gold quality
tibial nerve	UBERON:0001323	68.67	gold quality
ascending aorta	UBERON:0001496	68.12	gold quality
tongue squamous epithelium	UBERON:0006919	67.89	gold quality
thoracic aorta	UBERON:0001515	67.74	gold quality
squamous epithelium	UBERON:0006914	67.31	gold quality
adipose tissue	UBERON:0001013	67.12	gold quality
connective tissue	UBERON:0002384	66.77	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.88
E-CURD-53	no	34.92

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SP1, STAT6, TFAP2A

miRNA regulators (miRDB)

81 targeting ADRA2B, 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-3163	100.00	77.23	8605
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-3136-3P	99.57	66.59	781
HSA-MIR-7155-3P	99.57	66.48	794
HSA-MIR-4441	99.49	66.56	3216

Literature-anchored findings (GeneRIF, showing 40)

• findings show that NPC1b is expressed in the midgut epithelium and is essential for growth during larval development; findings suggest that NPC1b plays an early role in sterol absorption (PMID:17339027)
• Middle-aged white men carrying the DD genotype of the alpha(2B)-AR have a significantly increased risk for sudden cardiac death and myocardial infarction, especially before the age of 55 years. (PMID:12535806)
• No major functional significance of the alpha(2B) adrenergic receptor polymorphism in the present sample of morbidly obese subjects was found. (PMID:12822042)
• Alpha2-ARs in vascular smooth muscle cells reflect differential activity of alpha2-AR gene promoters. Alpha2C-ARs can be induced via p38 MAPK-dependent pathway. (PMID:12946937)
• A polymorphism in the (alpha)2B adrenoceptor gene associates with hypertension. (PMID:14744925)
• 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)
• The 12Glu9 polymorphism of ADRA2B is associated with impaired insulin secretion and may predict the development of Type 2 diabetes. (PMID:15309292)
• ADRA2A and ADRA2B each had a single haplotype block at least 11 and 16 kb in size (PMID:15592690)
• the del301-303 polymorphism of ADRA2B does not contribute significantly to interindividual in vivo variability in response to alpha2-AR activation in the hand vein (PMID:15864122)
• analysis of stability of ADRA2B and binding to small molecules after detergent solubilization (PMID:15893292)
• In Chinese men, the I allele of the ADRA2B gene is associated with higher blood pressure, but also with a more favourable metabolic phenotype. (PMID:16269962)
• Multiple stepwise linear regression identified alpha2B genotype as an independent predictor of age at onset of type 2 diabetes. (PMID:17039423)
• Leisure-time physical activity decreased the risk of type 2 diabetes in those with the 12Glu and 9Glu alleles of the ADRA2B gene. (PMID:17277585)
• study showed that genotype distribution and the frequency of the alpha 2 beta adrenergic receptor alleles was not different in Greek women with polycystic ovary syndrome and controls (PMID:17370102)
• alpha-2CDel AR appears to play only a minor role in presynaptic regulation of NA release and/or to be not hypofunctional in vivo in humans, but functional responsiveness of presynaptic alpha-2 AR declines with ageing. (PMID:17410123)
• Evidence for an association of the D allele with both presence and severity of neuropathy in patients with type 2 diabetes mellitus. (PMID:17516297)
• The decrease in intermuscular fat (IMF) in ADRalpha2bGlu9 carriers was significantly different from a nonsignificant increase in ADRalpha2bGlu9 noncarriers. (PMID:17595424)
• main finding was that men with the DD polymorphism of the ADRA2B gene and job strain have significantly higher blood pressure than all other gene-work characteristics combinations (PMID:17620957)
• {alpha}2-adrenergic receptor-mediated antilipolysis in human adipose tissue is inhibited by long chain fatty acids (PMID:17625217)
• a deletion variant of ADRA2B, the gene encoding the alpha2b-adrenergic receptor, is related to enhanced emotional memory in healthy Swiss subjects and in survivors of the Rwandan civil war who experienced highly aversive emotional situations. (PMID:17660814)
• These data indicate that alpha-2 adrenergic receptors contribute significantly to CBR-induced vasoconstriction in the human leg under resting conditions. (PMID:18054844)
• A vascular smooth muscle cell line stably expressing the human alpha 2B-adrenoceptor was generated by transfection of rat cells (PMID:18456256)
• we could not replicate the association of blood pressure and the metabolic phenotypes with ADRA2B I/D polymorphism (PMID:18596718)
• The ADRA2B D allele is associated with a favorable anthropometric and metabolic profile in Chinese population. (PMID:18854756)
• A variant of the ADRA2B gene is associated with essential hypertension with or without type 2 diabetes in Malaysian subjects. (PMID:18953403)
• The alpha(2C) Del322-325 polymorphism exclusively or in combination with the beta(1)Arg389 allele is not associated with an increased risk of adverse events in HF. (PMID:19477404)
• The I/D polymorphism is not consistently associated with metabolic syndrome and metabolic/anthropometric parameters but with diastolic blood pressure in an urban-based population of middle-aged Swedes. (PMID:19593211)
• A novel polymorphism in the coding region of the human alpha-2B adrenergic receptor has been identified and demonstrated to affect receptor function. (PMID:19728989)
• A functional deletion variant of ADRA2B is related to increased responsivity and connectivity of brain regions implicated in emotional memory. (PMID:19826083)
• The ADRA2B 301-303 deletion allele (ins/del and del/del, n = 18) was associated with resistance to desensitization. (PMID:20051907)
• carriage of the ADRA2B deletion abolished the relative memory impairment in homozygous COMT val158 carriers compared to met158 carriers. (PMID:20110158)
• gene x exercise interactions were observed for A2BGlu9/12 and B2Gln27Glu on change in lean soft tissue (LST, p = 0.02); exercisers on the A2BGlu9- background gained LST compared to a loss among controls over 12 months (p\0.05) (PMID:20401689)
• Data provide strong evidence indicating that Rab8 GTPase interacts with distinct motifs in the C termini of alpha(2B)-AR and beta(2)-AR and differentially modulates their traffic from the TGN to the cell surface. (PMID:20424170)
• the findings of this study do not support a functional significance of ADRA2B indel polymorphism at position -4825 relative to the start codon in the far upstream region of the promoter in the present migraine subjects. (PMID:20651814)
• Homozygote for insertion [I]/deletion allele of alpha(2B)-AR gene polymorphism is associated with silent myocardial ischemia in type 2 diabetes mellitus patients with coronary artery disease. (PMID:20692245)
• The noradrenaline-mediated depolarization of vascular smooth muscle cells is produced by activation of both alpha(1)-and alpha(2)-adrenoceptors. (PMID:20739228)
• Data do not show any association between the presence of the alpha2B-adrenergic receptor deletion allele and the occurrence of spontaneous abortions. (PMID:21159032)
• the ADRA2B polymorphism influences emotional memory formation but not memory retrieval in the amygdala and left inferior frontal gyrus. (PMID:21259387)
• Alpha2B-adrenergic receptor interaction with tubulin controls its transport from the endoplasmic reticulum to the cell surface (PMID:21357695)
• The significant novel finding from this study is that the affective modulation of T2 detection is influenced by a non-additive (epistatic) interaction between the ADRA2B and 5-HTTLPR insertion/deletion polymorphisms. (PMID:21854681)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	adra2b	ENSDARG00000102096
mus_musculus	Adra2b	ENSMUSG00000058620
rattus_norvegicus	Adra2b	ENSRNOG00000013887
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), ADRB3 (ENSG00000188778)

Protein

Protein identifiers

Alpha-2B adrenergic receptor — P18089 (reviewed: P18089)

Alternative names: Alpha-2 adrenergic receptor subtype C2, Alpha-2B adrenoreceptor

All UniProt accessions (1): P18089

UniProt curated annotations — full annotation on UniProt →

Function. Alpha-2 adrenergic receptors are G protein-coupled receptors for catecholamines that activate G(i/o) protein pathway, thereby promoting adenylyl cyclase inhibition, ERK1/2 stimulation, and voltage-gated calcium channels suppression. Control a variety of physiological processes, such as regulation of blood pressure, lipolysis and insulin release. The rank order of potency for agonists of ADRA2B is clonidine > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phentolamine > mianserine > spiperone > prazosin > alprenolol > propanolol > pindolol.

Subunit / interactions. Interacts with RAB26; RAB26 mediates cell surface transport from the Golgi. Interacts with PPP1R9B. Interacts with GGA1, GGA2 and GGA3; GGA1, GGA2 and GGA3 mediates transport from the Golgi to the cell membrane. Interacts with RAB43 (GTP-bound); RAB43 mediates ADRA2B ER-to-Golgi cell transport.

Subcellular location. Cell membrane.

Disease relevance. Epilepsy, familial adult myoclonic, 2 (FAME2) [MIM:607876] A form of familial myoclonic epilepsy, a neurologic disorder characterized by cortical hand tremors, myoclonic jerks and occasional generalized or focal seizures with a non-progressive or very slowly progressive disease course. Usually, myoclonic tremor is the presenting symptom, characterized by tremulous finger movements and myoclonic jerks of the limbs increased by action and posture. In a minority of patients, seizures are the presenting symptom. Some patients exhibit mild cognitive impairment. FAME2 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry.

Polymorphism. A rare polymorphic frameshift in position 451 produces a protein of 545 residues.

Similarity. Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRA2B sub-subfamily.

RefSeq proteins (1): NP_000673* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000207	ADRA2B_rcpt	Family
IPR000276	GPCR_Rhodpsn	Family
IPR002233	ADR_fam	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (45 total): helix 10, topological domain 8, transmembrane region 7, sequence variant 6, compositionally biased region 3, site 3, region of interest 2, turn 2, chain 1, lipid moiety-binding region 1, disulfide bond 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6K41	ELECTRON MICROSCOPY	2.9
6K42	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P18089-F1	72.81	0.42

Antibody-complex structures (SAbDab): 2 — 6K41, 6K42

Functional residue map

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

Catalytic / active sites (3): 92 (implicated in ligand binding); 176 (implicated in catechol agonist binding); 180 (implicated in catechol agonist binding)

Post-translational modifications (1): 442

Disulfide bonds (1): 85–164

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-390696	Adrenoceptors
R-HSA-392023	Adrenaline signalling through Alpha-2 adrenergic receptor
R-HSA-418594	G alpha (i) signalling events
R-HSA-418597	G alpha (z) signalling events
R-HSA-109582	Hemostasis
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
R-HSA-76002	Platelet activation, signaling and aggregation
R-HSA-76009	Platelet Aggregation (Plug Formation)

MSigDB gene sets: 193 (showing top): MODULE_92, GGTGTGT_MIR329, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, REACTOME_PLATELET_AGGREGATION_PLUG_FORMATION, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, REACTOME_G_ALPHA_Z_SIGNALLING_EVENTS, GOBP_PLATELET_ACTIVATION, MODULE_64, GOBP_POSITIVE_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_REGULATION_OF_SMOOTH_MUSCLE_CONTRACTION, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOCC_CELL_SURFACE, GOBP_NEUROGENESIS, GOBP_CELL_CELL_SIGNALING

GO Biological Process (19): regulation of vascular associated smooth muscle contraction (GO:0003056), epidermal growth factor receptor signaling pathway (GO:0007173), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193), cell-cell signaling (GO:0007267), female pregnancy (GO:0007565), negative regulation of norepinephrine secretion (GO:0010700), platelet activation (GO:0030168), negative regulation of epinephrine secretion (GO:0032811), positive regulation of MAPK cascade (GO:0043410), positive regulation of neuron differentiation (GO:0045666), positive regulation of blood pressure (GO:0045777), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), positive regulation of uterine smooth muscle contraction (GO:0070474), adrenergic receptor signaling pathway (GO:0071875), adenylate cyclase-inhibiting adrenergic receptor signaling pathway (GO:0071881), regulation of smooth muscle contraction (GO:0006940), signal transduction (GO:0007165), regulation of vasoconstriction (GO:0019229)

GO Molecular Function (5): alpha2-adrenergic receptor activity (GO:0004938), epinephrine binding (GO:0051379), G protein-coupled receptor activity (GO:0004930), adrenergic receptor activity (GO:0004935), protein binding (GO:0005515)

GO Cellular Component (4): cytosol (GO:0005829), plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
GPCR downstream signalling	2
Signaling by GPCR	2
Amine ligand-binding receptors	1
Platelet Aggregation (Plug Formation)	1
Signal Transduction	1
GPCR ligand binding	1
Class A/1 (Rhodopsin-like receptors)	1
Hemostasis	1
Platelet activation, signaling and aggregation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cell communication	2
signaling	2
negative regulation of catecholamine secretion	2
positive regulation of intracellular signal transduction	2
G protein-coupled receptor signaling pathway	2
adrenergic receptor signaling pathway	2
regulation of smooth muscle contraction	1
vascular associated smooth muscle contraction	1
regulation of vasoconstriction	1
ERBB signaling pathway	1
G protein-coupled receptor activity	1
signal transduction	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase inhibitor activity	1
multi-organism reproductive process	1
multi-multicellular organism process	1
regulation of norepinephrine secretion	1
norepinephrine secretion	1
cell activation	1
blood coagulation	1
regulation of epinephrine secretion	1
epinephrine secretion	1
MAPK cascade	1
regulation of MAPK cascade	1
neuron differentiation	1
positive regulation of cell differentiation	1
regulation of neuron differentiation	1
regulation of blood pressure	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
positive regulation of smooth muscle contraction	1
uterine smooth muscle contraction	1
regulation of uterine smooth muscle contraction	1
adrenergic receptor activity	1
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	1
regulation of muscle contraction	1
smooth muscle contraction	1
cellular process	1
regulation of cellular process	1

Protein interactions and networks

STRING

936 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADRA2B	SEC24C	P53992	745
ADRA2B	SEC24B	O95487	610
ADRA2B	SLC6A4	P31645	580
ADRA2B	SLC6A2	P23975	569
ADRA2B	RAB8A	P24407	536
ADRA2B	SEC24D	O94855	531
ADRA2B	SLC6A3	Q01959	521
ADRA2B	PTGS1	P23219	495
ADRA2B	SEC24A	O95486	493
ADRA2B	ADRA1D	P25100	485
ADRA2B	VWF	P04275	483
ADRA2B	RBP3	P10745	481
ADRA2B	DBH	P09172	460
ADRA2B	ADRA2A	P08913	453
ADRA2B	PPP1R9B	Q96SB3	441

IntAct

17 interactions, top by confidence:

A	B	Type	Score
RAB26	ADRA2B	psi-mi:“MI:0915”(physical association)	0.630
RAB26	ADRA2B	psi-mi:“MI:2364”(proximity)	0.630
ADRA2B	RAB26	psi-mi:“MI:0915”(physical association)	0.630
ADRA2B	RAB26	psi-mi:“MI:0407”(direct interaction)	0.630
ACKR3	ADRA2B	psi-mi:“MI:2364”(proximity)	0.420
ACKR3	ADRA2B	psi-mi:“MI:0914”(association)	0.420
ADRA2B	SH3GL1	psi-mi:“MI:0915”(physical association)	0.400
SH3GL2	ADRA2B	psi-mi:“MI:0915”(physical association)	0.400
ADRA2B	GGA2	psi-mi:“MI:0915”(physical association)	0.400
ADRA2B	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	ADRA2B	psi-mi:“MI:0915”(physical association)	0.400
ADRA2B	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	ADRA2B	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (9): GOLGA4 (Co-localization), GGA3 (Affinity Capture-Western), GGA3 (Reconstituted Complex), GGA2 (Affinity Capture-Western), GGA1 (Reconstituted Complex), GGA2 (Reconstituted Complex), EIF2B1 (Reconstituted Complex), ADRA2B (Reconstituted Complex), UCHL1 (Reconstituted Complex)

ESM2 similar proteins: O02662, O02666, O19025, O19032, O19054, O77721, O77830, P07700, P08588, P08913, P11615, P15823, P18089, P18090, P18825, P18841, P18871, P19328, P22086, P22909, P23944, P25100, P25115, P25962, P26255, P30545, P34971, P35368, P43141, P47899, P79148, P97714, P97717, Q01337, Q01338, Q17239, Q28838, Q28927, Q28998, Q60474

Diamond homologs: A0A287A2K5, C8YUV0, O00155, O02836, O08786, O15973, O18935, O19012, O19014, O19025, O19032, O19054, O19091, O62729, O77408, O77700, O77721, O77830, O97665, O97772, P04761, P08482, P0C5I1, P11229, P12657, P17200, P18089, P19328, P22270, P25021, P30545, P30551, P30552, P30553, P30796, P32211, P32238, P32239, P32302, P46627

SIGNOR signaling

17 interactions.

A	Effect	B	Mechanism
ADRA2B	“up-regulates activity”	GNAI1	binding
ADRA2B	“up-regulates activity”	GNAI3	binding
ADRA2B	“up-regulates activity”	GNAO1	binding
ADRA2B	“up-regulates activity”	GNAZ	binding
ADRA2B	“up-regulates activity”	GNA12	binding
(R)-noradrenaline	“up-regulates activity”	ADRA2B	“chemical activation”
brimonidine	“up-regulates activity”	ADRA2B	“chemical activation”
clonidine	“up-regulates activity”	ADRA2B	“chemical activation”
dexmedetomidine	“up-regulates activity”	ADRA2B	“chemical activation”
Guanabenz	“up-regulates activity”	ADRA2B	“chemical activation”
tolazoline	“down-regulates activity”	ADRA2B	“chemical inhibition”
oxymetazoline	“up-regulates activity”	ADRA2B	“chemical activation”
Guanfacine	“up-regulates activity”	ADRA2B	“chemical activation”
N-(2,6-dimethylphenyl)-5,6-dihydro-4H-1,3-thiazin-2-amine	“up-regulates activity”	ADRA2B	“chemical activation”
zotepine	“down-regulates activity”	ADRA2B	“chemical inhibition”
lofexidine	“up-regulates activity”	ADRA2B	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	6
Uncertain significance	73
Likely benign	16
Benign	4

Top pathogenic / likely-pathogenic (14)

Variant ID	HGVS	Classification
144712	GRCh38/hg38 2q11.1-11.2(chr2:95879602-97029672)x1	Pathogenic
146017	GRCh38/hg38 2q11.2(chr2:96073560-97062710)x1	Pathogenic
154733	GRCh38/hg38 2q11.2(chr2:96073560-97513144)x1	Pathogenic
4755375	GRCh38/hg38 2q11.1-11.2(chr2:95875947-97355895)x1	Pathogenic
57434	GRCh38/hg38 2q11.2(chr2:96100812-97285797)x1	Pathogenic
57543	GRCh38/hg38 2q11.1-11.2(chr2:95879602-97285797)x1	Pathogenic
687873	GRCh37/hg19 2q11.1-11.2(chr2:96552903-98118115)x1	Pathogenic
997821	Single allele	Pathogenic
2664653	NM_000682.7(ADRA2B):c.116C>T (p.Thr39Ile)	Likely pathogenic
443435	GRCh37/hg19 2q11.1-11.2(chr2:96468158-97871906)x3	Likely pathogenic
4682540	GRCh37/hg19 2p11.2-q11.2(chr2:85898497-97671333)x3	Likely pathogenic
545284	NC_000002.12:g.(?96063558)(97079140_?)del	Likely pathogenic
562641	GRCh37/hg19 2q11.1-11.2(chr2:96735977-98258828)x1	Likely pathogenic
814283	GRCh37/hg19 2q11.1-11.2(chr2:96712139-98254657)x1	Likely pathogenic

SpliceAI

184 predictions. Top by Δscore:

Variant	Effect	Δscore
2:96115000:A:T	acceptor_gain	0.8800
2:96115001:G:GT	acceptor_gain	0.8700
2:96114997:ACCAG:A	acceptor_gain	0.7600
2:96114998:CCAGC:C	acceptor_gain	0.7600
2:96115003:A:AT	acceptor_gain	0.7500
2:96114387:A:C	acceptor_gain	0.6700
2:96114198:G:T	acceptor_gain	0.6000
2:96115528:TGGG:T	donor_gain	0.6000
2:96114197:C:CT	acceptor_gain	0.5900
2:96114983:G:GT	acceptor_gain	0.5700
2:96114999:C:CT	acceptor_gain	0.5500
2:96114980:G:C	acceptor_gain	0.5300
2:96114991:AGGGG:A	acceptor_gain	0.5300
2:96114795:G:GA	donor_gain	0.5100
2:96114986:G:A	acceptor_gain	0.5100
2:96114984:A:AA	acceptor_gain	0.5000
2:96114985:A:AA	acceptor_gain	0.5000
2:96114802:A:T	donor_gain	0.4900
2:96114995:GAACC:G	acceptor_gain	0.4900
2:96114996:AACCA:A	acceptor_gain	0.4900
2:96114798:C:T	donor_gain	0.4600
2:96114197:C:T	acceptor_gain	0.4300
2:96114366:CTCTT:C	acceptor_gain	0.4300
2:96114367:TCTTT:T	acceptor_gain	0.4300
2:96114376:G:C	acceptor_gain	0.4300
2:96114387:A:AC	acceptor_gain	0.4300
2:96115006:G:GT	acceptor_gain	0.4300
2:96115531:G:T	donor_gain	0.4300
2:96115119:A:AC	donor_gain	0.4200
2:96113870:C:CC	acceptor_gain	0.4100

AlphaMissense

2882 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:96114882:G:T	P423H	1.000
2:96114884:G:C	N422K	1.000
2:96114884:G:T	N422K	1.000
2:96114896:G:C	N418K	1.000
2:96114896:G:T	N418K	1.000
2:96115010:A:C	F380L	1.000
2:96115010:A:T	F380L	1.000
2:96115012:A:G	F380L	1.000
2:96115829:G:C	S107R	1.000
2:96115829:G:T	S107R	1.000
2:96115831:T:G	S107R	1.000
2:96115977:T:A	D58V	1.000
2:96115977:T:G	D58A	1.000
2:96114851:G:C	F433L	0.999
2:96114851:G:T	F433L	0.999
2:96114853:A:G	F433L	0.999
2:96114874:A:G	Y426H	0.999
2:96114876:A:T	I425N	0.999
2:96114879:A:T	V424D	0.999
2:96114882:G:C	P423R	0.999
2:96114883:G:A	P423S	0.999
2:96114886:T:C	N422D	0.999
2:96114893:G:C	S419R	0.999
2:96114893:G:T	S419R	0.999
2:96114895:T:G	S419R	0.999
2:96114906:C:T	G415D	0.999
2:96114913:A:G	W413R	0.999
2:96114913:A:T	W413R	0.999
2:96115000:A:G	W384R	0.999
2:96115000:A:T	W384R	0.999

dbSNP variants (sampled 300 via entrez): RS1000048230 (2:96118322 T>C), RS1000169652 (2:96117940 A>G,T), RS1000231137 (2:96113141 C>A), RS1001121437 (2:96114160 C>T), RS1001171412 (2:96117650 G>A), RS1001213142 (2:96117894 A>C), RS1001221137 (2:96112554 C>T), RS1001936074 (2:96118018 G>A), RS1002009905 (2:96118360 A>G), RS1002523091 (2:96113478 A>G), RS1003290232 (2:96116731 A>G), RS1004486876 (2:96115159 G>A), RS1004732207 (2:96115998 A>C), RS1004815866 (2:96114964 T>C), RS1005803581 (2:96116634 A>G)

Disease associations

OMIM: gene MIM:104260 | disease phenotypes: MIM:607876, MIM:181500

GenCC curated gene-disease

Disease	Classification	Inheritance
benign adult familial myoclonic epilepsy	Supportive	Autosomal dominant
epilepsy, familial adult myoclonic, 2	Limited	Unknown
neurodevelopmental disorder	Limited	Autosomal recessive
epilepsy	Refuted Evidence	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
epilepsy	Refuted	AD

Mondo (6): epilepsy, familial adult myoclonic, 2 (MONDO:0011930), schizophrenia (MONDO:0005090), intellectual disability (MONDO:0001071), epilepsy (MONDO:0005027), benign adult familial myoclonic epilepsy (MONDO:0019448), neurodevelopmental disorder (MONDO:0700092)

Orphanet (3): Familial adult myoclonic epilepsy (Orphanet:86814), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

8 total (9 of 8 shown, HPO-id order):

HPO	Term
HP:0001249	Intellectual disability
HP:0001336	Myoclonus
HP:0002197	Generalized-onset seizure
HP:0002315	Headache
HP:0002353	EEG abnormality
HP:0002378	Hand tremor
HP:0007359	Focal-onset seizure
HP:0100576	Amaurosis fugax
HP:0100753	Schizophrenia

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002394_125	Monocyte percentage of white cells	2.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007989	monocyte percentage of leukocytes

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D004827	Epilepsy	C10.228.140.490
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625
C564313	Epilepsy, Myoclonic, Benign Adult Familial, Type 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL1942 (SINGLE PROTEIN), CHEMBL2095158 (PROTEIN FAMILY), CHEMBL2095203 (PROTEIN FAMILY), CHEMBL2331074 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

316 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 688,166 (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
CHEMBL1008	BEPRIDIL	4	11,776
CHEMBL1014	CANDESARTAN CILEXETIL	4	11,194
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1064	SIMVASTATIN	4	123,163
CHEMBL1065	METHYSERGIDE	4	8,455
CHEMBL1079	TIZANIDINE	4	12,099
CHEMBL1083659	SUVOREXANT	4	852
CHEMBL1085	ACETOPHENAZINE	4	5,134
CHEMBL11	IMIPRAMINE	4	48,893
CHEMBL1108	DROPERIDOL	4	16,888
CHEMBL111	RIMONABANT	4	15,726
CHEMBL1112	ARIPIPRAZOLE	4	24,205
CHEMBL1113	AMOXAPINE	4	20,128
CHEMBL1117	IDARUBICIN	4	136,065
CHEMBL1171837	PONATINIB	4	8,955
CHEMBL1172	DESLORATADINE	4	19,720
CHEMBL1173655	AFATINIB	4	15,144
CHEMBL1175	DULOXETINE	4	28,527
CHEMBL118	CELECOXIB	4	112,844
CHEMBL1194666	DIETHYLPROPION	4	12,073
CHEMBL1200406	DIMENHYDRINATE	4
CHEMBL1200492	NEFAZODONE HYDROCHLORIDE	4
CHEMBL1200517	DIHYDROERGOTAMINE MESYLATE	4
CHEMBL1200809	AZELASTINE HYDROCHLORIDE	4
CHEMBL1201	THIOTHIXENE	4
CHEMBL1201039	BENZTHIAZIDE	4
CHEMBL1201087	CABERGOLINE	4
CHEMBL1201203	BENZTROPINE	4
CHEMBL1201210	PROPIOMAZINE	4
CHEMBL1201216	DAPIPRAZOLE	4

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs29000568	ADRA2B		0.00	0
rs3813662	ADRA2B		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Adrenoceptors

Most potent curated ligand interactions (45 total), top 25:

Ligand	Action	Affinity	Parameter
dexmedetomidine	Full agonist	10.9	pIC50
lisuride	Antagonist	9.9	pKi
terguride	Antagonist	9.4	pKi
[3H]rauwolscine	Antagonist	9.2	pKd
[3H]MK-912	Antagonist	8.9	pKd
spiroxatrine	Antagonist	8.8	pKi
RX821002	Antagonist	8.7	pKi
atipamezole	Antagonist	8.6	pKi
RS79948	Antagonist	8.6	pKi
yohimbine	Antagonist	8.4	pKi
A-1262543	Partial agonist	8.4	pEC50
WB 4101	Antagonist	8.4	pKi
chlorpromazine	Antagonist	8.3	pKi
rauwolscine	Antagonist	8.3	pKi
roxindole	Antagonist	8.3	pKi
zotepine	Antagonist	8.2	pKi
MK-912	Antagonist	8.2	pKi
phentolamine	Antagonist	8.2	pKi
[125I]p-iodoclonidine	Partial agonist	8.1	pKd
[3H]RX821002	Antagonist	8.1	pKd
guanabenz	Agonist	7.9	pEC50
ARC-239	Antagonist	7.7	pKi
idazoxan	Antagonist	7.6	pKi
guanfacine	Full agonist	7.6	pEC50
bromocriptine	Antagonist	7.5	pKi

Binding affinities (BindingDB)

62 measured of 97 human assays (118 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
NSC_104911	KI	0.1 nM
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
MK-912	KI	0.42 nM
2-Chlor-11-(2-dimethylaminoaethoxy)-dibenzo(b,f)-thiepin	KI	0.5 nM
8-(2,3-Dihydro-benzo[1,4]dioxin-2-ylmethyl)-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one	KI	1 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
4-[4-(4-Chloro-phenyl)-4-hydroxy-piperidin-1-yl]-1-(4-fluoro-phenyl)-butan-1-one;propionate(HCl)	KI	2.92 nM
(S)-mianserin	KI	3 nM
Terguride	KI	3.47 nM
S18616	KI	3.98 nM
naphtaline	KI	4.57 nM
NSC_121850	KI	5.68 nM
p-AMINOCLONIDINE	KI	7.94 nM
CAS_67249-51-8	KI	7.94 nM
Bromocriptine+ (GTP+)	KI	12.9 nM
CAS_81447-78-1	KI	14.4 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
NSC_3519	KI	50.3 nM
cid_3396	KI	56 nM
CHEMBL297827	KI	102 nM
CHEMBL48341	KI	141 nM
2-[4-[3-[2-(trifluoromethyl)phenothiazin-10-yl]propyl]piperazin-1-yl]ethanol;hydrochloride	KI	146 nM
CAS_105182-45-4	KI	158 nM
(R)-5-(1-(2,3-dimethylphenyl)ethyl)-1H-imidazole	KI	200 nM
S32504	KI	257 nM
4-[2-(dipropylamino)ethyl]-1,3-dihydro-2H-indol-2-one	KI	288 nM
SMR000033635	KI	300 nM
NSC_133621	KI	316 nM
CAS_22189-31-7	KI	410 nM
4-[3-(2-chlorophenothiazin-10-yl)propyl]-1-piperazineethanol	KI	421 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
(chloropromazine) [3-(2-Chloro-phenothiazin-10-yl)-propyl]-dimethyl-amine	KI	480 nM
ST 91	KI	575 nM
1-(1-(4,4-bis(4-fluorophenyl)butyl)piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one	KI	650 nM
Idazoxan	KI	662 nM
Pramipexole	KI	692 nM
cid_2913535	KI	950 nM
SR 147778	KI	1000 nM
NSC_1576	KI	1000 nM
1-[2-[4-[5-chloro-1-(4-fluorophenyl)-indol-3-yl]-1-piperidyl]ethyl]imidazolidin-2-one	KI	1050 nM
rilmenidine	KI	1580 nM
2-(3-(5,7-dihydroxy-2-(4-hydroxyphenyl)-4-oxo-4H-chromen-8-yl)-4-hydroxyphenyl)-5,7-dihydroxy-4H-chromen-4-one	IC50	1630 nM
B-HT 920	KI	1700 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_24221-86-1	KI	2000 nM

ChEMBL bioactivities

1500 potent at pChembl≥5 of 1645 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.85	IC50	0.014	nM	CHEMBL553231
10.80	IC50	0.016	nM	CHEMBL557985
10.47	IC50	0.034	nM	CHEMBL537830
10.00	Ki	0.1	nM	RAUWOLSCINE
9.96	Ki	0.1096	nM	CHEMBL1256414
9.94	Ki	0.1148	nM	CHEMBL1256414
9.92	IC50	0.12	nM	CHEMBL538801
9.74	Ki	0.182	nM	CHEMBL1255723
9.70	Kd	0.1995	nM	CHEMBL279807
9.70	Kd	0.1995	nM	CHEMBL62912
9.69	Ki	0.2042	nM	CHEMBL1256378
9.62	Ki	0.237	nM	LISURIDE
9.60	IC50	0.25	nM	CHEMBL194837
9.60	Ki	0.2512	nM	CHEMBL5517941
9.60	Ki	0.25	nM	CHEMBL50390
9.59	EC50	0.26	nM	CHEMBL49137
9.59	IC50	0.26	nM	CHEMBL554581
9.56	Ki	0.2754	nM	CHEMBL1256414
9.52	Ki	0.3	nM	RAUWOLSCINE
9.46	Ki	0.3467	nM	CHEMBL1255724
9.40	Ki	0.4	nM	YOHIMBINE
9.40	Ki	0.4	nM	RAUWOLSCINE
9.30	EC50	0.5	nM	ASCORBIC ACID
9.30	AC50	0.5	nM	CEFEPIME
9.29	IC50	0.518	nM	LISURIDE
9.22	Ki	0.6	nM	YOHIMBINE
9.21	IC50	0.61	nM	CHEMBL164540
9.20	Kd	0.631	nM	CHEMBL25554
9.16	Ki	0.6918	nM	CHEMBL1256609
9.11	Ki	0.786	nM	PIPAMAZINE
9.10	Ki	0.8	nM	RAUWOLSCINE
9.09	Ki	0.82	nM	CHEMBL4755913
9.05	Ki	0.9	nM	YOHIMBINE
9.04	Ki	0.912	nM	CHEMBL10332
9.04	Ki	0.912	nM	CHEMBL1255771
9.02	IC50	0.955	nM	CHEMBL351483
8.94	Ki	1.16	nM	YOHIMBINE
8.94	Ki	1.148	nM	CHEMBL1255770
8.92	Ki	1.2	nM	RAUWOLSCINE
8.92	Ki	1.2	nM	CHEMBL298936
8.92	EC50	1.2	nM	CHEMBL298936
8.90	IC50	1.259	nM	CHEMBL163247
8.89	IC50	1.3	nM	CHEMBL189118
8.89	Ki	1.3	nM	RAUWOLSCINE
8.89	Ki	1.3	nM	CHEMBL49137
8.87	IC50	1.349	nM	CHEMBL165350
8.86	Ki	1.396	nM	ERGOCORNINE
8.85	Ki	1.413	nM	CHEMBL10332
8.85	Ki	1.413	nM	BRIMONIDINE
8.85	AC50	1.4	nM	ASENAPINE

PubChem BioAssay actives

1009 with measured affinity, of 3338 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
Naphazoline Hydrochloride	36185: Compound was evaluated for Adrenergic activity against Alpha-2 adrenergic receptor in human platelets	ic50	<0.0001	uM
5-(1-naphthalen-1-ylethyl)-1H-imidazole;hydrochloride	36187: Compound was tested for Adrenergic activity against Alpha-2 adrenergic receptor from rat aorta	ic50	<0.0001	uM
2-(1-naphthalen-2-ylethyl)-4,5-dihydro-1H-imidazole;hydrochloride	36185: Compound was evaluated for Adrenergic activity against Alpha-2 adrenergic receptor in human platelets	ic50	<0.0001	uM
2-(naphthalen-1-ylmethyl)-1H-imidazole;hydrochloride	36185: Compound was evaluated for Adrenergic activity against Alpha-2 adrenergic receptor in human platelets	ic50	<0.0001	uM
2-(1-naphthalen-1-ylethyl)-4,5-dihydro-1H-imidazole;hydrochloride	36185: Compound was evaluated for Adrenergic activity against Alpha-2 adrenergic receptor in human platelets	ic50	<0.0001	uM
5-(1-naphthalen-2-ylethyl)-1H-imidazole;hydrochloride	36185: Compound was evaluated for Adrenergic activity against Alpha-2 adrenergic receptor in human platelets	ic50	0.0001	uM
5-[(1aR,6aR)-1a,6-dihydro-1H-cyclopropa[a]inden-6a-yl]-1H-imidazole	516908: Displacement of [3H]-RX821002 from human adrenergic alpha2B receptor expressed in rat C6 cells after 120 mins by liquid scintillation counting	ki	0.0001	uM
methyl (1S,15S,18S,19S,20S)-18-hydroxy-1,3,11,12,14,15,16,17,18,19,20,21-dodecahydroyohimban-19-carboxylate	36340: Compound was evaluated for inhibition of binding of [3H]rauwolscine to Alpha-2 adrenergic receptor in opossum kidney	ki	0.0001	uM
3-methoxy-12-methylsulfonyl-5,6,8,8a,9,10,11,12a,13,13a-decahydroisoquinolino[2,1-g][1,6]naphthyridine	80588: Ability to reverse inhibitory effects of UK-14304 on the contraction of guinea pig ileum as a measure of alpha-2 adrenergic receptor antagonism.	kd	0.0002	uM
5-[(1S,1aR,6aS)-1-methyl-1a,6-dihydro-1H-cyclopropa[a]inden-6a-yl]-1H-imidazole	516908: Displacement of [3H]-RX821002 from human adrenergic alpha2B receptor expressed in rat C6 cells after 120 mins by liquid scintillation counting	ki	0.0002	uM
5-[(1S,1aR,6aS)-1-ethyl-1a,6-dihydro-1H-cyclopropa[a]inden-6a-yl]-1H-imidazole	516908: Displacement of [3H]-RX821002 from human adrenergic alpha2B receptor expressed in rat C6 cells after 120 mins by liquid scintillation counting	ki	0.0002	uM
(8aR,12aR,13aS)-3-methoxy-12-methylsulfonyl-5,6,8,8a,9,10,11,12a,13,13a-decahydroisoquinolino[2,1-g][1,6]naphthyridine	80588: Ability to reverse inhibitory effects of UK-14304 on the contraction of guinea pig ileum as a measure of alpha-2 adrenergic receptor antagonism.	kd	0.0002	uM
2-(2,4-dichlorophenoxy)-N-[2-[2-(dimethylamino)ethoxy]-4-methylquinolin-6-yl]acetamide	254838: Inhibitory concentration against alpha-2 adrenergic receptor	ic50	0.0003	uM
(3R)-5-chlorospiro[2,4-dihydro-1H-naphthalene-3,2’-5H-1,3-oxazole]-4’-amine	2065718: Binding affinity to human alpha2B-adrenoceptor	ki	0.0003	uM
N-(4,5-dihydro-1H-imidazol-2-yl)-5-methylquinoxalin-6-amine	36513: Compound was tested for concentration that produced 50% contractile response relative to maximum response to norepinephrine for Alpha-2 adrenergic receptor in rabbit vas deferens	ec50	0.0003	uM
2-(1-naphthalen-1-ylethyl)-1H-imidazole;hydrochloride	36185: Compound was evaluated for Adrenergic activity against Alpha-2 adrenergic receptor in human platelets	ic50	0.0003	uM
5-[(1S,1aR,6aS)-1-propyl-1a,6-dihydro-1H-cyclopropa[a]inden-6a-yl]-1H-imidazole	516908: Displacement of [3H]-RX821002 from human adrenergic alpha2B receptor expressed in rat C6 cells after 120 mins by liquid scintillation counting	ki	0.0003	uM
Yohimbine	36499: Compound was evaluated for inhibition of binding of [3H]yohimbine to Alpha-2 adrenergic receptor in opossum kidney	ki	0.0004	uM
3-[(6aR,9S)-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinolin-9-yl]-1,1-diethylurea	2060761: Ray2010 Assay 74 from Article : “Psychedelics and the human receptorome.”	ki	0.0005	uM
ascorbic acid	416324: Agonist activity at human adrenergic alpha2B receptor expressed in HEK293 cells coexpressing Gqi5 protein by FLIPR assay	ec50	0.0005	uM
2-(1-naphthalen-2-ylethyl)-1H-imidazole;oxalic acid	36185: Compound was evaluated for Adrenergic activity against Alpha-2 adrenergic receptor in human platelets	ic50	0.0006	uM
N-(2,3-dihydro-1,4-benzodioxin-3-ylmethyl)-2-(2,6-dimethoxyphenoxy)ethanamine	1123560: Binding affinity to alpha-adrenergic receptor (unknown origin) in central nervous system	kd	0.0006	uM
5-[(1aR,6S,6aR)-6-methyl-1a,6-dihydro-1H-cyclopropa[a]inden-6a-yl]-1H-imidazole	516908: Displacement of [3H]-RX821002 from human adrenergic alpha2B receptor expressed in rat C6 cells after 120 mins by liquid scintillation counting	ki	0.0007	uM
1-[4-[[4-(4,5-dihydro-1H-imidazol-2-ylamino)phenyl]methyl]phenyl]-2-propylguanidine;dihydrochloride	1728108: Displacement of [3H]-RX821002 from adrenergic alpha 2 receptor in human brain membrane by liquid scintillation spectroscopy	ki	0.0008	uM
2-(3-methoxy-2H-1,4-benzodioxin-3-yl)-4,5-dihydro-1H-imidazole	297456: Displacement of [3H]RX821002 from adrenergic alpha2 receptor in human brain frontal cortex	ki	0.0009	uM
5-[(1aR,6aR)-1a-methyl-1,6-dihydrocyclopropa[a]inden-6a-yl]-1H-imidazole	516908: Displacement of [3H]-RX821002 from human adrenergic alpha2B receptor expressed in rat C6 cells after 120 mins by liquid scintillation counting	ki	0.0009	uM
7-chloro-3-[2-(3,4-dihydro-1H-[1]benzofuro[3,2-c]pyridin-2-yl)ethyl]-2-methylpyrido[1,2-a]pyrimidin-4-one	35399: Binding affinity at human Alpha-2B adrenergic receptor in CHO cells by [3H]rauwolscine (1 nM) displacement.	ic50	0.0010	uM
5-[(1aR,6aR)-1,1-dimethyl-1a,6-dihydrocyclopropa[a]inden-6a-yl]-1H-imidazole	516908: Displacement of [3H]-RX821002 from human adrenergic alpha2B receptor expressed in rat C6 cells after 120 mins by liquid scintillation counting	ki	0.0011	uM
N-(4,5-dihydro-1H-imidazol-2-yl)-5-methyl-3,4-dihydro-2H-1,4-benzoxazin-6-amine	36513: Compound was tested for concentration that produced 50% contractile response relative to maximum response to norepinephrine for Alpha-2 adrenergic receptor in rabbit vas deferens	ec50	0.0012	uM
7,9-dichloro-3-[2-(3,4-dihydro-1H-[1]benzofuro[3,2-c]pyridin-2-yl)ethyl]-2-methylpyrido[1,2-a]pyrimidin-4-one	35399: Binding affinity at human Alpha-2B adrenergic receptor in CHO cells by [3H]rauwolscine (1 nM) displacement.	ic50	0.0013	uM
7-bromo-3-[2-(3,4-dihydro-1H-[1]benzofuro[3,2-c]pyridin-2-yl)ethyl]-2-methylpyrido[1,2-a]pyrimidin-4-one	35399: Binding affinity at human Alpha-2B adrenergic receptor in CHO cells by [3H]rauwolscine (1 nM) displacement.	ic50	0.0013	uM
(E)-N-[2-[2-(dimethylamino)ethyl-methylamino]-4-methylquinolin-6-yl]-3-[4-(trifluoromethoxy)phenyl]prop-2-enamide	254838: Inhibitory concentration against alpha-2 adrenergic receptor	ic50	0.0013	uM
Brimonidine	368170: Binding affinity to alpha2 adrenoceptor in human cortical membrane	ki	0.0014	uM
(3R,3aS)-3-[[4-[(E)-3-(4-fluorophenyl)-2-methylprop-2-enyl]piperazin-1-yl]methyl]-7,8-dimethoxy-3a,4-dihydro-3H-chromeno[4,3-c][1,2]oxazole	288095: Displacement of [3H]rawolscine from human cloned adrenergic alpha-2B receptor transfected in CHO cells	ki	0.0015	uM
3-[2-(3,4-dihydro-1H-[1]benzofuro[3,2-c]pyridin-2-yl)ethyl]-2,7-dimethylpyrido[1,2-a]pyrimidin-4-one	35399: Binding affinity at human Alpha-2B adrenergic receptor in CHO cells by [3H]rauwolscine (1 nM) displacement.	ic50	0.0015	uM
3-[2-(3,4-dihydro-1H-[1]benzofuro[3,2-c]pyridin-2-yl)ethyl]-2,6-dimethylpyrido[1,2-a]pyrimidin-4-one	35399: Binding affinity at human Alpha-2B adrenergic receptor in CHO cells by [3H]rauwolscine (1 nM) displacement.	ic50	0.0015	uM
N-(2,6-dichloro-4-iodophenyl)-4,5-dihydro-1H-imidazol-2-amine	36188: Inhibition of [3H]p-aminoclonidine (PAC) binding to alpha-2 adrenergic receptor of purified human platelet plasma membranes	ic50	0.0015	uM
N-[4-[[4-(4,5-dihydro-1H-imidazol-2-ylamino)phenyl]methyl]phenyl]-4,5-dihydro-1H-imidazol-2-amine	1728108: Displacement of [3H]-RX821002 from adrenergic alpha 2 receptor in human brain membrane by liquid scintillation spectroscopy	ki	0.0016	uM
5-[(1aR,6S,6aS)-6-ethyl-1a,6-dihydro-1H-cyclopropa[a]inden-6a-yl]-1H-imidazole	516908: Displacement of [3H]-RX821002 from human adrenergic alpha2B receptor expressed in rat C6 cells after 120 mins by liquid scintillation counting	ki	0.0016	uM
N-pyridin-4-ylisoquinolin-4-amine	2065718: Binding affinity to human alpha2B-adrenoceptor	ki	0.0017	uM
3-[2-(3,4-dihydro-1H-[1]benzofuro[3,2-c]pyridin-2-yl)ethyl]-9-hydroxy-2-methylpyrido[1,2-a]pyrimidin-4-one	35399: Binding affinity at human Alpha-2B adrenergic receptor in CHO cells by [3H]rauwolscine (1 nM) displacement.	ic50	0.0017	uM
1-[4-[[4-(4,5-dihydro-1H-imidazol-2-ylamino)phenyl]methyl]phenyl]-2-(furan-2-ylmethyl)guanidine;dihydrochloride	1728108: Displacement of [3H]-RX821002 from adrenergic alpha 2 receptor in human brain membrane by liquid scintillation spectroscopy	ki	0.0018	uM
Risperidone	36197: Binding affinity towards human alpha-2 adrenergic receptor	ki	0.0018	uM
Apraclonidine	36512: Compound was tested for concentration that produced 50% contractile relative response to maximum response to norepinephrine for Alpha-2 adrenergic receptor	ec50	0.0019	uM
9-chloro-3-[2-(3,4-dihydro-1H-[1]benzofuro[3,2-c]pyridin-2-yl)ethyl]-2-methyl-7-(trifluoromethyl)pyrido[1,2-a]pyrimidin-4-one	35399: Binding affinity at human Alpha-2B adrenergic receptor in CHO cells by [3H]rauwolscine (1 nM) displacement.	ic50	0.0019	uM
5-[(1aR,6aS)-spiro[1,1a-dihydrocyclopropa[a]indene-6,1’-cyclopropane]-6a-yl]-1H-imidazole	516908: Displacement of [3H]-RX821002 from human adrenergic alpha2B receptor expressed in rat C6 cells after 120 mins by liquid scintillation counting	ki	0.0019	uM
Dexmedetomidine	2065729: Agonist activity at alpha2B-adrenoceptor (unknown origin) expressed in U2OS-EGFP-NFAT2-alpha2B-AR cells assessed as increase in intracellular calcium level measured after 15 mins incubation by Micro automated microscopy	ec50	0.0019	uM
3-[2-(3,4-dihydro-1H-[1]benzofuro[3,2-c]pyridin-2-yl)ethyl]-9-methoxy-2-methylpyrido[1,2-a]pyrimidin-4-one	35399: Binding affinity at human Alpha-2B adrenergic receptor in CHO cells by [3H]rauwolscine (1 nM) displacement.	ic50	0.0020	uM
3-[[4-[(E)-3-phenylprop-2-enyl]piperazin-1-yl]methyl]-3a,4-dihydro-3H-chromeno[4,3-c][1,2]oxazole	36227: In vitro binding affinity towards human alpha-2B adrenergic receptor using [3H]rauwolscine	ki	0.0020	uM
3-[2-(3,4-dihydro-1H-[1]benzofuro[3,2-c]pyridin-2-yl)ethyl]-7-iodo-2-methylpyrido[1,2-a]pyrimidin-4-one	35399: Binding affinity at human Alpha-2B adrenergic receptor in CHO cells by [3H]rauwolscine (1 nM) displacement.	ic50	0.0021	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	2
Epinephrine	decreases reaction, increases expression, increases reaction, increases phosphorylation, affects binding (+2 more)	2
aristolochic acid I	increases expression	1
bisphenol A	increases expression	1
xylometazoline	affects binding, increases activity, increases abundance, decreases reaction	1
butyraldehyde	increases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects cotreatment, decreases expression, affects response to substance	1
pentanal	increases expression	1
2-methoxyidazoxan	affects binding, decreases reaction	1
licochalcone B	increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases expression, increases abundance	1
Benzo(a)pyrene	decreases expression	1
Cadmium	increases expression	1
Calcium	affects binding, increases abundance, increases activity	1
Clonidine	affects binding, increases activity	1
Diethylhexyl Phthalate	decreases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression, affects cotreatment	1
Norepinephrine	increases activity, increases abundance, decreases reaction, affects binding	1
Oxymetazoline	affects binding, increases activity, increases abundance, decreases reaction	1
Plant Extracts	affects cotreatment, decreases expression	1
Triclosan	decreases expression	1
Valproic Acid	increases methylation	1
1-Methyl-4-phenylpyridinium	increases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	increases expression	1

ChEMBL screening assays

596 unique, capped per target: 466 binding, 123 functional, 5 admet, 2 unclassified

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1016575	Binding	Displacement of [3H]RS79948-197 from human recombinant adrenergic alpha2B receptor expressed in CHO cells	Alpha2-adrenoreceptors profile modulation. 4. From antagonist to agonist behavior. — J Med Chem
CHEMBL1016576	Functional	Antagonist activity at human recombinant adrenergic alpha2B receptor expressed in CHO cells	Alpha2-adrenoreceptors profile modulation. 4. From antagonist to agonist behavior. — J Med Chem
CHEMBL1738037	Unclassified	PUBCHEM_BIOASSAY: Late-stage radioligand binding dose response assay to identify inhibitors of NADPH oxidase 1 (NOX1): PDSP screen Ki Set 2. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID1792, AID1796, AID182	PubChem BioAssay data set

Cellosaurus cell lines

6 cell lines: 3 spontaneously immortalized cell line, 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_9114	L-NGC-alpha2B L-cells	Spontaneously immortalized cell line	Male
CVCL_B8B0	Abcam HCT 116 ADRA2B KO	Cancer cell line	Male
CVCL_B9D2	Abcam A-549 ADRA2B KO	Cancer cell line	Male
CVCL_D2DT	Abcam MCF-7 ADRA2B KO	Cancer cell line	Female
CVCL_H391	CHO-K1/ADRA2B/Gqi5	Spontaneously immortalized cell line	Female
CVCL_KW27	PathHunter CHO-K1 ADRA2B beta-arrestin	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00004637	PHASE4	COMPLETED	Double-Blind, Placebo-Controlled Trial of Vitamin E as Add-on Therapy for Children With Epilepsy
NCT00043914	PHASE4	COMPLETED	Measurement Of Serum Levels Of Two Antiepileptic Drugs During Conversion In Patients With Epilepsy
NCT00132223	PHASE4	UNKNOWN	Effects on the Diagnostic Accuracy of Magnetic Imaging Angiographies of the Supra-Aortic Vessels by Three Different Magnetic Resonance Contrast Agents in Patients
NCT00133081	PHASE4	UNKNOWN	Study to Improve the Treatment of Epilepsy (SITE)
NCT00137709	PHASE4	UNKNOWN	Hormone Profiles in Adults With Newly Diagnosed Epilepsy
NCT00154076	PHASE4	COMPLETED	A Multicenter Comparative Trial of Zonisamide and Topiramate as Initial Monotherapy in Untreated Epilepsies
NCT00165828	PHASE4	TERMINATED	Efficacy and Safety of an add-on Treatment With Zonisamide in Adults With Focal Epileptic Seizures With or Without Secondary Generalization
NCT00181116	PHASE4	COMPLETED	Levetiracetam for Benign Rolandic Epilepsy
NCT00207935	PHASE4	COMPLETED	Use of Sustained Release Antiepileptic Medication (Depakote® ER) for Pediatric Epilepsy in a Mental Retardation/Developmental Disorder Population
NCT00215592	PHASE4	COMPLETED	Open Label, Zonegran (Zonisamide) In Partial Onset Seizures
NCT00266604	PHASE4	COMPLETED	A Study to Evaluate the Dosing, Effectiveness and Safety of Topiramate for the Treatment of Epilepsy
NCT00288639	PHASE4	COMPLETED	Lyrica (Pregabalin) Administered as an Add-on Therapy for Partial Seizures (LEADER).
NCT00312676	PHASE4	UNKNOWN	Compare Tolerability of an Overnight Switch to Gradual Switch Between Two Different Forms of Depakote
NCT00323947	PHASE4	COMPLETED	Methylphenidate for Treating Attention Deficit Hyperactivity Disorder in Children With Both ADHD and Epilepsy
NCT00385411	PHASE4	COMPLETED	Study of Valproate in Young Patients Suffering From Epilepsy
NCT00522418	PHASE4	TERMINATED	Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients
NCT00537940	PHASE4	COMPLETED	Comparative Study Of Pregabalin And Gabapentin As Adjunctive Therapy In Subjects With Partial Seizures
NCT00552526	PHASE4	UNKNOWN	Ketogenic Diet vs.Antiepileptic Drug Treatment in Drug Resistant Epilepsy
NCT00564915	PHASE4	COMPLETED	RCT of the Efficacy of the Ketogenic Diet in the Treatment of Epilepsy
NCT00571155	PHASE4	COMPLETED	Trial of Levetiracetam in Patients With Primary Brain Tumors and Symptomatic Seizures Who Undergo Surgery
NCT00572195	PHASE4	COMPLETED	RNS® System LTT Study
NCT00610532	PHASE4	TERMINATED	Evaluating the Transporter Protein Inhibitor Probenecid In Patients With Epilepsy
NCT00630357	PHASE4	COMPLETED	Trial to Evaluate the Safety and Efficacy of Keppra After Conversion to Mono-therapy in Subjects With Partial Epilepsy
NCT00630630	PHASE4	COMPLETED	Study on Safety and Efficacy of Levetiracetam in the Adjunctive Treatment of Female Subjects With C1 Catamenial Epilepsy
NCT00630968	PHASE4	COMPLETED	S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00631150	PHASE4	COMPLETED	A Phase IV-Pharmacovigilance Study of Keppra Greece - S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00659958	PHASE4	COMPLETED	ZAGAL Study: Evaluating Effectiveness and Tolerability of Zonisamide as Adjunctive Therapy in Patients With Partial Onset Seizures Treated With Two Antiepileptic Drugs
NCT00713622	PHASE4	COMPLETED	Comparing The Effect On Cognition Of Adjunctive Therapy With Zonisamide Versus Sodium Valproate
NCT00807989	PHASE4	COMPLETED	The Efficacy and Safety of Low Dose Combination of LTG and VPA Compared to CBZ Monotherapy
NCT00832884	PHASE4	COMPLETED	The Safety of Intravenous Lacosamide
NCT00869622	PHASE4	COMPLETED	Antiepileptic Drugs and Osteoporotic Prevention Trial
NCT00896987	PHASE4	COMPLETED	Lamotrigine Cognitive Function Study in Adult Untreated Epilepsies
NCT00952081	PHASE4	COMPLETED	A Pilot Study to Evaluate Efficacy and Safety of Clevidipine in Neurosurgical Patients
NCT01118455	PHASE4	TERMINATED	Trial to Assess Vagus Nerve Stimulation Therapy vs. Anti-Epileptic Drug (AED) Treatment in Children With Refractory Seizures
NCT01127165	PHASE4	COMPLETED	Low and High Dose Zonisamide in Children as Monotherapy
NCT01127256	PHASE4	COMPLETED	Comparative Study of Zonisamide and Carbamazepine as an Initial Monotherapy: Efficacy and Safety Evaluation
NCT01140867	PHASE4	COMPLETED	Open-label, Multi-center Trial of Zonisamide as Adjunctive Therapy in Patients With Uncontrolled Partial Epilepsy
NCT01175954	PHASE4	COMPLETED	Cognitive and Behavioral Effects of Lacosamide
NCT01229735	PHASE4	COMPLETED	Levetiracetam Versus Topiramate as Adjunctive Therapy to Evaluate Efficacy and Safety in Subjects With Refractory Partial Onset Seizures
NCT01244724	PHASE4	TERMINATED	Lexapro for Major Depression in Patients With Epilepsy