ADRA2A

Summary

ADRA2A (adrenoceptor alpha 2A, HGNC:281) is a protein-coding gene on chromosome 10q25.2, encoding Alpha-2A adrenergic receptor (P08913). Alpha-2 adrenergic receptors are G protein-coupled receptors for catecholamines that activate the G(i/o) protein pathway, thereby promoting adenylyl cyclase inhibition, ERK1/2 stimulation, and voltage-gated calcium channels suppression.

Alpha-2-adrenergic receptors are members of the G protein-coupled receptor superfamily. The alpha-2-adrenergic receptors are a type of adrenergic receptors (for adrenaline or epinephrine), which inhibit adenylate cyclase. These receptors include 3 highly homologous subtypes: alpha2A, alpha2B, and alpha2C. They are involved in regulating the release of neurotransmitter molecules from sympathetic nerves and from adrenergic neurons in the central nervous system. The sympathetic nervous system regulates cardiovascular function by activating adrenergic receptors in the heart, blood vessels and kidney. Studies in mouse revealed that both the alpha2A and alpha2C receptor subtypes were required for presynaptic transmitter release from the sympathetic nervous system in the heart and from central noradrenergic neurons. The alpha-2-adrenergic receptors are also involved in catecholamine signaling by extracellular regulated protein kinase 1 and 2 (ERK1/2) pathways. A clear association between the alpha-2-adrenergic receptor and disease has not been yet established.

Source: NCBI Gene 150 — RefSeq curated summary.

At a glance

• Gene–disease (curated): lipodystrophy (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 11
• Clinical variants (ClinVar): 79 total — 1 pathogenic
• Phenotypes (HPO): 14
• Druggable target: yes — 418 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000681

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:281
Approved symbol	ADRA2A
Name	adrenoceptor alpha 2A
Location	10q25.2
Locus type	gene with protein product
Status	Approved
Aliases	ADRAR
Ensembl gene	ENSG00000150594
Ensembl biotype	protein_coding
OMIM	104210
Entrez	150

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000280155

RefSeq mRNA: 1 — MANE Select: NM_000681 NM_000681

CCDS: CCDS7569

Canonical transcript exons

ENST00000280155 — 1 exons

Exon	Start	End
ENSE00000995573	111077029	111080907

Expression profiles

Bgee: expression breadth ubiquitous, 234 present calls, max score 94.32.

FANTOM5 (CAGE): breadth broad, TPM avg 8.1111 / max 618.2264, expressed in 650 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
107029	7.5254	631
107028	0.3473	177
107027	0.2384	123

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	94.32	gold quality
subcutaneous adipose tissue	UBERON:0002190	92.31	gold quality
endocervix	UBERON:0000458	91.57	gold quality
adipose tissue	UBERON:0001013	91.09	gold quality
connective tissue	UBERON:0002384	89.31	gold quality
ectocervix	UBERON:0012249	89.08	gold quality
mucosa of transverse colon	UBERON:0004991	88.35	gold quality
pericardium	UBERON:0002407	87.89	gold quality
gall bladder	UBERON:0002110	87.05	gold quality
ganglionic eminence	UBERON:0004023	86.60	gold quality
body of pancreas	UBERON:0001150	86.12	gold quality
adipose tissue of abdominal region	UBERON:0007808	86.06	gold quality
thoracic mammary gland	UBERON:0005200	85.96	gold quality
mammary gland	UBERON:0001911	85.91	gold quality
omental fat pad	UBERON:0010414	85.49	gold quality
peritoneum	UBERON:0002358	85.43	gold quality
right ovary	UBERON:0002118	84.11	gold quality
skin of hip	UBERON:0001554	83.85	gold quality
germinal epithelium of ovary	UBERON:0001304	83.55	gold quality
mucosa of paranasal sinus	UBERON:0005030	83.47	gold quality
pancreatic ductal cell	CL:0002079	82.96	gold quality
left ovary	UBERON:0002119	82.85	gold quality
uterine cervix	UBERON:0000002	82.57	gold quality
epithelial cell of pancreas	CL:0000083	82.45	gold quality
ileal mucosa	UBERON:0000331	82.21	gold quality
ovary	UBERON:0000992	82.18	gold quality
lymph node	UBERON:0000029	82.11	gold quality
mammary duct	UBERON:0001765	82.10	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.03	gold quality
pancreas	UBERON:0001264	81.86	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-8495	yes	363.49
E-GEOD-125970	yes	13.53
E-CURD-10	no	81.45
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SP1

miRNA regulators (miRDB)

71 targeting ADRA2A, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-1825	99.72	68.11	1089

Literature-anchored findings (GeneRIF, showing 40)

• results suggested that gg genotype and g allele at site -1296 in alpha(2A)-AR gene could associate with the susceptibility to motion sickness (PMID:12019440)
• Mutagenesis and peptide analysis of the DRY motif in the alpha2A adrenergic receptor (PMID:12054508)
• alpha 2-adrenergic receptor gene and body fat content and distribution: role for the ADRA2A gene in determining the propensity to store fat in the abdominal area, independent of total body fatness (PMID:12080184)
• transgenic mouse with human alpha 2A receptors will serve as a model of diet-induced obesity (PMID:12370125)
• An interaction between beta(1)AR and alpha(2A)AR is regulated by glycosylation and may play a key role in cross-talk and mutual regulation between these receptors. (PMID:12529373)
• the inheritance of polymorphisms in the ADRA2A and ADRA1C genes in 113 nuclear families provided no significant evidence for linkage for these two genes; these genes are not major genetic factors contributing to the susceptibility to GTS (PMID:12707939)
• There seems to be a small effect of ADRA2A on attention deficit disorder with hyperactivity either as a susceptibility gene or as a modulator of its severity. (PMID:12815749)
• 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)
• Results suggest that imidazoline-1 receptors (I(1)R) and alpha(2)-noradrenergic receptors (alpha(2)AR) may interact with each other. (PMID:15028622)
• Estrogen attenuates the lipolytic response through up-regulation of the number of antilipolytic alpha2A-adrenergic receptors only in sc and not in visceral fat depots. (PMID:15070958)
• a significant correlation was observed between the level of mRNA and protein quantified in the brain of the same subjects, indicating that protein synthesis of adrenergic, alpha-2A-, receptor was not influenced by post-translational regulatory mechanisms (PMID:15199368)
• alpha(2A)-AR and MOR hetero-oligomers, although they occur, do not have an obligatory functional influence on one another (PMID:15494033)
• This study supports the hypothesis that an allele of the ADRA2A gene is associated and linked with the ADHD combined subtype and suggests that the DraI polymorphism of ADRA2A is linked to a causative polymorphism. (PMID:15520832)
• ADRA2A and ADRA2B each had a single haplotype block at least 11 and 16 kb in size (PMID:15592690)
• GRK2 binding is critical not only for alpha2A-adrenergic receptor phosphorylation but also for full activity of the kinase. (PMID:15653687)
• Our results show the genotype GG adrenergic alpha2a receptor with higher mean body weight gain than genotype CC. The finding identify a genetic factor associated with clozapine-induced weight gain in schizophrenic patients. (PMID:15795790)
• ADRA2A gene may be involved in attention deficit disorder with hyperactivity (PMID:16172611)
• Preliminary evidence for association of ADRA2A with comorbid ADHD and reading disability (PMID:16178932)
• Results provide weak evidence for a possible role of ADRA2A in attention-deficit/hyperactivity disorder symptom expression. (PMID:16389583)
• Common genetic ADRA2A variants are not important determinants of baseline cardiovascular measures (plasma norepinephrine, heart rate, and blood pressure) in healthy volunteers (PMID:16513442)
• These results suggest a possible role of APLP1 in regulation of alpha2A-adrenergic receptor trafficking. (PMID:16531006)
• Thus, the alpha(2C)AR alters alpha(2A)AR signaling by forming oligomers, and these complexes, which appear to be preferred over the homodimers, should be considered a functional signaling unit in cells in which both subtypes are expressed. (PMID:16605244)
• Both DraI restriction fragment length polymorphism in ADRA2A and ADRA2C (Del 322 to 325) can be excluded as major candidate alleles for hypertension in blacks. (Alpha2 adrenergic receptors ADRA2A and ADRA2C) (PMID:16636200)
• ADRA2A may be associated with attention-deficit/hyperactivity disorder (ADHD) inattentive symptoms. (PMID:16806103)
• Data demonstrate that the alpha(2A)AR evokes ERK phosphorylation through both an arrestin/Src-dependent and a Src-independent pathway, both of which are G protein dependent and converge on the Ras-Raf-MEK pathway. (PMID:16809338)
• we screened the sequence variations in the transcriptional region of ADRA2A gene and analyzed the relationship between the two common polymorphisms and platelet function (PMID:16854373)
• Genetic and the binding studies indicate that the alpha-2 adrenergic receptor may play a role in attention deficit hyperactivity disorder. (PMID:16917924)
• No association between ADRA2A polymorphisms and schizophrenia. (PMID:17034020)
• In the present study it was found that stimulated alpha2-adrenergic receptors induce delayed transactivation of TrkA in PC12 cells. (PMID:17215105)
• The C-1291G genotype had a significant effect on the consumption of ready-made sweet food products. (PMID:17522710)
• there is a role for the ADRA2A polymorphism in the predisposition to tobacco smoking (PMID:17612790)
• In conclusion, alpha(2A)-adrenoreceptor activates ERK and Akt in intestinal cells by a common pathway which depends on PI3-kinase activation and results from EGF receptor transactivation. (PMID:17655843)
• With CC and CG genotypes girls had higher scores on extraversion scales than boys, but with GG genotype boys score higher than girls with GG genotype. (PMID:17894416)
• Polymorphisms are not associated with Toureett’s syndrome in this study. (PMID:18075481)
• the influence of the G allele at the ADRA2A -1291 C > G polymorphism on the improvement of inattentive symptoms with methylphenidate in children with all ADHD subtypes. (PMID:18200436)
• Involvement of the ADRA2A MspI and DraI polymorphisms in the etiology of ADHD in Korean subjects. (PMID:18314873)
• PAR4-pretreated platelets, epinephrine caused dense granule secretion, and subsequent signaling from the ATP-gated P2X(1)-receptor and the alpha(2A)-adrenergic receptor induced aggregation. (PMID:18480058)
• Our results raise the possibility that promoter genetic variation in the ADRA2A gene is associated with either suicide or violent suicide in females (PMID:18547701)
• shows strong affinity to idazoxan and excists in MAO of mitochondria which has imidazoline-ligand binding sites in its molecule. (PMID:18561481)
• the alpha 2A adrenergic receptor 2372A/G polymorphism is associated with plasma von Willebrand factor levels in a general population. (PMID:18600088)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	adra2a	ENSDARG00000040841
mus_musculus	Adra2a	ENSMUSG00000033717
rattus_norvegicus	Adra2a	ENSRNOG00000047545
caenorhabditis_elegans	ser-5	WBGENE00008890

Paralogs (18): ADRB1 (ENSG00000043591), ADRA1A (ENSG00000120907), DRD2 (ENSG00000149295), GPR101 (ENSG00000165370), ADRB2 (ENSG00000169252), ADRA1B (ENSG00000170214), ADRA1D (ENSG00000171873), OR5T3 (ENSG00000172489), OR56A1 (ENSG00000180934), OR5T1 (ENSG00000181698), OR5T2 (ENSG00000181718), OR56A4 (ENSG00000183389), ADRA2C (ENSG00000184160), OR56A3 (ENSG00000184478), OR13F1 (ENSG00000186881), OR56A5 (ENSG00000188691), ADRB3 (ENSG00000188778), ADRA2B (ENSG00000274286)

Protein

Protein identifiers

Alpha-2A adrenergic receptor — P08913 (reviewed: P08913)

Alternative names: Alpha-2 adrenergic receptor subtype C10, Alpha-2A adrenoreceptor

All UniProt accessions (1): P08913

UniProt curated annotations — full annotation on UniProt →

Function. Alpha-2 adrenergic receptors are G protein-coupled receptors for catecholamines that activate the 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. ADRA2A and ADRA2C mediates the presynaptic feedback inhibition of neurotransmitter release from noradrenergic nerve terminals in sympathetic and central nervous systems. ADRA2A inhibits transmitter release at high stimulation frequencies, whereas ADRA2C modulates neurotransmission at lower levels of nerve activity. The rank order of potency for agonists of ADRA2A is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol.

Subcellular location. Cell membrane.

Disease relevance. Lipodystrophy, familial partial, 8 (FPLD8) [MIM:620679] An autosomal dominant form of partial lipodystrophy, a disorder characterized by abnormal subcutaneous fat distribution. FPLD8 patients show selective loss of subcutaneous adipose tissue from the limbs, beginning around 13 to 15 years of age, and abnormal accumulation of subcutaneous adipose tissue in the dorsal neck and face, as well as in the posterior thoracic and abdominal regions. The disorder is associated with metabolic abnormalities, including diabetes mellitus and hyperlipidemia. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRA2A sub-subfamily.

RefSeq proteins (1): NP_000672* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR001946	ADRA2A_rcpt	Family
IPR002233	ADR_fam	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (73 total): helix 20, mutagenesis site 10, topological domain 8, transmembrane region 7, site 6, sequence conflict 4, sequence variant 3, strand 3, turn 3, modified residue 2, glycosylation site 2, chain 1, region of interest 1, compositionally biased region 1, lipid moiety-binding region 1, disulfide bond 1

Structure

Experimental structures (PDB)

19 structures.

PDB	Method	Resolution (Å)
6KUX	X-RAY DIFFRACTION	2.7
9PLO	ELECTRON MICROSCOPY	2.74
9CBL	ELECTRON MICROSCOPY	2.8
9PLN	ELECTRON MICROSCOPY	2.8
7EJ8	ELECTRON MICROSCOPY	3
6KUY	X-RAY DIFFRACTION	3.2
7EJ0	ELECTRON MICROSCOPY	3.2
9CBM	ELECTRON MICROSCOPY	3.2
9PQD	ELECTRON MICROSCOPY	3.29
7EJK	ELECTRON MICROSCOPY	3.4
7W7E	ELECTRON MICROSCOPY	3.4
9IQR	ELECTRON MICROSCOPY	3.4
7W6P	ELECTRON MICROSCOPY	3.47
7EJA	ELECTRON MICROSCOPY	3.6
6K42	ELECTRON MICROSCOPY	4.1
1HLL	SOLUTION NMR
1HO9	SOLUTION NMR
1HOD	SOLUTION NMR
1HOF	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08913-F1	71.70	0.41

Antibody-complex structures (SAbDab): 7 — 6K42, 7EJ0, 7EJ8, 7EJA, 7EJK, 7W6P, 7W7E

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 (6): 128 (implicated in norepinephrine binding); 215 (implicated in catechol and norepinephrine agonist binding and receptor activation); 219 (implicated in catechol agonist binding and receptor activation); 409 (implicated in norepinephrine binding and receptor activation); 427 (implicated in norepinephrine binding and receptor activation); 431 (implicated in norepinephrine binding and receptor activation)

Post-translational modifications (3): 346, 368, 457

Disulfide bonds (1): 121–203

Glycosylation sites (2): 25, 29

Mutagenesis-validated functional residues (10):

Position	Phenotype
94	no change in binding affinity. eliminates guanine nucleotide-sensitive agonist binding.
128	loss of receptor activation by norepinephrine.
128	no binding to yohimbine. increase in adenylate cyclase activity.
145	lower affinity for agonists. eliminates guanine nucleotide-sensitive agonist binding.
215	lower affinity for agonists. no change in guanine nucleotide-sensitive agonist binding. impaired receptor activation by
219	lower affinity for agonists. reduced guanine nucleotide-sensitive agonist binding.
409	impaired receptor activation by norepinephrine.
427	impaired receptor activation by norepinephrine.
427	350-fold reduced affinity for alpha-2 antagonist yohimbine, 3000-fold increase for beta-antagonist alprenolol.
431	impaired receptor activation by norepinephrine.

Function

Pathways and Gene Ontology

Reactome pathways

19 pathways

ID	Pathway
R-HSA-390696	Adrenoceptors
R-HSA-392023	Adrenaline signalling through Alpha-2 adrenergic receptor
R-HSA-400042	Adrenaline,noradrenaline inhibits insulin secretion
R-HSA-418594	G alpha (i) signalling events
R-HSA-418597	G alpha (z) signalling events
R-HSA-5683826	Surfactant metabolism
R-HSA-109582	Hemostasis
R-HSA-1430728	Metabolism
R-HSA-162582	Signal Transduction
R-HSA-163685	Integration of energy metabolism
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-392499	Metabolism of proteins
R-HSA-422356	Regulation of insulin secretion
R-HSA-500792	GPCR ligand binding
R-HSA-76002	Platelet activation, signaling and aggregation
R-HSA-76009	Platelet Aggregation (Plug Formation)

MSigDB gene sets: 418 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, GOBP_DIGESTION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, BENPORATH_ES_WITH_H3K27ME3, GOBP_SENSORY_PERCEPTION_OF_TEMPERATURE_STIMULUS, GOBP_REGULATION_OF_ERBB_SIGNALING_PATHWAY, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_CIRCULATORY_SYSTEM_PROCESS, REACTOME_ADRENALINE_NORADRENALINE_INHIBITS_INSULIN_SECRETION, GOBP_NEGATIVE_REGULATION_OF_LIPID_METABOLIC_PROCESS, REACTOME_PLATELET_AGGREGATION_PLUG_FORMATION, GOBP_NEGATIVE_REGULATION_OF_MUSCLE_CONTRACTION, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, REACTOME_G_ALPHA_Z_SIGNALLING_EVENTS, GOBP_PLATELET_ACTIVATION

GO Biological Process (43): positive regulation of cytokine production (GO:0001819), DNA replication (GO:0006260), epidermal growth factor receptor signaling pathway (GO:0007173), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193), Ras protein signal transduction (GO:0007265), Rho protein signal transduction (GO:0007266), female pregnancy (GO:0007565), positive regulation of cell population proliferation (GO:0008284), negative regulation of norepinephrine secretion (GO:0010700), regulation of vasoconstriction (GO:0019229), actin cytoskeleton organization (GO:0030036), platelet activation (GO:0030168), positive regulation of cell migration (GO:0030335), negative regulation of epinephrine secretion (GO:0032811), cellular response to hormone stimulus (GO:0032870), vasodilation (GO:0042311), glucose homeostasis (GO:0042593), fear response (GO:0042596), positive regulation of potassium ion transport (GO:0043268), response to morphine (GO:0043278), positive regulation of MAPK cascade (GO:0043410), positive regulation of epidermal growth factor receptor signaling pathway (GO:0045742), negative regulation of calcium ion-dependent exocytosis (GO:0045955), negative regulation of insulin secretion (GO:0046676), intestinal absorption (GO:0050892), thermoception (GO:0050955), negative regulation of lipid catabolic process (GO:0050995), positive regulation of membrane protein ectodomain proteolysis (GO:0051044), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), negative regulation of calcium ion transport (GO:0051926), negative regulation of insulin secretion involved in cellular response to glucose stimulus (GO:0061179), negative regulation of uterine smooth muscle contraction (GO:0070473), adrenergic receptor signaling pathway (GO:0071875), adenylate cyclase-activating adrenergic receptor signaling pathway (GO:0071880), adenylate cyclase-inhibiting adrenergic receptor signaling pathway (GO:0071881), phospholipase C-activating adrenergic receptor signaling pathway (GO:0071882), positive regulation of wound healing (GO:0090303), response to alcohol (GO:0097305)

GO Molecular Function (14): alpha2-adrenergic receptor activity (GO:0004938), protein kinase binding (GO:0019901), alpha-1B adrenergic receptor binding (GO:0031692), alpha-2C adrenergic receptor binding (GO:0031696), thioesterase binding (GO:0031996), heterotrimeric G-protein binding (GO:0032795), protein homodimerization activity (GO:0042803), protein heterodimerization activity (GO:0046982), epinephrine binding (GO:0051379), norepinephrine binding (GO:0051380), G protein-coupled receptor activity (GO:0004930), adrenergic receptor activity (GO:0004935), guanyl-nucleotide exchange factor activity (GO:0005085), protein binding (GO:0005515)

GO Cellular Component (13): cytoplasm (GO:0005737), plasma membrane (GO:0005886), basolateral plasma membrane (GO:0016323), neuronal cell body (GO:0043025), signaling receptor complex (GO:0043235), axon terminus (GO:0043679), presynaptic active zone membrane (GO:0048787), dopaminergic synapse (GO:0098691), postsynaptic density membrane (GO:0098839), glutamatergic synapse (GO:0098978), GABA-ergic synapse (GO:0098982), membrane (GO:0016020), postsynaptic membrane (GO:0045211)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
GPCR downstream signalling	2
Signaling by GPCR	2
Amine ligand-binding receptors	1
Platelet Aggregation (Plug Formation)	1
Regulation of insulin secretion	1
Metabolism of proteins	1
Metabolism	1
Signal Transduction	1
GPCR ligand binding	1
Class A/1 (Rhodopsin-like receptors)	1
Integration of energy metabolism	1
Hemostasis	1
Platelet activation, signaling and aggregation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
synapse	3
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	2
small GTPase-mediated signal transduction	2
negative regulation of catecholamine secretion	2
blood vessel diameter maintenance	2
adrenergic receptor binding	2
protein dimerization activity	2
cation binding	2
catecholamine binding	2
cellular anatomical structure	2
synaptic membrane	2
cytokine production	1
regulation of cytokine production	1
positive regulation of gene expression	1
positive regulation of multicellular organismal process	1
DNA metabolic process	1
DNA biosynthetic process	1
ERBB signaling pathway	1
G protein-coupled receptor activity	1
signal transduction	1
adenylate cyclase activator activity	1
adenylate cyclase inhibitor activity	1
multi-organism reproductive process	1
multi-multicellular organism process	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
regulation of norepinephrine secretion	1
norepinephrine secretion	1
vasoconstriction	1
regulation of blood circulation	1
cytoskeleton organization	1
actin filament-based process	1
cell activation	1
blood coagulation	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
regulation of epinephrine secretion	1
epinephrine secretion	1

Protein interactions and networks

STRING

1218 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADRA2A	SLC6A3	Q01959	815
ADRA2A	SLC6A2	P23975	788
ADRA2A	COMT	P21964	720
ADRA2A	DBH	P09172	710
ADRA2A	SLC6A4	P31645	701
ADRA2A	OPRM1	P35372	669
ADRA2A	SNAP25	P13795	652
ADRA2A	KCNN3	Q9UGI6	649
ADRA2A	ARRB2	P32121	644
ADRA2A	MAOA	P21397	611
ADRA2A	SCN8A	Q9UQD0	598
ADRA2A	GNAQ	P50148	580
ADRA2A	C2CD4B	A6NLJ0	570
ADRA2A	SAG	P10523	568
ADRA2A	GRK5	P34947	563

IntAct

16 interactions, top by confidence:

A	B	Type	Score
ADRA2A	ADRA2A	psi-mi:“MI:2364”(proximity)	0.470
ADRA2A	ADRA2C	psi-mi:“MI:2364”(proximity)	0.470
ADRA2A	ADRA2C	psi-mi:“MI:0915”(physical association)	0.470
ADRA2A	ADRA2A	psi-mi:“MI:0915”(physical association)	0.470
ADRA2A	SH3GL3	psi-mi:“MI:0915”(physical association)	0.400
SH3GL2	ADRA2A	psi-mi:“MI:0915”(physical association)	0.400
ADRA2A	SH3GL1	psi-mi:“MI:0915”(physical association)	0.400
	ADRA2A	psi-mi:“MI:0915”(physical association)	0.400
RAMP1	ADRA2A	psi-mi:“MI:0915”(physical association)	0.400
ADRA2A	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	ADRA2A	psi-mi:“MI:0915”(physical association)	0.400
ADRA2A	Hacd3	psi-mi:“MI:0915”(physical association)	0.400
PSMD2	ADRA2A	psi-mi:“MI:0915”(physical association)	0.400
Usp19	ADRA2A	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (12): GGA3 (Reconstituted Complex), ADRA2A (Reconstituted Complex), ADRA2A (Cross-Linking-MS (XL-MS)), UCHL1 (Two-hybrid), UCHL1 (Reconstituted Complex), UCHL1 (Affinity Capture-Western), GNAI2 (FRET), GNB1 (FRET), GNG2 (FRET), ADRA2A (Protein-peptide), ADRA2A (FRET), GNAO1 (FRET)

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: E7EM37, G3M4F8, O02213, O08890, O18935, O19014, O19025, O42384, O42385, O73810, O77715, O77723, O77830, P08908, P08909, P08913, P11614, P14416, P18825, P18871, P19020, P20288, P21917, P22086, P22270, P22909, P24628, P28221, P28222, P28334, P28335, P28564, P28566, P30545, P30728, P30729, P30939, P32304, P32305, P34968

SIGNOR signaling

22 interactions.

A	Effect	B	Mechanism
ADRA2A	“up-regulates activity”	GNAI1	binding
ADRA2A	“up-regulates activity”	GNAI3	binding
ADRA2A	“up-regulates activity”	GNAO1	binding
ADRA2A	“up-regulates activity”	GNAZ	binding
(R)-noradrenaline	“up-regulates activity”	ADRA2A	“chemical activation”
brimonidine	“up-regulates activity”	ADRA2A	“chemical activation”
clonidine	“up-regulates activity”	ADRA2A	“chemical activation”
dexmedetomidine	“up-regulates activity”	ADRA2A	“chemical activation”
Guanabenz	“up-regulates activity”	ADRA2A	“chemical activation”
tolazoline	“down-regulates activity”	ADRA2A	“chemical inhibition”
oxymetazoline	“up-regulates activity”	ADRA2A	“chemical activation”
Guanfacine	“up-regulates activity”	ADRA2A	“chemical activation”
N-(2,6-dimethylphenyl)-5,6-dihydro-4H-1,3-thiazin-2-amine	“up-regulates activity”	ADRA2A	“chemical activation”
PRKCD	“up-regulates activity”	ADRA2A	phosphorylation
GRK2	“down-regulates activity”	ADRA2A	phosphorylation
lurasidone	“down-regulates activity”	ADRA2A	“chemical inhibition”
lofexidine	“up-regulates activity”	ADRA2A	“chemical activation”
apraclonidine	“up-regulates activity”	ADRA2A	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	67
Likely benign	8
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2691730	NM_000681.4(ADRA2A):c.*427A>G	Pathogenic

SpliceAI

49 predictions. Top by Δscore:

Variant	Effect	Δscore
10:111077362:G:GT	donor_gain	0.8000
10:111079278:T:TA	acceptor_gain	0.7600
10:111077462:A:AG	donor_gain	0.6200
10:111079225:C:G	acceptor_gain	0.5300
10:111077223:A:T	donor_gain	0.3900
10:111077258:G:GT	donor_gain	0.3900
10:111077685:A:C	acceptor_gain	0.3900
10:111077444:G:T	donor_gain	0.3800
10:111079379:G:GT	donor_gain	0.3800
10:111080296:TCCAG:T	acceptor_gain	0.3800
10:111077562:G:GT	donor_gain	0.3700
10:111077457:C:CA	donor_gain	0.3600
10:111077646:A:G	acceptor_gain	0.3600
10:111079224:AC:A	acceptor_gain	0.3500
10:111077463:T:G	donor_gain	0.3400
10:111080298:CAGTG:C	acceptor_gain	0.3400
10:111078115:C:CT	acceptor_gain	0.3200
10:111079224:A:AG	acceptor_gain	0.3200
10:111080297:CCAG:C	acceptor_gain	0.3200
10:111077444:G:GT	donor_gain	0.3100
10:111077732:C:A	acceptor_gain	0.3100
10:111079223:C:G	acceptor_gain	0.2800
10:111079283:C:CA	acceptor_gain	0.2700
10:111077475:T:G	donor_gain	0.2600
10:111077645:A:AC	acceptor_gain	0.2600
10:111077262:G:GT	donor_gain	0.2500
10:111077471:GGGAT:G	donor_gain	0.2400
10:111077472:GGATG:G	donor_gain	0.2400
10:111077553:ACACG:A	donor_loss	0.2400
10:111077554:CACG:C	donor_loss	0.2400

AlphaMissense

2986 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:111078194:C:A	N66K	1.000
10:111078194:C:G	N66K	1.000
10:111078232:T:A	L79H	1.000
10:111078232:T:C	L79P	1.000
10:111078256:T:A	L87Q	1.000
10:111078265:T:A	L90Q	1.000
10:111078265:T:C	L90P	1.000
10:111078276:G:C	D94H	1.000
10:111078277:A:C	D94A	1.000
10:111078277:A:G	D94G	1.000
10:111078277:A:T	D94V	1.000
10:111078412:T:C	L139P	1.000
10:111078421:T:A	I142N	1.000
10:111078423:A:C	S143R	1.000
10:111078425:C:A	S143R	1.000
10:111078425:C:G	S143R	1.000
10:111078427:T:C	L144P	1.000
10:111078430:A:C	D145A	1.000
10:111078430:A:T	D145V	1.000
10:111078432:C:A	R146S	1.000
10:111078433:G:C	R146P	1.000
10:111078513:T:A	W173R	1.000
10:111078513:T:C	W173R	1.000
10:111079168:T:A	L391Q	1.000
10:111079168:T:C	L391P	1.000
10:111079188:T:C	F398L	1.000
10:111079190:C:A	F398L	1.000
10:111079190:C:G	F398L	1.000
10:111079200:T:A	W402R	1.000
10:111079200:T:C	W402R	1.000

dbSNP variants (sampled 300 via entrez): RS1000498121 (10:111080966 A>G), RS1000763258 (10:111075118 C>T), RS1001765223 (10:111076434 T>C), RS1001864049 (10:111080006 A>G), RS1001955436 (10:111076198 TAGG>T), RS1002553556 (10:111077458 G>A), RS1003225113 (10:111077742 T>C), RS1003792959 (10:111077647 G>A), RS1003840369 (10:111078904 C>G,T), RS1004192709 (10:111078801 G>A,C), RS1004790812 (10:111080084 C>T), RS1004855490 (10:111080963 G>A), RS1005138458 (10:111080691 G>A,T), RS1005180206 (10:111076940 T>G), RS1005246646 (10:111080508 G>T)

Disease associations

OMIM: gene MIM:104210 | disease phenotypes: MIM:610759, MIM:620679

GenCC curated gene-disease

Disease	Classification	Inheritance
lipodystrophy	Limited	Autosomal dominant
lipodystrophy, familial partial, type 8	Limited	Autosomal dominant

Mondo (4): Cornelia de Lange syndrome 3 (MONDO:0012555), RASopathy (MONDO:0021060), lipodystrophy, familial partial, type 8 (MONDO:0958022), lipodystrophy (MONDO:0006573)

Orphanet (2): Cornelia de Lange syndrome (Orphanet:199), RASopathy (Orphanet:536391)

HPO phenotypes

14 total (14 of 14 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000819	Diabetes mellitus
HP:0000822	Hypertension
HP:0000956	Acanthosis nigricans
HP:0001997	Gout
HP:0002149	Hyperuricemia
HP:0002155	Hypertriglyceridemia
HP:0002240	Hepatomegaly
HP:0002870	Obstructive sleep apnea
HP:0003074	Hyperglycemia
HP:0003236	Elevated circulating creatine kinase concentration
HP:0003621	Juvenile onset
HP:0009125	Lipodystrophy
HP:0025383	Dorsocervical fat pad

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST000568_11	Fasting blood glucose	3.000000e-16
GCST000693_11	Platelet aggregation	3.000000e-12
GCST001527_29	Fasting blood glucose (BMI interaction)	9.000000e-08
GCST002981_2	Longitudinal alcohol consumption	5.000000e-07
GCST005180_3	Homeostasis model assessment of beta-cell function	2.000000e-06
GCST005186_28	Fasting blood glucose	2.000000e-07
GCST008171_10	Platelet aggregation	1.000000e-08
GCST008171_13	Platelet aggregation	1.000000e-07
GCST008171_24	Platelet aggregation	3.000000e-06
GCST010142_18	Fish- and plant-related diet	3.000000e-10
GCST010142_84	Fish- and plant-related diet	4.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0007645	longitudinal alcohol consumption measurement
EFO:0004469	HOMA-B
EFO:0008111	diet measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008060	Lipodystrophy	C17.800.849.391; C18.452.584.625; C18.452.880.391

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (6): CHEMBL1867 (SINGLE PROTEIN), CHEMBL2095158 (PROTEIN FAMILY), CHEMBL2095203 (PROTEIN FAMILY), CHEMBL2331074 (PROTEIN FAMILY), CHEMBL3883321 (PROTEIN COMPLEX), CHEMBL3885512 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

418 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 434,835 (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
CHEMBL1014	CANDESARTAN CILEXETIL	4	11,194
CHEMBL1017	TELMISARTAN	4	27,457
CHEMBL1023	BEXAROTENE	4	40,951
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1065	METHYSERGIDE	4	8,455
CHEMBL1079	TIZANIDINE	4	12,099
CHEMBL1085	ACETOPHENAZINE	4	5,134
CHEMBL1088	MESORIDAZINE	4	12,814
CHEMBL1089	PHENELZINE	4	18,793
CHEMBL1106	EPINASTINE	4	8,530
CHEMBL1108	DROPERIDOL	4	16,888
CHEMBL1112	ARIPIPRAZOLE	4	24,205
CHEMBL1113	AMOXAPINE	4	20,128
CHEMBL1162	NORETHINDRONE	4	91,150
CHEMBL1172	DESLORATADINE	4	19,720
CHEMBL117785	TETRABENAZINE	4	9,645
CHEMBL1189679	PALONOSETRON	4	9,399
CHEMBL1194666	DIETHYLPROPION	4	12,073
CHEMBL1200329	TIZANIDINE HYDROCHLORIDE	4	3,451
CHEMBL1200406	DIMENHYDRINATE	4	26,424
CHEMBL1200492	NEFAZODONE HYDROCHLORIDE	4
CHEMBL1200494	GUANFACINE HYDROCHLORIDE	4
CHEMBL1200517	DIHYDROERGOTAMINE MESYLATE	4
CHEMBL1200791	OXYMETAZOLINE HYDROCHLORIDE	4
CHEMBL1200809	AZELASTINE HYDROCHLORIDE	4
CHEMBL1201	THIOTHIXENE	4
CHEMBL1201039	BENZTHIAZIDE	4
CHEMBL1201087	CABERGOLINE	4
CHEMBL1201196	SERTACONAZOLE	4
CHEMBL1201203	BENZTROPINE	4

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

PharmGKB clinical annotations

8 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1800035	Efficacy	3	dexmedetomidine	Pain;Postoperative
rs1800544	Other	3	dexmedetomidine
rs1800544	Efficacy	3	milnacipran	Depressive Disorder
rs1800544	Efficacy	3	Selective serotonin reuptake inhibitors	Major Depressive Disorder
rs1800544	Efficacy	4	methylphenidate	Attention Deficit Disorder with Hyperactivity
rs1800545	Efficacy	3	atenolol	Hypertrophy;Left Ventricular
rs201376588	Efficacy	3	dexmedetomidine	Pain;Postoperative
rs775887911	Efficacy	3	dexmedetomidine	Pain;Postoperative

PharmGKB variants

12 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1800544	ADRA2A	3	2.75	4	dexmedetomidine;methylphenidate;Selective serotonin reuptake inhibitors;milnacipran
rs1800545	ADRA2A	3	2.00	1	atenolol
rs2484516	ADRA2A		0.00	0
rs11195419	ADRA2A		0.00	0
rs1800038	ADRA2A		0.00	0
rs3750625	ADRA2A		0.00	0
rs11195418	ADRA2A		0.00	0
rs553668	ADRA2A		0.00	0
rs1800035	ADRA2A	3	2.75	1	dexmedetomidine
rs201376588	ADRA2A	3	2.75	1	dexmedetomidine
rs775887911	ADRA2A	3	2.75	1	dexmedetomidine
rs521674	ADRA2A		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Adrenoceptors

Most potent curated ligand interactions (51 total), top 25:

Ligand	Action	Affinity	Parameter
lisuride	Antagonist	10.3	pKi
[3H]rauwolscine	Antagonist	9.5	pKd
[3H]RX821002	Antagonist	9.5	pKd
terguride	Antagonist	9.5	pKi
RX821002	Antagonist	9.4	pKi
[3H]brimonidine (UK14304)	Agonist	9.1	pKd
RS79948	Antagonist	8.9	pKi
WB 4101	Antagonist	8.9	pKi
brimonidine (UK14304)	Agonist	8.9	pIC50
[3H]MK-912	Antagonist	8.9	pKd
[125I]p-iodoclonidine	Partial agonist	8.8	pKd
yohimbine	Antagonist	8.7	pKi
atipamezole	Antagonist	8.7	pKi
MK-912	Antagonist	8.7	pKi
apraclonidine	Agonist	8.5	pKi
rauwolscine	Antagonist	8.4	pKi
oxymetazoline	Partial agonist	8.4	pIC50
lofexidine	Agonist	8.36	pKi
muscarinic toxin 3	Antagonist	8.3	pKi
bromocriptine	Antagonist	8.3	pKi
BRL 44408	Antagonist	8.2	pKi
idazoxan	Antagonist	8.0	pKi
cabergoline	Antagonist	7.9	pKi
guanabenz	Agonist	7.7	pKi
[3H]clonidine	Partial agonist	7.6	pKd

Binding affinities (BindingDB)

98 measured of 146 human assays (189 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
WIN 53782	KI	0.05 nM
CAS_76727-72-5	KI	0.06 nM
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
NSC_125992	KI	0.2 nM
(S,S)-reboxetine	KI	0.3 nM
NSC_71310	KI	0.33 nM
CAS_196343	KI	0.36 nM
WIN 52664	KI	0.4 nM
MK-912	KI	0.42 nM
2-Chlor-11-(2-dimethylaminoaethoxy)-dibenzo(b,f)-thiepin	KI	0.5 nM
3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N-methylpropan-1-amine	KI	0.6 nM
CAS_34772	KI	0.93 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
N-[(2S,11bR)-2,3,4,6,7,11b-hexahydro-1H-benzo[a]quinolizin-2-yl]-N-methylbutane-1-sulfonamide hydrochloride	KI	1.4 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
CAS_133816	KI	2.2 nM
4-[4-(4-Chloro-phenyl)-4-hydroxy-piperidin-1-yl]-1-(4-fluoro-phenyl)-butan-1-one;propionate(HCl)	KI	2.92 nM
8-[4-(4-fluorophenyl)-4-keto-butyl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one	KI	2.94 nM	US-9359372: Hexahydrodibenzo[a,g]quinolizine compound, preparation method thereof, pharmaceutical composition and use thereof
(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
CAS_133305	KI	8.7 nM
CAS_125697	KI	11 nM
Bromocriptine+ (GTP+)	KI	12.9 nM
CAS_81447-78-1	KI	14.4 nM
MLS001401388	KI	16 nM
NSC_54746	KI	19.9 nM
L-644,763	KI	20 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
L-639,019	KI	35 nM
NSC_8966	KI	38 nM
NSC_3519	KI	50.3 nM
cid_3396	KI	56 nM
Zanaflex	KI	62 nM
2-{3-[4-(3-chlorophenyl)piperazin-1-yl]propyl}-5-ethyl-4-(2-phenoxyethyl)-2,4-dihydro-3H-1,2,4-triazol-3-one	KI	80 nM
NSC_40589	KI	85 nM
2-{3-[4-(3-chlorophenyl)piperazin-1-yl]propyl}[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one	KI	96 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
cis-doxepin	KI	276 nM

ChEMBL bioactivities

2152 potent at pChembl≥5 of 2381 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
10.55	Ki	0.02818	nM	CHEMBL1256414
10.47	IC50	0.034	nM	CHEMBL537830
10.38	Ki	0.04169	nM	CHEMBL4482861
10.27	Ki	0.0537	nM	CHEMBL4536304
10.18	Ki	0.06607	nM	CHEMBL4438801
10.16	Ki	0.06918	nM	CHEMBL1256414
10.10	Ki	0.07943	nM	CHEMBL1256414
10.00	Ki	0.1	nM	CHEMBL435352
10.00	Ki	0.1	nM	CHEMBL176261
10.00	Ki	0.1	nM	RAUWOLSCINE
9.94	Ki	0.116	nM	LISURIDE
9.92	IC50	0.12	nM	CHEMBL538801
9.86	Ki	0.138	nM	CHEMBL1255723
9.76	Ki	0.1738	nM	CHEMBL1256378
9.70	Ki	0.2	nM	CHEMBL180470
9.70	Kd	0.1995	nM	CHEMBL279807
9.70	Kd	0.1995	nM	CHEMBL62912
9.67	IC50	0.2138	nM	CHEMBL351483
9.66	Ki	0.2188	nM	CHEMBL1256609
9.64	EC50	0.23	nM	CHEMBL5532450
9.62	Ki	0.2399	nM	CHEMBL605405
9.62	IC50	0.2399	nM	CHEMBL162682
9.60	IC50	0.25	nM	CHEMBL194837
9.60	Ki	0.25	nM	CHEMBL50390
9.59	EC50	0.26	nM	CHEMBL49137
9.59	IC50	0.26	nM	CHEMBL554581
9.54	Ki	0.29	nM	OXYMETAZOLINE
9.54	EC50	0.29	nM	CLONIDINE
9.54	IC50	0.2884	nM	CHEMBL163190
9.53	IC50	0.2951	nM	CHEMBL162490
9.52	Ki	0.3	nM	CHEMBL91157
9.52	Ki	0.3	nM	CHEMBL419316
9.52	Ki	0.3	nM	RAUWOLSCINE
9.52	Ki	0.3	nM	CHEMBL319119
9.52	Ki	0.3	nM	CHEMBL100879
9.51	IC50	0.31	nM	LISURIDE
9.50	Ki	0.3162	nM	CHEMBL5517941
9.50	EC50	0.3162	nM	CLONIDINE
9.49	Ki	0.3236	nM	CHEMBL4483022
9.48	Ki	0.3311	nM	CHEMBL1255617
9.47	IC50	0.3388	nM	CHEMBL162232
9.46	IC50	0.3467	nM	CHEMBL162370
9.45	IC50	0.3548	nM	CHEMBL165350
9.44	Ki	0.3631	nM	CHEMBL10332
9.41	Ki	0.39	nM	CHEMBL554019
9.41	Ki	0.387	nM	DIHYDROERGOTAMINE
9.40	Ki	0.4	nM	CHEMBL176116
9.40	Ki	0.4	nM	YOHIMBINE

PubChem BioAssay actives

1279 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
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
3-diethoxyphosphoryl-3,5-diphenyl-3a,6a-dihydropyrrolo[3,4-c]pyrrole-4,6-dione	1561258: Displacement of [3H]RX821002 from alpha2-AR in human brain frontal cortex incubated for 30 mins by liquid scintillation spectrometry	ki	<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-[(1aR,6aR)-1a,6-dihydro-1H-cyclopropa[a]inden-6a-yl]-1H-imidazole	516907: Displacement of [3H]-RX821002 from human adrenergic alpha2A receptor expressed in rat C6 cells after 120 mins by liquid scintillation counting	ki	<0.0001	uM
2-[[(3R,3aS)-3-[[4-[(E)-2-methyl-3-phenylprop-2-enyl]piperazin-1-yl]methyl]-3a,4-dihydro-3H-chromeno[4,3-c][1,2]oxazol-7-yl]oxy]-N,N-dimethylethanamine	238678: Binding affinity for alpha-2A adrenergic receptor	ki	0.0001	uM
(3R,3aS)-7-(2-methoxyethoxy)-3-[[4-[(E)-2-methyl-3-phenylprop-2-enyl]piperazin-1-yl]methyl]-3a,4-dihydro-3H-chromeno[4,3-c][1,2]oxazole	238678: Binding affinity for alpha-2A adrenergic receptor	ki	0.0001	uM
3-diethoxyphosphoryl-5-(3-nitrophenyl)-3-phenyl-3a,6a-dihydropyrrolo[3,4-c]pyrrole-4,6-dione	1561258: Displacement of [3H]RX821002 from alpha2-AR in human brain frontal cortex incubated for 30 mins by liquid scintillation spectrometry	ki	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-[(1S,1aR,6aS)-1-ethyl-1a,6-dihydro-1H-cyclopropa[a]inden-6a-yl]-1H-imidazole	516907: Displacement of [3H]-RX821002 from human adrenergic alpha2A 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
(3R,3aS)-3-[[4-[(E)-2-methyl-3-phenylprop-2-enyl]piperazin-1-yl]methyl]-3a,4-dihydro-3H-chromeno[4,3-c][1,2]oxazol-7-ol	238678: Binding affinity for alpha-2A adrenergic receptor	ki	0.0002	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-(8-bromo-3,4-dihydro-2H-chromen-4-yl)-1H-imidazole	2065728: Agonist activity at alpha2A-adrenoceptor (unknown origin) expressed in CHO-alpha2-AR-PKAcatEGFP cells assessed as intracellular cAMP concentration by measuring PKA translocation after 15 mins incubation by PKA redistribution assay	ec50	0.0002	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	36067: Binding affinity at human Alpha-2A adrenergic receptor in CHO cells by [3H]rauwolscine (1 nM) displacement.	ic50	0.0002	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	36067: Binding affinity at human Alpha-2A adrenergic receptor in CHO cells by [3H]rauwolscine (1 nM) displacement.	ic50	0.0002	uM
2,8-dimethyl-5-[(Z)-2-phenylethenyl]-3,4-dihydro-1H-pyrido[4,3-b]indole	452265: Displacement of [3H]MK-912 from human recombinant adrenergic alpha2A receptor expressed in insect Sf9 cells	ki	0.0002	uM
5-[(1aR,6S,6aR)-6-methyl-1a,6-dihydro-1H-cyclopropa[a]inden-6a-yl]-1H-imidazole	516907: Displacement of [3H]-RX821002 from human adrenergic alpha2A receptor expressed in rat C6 cells after 120 mins by liquid scintillation counting	ki	0.0002	uM
5-[(1S,1aR,6aS)-1-methyl-1a,6-dihydro-1H-cyclopropa[a]inden-6a-yl]-1H-imidazole	516907: Displacement of [3H]-RX821002 from human adrenergic alpha2A 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
(3R,3aS)-3-[[4-[(E)-3-(2,5-difluorophenyl)-2-methylprop-2-enyl]piperazin-1-yl]methyl]-7,8-dimethoxy-3a,4-dihydro-3H-chromeno[4,3-c][1,2]oxazole	35948: In vitro binding affinity to the human alpha-2A adrenergic receptor	ki	0.0003	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	2065717: Binding affinity to human alpha2A-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
3-[2-(3,4-dihydro-1H-[1]benzofuro[3,2-c]pyridin-2-yl)ethyl]-2,7-dimethylpyrido[1,2-a]pyrimidin-4-one	36067: Binding affinity at human Alpha-2A adrenergic receptor in CHO cells by [3H]rauwolscine (1 nM) displacement.	ic50	0.0003	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	36067: Binding affinity at human Alpha-2A adrenergic receptor in CHO cells by [3H]rauwolscine (1 nM) displacement.	ic50	0.0003	uM
Clonidine	2104625: Agonist activity at human recombinant adrenergic alpha-2A receptor expressed in CHO-K1 cells co-transfected with 22F-Glosensor assessed as inhibition of cAMP production measured after 30 mins incubation by Microbeta2Micro-plate counter analysis	ec50	0.0003	uM
(3R,3aS)-7,8-dimethoxy-3-[[4-[(E)-2-methyl-3-phenylprop-2-enyl]piperazin-1-yl]methyl]-3a,4-dihydro-3H-chromeno[4,3-c][1,2]oxazole	239434: Inhibition of [3H]- rauwolscine binding to human alpha-2A adrenergic receptor	ki	0.0003	uM
(3R,3aS)-7,8-dimethoxy-3-[[4-[(E)-3-phenylbut-2-enyl]piperazin-1-yl]methyl]-3a,4-dihydro-3H-chromeno[4,3-c][1,2]oxazole	239434: Inhibition of [3H]- rauwolscine binding to human alpha-2A adrenergic receptor	ki	0.0003	uM
(3R,3aS)-7,8-dimethoxy-3-[[4-[(E)-3-thiophen-2-ylbut-2-enyl]piperazin-1-yl]methyl]-3a,4-dihydro-3H-chromeno[4,3-c][1,2]oxazole	35948: In vitro binding affinity to the human alpha-2A adrenergic receptor	ki	0.0003	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	36067: Binding affinity at human Alpha-2A adrenergic receptor in CHO cells by [3H]rauwolscine (1 nM) displacement.	ic50	0.0003	uM
3-[2-(3,4-dihydro-1H-[1]benzofuro[3,2-c]pyridin-2-yl)ethyl]-2,6,8-trimethylpyrido[1,2-a]pyrimidin-4-one	36067: Binding affinity at human Alpha-2A adrenergic receptor in CHO cells by [3H]rauwolscine (1 nM) displacement.	ic50	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
Oxymetazoline	1063789: Displacement of [125I]Clonidine from adrenergic alpha2A receptor (unknown origin)	ki	0.0003	uM
5-[(1aR,6aS)-spiro[1,1a-dihydrocyclopropa[a]indene-6,1’-cyclopropane]-6a-yl]-1H-imidazole	516907: Displacement of [3H]-RX821002 from human adrenergic alpha2A receptor expressed in rat C6 cells after 120 mins by liquid scintillation counting	ki	0.0003	uM
2-(3-methoxy-2H-1,4-benzodioxin-3-yl)-4,5-dihydro-1H-imidazole	339888: Displacement of [3H]RS79948-197 from human recombinant adrenergic alpha2A receptor expressed in CHO cells	ki	0.0004	uM
[(3R,3aS)-3-[[4-[(E)-2-methyl-3-phenylprop-2-enyl]piperazin-1-yl]methyl]-3a,4-dihydro-3H-chromeno[4,3-c][1,2]oxazol-7-yl] acetate	238678: Binding affinity for alpha-2A adrenergic receptor	ki	0.0004	uM
3-[2-(3,4-dihydro-1H-[1]benzofuro[3,2-c]pyridin-2-yl)ethyl]-2,8-dimethylpyrido[1,2-a]pyrimidin-4-one	36067: Binding affinity at human Alpha-2A adrenergic receptor in CHO cells by [3H]rauwolscine (1 nM) displacement.	ic50	0.0004	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	36067: Binding affinity at human Alpha-2A adrenergic receptor in CHO cells by [3H]rauwolscine (1 nM) displacement.	ic50	0.0004	uM
(1S,15R,18S,19R,20S)-18-hydroxy-N-[10-[[(1S,15R,18S,19R,20S)-18-hydroxy-1,3,11,12,14,15,16,17,18,19,20,21-dodecahydroyohimban-19-carbonyl]amino]decyl]-1,3,11,12,14,15,16,17,18,19,20,21-dodecahydroyohimban-19-carboxamide;dihydrochloride	35935: Binding affinity against human Alpha-2A adrenergic receptor expressed stably in CHO cells using [3H]rauwolscine as radioligand	ki	0.0004	uM
5-[(1aR,6aR)-1a-methyl-1,6-dihydrocyclopropa[a]inden-6a-yl]-1H-imidazole	516907: Displacement of [3H]-RX821002 from human adrenergic alpha2A receptor expressed in rat C6 cells after 120 mins by liquid scintillation counting	ki	0.0004	uM
5-[(1S,1aR,6aS)-1-propyl-1a,6-dihydro-1H-cyclopropa[a]inden-6a-yl]-1H-imidazole	516907: Displacement of [3H]-RX821002 from human adrenergic alpha2A receptor expressed in rat C6 cells after 120 mins by liquid scintillation counting	ki	0.0004	uM
3-[2-(3,4-dihydro-1H-[1]benzofuro[3,2-c]pyridin-2-yl)ethyl]-2-methylpyrido[1,2-a]pyrimidin-4-one	36067: Binding affinity at human Alpha-2A adrenergic receptor in CHO cells by [3H]rauwolscine (1 nM) displacement.	ic50	0.0005	uM
1-[(7-methyl-2,3-dihydro-1H-inden-4-yl)oxy]-3-(propan-2-ylamino)butan-2-ol	752260: Binding affinity to human adrenergic alpha2 receptor by radioligand displacement assay	ic50	0.0005	uM
7-methoxy-3-[[4-[(E)-3-phenylprop-2-enyl]piperazin-1-yl]methyl]-3a,4-dihydro-3H-chromeno[4,3-c][1,2]oxazole	35947: In vitro binding affinity towards human alpha-2A adrenergic receptor using [3H]rauwolscine	ki	0.0005	uM
(3R,3aS)-3-[[4-[(E)-3-(furan-2-yl)but-2-enyl]piperazin-1-yl]methyl]-7,8-dimethoxy-3a,4-dihydro-3H-chromeno[4,3-c][1,2]oxazole	35948: In vitro binding affinity to the human alpha-2A adrenergic receptor	ki	0.0005	uM
(3R,3aS)-7-methoxy-3-[[4-[(E)-2-methyl-3-phenylprop-2-enyl]piperazin-1-yl]methyl]-3a,4-dihydro-3H-chromeno[4,3-c][1,2]oxazole	238678: Binding affinity for alpha-2A adrenergic receptor	ki	0.0005	uM
5-[(1aR,6S,6aS)-6-ethyl-1a,6-dihydro-1H-cyclopropa[a]inden-6a-yl]-1H-imidazole	516907: Displacement of [3H]-RX821002 from human adrenergic alpha2A receptor expressed in rat C6 cells after 120 mins by liquid scintillation counting	ki	0.0005	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, increases methylation	4
entinostat	increases expression, affects cotreatment	2
Decitabine	affects expression, increases expression	2
Epinephrine	increases phosphorylation, affects binding, increases activity, increases abundance, decreases reaction (+2 more)	2
Norepinephrine	affects binding, decreases reaction, increases activity, increases abundance	2
Tobacco Smoke Pollution	decreases expression, decreases methylation	2
Doxazosin	decreases reaction, increases activity, decreases expression, affects binding	2
Dexmedetomidine	affects binding, increases activity, decreases reaction	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression, affects cotreatment	1
aminomethylphosphonic acid (AMPA)	increases expression	1
bisphenol A	decreases expression	1
xylometazoline	affects binding, decreases reaction	1
2-methyl-4-isothiazolin-3-one	increases expression	1
trichostatin A	increases expression	1
amitraz	decreases activity	1
talipexole	affects binding, decreases reaction, increases activity	1
phenethylamine	affects binding	1
moxonidine	affects binding, increases activity	1
5,6-dihydroxy-1-(2-imidazolinyl)tetralin	affects binding, increases activity	1
2-methoxyidazoxan	affects binding, decreases reaction	1
1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione	affects binding, decreases reaction, increases activity	1
pentabromodiphenyl ether	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Brimonidine Tartrate	affects binding, decreases reaction, increases activity, increases reaction	1

ChEMBL screening assays

896 unique, capped per target: 687 binding, 190 functional, 17 admet, 2 unclassified

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1007882	Binding	Inhibition of adrenergic alpha2A receptor	Discovery of imidazo[1,2-b]thiazole derivatives as novel SIRT1 activators. — J Med Chem
CHEMBL1015737	Functional	Antagonist activity at human recombinant adrenergic alpha2A receptor expressed in CHO cells	Alpha2-adrenoreceptors profile modulation. 4. From antagonist to agonist behavior. — J Med Chem
CHEMBL1737999	Unclassified	PUBCHEM_BIOASSAY: Late-stage radioligand binding dose response assay to identify inhibitors of NADPH oxidase 1 (NOX1): PDSP screen Ki. (Class of assay: screening) [Related pubchem assays (depositor defined):AID1792, AID1796, AID1823, AID253	PubChem BioAssay data set

Cellosaurus cell lines

7 cell lines: 5 spontaneously immortalized cell line, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_9112	L-alpha-2A L-cells	Spontaneously immortalized cell line	Male
CVCL_D9X9	Ubigene HeLa ADRA2A KO	Cancer cell line	Female
CVCL_H390	CHO-K1/ADRA2A/Galpha15	Spontaneously immortalized cell line	Female
CVCL_KS26	GeneBLAzer ADRA2A-Gqo5-NFAT-bla CHO-K1	Spontaneously immortalized cell line	Female
CVCL_KU76	cAMP Hunter CHO-K1 ADRA2A Gi	Spontaneously immortalized cell line	Female
CVCL_KW26	PathHunter CHO-K1 ADRA2A beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_ZJ95	Tango ADRA2A-bla U2OS	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00005764	PHASE4	COMPLETED	A Study of Increased Lactic Acid and Abnormal Fat Distribution in HIV-Positive Patients
NCT00006190	PHASE4	COMPLETED	A Study to Determine How and Why HIV-Infected Subjects on Anti-viral Treatment Develop Lipodystrophy
NCT00119769	PHASE4	COMPLETED	The Effect of Low-Dose Human Growth Hormone Therapy in HIV Infected Patients
NCT00192621	PHASE4	COMPLETED	Seronegatives and Metabolic Abnormalities Protocol 2 (SAMA002): Study to Compare the Effect of Kaletra and Combivir® in HIV-Negative Healthy Subjects
NCT00202228	PHASE4	COMPLETED	Lactate Metabolism Study in HIV Infected Persons
NCT00227500	PHASE4	COMPLETED	Pravastatin for Hyperlipidaemia in HIV.
NCT00360139	PHASE4	WITHDRAWN	Clinical Trial to Determine the Efficacy of Sculptra™ Dermal Filler for the Correction of Contour Deformities Caused by Lipoatrophy
NCT00426296	PHASE4	UNKNOWN	SHARE: Simple HAART With Abacavir, Reyataz, and Epivir
NCT00865007	PHASE4	COMPLETED	Lopinavir/r Monotherapy Versus Abacavir/Lamivudine and Lopinavir/r for Limb Fat Recovery in Persons With Lipoatrophy
NCT01612858	PHASE4	COMPLETED	Metabolic Abnormalities in HIV-infected Persons
NCT00006412	PHASE3	COMPLETED	Safety and Effectiveness of Fenofibrate and Pravastatin in HIV-Positive Patients With Abnormal Blood Lipids
NCT00082628	PHASE3	COMPLETED	Treatment of Abnormal Adipose Tissue Accumulation in Human Immunodeficiency Virus (HIV) Patients
NCT00123253	PHASE3	COMPLETED	TH9507 in Patients With HIV-Associated Lipodystrophy
NCT00608023	PHASE3	COMPLETED	TH9507 Extension Study in Patients With HIV-Associated Lipodystrophy
NCT02262832	PHASE3	ACTIVE_NOT_RECRUITING	Compassionate Use of Metreleptin in Previously Treated People With Generalized Lipodystrophy
NCT04860063	PHASE3	UNKNOWN	Effect of Berberine on Metabolic Syndrome, Efficacy and Safety in Combination With Antiretroviral Therapy in PLWH.
NCT00005905	PHASE2	COMPLETED	Leptin to Treat Lipodystrophy
NCT00021463	PHASE2	COMPLETED	Changing to Nonprotease Inhibitor Treatment to Improve Side Effects
NCT00025883	PHASE2	COMPLETED	Leptin to Treat Lipodystrophy
NCT00119379	PHASE2	COMPLETED	Effectiveness of Nucleoside Supplementation or Switch to Tenofovir in Reversing Fat Loss in HIV Infected Adults
NCT00461552	PHASE2	COMPLETED	Therapeutic Approaches to HAART-Induced Lipodystrophy
NCT00647946	PHASE2	COMPLETED	Study to Evaluate Changes in Limb Fat When Switching From a Thymidine Analogue
NCT00656175	PHASE2	COMPLETED	Raltegravir Therapy for Women With HIV and Fat Accumulation
NCT01679197	PHASE2	COMPLETED	Clinical Protocol to Investigate the Efficacy of Recombinant Human Leptin (Metreleptin) in Nonalcoholic Steatohepatitis (NASH) or Nonalcoholic Fatty Liver Disease (NAFLD) Associated With Lipodystrophy
NCT01778556	PHASE2	COMPLETED	Short-term Effects of Leptin in People With Lipodystrophy
NCT02262806	PHASE2	ACTIVE_NOT_RECRUITING	Compassionate Use of Metreleptin in Previously Treated People With Partial Lipodystrophy
NCT02639286	PHASE2	COMPLETED	Efficacy, Safety and Tolerability of ISIS 304801 in People With Partial Lipodystrophy With an Open-Label Extension
NCT07313787	PHASE2	NOT_YET_RECRUITING	Effects of Meal Macronutrients on Postprandial Lipids
NCT00006185	PHASE1	COMPLETED	Underlying Abnormalities in Fat and Muscle Leading to Lipodystrophy Syndrome
NCT00017758	PHASE1	COMPLETED	The Effect of Efavirenz and Nelfinavir on the Blood Levels of Certain Lipid-Lowering Drugs
NCT00715546	PHASE1	UNKNOWN	Autologous Adipose-Derived Stem Cell Transplantation in Patients With Lipodystrophy
NCT02034786	PHASE1	UNKNOWN	Safety Study of Filler Agent Composed of Autologous Mesenchymal Stem Cells and Hyaluronic Acid
NCT02647853	PHASE1	COMPLETED	Phase 1 Study to Assess the Safety and Tolerability of TAT4 Gel in Healthy Volunteers
NCT00910936	PHASE2/PHASE3	UNKNOWN	Exercise for Patients With HIV Infections
NCT00001142	Not specified	COMPLETED	Metabolism and Body Shape of Healthy Children and Children With Chronic Infections
NCT00004329	Not specified	COMPLETED	Study of Alpha-2 Adrenergic Receptor Dysfunction in Regional Lipoatrophy
NCT00006064	Not specified	COMPLETED	The Effect of Anti-HIV Treatment on Body Characteristics of HIV-Infected Children
NCT00006290	Not specified	COMPLETED	Perceived Changes in Body Build and Image in Patients Who Are Now Taking or Recently Have Stopped Taking Anti-HIV Drugs
NCT00015691	Not specified	COMPLETED	Metformin and Rosiglitazone, Alone or in Combination, in HIV-Infected Patients With Insulin and Fat Abnormalities
NCT00028314	Not specified	COMPLETED	Effects of Treatment Changes on Fat Wasting in the Arms and Legs of HIV Patients