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ADRA2C

gene
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Also known as ADRARL2

Summary

ADRA2C (adrenoceptor alpha 2C, HGNC:283) is a protein-coding gene on chromosome 4p16.3, encoding Alpha-2C adrenergic receptor (P18825). 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. They include 3 highly homologous subtypes: alpha2A, alpha2B, and alpha2C. These receptors have a critical role in regulating neurotransmitter release from sympathetic nerves and from adrenergic neurons in the central nervous system. The mouse studies revealed that both the alpha2A and alpha2C subtypes were required for normal presynaptic control of transmitter release from sympathetic nerves in the heart and from central noradrenergic neurons. The alpha2A subtype inhibited transmitter release at high stimulation frequencies, whereas the alpha2C subtype modulated neurotransmission at lower levels of nerve activity. This gene encodes the alpha2C subtype, which contains no introns in either its coding or untranslated sequences.

Source: NCBI Gene 152 — RefSeq curated summary.

At a glance

  • GWAS associations: 4
  • Clinical variants (ClinVar): 84 total — 5 pathogenic
  • Druggable target: yes — 330 molecules with ChEMBL bioactivity
  • MANE Select transcript: NM_000683

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:283
Approved symbolADRA2C
Nameadrenoceptor alpha 2C
Location4p16.3
Locus typegene with protein product
StatusApproved
AliasesADRARL2
Ensembl geneENSG00000184160
Ensembl biotypeprotein_coding
OMIM104250
Entrez152

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000330055, ENST00000509482

RefSeq mRNA: 1 — MANE Select: NM_000683 NM_000683

CCDS: CCDS47004

Canonical transcript exons

ENST00000330055 — 1 exons

ExonStartEnd
ENSE0000129342037663853768526

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 96.85.

FANTOM5 (CAGE): breadth broad, TPM avg 1.9269 / max 59.0375, expressed in 564 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter IDTPM avgSamples expressed
467231.1293434
467240.7976324

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
deciduaUBERON:000245096.85gold quality
endocervixUBERON:000045896.35gold quality
descending thoracic aortaUBERON:000234595.60gold quality
thoracic aortaUBERON:000151595.41gold quality
ascending aortaUBERON:000149695.35gold quality
aortaUBERON:000094794.09gold quality
popliteal arteryUBERON:000225093.18gold quality
tibial arteryUBERON:000761093.14gold quality
saphenous veinUBERON:000731890.08gold quality
vena cavaUBERON:000408789.95gold quality
cervix squamous epitheliumUBERON:000692289.85silver quality
right coronary arteryUBERON:000162589.38gold quality
skeletal muscle tissue of rectus abdominisUBERON:000451189.00silver quality
stromal cell of endometriumCL:000225588.64gold quality
nippleUBERON:000203088.27gold quality
putamenUBERON:000187487.65gold quality
coronary arteryUBERON:000162187.51gold quality
ectocervixUBERON:001224987.48gold quality
left coronary arteryUBERON:000162687.45gold quality
buccal mucosa cellCL:000233687.26silver quality
tendon of biceps brachiiUBERON:000818887.10gold quality
body of uterusUBERON:000985387.01gold quality
seminal vesicleUBERON:000099886.88gold quality
myometriumUBERON:000129686.74gold quality
caudate nucleusUBERON:000187386.31gold quality
pericardiumUBERON:000240786.24gold quality
cauda epididymisUBERON:000436086.16gold quality
lateral globus pallidusUBERON:000247685.66silver quality
uterine cervixUBERON:000000285.30gold quality
pancreatic ductal cellCL:000207984.81silver quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-ANND-3yes4.17

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

20 targeting ADRA2C, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-520D-5P99.9873.344883
HSA-MIR-524-5P99.9873.434882
HSA-MIR-96-5P99.9572.802140
HSA-MIR-1213399.9271.822006
HSA-MIR-1271-5P99.9171.991972
HSA-MIR-605-3P99.8869.221833
HSA-MIR-182-5P99.8774.032589
HSA-MIR-10393-3P99.7266.56961
HSA-MIR-6801-5P99.7266.50981
HSA-MIR-447099.6669.351767
HSA-MIR-451699.6167.783390
HSA-MIR-4687-3P99.4866.41968
HSA-MIR-449B-3P99.2067.241047
HSA-MIR-427999.1966.702437
HSA-MIR-7160-5P99.1167.172207
HSA-MIR-425499.1165.151315
HSA-MIR-443499.1067.011984
HSA-MIR-570399.1067.092053
HSA-MIR-330-5P98.7367.631788
HSA-MIR-428697.2064.371587

Literature-anchored findings (GeneRIF, showing 40)

  • 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)
  • Increased expression of alpha(2C)-adrenoceptors may contribute to enhanced cold-induced vasoconstriction and Raynaud’s phenomenon. (PMID:15345481)
  • ADRA2C had one haplotype block of 10 kb (PMID:15592690)
  • alpha2CDel322-325 polymorphism is associated with increased sympathetic nervous and adrenomedullary hormonal activities, both during supine rest and during pharmacologically evoked catecholamine release (PMID:15861038)
  • A genetic variant of the alpha 2C-adrenoceptor subtype–resulting from the deletion of four consecutive amino acids at codons 322-325–confers a change in brain function playing a role in the pathogenesis of major depressive disorder. (PMID:16407897)
  • Genetic variations of the alpha and beta adrenergic receptors (alpha 2C Del322-325 allele) were found to be significant predictors of vasospastic angina (PMID:16569551)
  • 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)
  • alpha(2)-ARs might contribute neurotrophic actions in vivo synergistically or in permutation with other neurotrophic factors (PMID:17192578)
  • The ADRA2C deletion polymorphism had no effect on markers of resting sympathetic activity and cardiovascular measures, and did not account for ethnic differences in blood pressure. (PMID:17351367)
  • An estrogen-dependent increase in expression of cold-sensitive alpha(2C)-ARs may contribute to the increased activity of cold-induced vasoconstriction under estrogen-replete conditions (PMID:17644575)
  • Polymorphisms are not associated with Toureett’s syndrome in this study. (PMID:18075481)
  • Homozygosity for the alpha 2C Del322-325 polymorphism is not associated with heart failure in black South Africans (PMID:18320080)
  • Because the alpha(2C)-adrenoceptor distribution pattern is conserved between rodents and humans, studies on the role of the alpha(2C)-adrenoceptor in rodent models of neuropsychiatric disorders may be relevant also for human diseases. (PMID:18435421)
  • Cyclic AMP acts through Rap1 and JNK signaling to increase expression of cutaneous smooth muscle alpha2C-adrenoceptors. (PMID:18487435)
  • Genetic variants in the alpha2C-adrenoceptor and G-protein contribute to ethnic differences in cardiovascular stress responses (PMID:18698227)
  • Genotype and haplotype of ADRA2C did not significantly affect survival in metoprolol-treated or carvedilol-treated heart failure patients. (PMID:18702968)
  • Beta1- and alpha2c-adrenoreceptor variants as predictors of clinical aspects of dilated cardiomyopathy in people of African ancestry. (PMID:18776959)
  • Our findings provide important evidence that the ADRA2C polymorphism is involved in the etiology of ADHD in Korean subjects. (PMID:18835330)
  • Three polymorphisms in ADRA2C and five polymorphisms in ADRB1 were involved in eight cross-validated epistatic interactions identifying several two-locus genotype classes with significant relative risks of death/transplant in heart failure patients (PMID:18947427)
  • Genotype polymorphism frequencies for B1 receptor (amino acid positions 389 and 49) and alpha 2c receptor (deletion 322-325) are not significantly different in SC patients compared to female controls. (PMID:19167638)
  • The common ADRA2C variant affected pain perception before and after dexmedetomidine but did not affect other cognitive responses (PMID:19423370)
  • The ADRA2C del322-325 variant did not affect vascular sensitivity to local cold exposure. (PMID:19444546)
  • the norepinephrine lowering and clinical therapeutic responses to bucindolol were strongly influenced by alpha(2C) receptor genotype (PMID:19880803)
  • The alpha(2C)-Del322-325 polymorphism does not exhibit reduced signalling to adenylyl cyclase and may not represent a clinically important phenotype. (PMID:20128806)
  • alpha1b and alpha2c AR is over-expressed in basal-like breast tumours of poor prognosis (PMID:21298476)
  • there is little evidence for an association between alpha(2C)Del322-325 polymorphism and an increased prevalence of left ventricular hypertrophy in patients with systemic hypertension. (PMID:22040172)
  • the predicted signal peptide in the N-terminal tail of the alpha(2C)-adrenoceptor does not act as a cleavable signal peptide (PMID:22503931)
  • The ADRA2A and ADRA2C polymorphisms did not contribute to an increased risk of ischemic stroke or any pathophysiological subtype (PMID:22560155)
  • Bucindolol prevents ventricular arrhythmias in subjects with heart failure and reduced left ventricular ejection fractions, and this effect is modulated by adrenergic alpha 2 receptor polymorphisms. (PMID:23275278)
  • the region comprising the N-terminal half of The receptors contributed to the alpha2C-selectivity of drug binding. (PMID:23868076)
  • Genetic variants of ADRA2C do not alter intracellular localization or plasma membrane trafficking. (PMID:24643471)
  • the ADRA2C 322-325I/D genotype is a novel genetic risk marker for SBI among individuals with hyperhomocysteinemia. (PMID:24676565)
  • alpha2C-adrenoreceptor interaction with filamin-2 (PMID:25110951)
  • Adrenergic receptor genotype influences heart failure severity and beta-blocker response in children with dilated cardiomyopathy. (PMID:25406899)
  • ADRA2c is associated with heart rate recovery after exercise. (PMID:26058836)
  • Common polymorphisms in the ADRA2C gene are not associated with orthostatic hypotension risk in Chinese. (PMID:26427149)
  • Immunoreactivity for ADRA2C was densely distributed in vascular smooth muscle of nasal turbinates. (PMID:26739946)
  • The frequency of alpha2CDel322-325-AR in suicide and non-suicide victims was similar. Genotype frequencies for the alpha2CDel322-325-AR polymorphism in depressed and schizophrenic subjects were higher than in controls, but these differences did not reach statistical significance. The results indicate that alpha2CDel322-325-AR may play a role in the pathophysiology of opiate abuse and dependence. (PMID:27007576)
  • alpha2A- and alpha2C-adrenoceptors are functional receptors for norepinephrine, dopamine, and other previously assumed selective D2-like receptor ligands. (PMID:29552726)
  • High alpha2-Adrenergic Receptor expression is associated with Pathogenesis of Preeclampsia and Fetal Growth Restriction. (PMID:30273604)

Cross-species orthologs

4 orthologs

OrganismSymbolGene ID
danio_rerioadra2cENSDARG00000069669
mus_musculusAdra2cENSMUSG00000045318
rattus_norvegicusAdra2cENSRNOG00000084818
caenorhabditis_elegansser-5WBGENE00008890

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), OR56A3 (ENSG00000184478), OR13F1 (ENSG00000186881), OR56A5 (ENSG00000188691), ADRB3 (ENSG00000188778), ADRA2B (ENSG00000274286)

Protein

Protein identifiers

Alpha-2C adrenergic receptor — P18825 (reviewed: P18825)

Alternative names: Alpha-2 adrenergic receptor subtype C4, Alpha-2C adrenoreceptor

All UniProt accessions (3): D6RGL0, P18825, Q4W594

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 physiological agonists of ADRA2C is epinephrine > norepinephrine > dopamine.

Subcellular location. Cell membrane.

Polymorphism. The Del322-325 variant has a significant loss of function. It is approximately 10 times more frequent in African-Americans compared with Caucasians (allele frequencies 0.381 versus 0.040).

Similarity. Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRA2C sub-subfamily.

RefSeq proteins (1): NP_000674* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000276GPCR_RhodpsnFamily
IPR000735ADRA2C_rcptFamily
IPR002233ADR_famFamily
IPR017452GPCR_Rhodpsn_7TMDomain

Pfam: PF00001

UniProt features (46 total): helix 16, topological domain 8, transmembrane region 7, sequence conflict 4, site 3, compositionally biased region 2, glycosylation site 2, chain 1, region of interest 1, disulfide bond 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDBMethodResolution (Å)
6KUWX-RAY DIFFRACTION2.8

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P18825-F174.700.37

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): 131 (implicated in ligand binding); 214 (implicated in catechol agonist binding and receptor activation); 218 (implicated in catechol agonist binding and receptor activation)

Disulfide bonds (1): 124–202

Glycosylation sites (2): 19, 33

Function

Pathways and Gene Ontology

Reactome pathways

19 pathways

IDPathway
R-HSA-390696Adrenoceptors
R-HSA-392023Adrenaline signalling through Alpha-2 adrenergic receptor
R-HSA-400042Adrenaline,noradrenaline inhibits insulin secretion
R-HSA-418594G alpha (i) signalling events
R-HSA-418597G alpha (z) signalling events
R-HSA-5683826Surfactant metabolism
R-HSA-109582Hemostasis
R-HSA-1430728Metabolism
R-HSA-162582Signal Transduction
R-HSA-163685Integration of energy metabolism
R-HSA-372790Signaling by GPCR
R-HSA-373076Class A/1 (Rhodopsin-like receptors)
R-HSA-375280Amine ligand-binding receptors
R-HSA-388396GPCR downstream signalling
R-HSA-392499Metabolism of proteins
R-HSA-422356Regulation of insulin secretion
R-HSA-500792GPCR ligand binding
R-HSA-76002Platelet activation, signaling and aggregation
R-HSA-76009Platelet Aggregation (Plug Formation)

MSigDB gene sets: 206 (showing top): WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_CIRCULATORY_SYSTEM_PROCESS, REACTOME_ADRENALINE_NORADRENALINE_INHIBITS_INSULIN_SECRETION, REACTOME_PLATELET_AGGREGATION_PLUG_FORMATION, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, REACTOME_G_ALPHA_Z_SIGNALLING_EVENTS, GCANCTGNY_MYOD_Q6, GOBP_PLATELET_ACTIVATION, GOBP_INSULIN_SECRETION, GOBP_POSITIVE_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_REGULATION_OF_SMOOTH_MUSCLE_CONTRACTION, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_NEGATIVE_REGULATION_OF_PEPTIDE_SECRETION, GOBP_HORMONE_TRANSPORT

GO Biological Process (15): regulation of smooth muscle contraction (GO:0006940), epidermal growth factor receptor signaling pathway (GO:0007173), G protein-coupled receptor signaling pathway (GO:0007186), cell-cell signaling (GO:0007267), negative regulation of norepinephrine secretion (GO:0010700), regulation of vasoconstriction (GO:0019229), 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), negative regulation of insulin secretion (GO:0046676), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), adrenergic receptor signaling pathway (GO:0071875), adenylate cyclase-inhibiting adrenergic receptor signaling pathway (GO:0071881), signal transduction (GO:0007165)

GO Molecular Function (9): alpha2-adrenergic receptor activity (GO:0004938), alpha-2A adrenergic receptor binding (GO:0031694), protein homodimerization activity (GO:0042803), protein heterodimerization activity (GO:0046982), epinephrine binding (GO:0051379), 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 (4): cytoplasm (GO:0005737), endosome (GO:0005768), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-13 pathways:

CategoryPathways
GPCR downstream signalling2
Signaling by GPCR2
Amine ligand-binding receptors1
Platelet Aggregation (Plug Formation)1
Regulation of insulin secretion1
Metabolism of proteins1
Metabolism1
Signal Transduction1
GPCR ligand binding1
Class A/1 (Rhodopsin-like receptors)1
Integration of energy metabolism1
Hemostasis1
Platelet activation, signaling and aggregation1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cell communication2
signaling2
negative regulation of catecholamine secretion2
positive regulation of intracellular signal transduction2
G protein-coupled receptor signaling pathway2
adrenergic receptor signaling pathway2
protein dimerization activity2
cellular anatomical structure2
regulation of muscle contraction1
smooth muscle contraction1
ERBB signaling pathway1
G protein-coupled receptor activity1
signal transduction1
regulation of norepinephrine secretion1
norepinephrine secretion1
vasoconstriction1
blood vessel diameter maintenance1
regulation of blood circulation1
cell activation1
blood coagulation1
regulation of epinephrine secretion1
epinephrine secretion1
MAPK cascade1
regulation of MAPK cascade1
neuron differentiation1
positive regulation of cell differentiation1
regulation of neuron differentiation1
insulin secretion1
negative regulation of protein secretion1
regulation of insulin secretion1
negative regulation of peptide hormone secretion1
phosphatidylinositol 3-kinase/protein kinase B signal transduction1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction1
adrenergic receptor activity1
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway1
cellular process1
regulation of cellular process1
cellular response to stimulus1
alpha-adrenergic receptor activity1
adrenergic receptor binding1

Protein interactions and networks

STRING

938 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
ADRA2CSLC6A3Q01959777
ADRA2CSLC6A2P23975698
ADRA2CYES1P07947691
ADRA2CDBHP09172669
ADRA2CSLC6A4P31645639
ADRA2CAGTR1P30556627
ADRA2CADRB2P07550567
ADRA2CGRIN1P35437536
ADRA2CGNAQP50148518
ADRA2CAGTP01019497
ADRA2CPTGS1P23219493
ADRA2CGRM6O15303489
ADRA2CADRA1BP35368486
ADRA2CADRA2AP08913485
ADRA2CDRD2P14416461

IntAct

46 interactions, top by confidence:

ABTypeScore
ADRA2CMDFIpsi-mi:“MI:0915”(physical association)0.560
ADRA2Cpsi-mi:“MI:0915”(physical association)0.560
ADRA2CCNPY2psi-mi:“MI:0915”(physical association)0.560
ADRA2CCHCHD2psi-mi:“MI:0915”(physical association)0.560
ADRA2CKLHL38psi-mi:“MI:0915”(physical association)0.560
ADRA2CMKRN3psi-mi:“MI:0915”(physical association)0.560
MEIS2ADRA2Cpsi-mi:“MI:0915”(physical association)0.560
HGSADRA2Cpsi-mi:“MI:0915”(physical association)0.560
KRT34ADRA2Cpsi-mi:“MI:0915”(physical association)0.560
ADRA2CP4HA3psi-mi:“MI:0915”(physical association)0.560
ADRA2CWWOXpsi-mi:“MI:0915”(physical association)0.560
ADRA2CCCDC24psi-mi:“MI:0915”(physical association)0.560
ADRA2AADRA2Cpsi-mi:“MI:2364”(proximity)0.470
ADRA2CADRA2Cpsi-mi:“MI:2364”(proximity)0.470
ADRA2AADRA2Cpsi-mi:“MI:0915”(physical association)0.470
ADRA2CADRA2Cpsi-mi:“MI:0915”(physical association)0.470
RAMP1ADRA2Cpsi-mi:“MI:0915”(physical association)0.400
ADRA2CRAMP3psi-mi:“MI:0915”(physical association)0.400
RAMP3ADRA2Cpsi-mi:“MI:0915”(physical association)0.400
SLC15A3GXYLT2psi-mi:“MI:0914”(association)0.350
ADRA2CMDFIpsi-mi:“MI:0915”(physical association)0.000
ADRA2Cpsi-mi:“MI:0915”(physical association)0.000
CNPY2ADRA2Cpsi-mi:“MI:0915”(physical association)0.000
KRT34ADRA2Cpsi-mi:“MI:0915”(physical association)0.000
P4HA3ADRA2Cpsi-mi:“MI:0915”(physical association)0.000
WWOXADRA2Cpsi-mi:“MI:0915”(physical association)0.000
CHCHD2ADRA2Cpsi-mi:“MI:0915”(physical association)0.000

BioGRID (19): ADRA2C (Affinity Capture-RNA), ADRA2C (Two-hybrid), ADRA2C (Two-hybrid), ADRA2C (Two-hybrid), ADRA2C (Two-hybrid), ADRA2C (Two-hybrid), ADRA2C (Two-hybrid), ADRA2C (Two-hybrid), ADRA2C (Two-hybrid), ADRA2C (Two-hybrid), HGS (Two-hybrid), WWOX (Two-hybrid), CNPY2 (Two-hybrid), EIF2B1 (Reconstituted Complex), ADRA2C (Reconstituted Complex)

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

Diamond homologs: 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

17 interactions.

AEffectBMechanism
ADRA2C“up-regulates activity”GNAI1binding
ADRA2C“up-regulates activity”GNAI3binding
ADRA2C“up-regulates activity”GNAO1binding
ADRA2C“up-regulates activity”GNAZbinding
(R)-noradrenaline“up-regulates activity”ADRA2C“chemical activation”
brimonidine“up-regulates activity”ADRA2C“chemical activation”
clonidine“up-regulates activity”ADRA2C“chemical activation”
dexmedetomidine“up-regulates activity”ADRA2C“chemical activation”
Guanabenz“up-regulates activity”ADRA2C“chemical activation”
tolazoline“down-regulates activity”ADRA2C“chemical inhibition”
oxymetazoline“up-regulates activity”ADRA2C“chemical activation”
Guanfacine“up-regulates activity”ADRA2C“chemical activation”
N-(2,6-dimethylphenyl)-5,6-dihydro-4H-1,3-thiazin-2-amine“up-regulates activity”ADRA2C“chemical activation”
lurasidone“down-regulates activity”ADRA2C“chemical inhibition”
lofexidine“up-regulates activity”ADRA2C“chemical activation”
apraclonidine“up-regulates activity”ADRA2C“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic5
Likely pathogenic0
Uncertain significance69
Likely benign6
Benign4

Top pathogenic / likely-pathogenic (5)

Variant IDHGVSClassification
1073308NC_000004.11:g.(?2200251)(5710240_?)delPathogenic
1341071GRCh37/hg19 4p16.3-15.31(chr4:68345-20587167)x1Pathogenic
1704651GRCh37/hg19 4p16.3-12(chr4:114784-47569569)x3Pathogenic
441812GRCh37/hg19 4p16.3-q13.1(chr4:68345-66440622)x3Pathogenic
4755361GRCh38/hg38 4p16.3(chr4:49556-3910769)x1Pathogenic

SpliceAI

109 predictions. Top by Δscore:

VariantEffectΔscore
4:3767806:CAG:Cacceptor_gain0.8400
4:3767805:TCAGC:Tacceptor_gain0.8100
4:3767807:A:AGacceptor_gain0.7700
4:3767808:G:GGacceptor_gain0.7700
4:3767721:T:TAdonor_gain0.7400
4:3767722:G:GAdonor_gain0.7300
4:3767503:C:Tdonor_gain0.6900
4:3767807:AGC:Aacceptor_gain0.6900
4:3767804:TTCAG:Tacceptor_gain0.6800
4:3767419:C:Tdonor_gain0.6700
4:3767808:GCT:Gacceptor_gain0.6100
4:3767808:GC:Gacceptor_gain0.6000
4:3767808:GCTAC:Gacceptor_gain0.5900
4:3767789:T:Aacceptor_gain0.5800
4:3767737:G:GTdonor_gain0.5400
4:3767787:G:GAacceptor_gain0.5400
4:3767808:G:Cacceptor_gain0.5200
4:3767785:C:CAacceptor_gain0.5100
4:3767788:C:Aacceptor_gain0.5100
4:3767373:C:Adonor_gain0.4700
4:3767462:G:GTdonor_gain0.4500
4:3767730:C:Tdonor_gain0.4500
4:3767375:T:TAdonor_gain0.4400
4:3767814:GCCT:Gacceptor_gain0.4400
4:3767501:G:GTdonor_gain0.4300
4:3767805:TCAG:Tacceptor_loss0.4300
4:3767806:CAGC:Cacceptor_loss0.4300
4:3767807:A:Cacceptor_loss0.4300
4:3767808:GCTA:Gacceptor_gain0.4200
4:3767809:C:Gacceptor_gain0.4200

AlphaMissense

2924 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
4:3766808:G:CG68R1.000
4:3766813:C:AN69K1.000
4:3766813:C:GN69K1.000
4:3766872:T:CF89S1.000
4:3766875:T:AL90Q1.000
4:3766884:T:CL93P1.000
4:3766887:C:AA94D1.000
4:3766895:G:CD97H1.000
4:3766896:A:CD97A1.000
4:3766896:A:GD97G1.000
4:3766896:A:TD97V1.000
4:3767040:T:AI145N1.000
4:3767040:T:CI145T1.000
4:3767040:T:GI145S1.000
4:3767042:A:CS146R1.000
4:3767044:C:AS146R1.000
4:3767044:C:GS146R1.000
4:3767046:T:CL147P1.000
4:3767051:C:AR149S1.000
4:3767052:G:CR149P1.000
4:3767132:T:AW176R1.000
4:3767132:T:CW176R1.000
4:3767261:T:CF219L1.000
4:3767263:C:AF219L1.000
4:3767263:C:GF219L1.000
4:3767271:C:AP222H1.000
4:3767777:T:CF391L1.000
4:3767779:C:AF391L1.000
4:3767779:C:GF391L1.000
4:3767789:T:AW395R1.000

dbSNP variants (sampled 300 via entrez): RS1000062728 (4:3764662 A>C), RS1000093541 (4:3764486 C>T), RS1002395820 (4:3764451 A>C), RS1003723943 (4:3768304 G>A), RS1004276565 (4:3765324 T>C), RS1004290318 (4:3764937 C>A,T), RS1005231533 (4:3764422 C>T), RS1006563297 (4:3769008 C>T), RS1006564457 (4:3768598 C>G,T), RS1006730695 (4:3765592 CGCCTGCGCCCAT>C), RS1006746207 (4:3768491 A>G,T), RS1007218837 (4:3768340 A>G), RS1008477616 (4:3765350 G>A), RS1008565834 (4:3764438 G>A), RS1008570468 (4:3766516 C>G,T)

Disease associations

OMIM: gene MIM:104250 | disease phenotypes: MIM:193530, MIM:225500

GenCC curated gene-disease

Mondo (2): acrofacial dysostosis, Weyers type (MONDO:0008673), Ellis-van Creveld syndrome (MONDO:0009162)

Orphanet (2): Ellis Van Creveld syndrome (Orphanet:289), Acrofacial dysostosis, Weyers type (Orphanet:952)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

StudyTraitp-value
GCST002928_17Nickel levels3.000000e-06
GCST004749_100Lung cancer in ever smokers5.000000e-06
GCST008062_26Blood urea nitrogen levels6.000000e-10
GCST008648_1Urinary potassium excretion2.000000e-19

EFO canonical traits (1, from GWAS)

EFO IDTrait name
EFO:0009283potassium measurement

MeSH disease descriptors (2)

DescriptorNameTree numbers
D004613Ellis-Van Creveld SyndromeC05.116.099.708.327; C16.131.077.350.398; C16.131.831.350.398; C16.320.850.250.398; C17.800.804.350.398; C17.800.827.250.398
C536695Weyers acrofacial dysostosis (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL1916 (SINGLE PROTEIN), CHEMBL2095158 (PROTEIN FAMILY), CHEMBL2095203 (PROTEIN FAMILY), CHEMBL2331074 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

330 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 597,419 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL1008BEPRIDIL411,776
CHEMBL1014CANDESARTAN CILEXETIL411,194
CHEMBL1017TELMISARTAN427,457
CHEMBL104CLOTRIMAZOLE456,325
CHEMBL1064SIMVASTATIN4123,163
CHEMBL1065METHYSERGIDE48,455
CHEMBL1079TIZANIDINE412,099
CHEMBL1085ACETOPHENAZINE45,134
CHEMBL11IMIPRAMINE448,893
CHEMBL1108DROPERIDOL416,888
CHEMBL111RIMONABANT415,726
CHEMBL1110ALOSETRON410,794
CHEMBL1112ARIPIPRAZOLE424,205
CHEMBL1113AMOXAPINE420,128
CHEMBL1117IDARUBICIN4136,065
CHEMBL1171837PONATINIB48,955
CHEMBL1172DESLORATADINE419,720
CHEMBL117287PRUCALOPRIDE42,516
CHEMBL1175DULOXETINE428,527
CHEMBL1189679PALONOSETRON49,399
CHEMBL1200438TIOCONAZOLE4
CHEMBL1200492NEFAZODONE HYDROCHLORIDE4
CHEMBL1200515DESERPIDINE4
CHEMBL1200517DIHYDROERGOTAMINE MESYLATE4
CHEMBL1200661UNOPROSTONE ISOPROPYL4
CHEMBL1200776CINACALCET HYDROCHLORIDE4
CHEMBL1201THIOTHIXENE4
CHEMBL1201039BENZTHIAZIDE4
CHEMBL1201087CABERGOLINE4
CHEMBL1201203BENZTROPINE4

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

PharmGKB clinical annotations

3 annotations.

VariantTypeLevelDrugsPhenotypes
rs11269124Efficacy3clonidineLiver Cirrhosis
rs61767072Efficacy3bucindololHeart Failure
rs61767072Efficacy3Beta Blocking AgentsCardiomyopathy;Dilated;Death

PharmGKB variants

2 variants.

VariantGenesLevelScore#Clin annotsDrugs
rs11269124ADRA2C32.251clonidine
rs61767072ADRA2C33.002bucindolol;Beta Blocking Agents

PharmGKB dosing guidelines

1 guidelines.

SourceDrugGuidelineDosing?Recommendation?
CPICacebutolol;atenolol;betaxolol;bisoprolol;carvedilol;esmolol;labetalol;metoprolol;nadolol;nebivolol;pindolol;propranolol;sotalolAnnotation of CPIC Guideline for acebutolol, atenolol, betaxolol, bisoprolol, carvedilol, esmolol, labetalol, metoprolol, nadolol, nebivolol, pindolol, propranolol, sotalol and ADRA2C, ADRB1, GRK4, GRK5

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Adrenoceptors

Most potent curated ligand interactions (49 total), top 25:

LigandActionAffinityParameter
ORM-12741Antagonist11.0pKi
[3H]MK-912Antagonist10.1pKd
MK-912Antagonist10.0pKi
[3H]rauwolscineAntagonist9.9pKd
lisurideAntagonist9.9pKi
RS79948Antagonist9.4pKi
WB 4101Antagonist9.4pKi
dexmedetomidineAgonist9.2pIC50
[3H]RX821002Antagonist9.2pKd
rauwolscineAntagonist9.1pKi
tergurideAntagonist9.1pKi
spiroxatrineAntagonist9.0pKi
ORM-10921Antagonist8.9pKi
[125I]p-iodoclonidinePartial agonist8.9pKd
yohimbineAntagonist8.8pKi
RX821002Antagonist8.8pKi
roxindoleAntagonist8.8pKi
atipamezoleAntagonist8.5pKi
prazosinAntagonist8.0pKi
lurasidoneAntagonist8.0pKi
phentolamineAntagonist7.9pKi
EGIS-11150Antagonist7.89pKi
JP1302Antagonist7.8pKB
cabergolineAntagonist7.7pKi
idazoxanAntagonist7.7pKi

Binding affinities (BindingDB)

75 measured of 116 human assays (142 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValuePatent
NSC_104911KI0.1 nM
roxindoleKI0.11 nM
MK-912KI0.42 nM
2-Chlor-11-(2-dimethylaminoaethoxy)-dibenzo(b,f)-thiepinKI0.5 nM
8-(2,3-Dihydro-benzo[1,4]dioxin-2-ylmethyl)-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-oneKI1 nM
5-[2-(4-Benzo[d]isothiazol-3-yl-piperazin-1-yl)-ethyl]-6-chloro-1,3-dihydro-indol-2-oneKI1.9 nM
PermaxKI1.91 nM
4-[4-(4-Chloro-phenyl)-4-hydroxy-piperidin-1-yl]-1-(4-fluoro-phenyl)-butan-1-one;propionate(HCl)KI2.92 nM
TergurideKI3.47 nM
S18616KI3.98 nM
naphtalineKI4.57 nM
[2-(1-methoxybutan-2-ylamino)pyrimidin-5-yl]-[4-(7-methoxy-3,4-dihydro-1H-isoquinolin-2-yl)piperidin-1-yl]methanoneIC505 nMUS-10323020: Substituted piperidinyl tetrahydroquinolines
p-AMINOCLONIDINEKI7.94 nM
CAS_67249-51-8KI7.94 nM
Bromocriptine+ (GTP+)KI12.9 nM
CHEMBL295186EC5014 nM
CAS_81447-78-1KI14.4 nM
[4-(7-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)piperidin-1-yl]-[2-(2-oxa-6-azaspiro[3.3]heptan-6-yl)pyrimidin-5-yl]methanoneIC5016 nMUS-10323020: Substituted piperidinyl tetrahydroquinolines
NSC_54746KI19.9 nM
[2-(1-methoxybutan-2-ylamino)pyrimidin-5-yl]-[4-(6-methoxy-3,4-dihydro-1H-isoquinolin-2-yl)piperidin-1-yl]methanoneIC5020 nMUS-10323020: Substituted piperidinyl tetrahydroquinolines
8-(3’-Fluorophenethyl)amino-4-oxapentacyclo[5.4.1.02,6.03,10.05,9.08,11]dodecaneKI20 nM
CHEMBL296660EC5021 nM
[4-(3,4-dihydro-1H-isoquinolin-2-yl)piperidin-1-yl]-[2-(2-oxa-6-azaspiro[3.3]heptan-6-yl)pyrimidin-5-yl]methanoneIC5023 nMUS-10323020: Substituted piperidinyl tetrahydroquinolines
[4-(7-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)piperidin-1-yl]-[2-(1-methoxybutan-2-ylamino)pyrimidin-5-yl]methanoneIC5024 nMUS-10323020: Substituted piperidinyl tetrahydroquinolines
[4-(3,4-dihydro-1H-isoquinolin-2-yl)piperidin-1-yl]-[2-(2,6-dimethylmorpholin-4-yl)pyrimidin-5-yl]methanoneIC5024 nMUS-10323020: Substituted piperidinyl tetrahydroquinolines
[4-(3,4-dihydro-1H-isoquinolin-2-yl)piperidin-1-yl]-[2-(1,1-dioxo-1,4-thiazinan-4-yl)pyrimidin-5-yl]methanoneIC5026 nMUS-10323020: Substituted piperidinyl tetrahydroquinolines
[4-(6-methoxy-3,4-dihydro-1H-isoquinolin-2-yl)piperidin-1-yl]-[2-(2-oxa-6-azaspiro[3.3]heptan-6-yl)pyrimidin-5-yl]methanoneIC5030 nMUS-10323020: Substituted piperidinyl tetrahydroquinolines
[4-(3,4-dihydro-1H-isoquinolin-2-yl)piperidin-1-yl]-[2-(1-methoxybutan-2-ylamino)pyrimidin-5-yl]methanoneIC5031 nMUS-10323020: Substituted piperidinyl tetrahydroquinolines
1-(4-{3-[4-(6-Fluoro-benzo[d]isoxazol-3-yl)-piperidin-1-yl]-propoxy}-3-methoxy-phenyl)-ethanoneKI33 nM
Fluorocarazolol,(S)KI34 nM
NSC_3519KI50.3 nM
cid_3396KI56 nM
[4-(3,4-dihydro-1H-isoquinolin-2-yl)piperidin-1-yl]-[2-(1-hydroxybutan-2-ylamino)pyrimidin-5-yl]methanoneIC5068 nMUS-10323020: Substituted piperidinyl tetrahydroquinolines
[4-(3,4-dihydro-1H-isoquinolin-2-yl)piperidin-1-yl]-[2-(2,2-dimethylmorpholin-4-yl)pyrimidin-5-yl]methanoneIC5068 nMUS-10323020: Substituted piperidinyl tetrahydroquinolines
[4-(3,4-dihydro-1H-isoquinolin-2-yl)piperidin-1-yl]-[2-(2-methoxyethylamino)pyrimidin-5-yl]methanoneIC5082 nMUS-10323020: Substituted piperidinyl tetrahydroquinolines
(2R)-1-[5-[4-(3,4-dihydro-1H-isoquinolin-2-yl)piperidine-1-carbonyl]pyrimidin-2-yl]pyrrolidine-2-carboxylic acidIC5096 nMUS-10323020: Substituted piperidinyl tetrahydroquinolines
2-[4-[3-[2-(trifluoromethyl)phenothiazin-10-yl]propyl]piperazin-1-yl]ethanol;hydrochlorideKI146 nM
4-amino-5-chloro-2-methoxy-N-(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)benzamideKI150 nM
CAS_105182-45-4KI158 nM
(R)-5-(1-(2,3-dimethylphenyl)ethyl)-1H-imidazoleKI200 nM
S32504KI257 nM
4-[2-(dipropylamino)ethyl]-1,3-dihydro-2H-indol-2-oneKI288 nM
SMR000033635KI300 nM
NSC_133621KI316 nM
CAS_22189-31-7KI410 nM
4-[3-(2-chlorophenothiazin-10-yl)propyl]-1-piperazineethanolKI421 nM
NSC_4850KI447 nM
CAS_85760-74-3IC50462 nMUS-9359372: Hexahydrodibenzo[a,g]quinolizine compound, preparation method thereof, pharmaceutical composition and use thereof
(chloropromazine) [3-(2-Chloro-phenothiazin-10-yl)-propyl]-dimethyl-amineKI480 nM
ST 91KI575 nM

ChEMBL bioactivities

1756 potent at pChembl≥5 of 1906 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
10.85IC500.014nMCHEMBL553231
10.80IC500.016nMCHEMBL557985
10.52Ki0.03nMCHEMBL435352
10.47IC500.034nMCHEMBL537830
10.07IC500.085nMCHEMBL4878875
10.00Ki0.1nMCHEMBL91157
10.00Ki0.1nMCHEMBL2112985
10.00Ki0.1nMCHEMBL180470
10.00Ki0.1nMCHEMBL176261
10.00Ki0.1nMCHEMBL390718
10.00Ki0.1nMRAUWOLSCINE
9.92IC500.12nMCHEMBL538801
9.89Ki0.1288nMCHEMBL1256414
9.77Ki0.1698nMCHEMBL1255723
9.75Ki0.1778nMCHEMBL1256414
9.70Ki0.2nMCHEMBL91157
9.70Ki0.2nMCHEMBL419316
9.70Ki0.2nMCHEMBL176002
9.70Ki0.2nMCHEMBL179237
9.70Ki0.2nMCHEMBL176116
9.70Ki0.2nMCHEMBL175853
9.70Kd0.1995nMCHEMBL279807
9.70Kd0.1995nMCHEMBL62912
9.70Ki0.2nMCHEMBL98646
9.70Ki0.2nMCHEMBL101596
9.70Ki0.2nMCHEMBL319119
9.70Ki0.2nMCHEMBL100879
9.70Ki0.2nMCHEMBL263424
9.70Ki0.2nMCHEMBL93171
9.60IC500.25nMCHEMBL194837
9.60Ki0.2512nMYOHIMBINE
9.60Ki0.25nMCHEMBL50390
9.59IC500.26nMCHEMBL4875484
9.59EC500.26nMCHEMBL49137
9.59IC500.26nMCHEMBL554581
9.58Ki0.263nMCHEMBL1256414
9.57Ki0.27nMCHEMBL318235
9.53Ki0.2951nMCHEMBL1256378
9.52Ki0.3nMCHEMBL175911
9.52Ki0.3nMRAUWOLSCINE
9.52Ki0.3nMCHEMBL328195
9.52Ki0.3nMCHEMBL98541
9.50Ki0.3162nMCHEMBL5517941
9.49IC500.32nMCHEMBL4852159
9.43IC500.37nMCHEMBL4876214
9.40Ki0.4nMYOHIMBINE
9.40Ki0.4nMRAUWOLSCINE
9.40Ki0.4nMCHEMBL99868
9.40Ki0.4nMCHEMBL319530
9.38IC500.42nMCHEMBL4868807

PubChem BioAssay actives

1295 with measured affinity, of 3824 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.

CompoundAssayTypeValueUnit
Naphazoline Hydrochloride36185: Compound was evaluated for Adrenergic activity against Alpha-2 adrenergic receptor in human plateletsic50<0.0001uM
(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]oxazole238679: Binding affinity for alpha-2C adrenergic receptorki<0.0001uM
5-(1-naphthalen-1-ylethyl)-1H-imidazole;hydrochloride36187: Compound was tested for Adrenergic activity against Alpha-2 adrenergic receptor from rat aortaic50<0.0001uM
2-(1-naphthalen-2-ylethyl)-4,5-dihydro-1H-imidazole;hydrochloride36185: Compound was evaluated for Adrenergic activity against Alpha-2 adrenergic receptor in human plateletsic50<0.0001uM
2-(naphthalen-1-ylmethyl)-1H-imidazole;hydrochloride36185: Compound was evaluated for Adrenergic activity against Alpha-2 adrenergic receptor in human plateletsic50<0.0001uM
2-(1-naphthalen-1-ylethyl)-4,5-dihydro-1H-imidazole;hydrochloride36185: Compound was evaluated for Adrenergic activity against Alpha-2 adrenergic receptor in human plateletsic50<0.0001uM
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-dimethylethanamine238679: Binding affinity for alpha-2C adrenergic receptorki0.0001uM
(3R,3aR)-7,8-dimethoxy-3-[[4-[(E)-2-methyl-3-phenylprop-2-enyl]piperazin-1-yl]methyl]-3,3a,4,5-tetrahydro-[1,2]oxazolo[4,3-c]quinoline238679: Binding affinity for alpha-2C adrenergic receptorki0.0001uM
(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-ol238679: Binding affinity for alpha-2C adrenergic receptorki0.0001uM
7,8-dimethoxy-3-[[4-[(E)-2-methyl-3-phenylprop-2-enyl]piperazin-1-yl]methyl]-3,3a,4,5-tetrahydro-[1,2]oxazolo[4,3-c]quinoline288096: Displacement of [3H]rawolscine from human cloned adrenergic Alpha-2C receptor transfected in CHO cellski0.0001uM
2-[4-[3-(cyclobutyloxymethyl)piperidin-1-yl]piperidin-1-yl]-N-[(3,5-difluoro-2-pyridinyl)methyl]-1,3-thiazole-5-carboxamide1771853: Inhibition of human alpha 2C adrenergic receptor expressed in CHO-K1 cells coexpressing Gaq and aequorin assessed as suppression of noradrenaline-induced intracellular calcium release by bioluminescence assayic500.0001uM
(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]oxazole239372: Inhibition of [3H]- rauwolscine binding to alpha-2C adrenergic receptorki0.0001uM
5-(1-naphthalen-2-ylethyl)-1H-imidazole;hydrochloride36185: Compound was evaluated for Adrenergic activity against Alpha-2 adrenergic receptor in human plateletsic500.0001uM
5-[(1aR,6aR)-1a,6-dihydro-1H-cyclopropa[a]inden-6a-yl]-1H-imidazole516909: Displacement of [3H]-RX821002 from human adrenergic Alpha-2C receptor expressed in rat C6 cells after 120 mins by liquid scintillation countingki0.0001uM
methyl (1S,15S,18S,19S,20S)-18-hydroxy-1,3,11,12,14,15,16,17,18,19,20,21-dodecahydroyohimban-19-carboxylate36340: Compound was evaluated for inhibition of binding of [3H]rauwolscine to Alpha-2 adrenergic receptor in opossum kidneyki0.0001uM
[(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] 2-methoxyacetate238679: Binding affinity for alpha-2C adrenergic receptorki0.0002uM
(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]oxazole36406: In vitro binding affinity to human alpha-2C adrenergic receptorki0.0002uM
[(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] acetate238679: Binding affinity for alpha-2C adrenergic receptorki0.0002uM
(3R,3aS)-7-[2-(2-ethoxyethoxy)ethoxy]-3-[[4-[(E)-2-methyl-3-phenylprop-2-enyl]piperazin-1-yl]methyl]-3a,4-dihydro-3H-chromeno[4,3-c][1,2]oxazole238679: Binding affinity for alpha-2C adrenergic receptorki0.0002uM
3-methoxy-12-methylsulfonyl-5,6,8,8a,9,10,11,12a,13,13a-decahydroisoquinolino[2,1-g][1,6]naphthyridine80588: Ability to reverse inhibitory effects of UK-14304 on the contraction of guinea pig ileum as a measure of alpha-2 adrenergic receptor antagonism.kd0.0002uM
(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]oxazole239372: Inhibition of [3H]- rauwolscine binding to alpha-2C adrenergic receptorki0.0002uM
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]oxazole36405: In vitro binding affinity towards human adrenergic alpha-2C adrenergic receptor using [3H]rauwolscineki0.0002uM
(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]oxazole36406: In vitro binding affinity to human alpha-2C adrenergic receptorki0.0002uM
(3R,3aS)-3-[[4-[(E)-3-(3-fluorophenyl)-2-methylprop-2-enyl]piperazin-1-yl]methyl]-7,8-dimethoxy-3a,4-dihydro-3H-chromeno[4,3-c][1,2]oxazole36406: In vitro binding affinity to human alpha-2C adrenergic receptorki0.0002uM
(3R,3aS)-7,8-dimethoxy-3-[[4-[(E)-2-methyl-3-thiophen-2-ylprop-2-enyl]piperazin-1-yl]methyl]-3a,4-dihydro-3H-chromeno[4,3-c][1,2]oxazole36406: In vitro binding affinity to human alpha-2C adrenergic receptorki0.0002uM
(3R,3aS)-7,8-dimethoxy-3-[[4-[(E)-2-methyl-3-thiophen-3-ylprop-2-enyl]piperazin-1-yl]methyl]-3a,4-dihydro-3H-chromeno[4,3-c][1,2]oxazole36406: In vitro binding affinity to human alpha-2C adrenergic receptorki0.0002uM
(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]oxazole238679: Binding affinity for alpha-2C adrenergic receptorki0.0002uM
5-[(1S,1aR,6aS)-1-ethyl-1a,6-dihydro-1H-cyclopropa[a]inden-6a-yl]-1H-imidazole516909: Displacement of [3H]-RX821002 from human adrenergic Alpha-2C receptor expressed in rat C6 cells after 120 mins by liquid scintillation countingki0.0002uM
(8aR,12aR,13aS)-3-methoxy-12-methylsulfonyl-5,6,8,8a,9,10,11,12a,13,13a-decahydroisoquinolino[2,1-g][1,6]naphthyridine80588: Ability to reverse inhibitory effects of UK-14304 on the contraction of guinea pig ileum as a measure of alpha-2 adrenergic receptor antagonism.kd0.0002uM
(3R,3aS)-3-[[4-[(E)-3-(4-fluorophenyl)but-2-enyl]piperazin-1-yl]methyl]-7,8-dimethoxy-3a,4-dihydro-3H-chromeno[4,3-c][1,2]oxazole36406: In vitro binding affinity to human alpha-2C adrenergic receptorki0.0003uM
2-(2,4-dichlorophenoxy)-N-[2-[2-(dimethylamino)ethoxy]-4-methylquinolin-6-yl]acetamide254838: Inhibitory concentration against alpha-2 adrenergic receptoric500.0003uM
[(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] cyclopropanecarboxylate238679: Binding affinity for alpha-2C adrenergic receptorki0.0003uM
2-[4-(5-azaspiro[2.5]octan-5-yl)-3-fluoropiperidin-1-yl]-N-[(3,5-difluoro-2-pyridinyl)methyl]-1,3-thiazole-5-carboxamide1771853: Inhibition of human alpha 2C adrenergic receptor expressed in CHO-K1 cells coexpressing Gaq and aequorin assessed as suppression of noradrenaline-induced intracellular calcium release by bioluminescence assayic500.0003uM
N-[(3,5-difluoro-2-pyridinyl)methyl]-2-[4-(8-methoxy-3,4-dihydro-1H-isoquinolin-2-yl)piperidin-1-yl]-1,3-thiazole-5-carboxamide1771853: Inhibition of human alpha 2C adrenergic receptor expressed in CHO-K1 cells coexpressing Gaq and aequorin assessed as suppression of noradrenaline-induced intracellular calcium release by bioluminescence assayic500.0003uM
(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]oxazole288096: Displacement of [3H]rawolscine from human cloned adrenergic Alpha-2C receptor transfected in CHO cellski0.0003uM
(3R)-5-chlorospiro[2,4-dihydro-1H-naphthalene-3,2’-5H-1,3-oxazole]-4’-amine2065719: Binding affinity to human alpha2C-adrenoceptorki0.0003uM
N-(4,5-dihydro-1H-imidazol-2-yl)-5-methylquinoxalin-6-amine36513: Compound was tested for concentration that produced 50% contractile response relative to maximum response to norepinephrine for Alpha-2 adrenergic receptor in rabbit vas deferensec500.0003uM
(3R,3aS)-7,8-dimethoxy-3-[[4-[(E)-3-thiophen-3-ylbut-2-enyl]piperazin-1-yl]methyl]-3a,4-dihydro-3H-chromeno[4,3-c][1,2]oxazole36406: In vitro binding affinity to human alpha-2C adrenergic receptorki0.0003uM
2-(1-naphthalen-1-ylethyl)-1H-imidazole;hydrochloride36185: Compound was evaluated for Adrenergic activity against Alpha-2 adrenergic receptor in human plateletsic500.0003uM
5-[(1S,1aR,6aS)-1-methyl-1a,6-dihydro-1H-cyclopropa[a]inden-6a-yl]-1H-imidazole516909: Displacement of [3H]-RX821002 from human adrenergic Alpha-2C receptor expressed in rat C6 cells after 120 mins by liquid scintillation countingki0.0003uM
Yohimbine2065068: Displacement of [3H]RX821,002 from human ADRA2C expressed in CHO cellski0.0003uM
2-[4-[3-[(2,2-difluorocyclopropyl)methoxy]piperidin-1-yl]piperidin-1-yl]-N-[(3,5-difluoro-2-pyridinyl)methyl]-1,3-thiazole-5-carboxamide1771853: Inhibition of human alpha 2C adrenergic receptor expressed in CHO-K1 cells coexpressing Gaq and aequorin assessed as suppression of noradrenaline-induced intracellular calcium release by bioluminescence assayic500.0004uM
N-[(3,5-difluoro-2-pyridinyl)methyl]-2-[4-(7-methyl-3,4-dihydro-1H-isoquinolin-2-yl)piperidin-1-yl]-1,3-thiazole-5-carboxamide1771853: Inhibition of human alpha 2C adrenergic receptor expressed in CHO-K1 cells coexpressing Gaq and aequorin assessed as suppression of noradrenaline-induced intracellular calcium release by bioluminescence assayic500.0004uM
3-[(6aR,9S)-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinolin-9-yl]-1,1-diethylurea2060761: Ray2010 Assay 74 from Article : “Psychedelics and the human receptorome.”ki0.0004uM
(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]oxazole36406: In vitro binding affinity to human alpha-2C adrenergic receptorki0.0004uM
(3R,3aS)-7,8-dimethoxy-3-[[4-[(E)-3-(2-methoxyphenyl)-2-methylprop-2-enyl]piperazin-1-yl]methyl]-3a,4-dihydro-3H-chromeno[4,3-c][1,2]oxazole36406: In vitro binding affinity to human alpha-2C adrenergic receptorki0.0004uM
5-[(1S,1aR,6aS)-1-propyl-1a,6-dihydro-1H-cyclopropa[a]inden-6a-yl]-1H-imidazole516909: Displacement of [3H]-RX821002 from human adrenergic Alpha-2C receptor expressed in rat C6 cells after 120 mins by liquid scintillation countingki0.0004uM
(3R,3aS)-7-cyclopentyloxy-3-[[4-[(E)-2-methyl-3-phenylprop-2-enyl]piperazin-1-yl]methyl]-3a,4-dihydro-3H-chromeno[4,3-c][1,2]oxazole238679: Binding affinity for alpha-2C adrenergic receptorki0.0005uM
[(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] prop-2-enoate238679: Binding affinity for alpha-2C adrenergic receptorki0.0005uM
[(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] pyridine-4-carboxylate238679: Binding affinity for alpha-2C adrenergic receptorki0.0005uM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
Benzo(a)pyreneaffects methylation, decreases expression, increases methylation4
Dexamethasoneincreases expression, affects cotreatment, decreases expression2
Epinephrineincreases activity, increases abundance, decreases reaction, increases expression, increases reaction (+2 more)2
Tretinoindecreases expression, increases expression2
xylometazolineaffects binding, decreases reaction1
quercitrinincreases expression1
sodium arseniteaffects cotreatment, increases abundance, increases expression1
manganese chlorideincreases abundance, increases expression, affects cotreatment1
sulindac sulfidedecreases expression1
phenethylamineaffects binding1
S-(1,2-dichlorovinyl)cysteineaffects cotreatment, decreases expression1
2-methoxyidazoxanaffects binding, decreases reaction1
fipronilaffects cotreatment, increases expression1
K 7174decreases expression1
bardoxolone methyldecreases activity1
abrineincreases expression1
bisphenol Sdecreases expression, affects cotreatment1
Sunitinibincreases expression1
Vorinostatdecreases expression1
Air Pollutantsincreases abundance, increases expression1
Arsenicaffects cotreatment, increases abundance, increases expression1
Calciumaffects binding, increases abundance, increases activity1
Clonidineaffects binding, increases activity1
DEETaffects cotreatment, increases expression1
Estradiolincreases expression1
Colforsinaffects localization, affects reaction, increases expression1
Indomethacinaffects cotreatment, decreases expression1
Lipopolysaccharidesaffects cotreatment, decreases expression1
Manganeseincreases abundance, increases expression, affects cotreatment1
Metoprololaffects cotreatment, affects response to substance1

ChEMBL screening assays

647 unique, capped per target: 503 binding, 135 functional, 7 admet, 2 unclassified

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1016579BindingDisplacement of [3H]RS79948-197 from human recombinant adrenergic Alpha-2C receptor expressed in CHO cellsAlpha2-adrenoreceptors profile modulation. 4. From antagonist to agonist behavior. — J Med Chem
CHEMBL1016580FunctionalAntagonist activity at human recombinant adrenergic Alpha-2C receptor expressed in CHO cellsAlpha2-adrenoreceptors profile modulation. 4. From antagonist to agonist behavior. — J Med Chem
CHEMBL1737952UnclassifiedPUBCHEM_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, AID182PubChem BioAssay data set

Cellosaurus cell lines

5 cell lines: 4 spontaneously immortalized cell line, 1 cancer cell line

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

CellosaurusNameCategorySex
CVCL_9113L-alpha-2C L-cellsSpontaneously immortalized cell lineMale
CVCL_H392CHO-K1/ADRA2C/Galpha15Spontaneously immortalized cell lineFemale
CVCL_KU77cAMP Hunter CHO-K1 ADRA2C GiSpontaneously immortalized cell lineFemale
CVCL_KW28PathHunter CHO-K1 ADRA2C beta-arrestinSpontaneously immortalized cell lineFemale
CVCL_KZ72PathHunter U2OS ADRA2C Total GPCR InternalizationCancer cell lineFemale

Clinical trials (associated diseases)

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

TrialPhaseStatusTitle
NCT02157038Not specifiedCOMPLETEDNeuromuscular Mechanisms Underlying Poor Recovery From Whiplash Injuries

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
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v2.0.2

Sources 81

This page pulls from 81 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgtopdb_interactiongwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot