ADRA1A

Summary

ADRA1A (adrenoceptor alpha 1A, HGNC:277) is a protein-coding gene on chromosome 8p21.2, encoding Alpha-1A adrenergic receptor (P35348). Alpha-1 adrenergic receptors are G protein-coupled receptors for catecholamines that signal through the G(q) family of G proteins, including G(q) and G(11).

Alpha-1-adrenergic receptors (alpha-1-ARs) are members of the G protein-coupled receptor superfamily. They activate mitogenic responses and regulate growth and proliferation of many cells. There are 3 alpha-1-AR subtypes: alpha-1A, -1B and -1D, all of which signal through the Gq/11 family of G-proteins and different subtypes show different patterns of activation. This gene encodes alpha-1A-adrenergic receptor. Alternative splicing of this gene generates four transcript variants, which encode four different isoforms with distinct C-termini but having similar ligand binding properties.

Source: NCBI Gene 148 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 79 total — 2 pathogenic
• Druggable target: yes — 537 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000680

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:277
Approved symbol	ADRA1A
Name	adrenoceptor alpha 1A
Location	8p21.2
Locus type	gene with protein product
Status	Approved
Aliases	ADRA1L1
Ensembl gene	ENSG00000120907
Ensembl biotype	protein_coding
OMIM	104221
Entrez	148

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 7 protein_coding, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000276393, ENST00000354550, ENST00000380572, ENST00000380573, ENST00000380582, ENST00000380586, ENST00000518621, ENST00000518810, ENST00000519096, ENST00000519229, ENST00000521711

RefSeq mRNA: 6 — MANE Select: NM_000680 NM_000680, NM_001322503, NM_001322504, NM_033302, NM_033303, NM_033304

CCDS: CCDS34869, CCDS6052, CCDS6053, CCDS6054, CCDS83269

Canonical transcript exons

ENST00000380573 — 3 exons

Exon	Start	End
ENSE00001621444	26768809	26770666
ENSE00002121442	26866936	26867278
ENSE00002122586	26864087	26865655

Expression profiles

Bgee: expression breadth ubiquitous, 171 present calls, max score 93.87.

FANTOM5 (CAGE): breadth broad, TPM avg 1.1788 / max 111.6639, expressed in 247 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92425	0.8146	196
92426	0.2337	114
92423	0.0433	13
92427	0.0383	12
92428	0.0373	13
92422	0.0116	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	93.87	gold quality
buccal mucosa cell	CL:0002336	88.43	gold quality
liver	UBERON:0002107	87.51	gold quality
right lung	UBERON:0002167	81.80	gold quality
apex of heart	UBERON:0002098	80.77	gold quality
heart left ventricle	UBERON:0002084	80.59	gold quality
cardiac ventricle	UBERON:0002082	80.35	gold quality
heart right ventricle	UBERON:0002080	79.90	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.57	gold quality
cauda epididymis	UBERON:0004360	75.57	gold quality
upper lobe of left lung	UBERON:0008952	74.03	gold quality
upper lobe of lung	UBERON:0008948	73.04	gold quality
spleen	UBERON:0002106	72.97	gold quality
omental fat pad	UBERON:0010414	72.91	gold quality
peritoneum	UBERON:0002358	72.86	gold quality
adipose tissue of abdominal region	UBERON:0007808	71.89	gold quality
mucosa of stomach	UBERON:0001199	70.91	gold quality
subcutaneous adipose tissue	UBERON:0002190	70.10	gold quality
cingulate cortex	UBERON:0003027	69.66	gold quality
prostate gland	UBERON:0002367	69.43	gold quality
anterior cingulate cortex	UBERON:0009835	69.37	gold quality
adipose tissue	UBERON:0001013	68.79	gold quality
colonic epithelium	UBERON:0000397	68.67	silver quality
popliteal artery	UBERON:0002250	68.45	gold quality
tibial artery	UBERON:0007610	68.35	gold quality
heart	UBERON:0000948	68.08	gold quality
amygdala	UBERON:0001876	67.83	gold quality
prefrontal cortex	UBERON:0000451	67.78	gold quality
connective tissue	UBERON:0002384	67.54	gold quality
corpus callosum	UBERON:0002336	67.13	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	5.18

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, SP1, TEAD1, TFAP2A

miRNA regulators (miRDB)

22 targeting ADRA1A, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-7109-5P	99.18	66.13	1057
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-876-3P	98.76	68.23	945
HSA-MIR-4303	98.01	68.13	2304
HSA-MIR-5192	96.89	63.35	879
HSA-MIR-152-5P	96.42	66.59	960

Literature-anchored findings (GeneRIF, showing 40)

• Data show thah activation of alpha(1)A- or alpha(1)B-adrenergic receptors inhibits serum-promoted cell proliferation, whereas alpha(1)D-AR activation does not show such an inhibitory effect. (PMID:12409310)
• 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)
• alpha1-ARs play a role in promoting human prostate cancer epithelial cell proliferation via transient receptor potential channels (PMID:12782672)
• These studies suggest that gC1qR interacts specifically with alpha1B- and alpha1D-, but not alpha1A-ARs, and this interaction depends on the presence of an intact C-tail. (PMID:14626446)
• Candidate gene for benign prostatic hyperplasia. (PMID:15136785)
• alpha(1A)- and alpha(1D)-adrenergic receptors mediate G(1)-S cell-cycle arrest (PMID:15297446)
• alpha1A-adrenoceptor structural computer model (PMID:15474515)
• alpha(1a)-ARs recycle rapidly by an agonist-independent, constitutive, beta-arrestin-dependent process and that this can transport “alpha-blockers” into cells carrying these receptors. (PMID:15626751)
• The N terminus of RGS2 was required for association with alpha1A-ARs and inhibition of signaling, and amino acids Lys219, Ser220, and Arg238 within the alpha1A-AR i3 loop were found to be essential for this interaction (PMID:15917235)
• Genetic variations in the ADRA1A gene are significantly associated with essential hypertension in this Chinese population. (PMID:16685204)
• mTLD interacts with alpha(1A)-AR directly, alters the subcellular localization of receptor, and influences agonist-induced alpha(1A)-AR internalization and calcium signaling. (PMID:16690783)
• Doxazosin inhibits AP2alpha activity independent of alpha(1)-adrenoceptor blockade and increases the ABCA1 expression and HDL biogenesis (PMID:17556657)
• In the proximal and medial ureter, the distribution of ARs was alpha 1d > or = alpha 1a > alpha 1b; In the distal ureter, the distribution of ARs was alpha 1d > alpha 1a > alpha 1b (PMID:17681068)
• expression in distal ureter significantly higher than in proximal and mid ureter (PMID:17973108)
• ADRA1A expression was decreased in end stage renal disease. Functional receptor changes mediated vascular hypersensitivity to phenylephrine. (PMID:18257748)
• The presence of alpha(1A)-adrenoceptors in epididymal smooth muscle and epithelial cells indicates their contribution to smooth muscle contractile responses and a possible role in the activities of the epithelium lining the epididymal duct. (PMID:18351393)
• These findings demonstrate differences in internalization between the alpha1a- and alpha1b-AR and provide evidence that the lack of significant endocytosis of the alpha1a-AR is linked to its poor interaction with beta-arrestins as well as with AP50. (PMID:18523139)
• These findings suggest that stimulation of cutaneous alpha(1)-adrenoceptors increased the excitability of heat-sensitized nociceptive afferents. (PMID:18524654)
• These data provide evidence for a potential clinical relevance for alpha(1)-AAB in hypertensive patients, and the notion of immunity as a possible cause of hypertension. (PMID:19011682)
• Arg347Cys polymorphism is associated with blood pressure phenotypes, in a large sample of Brazilians from an urban population (PMID:19105822)
• Administration of an alpha-1A-specific blocker reduced analgesic dosage and colic episodes after shock wave lithotripsy of lower ureteral stones. (PMID:19322003)
• strongest signal emerged from SNPs in the promoter region (rs3808585) and in an intron (rs17426222, rs4732682, rs573514) of ADRA1A, all located within the same haplotype block (PMID:19352218)
• Arg347Cys polymorphism of alpha1A-adrenoceptor gene is associated with blood pressure response to nifedipine GITS. (PMID:19444285)
• The localization of alpha1AAR in lipid rafts directly impacts both basal and activated receptor signaling. (PMID:19520158)
• Adrenergic receptor (alpha(1A)-AR, beta(2)-AR, and beta(3)-AR) gene polymorphisms are related to the risk of developing fibromyalgia (FM) and are also linked to different domains of the FM syndrome. (PMID:19565482)
• Genetic variations in alpha-1A and beta-2 adrenergic receptors (ADRA1A, ADRB2) have been associated with changes in smooth muscle tone in various tissues, and implicated in bronchial hyper-responsiveness, metabolic syndrome, and other disorders. (PMID:19730237)
• alpha(1A)-adrenoceptor stimulation in androgen-independent prostate cancer cells via caveolae constitutes one of the mechanisms contributing to their protection from thapsigargin-induced apoptosis (PMID:19763272)
• Our study suggests that the ADRA1A gene is involved in weight gain among schizophrenia patients treated with antipsychotics. (PMID:19918262)
• Report alpha1A and alpha1B subtypes are both present in human myocardium, but alpha1D binding is not, and the alpha1 subtypes are not downregulated in heart failure. (PMID:19919991)
• Report a new alpha(1A)AR-CMC-online-HPLC/MS method can be applied for screening active components acting on alpha(1A)AR from traditional Chinese medicines exemplified by Radix Caulophylli. (PMID:20004544)
• No association of the polmorphisms Arg492Cys (ADRA1A gene), Ser49Gly and Arg389Gly (ADRB1), Arg16Gly and Gln27Glu (ADRB2), 825C/T (GNB3), -1021C/T (DBH) and S/L (SLC6A4) with both tilt test outcomes and new syncopal episodes was found (PMID:20129829)
• This study suggests the rs1048101 single nucleotide polymorphism within the alpha1a-adrenoceptor as one risk factor for the development of CRPS I after the distal radius fracture. (PMID:20173430)
• The mRNA expression of alpha1a-AR subtypes in bladder detrusor and posterior urethra was significantly higher in the inflammation group than in controls. (PMID:21223784)
• interactions between metal ions and the alpha(1A)-adrenoceptor with affinities compatible with physiological concentrations (PMID:21262225)
• the rs17055869 SNP near the 3’ end of ADRA1A is significantly associated with metabolic syndrome and it may be involved in determining a greater level of sympathetic activation in metabolic syndrome patients (PMID:21519279)
• Study of alpha1-AR subtype expression on both human monocytes and macrophages illustrates a mechanism by which increased interleukin (IL)-1beta production can be modulated by alpha1-AR input. (PMID:21571945)
• Data suggest that the endocytic pathway is involved in alpha(1A)-AR-induced ERK1/2 activation, which is independent of G(q)/PLC/PKC signaling. (PMID:21738688)
• [review] Altered adrenergic receptor signaling following brain trauma contributes to memory dysfunction. (PMID:21792097)
• Alpha1-adrenoceptor signaling in the human prostate involves regulation of p38 mitogen-activated protein kinase (PMID:21982020)
• Presence of the Arg347 allele in the ADRA1A gene is a risk factor for occurrence of more severe metabolic abnormalities in patients with schizophrenia. (PMID:22037178)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	adra1aa	ENSDARG00000028725
mus_musculus	Adra1a	ENSMUSG00000045875
rattus_norvegicus	Adra1a	ENSRNOG00000009522
caenorhabditis_elegans	ser-5	WBGENE00008890

Paralogs (18): ADRB1 (ENSG00000043591), DRD2 (ENSG00000149295), ADRA2A (ENSG00000150594), GPR101 (ENSG00000165370), ADRB2 (ENSG00000169252), ADRA1B (ENSG00000170214), ADRA1D (ENSG00000171873), OR5T3 (ENSG00000172489), OR56A1 (ENSG00000180934), OR5T1 (ENSG00000181698), OR5T2 (ENSG00000181718), OR56A4 (ENSG00000183389), ADRA2C (ENSG00000184160), OR56A3 (ENSG00000184478), OR13F1 (ENSG00000186881), OR56A5 (ENSG00000188691), ADRB3 (ENSG00000188778), ADRA2B (ENSG00000274286)

Protein

Protein identifiers

Alpha-1A adrenergic receptor — P35348 (reviewed: P35348)

Alternative names: Alpha-1A adrenoreceptor, Alpha-1C adrenergic receptor, Alpha-adrenergic receptor 1c

All UniProt accessions (3): B0ZBD3, E7EW16, P35348

UniProt curated annotations — full annotation on UniProt →

Function. Alpha-1 adrenergic receptors are G protein-coupled receptors for catecholamines that signal through the G(q) family of G proteins, including G(q) and G(11). Upon activation, they stimulate the phosphatidylinositol-calcium second messenger pathway, leading to calcium release from intracellular stores and activation of protein kinase C. ADRA1A binds the catecholamine ligands norepinephrine and epinephrine. Can also couple to G(14) protein. Nuclear ADRA1A forms heterooligomers with ADRA1B to regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes. At the plasma membrane, ADRA1A interacts with CAVIN4/MURC to regulates ERK activation in cardiomyocytes, contributing to the regulation of cardiac hypertrophy. Additionally, functions as a vasopressor in resistance arteries and plays a role in maintaining normal arterial blood pressure.

Subunit / interactions. Homo- and heterooligomer. Heterooligomerizes with ADRA1B homooligomers in cardiac myocytes. Interacts with CAVIN4.

Subcellular location. Nucleus membrane. Cell membrane. Cytoplasm. Membrane. Caveola.

Tissue specificity. Expressed in heart, brain, liver and prostate, but not in kidney, lung, adrenal, aorta and pituitary. Within the prostate, expressed in the apex, base, periurethral and lateral lobe. Isoform 4 is the most abundant isoform expressed in the prostate with high levels also detected in liver and heart.

Post-translational modifications. C-terminal Ser or Thr residues may be phosphorylated.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRA1A sub-subfamily.

Isoforms (9)

UniProt ID	Names	Canonical?
P35348-1	1, Alpha 1c-1, Alpha(1A-1)	yes
P35348-2	2, Alpha 1c-2, Alpha(1A-2)
P35348-3	3, Alpha 1c-3, Alpha(1A-3)
P35348-4	4, Alpha(1A-4)
P35348-5	5
P35348-6	6
P35348-7	7, 2b/3b
P35348-8	8, 2c
P35348-9	9, 3c

RefSeq proteins (6): NP_000671, NP_001309432, NP_001309433, NP_150645, NP_150646, NP_150647 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR001004	ADRA1A_rcpt	Family
IPR002233	ADR_fam	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (79 total): sequence conflict 14, helix 13, splice variant 12, topological domain 8, transmembrane region 7, sequence variant 5, mutagenesis site 5, glycosylation site 3, turn 3, binding site 2, strand 2, chain 1, short sequence motif 1, modified residue 1, lipid moiety-binding region 1, disulfide bond 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
8THK	ELECTRON MICROSCOPY	2.6
8HN1	ELECTRON MICROSCOPY	2.9
7YM8	ELECTRON MICROSCOPY	2.92
9M4Q	ELECTRON MICROSCOPY	2.99
8THL	ELECTRON MICROSCOPY	3.1
9M4T	ELECTRON MICROSCOPY	3.19
9IQV	ELECTRON MICROSCOPY	3.3
7YMJ	ELECTRON MICROSCOPY	3.35
7YMH	ELECTRON MICROSCOPY	3.52

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35348-F1	70.73	0.44

Antibody-complex structures (SAbDab): 6 — 7YM8, 7YMH, 7YMJ, 8HN1, 8THK, 8THL

Functional residue map

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

Ligand- & substrate-binding residues (2): 106; 188

Post-translational modifications (2): 215, 345

Disulfide bonds (1): 99–176

Glycosylation sites (3): 7, 13, 22

Mutagenesis-validated functional residues (5):

Position	Phenotype
334	abolishes targeting to the nuclear membrane of cardiac myocytes; when associated with a-335; a-342; a-348 and a-349.
335	abolishes targeting to the nuclear membrane of cardiac myocytes; when associated with a-334; a-342; a-348 and a-349.
342	abolishes targeting to the nuclear membrane of cardiac myocytes; when associated with a-334; a-335; a-348 and a-349.
348	abolishes targeting to the nuclear membrane of cardiac myocytes; when associated with a-334; a-335; a-342 and a-349.
349	abolishes targeting to the nuclear membrane of cardiac myocytes; when associated with a-334; a-335; a-342 and a-348.

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-390696	Adrenoceptors
R-HSA-416476	G alpha (q) signalling events
R-HSA-416482	G alpha (12/13) signalling events
R-HSA-162582	Signal Transduction
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-375280	Amine ligand-binding receptors
R-HSA-388396	GPCR downstream signalling
R-HSA-500792	GPCR ligand binding

MSigDB gene sets: 316 (showing top): AP1_01, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_MUSCLE_TISSUE_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_GROWTH, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_SYSTEMIC_ARTERIAL_BLOOD_PRESSURE, GOBP_REGULATION_OF_SMOOTH_MUSCLE_CONTRACTION, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_POSITIVE_REGULATION_OF_ACTION_POTENTIAL, MEF2_02, CHX10_01, GOBP_REFLEX

GO Biological Process (37): MAPK cascade (GO:0000165), negative regulation of heart rate involved in baroreceptor response to increased systemic arterial blood pressure (GO:0001985), norepinephrine-epinephrine vasoconstriction involved in regulation of systemic arterial blood pressure (GO:0001994), positive regulation of heart rate by epinephrine-norepinephrine (GO:0001996), positive regulation of the force of heart contraction by epinephrine-norepinephrine (GO:0001997), apoptotic process (GO:0006915), smooth muscle contraction (GO:0006939), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), positive regulation of cytosolic calcium ion concentration (GO:0007204), cell-cell signaling (GO:0007267), adult heart development (GO:0007512), negative regulation of cell population proliferation (GO:0008285), response to xenobiotic stimulus (GO:0009410), response to hormone (GO:0009725), negative regulation of autophagy (GO:0010507), positive regulation of cardiac muscle hypertrophy (GO:0010613), positive regulation of synaptic transmission, GABAergic (GO:0032230), intracellular signal transduction (GO:0035556), positive regulation of MAPK cascade (GO:0043410), positive regulation of action potential (GO:0045760), positive regulation of vasoconstriction (GO:0045907), positive regulation of smooth muscle contraction (GO:0045987), positive regulation of cardiac muscle contraction (GO:0060452), cell growth involved in cardiac muscle cell development (GO:0061049), positive regulation of ERK1 and ERK2 cascade (GO:0070374), adenylate cyclase-activating adrenergic receptor signaling pathway (GO:0071880), phospholipase C-activating adrenergic receptor signaling pathway (GO:0071882), pilomotor reflex (GO:0097195), neuron-glial cell signaling (GO:0150099), regulation of muscle contraction (GO:0006937), regulation of blood pressure (GO:0008217), regulation of vasoconstriction (GO:0019229), organ growth (GO:0035265), regulation of cardiac muscle contraction (GO:0055117), adrenergic receptor signaling pathway (GO:0071875)

GO Molecular Function (5): alpha1-adrenergic receptor activity (GO:0004937), protein heterodimerization activity (GO:0046982), G protein-coupled receptor activity (GO:0004930), adrenergic receptor activity (GO:0004935), protein binding (GO:0005515)

GO Cellular Component (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), caveola (GO:0005901), nuclear membrane (GO:0031965), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-6 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
positive regulation of blood pressure by epinephrine-norepinephrine	3
cell communication	2
signaling	2
signal transduction	2
G protein-coupled receptor signaling pathway	2
response to chemical	2
intracellular anatomical structure	2
intracellular signaling cassette	1
baroreceptor response to increased systemic arterial blood pressure	1
negative regulation of heart rate	1
vasoconstriction	1
positive regulation of heart rate	1
positive regulation of the force of heart contraction by chemical signal	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
muscle contraction	1
cellular process	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
phospholipase C activator activity	1
regulation of biological quality	1
heart development	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
response to endogenous stimulus	1
autophagy	1
negative regulation of catabolic process	1
regulation of autophagy	1
cardiac muscle hypertrophy	1
regulation of cardiac muscle hypertrophy	1
positive regulation of muscle hypertrophy	1
regulation of synaptic transmission, GABAergic	1
positive regulation of synaptic transmission	1
synaptic transmission, GABAergic	1
alpha-adrenergic receptor activity	1
protein dimerization activity	1

Protein interactions and networks

STRING

1270 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADRA1A	GNAQ	P50148	869
ADRA1A	GNA11	P29992	682
ADRA1A	GNA12	Q03113	673
ADRA1A	GNA13	Q14344	664
ADRA1A	ARHGEF12	Q9NZN5	664
ADRA1A	ARRB2	P32121	642
ADRA1A	GRIK1	P39086	581
ADRA1A	NAPA	P54920	572
ADRA1A	AVPR1A	P37288	571
ADRA1A	AGT	P01019	559
ADRA1A	RGS2	P41220	525
ADRA1A	SLC6A2	P23975	524
ADRA1A	ACKR3	P25106	517
ADRA1A	HCLS1	P14317	513
ADRA1A	SUCLG1	P53597	513

IntAct

48 interactions, top by confidence:

A	B	Type	Score
ADRA1A	CXCR4	psi-mi:“MI:2364”(proximity)	0.610
CXCR4	ADRA1A	psi-mi:“MI:2364”(proximity)	0.610
CXCR4	ADRA1A	psi-mi:“MI:0914”(association)	0.610
ADRA1A	CLTC	psi-mi:“MI:0915”(physical association)	0.460
ADRA1A	CLTA	psi-mi:“MI:0915”(physical association)	0.460
ADRA1A	CLTB	psi-mi:“MI:0915”(physical association)	0.460
ADRA1A	CLTC	psi-mi:“MI:0403”(colocalization)	0.460
ADRA1A	CLTA	psi-mi:“MI:0403”(colocalization)	0.460
ADRA1A	CLTB	psi-mi:“MI:0403”(colocalization)	0.460
ACKR3	ADRA1A	psi-mi:“MI:2364”(proximity)	0.420
ACKR3	ADRA2B	psi-mi:“MI:0914”(association)	0.420
ACKR3		psi-mi:“MI:2364”(proximity)	0.410
ADRA1A	Arrb1	psi-mi:“MI:0915”(physical association)	0.400
ADRA1A	VIM	psi-mi:“MI:0915”(physical association)	0.400
ADRA1A	ADRA1A	psi-mi:“MI:0915”(physical association)	0.400
ADRA1B	ADRA1A	psi-mi:“MI:0915”(physical association)	0.400
ATP6AP2	ADRA1A	psi-mi:“MI:0915”(physical association)	0.370
CD81	ADRA1A	psi-mi:“MI:0915”(physical association)	0.370
TMEM234	ADRA1A	psi-mi:“MI:0915”(physical association)	0.370
FAM241B	ADRA1A	psi-mi:“MI:0915”(physical association)	0.370
FAM50B	ADRA1A	psi-mi:“MI:0915”(physical association)	0.370
ADGRA3	ADRA1A	psi-mi:“MI:0915”(physical association)	0.370
GPR37	ADRA1A	psi-mi:“MI:0915”(physical association)	0.370
GDE1	ADRA1A	psi-mi:“MI:0915”(physical association)	0.370
HHATL	ADRA1A	psi-mi:“MI:0915”(physical association)	0.370
KLHL22	ADRA1A	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (29): ADRA1A (FRET), ADRA1B (FRET), ADRA1B (Affinity Capture-Western), ADRA1A (Affinity Capture-MS), RAB31 (Proximity Label-MS), ADRA1A (Proximity Label-MS), ATP6AP2 (Two-hybrid), CD81 (Two-hybrid), TMEM234 (Two-hybrid), C10orf35 (Two-hybrid), FAM50B (Two-hybrid), GPR125 (Two-hybrid), GPR37 (Two-hybrid), GDE1 (Two-hybrid), HHATL (Two-hybrid)

ESM2 similar proteins: B2RPY5, B3DM66, O02824, O73810, O77680, P14416, P15823, P18130, P18841, P18901, P19020, P20288, P21728, P21918, P25115, P30728, P31389, P35348, P35367, P35368, P41596, P42288, P42290, P42291, P43140, P50130, P52702, P53452, P53453, P53454, P60026, P61168, P61169, P97717, P97718, Q16950, Q18775, Q19084, Q24563, Q2YDN1

Diamond homologs: A0A4W3GG95, A0A6I8PUB9, A6QLE7, A6QNL7, B5X337, D4A7K7, E7FEL0, E9QJ73, O00254, O02666, O02824, O46685, O55197, O73810, O77408, O77621, O89039, O93361, P11613, P18130, P20288, P21556, P25105, P25106, P28566, P32246, P32249, P32250, P34996, P35346, P35348, P35351, P35366, P35374, P35383, P35411, P41231, P43140, P43657, P46002

SIGNOR signaling

21 interactions.

A	Effect	B	Mechanism
8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione	down-regulates	ADRA1A	“chemical inhibition”
silodosin	down-regulates	ADRA1A	“chemical inhibition”
ADRA1A	“up-regulates activity”	GNAS	binding
ADRA1A	“up-regulates activity”	GNAL	binding
ADRA1A	“up-regulates activity”	GNAQ	binding
ADRA1A	“up-regulates activity”	GNA14	binding
ADRA1A	“up-regulates activity”	GNA13	binding
(R)-noradrenaline	“up-regulates activity”	ADRA1A	“chemical activation”
terazosin	“down-regulates activity”	ADRA1A	“chemical inhibition”
phentolamine	“down-regulates activity”	ADRA1A	“chemical inhibition”
silodosin	“down-regulates activity”	ADRA1A	“chemical inhibition”
(S)-adrenaline	“up-regulates activity”	ADRA1A	“chemical activation”
methoxamine	“up-regulates activity”	ADRA1A	“chemical activation”
(R)-adrenaline	“up-regulates activity”	ADRA1A	“chemical activation”
oxymetazoline	“up-regulates activity”	ADRA1A	“chemical activation”
“(4S)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid O5-[3-(4,4-diphenyl-1-piperidinyl)propyl] ester O3-methyl ester”	“down-regulates activity”	ADRA1A	“chemical inhibition”
N-(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)-2-(2,6-dimethoxyphenoxy)ethanamine	“down-regulates activity”	ADRA1A	“chemical inhibition”
prazosin	“down-regulates activity”	ADRA1A	“chemical inhibition”
tamsulosin	“down-regulates activity”	ADRA1A	“chemical inhibition”
ADRA1A	“up-regulates activity”	GNA11	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	68
Likely benign	1
Benign	5

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
149021	GRCh38/hg38 8p21.2-12(chr8:25171103-31750600)x1	Pathogenic
395721	GRCh37/hg19 8p21.2-12(chr8:24514488-34808438)	Pathogenic

SpliceAI

595 predictions. Top by Δscore:

Variant	Effect	Δscore
8:26772402:T:TA	donor_gain	0.9900
8:26864080:GACTT:G	donor_loss	0.9900
8:26864081:ACTT:A	donor_loss	0.9900
8:26864082:CTTAC:C	donor_loss	0.9900
8:26864083:TTACC:T	donor_loss	0.9900
8:26864084:T:TG	donor_loss	0.9900
8:26864085:A:AC	donor_gain	0.9900
8:26864085:A:AG	donor_loss	0.9900
8:26864086:C:CC	donor_gain	0.9900
8:26864086:C:T	donor_loss	0.9900
8:26770663:GACC:G	acceptor_gain	0.9800
8:26770665:CC:C	acceptor_gain	0.9800
8:26770666:CC:C	acceptor_gain	0.9800
8:26770667:C:CC	acceptor_gain	0.9800
8:26772392:T:A	donor_gain	0.9800
8:26772396:TCC:T	donor_gain	0.9800
8:26770664:ACCC:A	acceptor_loss	0.9700
8:26770666:CCTGG:C	acceptor_loss	0.9700
8:26770668:T:A	acceptor_loss	0.9700
8:26864086:CCAAT:C	donor_gain	0.9700
8:26864086:CCA:C	donor_gain	0.9600
8:26770662:AGACC:A	acceptor_gain	0.9500
8:26864086:CCAA:C	donor_gain	0.9500
8:26772395:TTCC:T	donor_gain	0.9400
8:26856120:T:C	acceptor_gain	0.9400
8:26772397:C:CT	donor_gain	0.9300
8:26794302:C:CT	acceptor_gain	0.9300
8:26770667:C:T	acceptor_gain	0.9200
8:26770664:ACC:A	acceptor_gain	0.9100
8:26770665:CCC:C	acceptor_gain	0.9100

AlphaMissense

3033 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:26864117:A:G	W285R	0.999
8:26864117:A:T	W285R	0.999
8:26864127:G:C	F281L	0.999
8:26864127:G:T	F281L	0.999
8:26864129:A:G	F281L	0.999
8:26864158:G:T	A271D	0.999
8:26864159:C:G	A271P	0.999
8:26864391:G:C	F193L	0.999
8:26864391:G:T	F193L	0.999
8:26864393:A:G	F193L	0.999
8:26864443:C:G	C176S	0.999
8:26864444:A:T	C176S	0.999
8:26864599:C:G	R124P	0.999
8:26864694:C:A	W92C	0.999
8:26864694:C:G	W92C	0.999
8:26770576:A:T	I325K	0.998
8:26770584:G:C	N322K	0.998
8:26770584:G:T	N322K	0.998
8:26770593:G:C	S319R	0.998
8:26770593:G:T	S319R	0.998
8:26770595:T:G	S319R	0.998
8:26770596:G:C	N318K	0.998
8:26770596:G:T	N318K	0.998
8:26770606:C:T	G315E	0.998
8:26770607:C:G	G315R	0.998
8:26770607:C:T	G315R	0.998
8:26770613:A:G	W313R	0.998
8:26770613:A:T	W313R	0.998
8:26864103:G:C	F289L	0.998
8:26864103:G:T	F289L	0.998

dbSNP variants (sampled 300 via entrez): RS1000011190 (8:26787139 G>A), RS1000025875 (8:26842591 A>G), RS1000031923 (8:26768756 T>G), RS1000072785 (8:26856035 A>G), RS1000097719 (8:26754856 T>A), RS1000105944 (8:26830343 T>C), RS1000119854 (8:26812400 T>C), RS1000173994 (8:26800619 C>G), RS1000208346 (8:26845220 A>G), RS1000225200 (8:26838690 C>A), RS1000231771 (8:26784577 G>A,C), RS1000234395 (8:26823229 C>G,T), RS1000237065 (8:26773920 T>A), RS1000271088 (8:26806124 C>A), RS1000314193 (8:26757611 A>G)

Disease associations

OMIM: gene MIM:104221 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001651_58	Response to amphetamines	7.000000e-06
GCST006190_46	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	2.000000e-07
GCST006193_29	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	3.000000e-09
GCST006193_69	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	2.000000e-06
GCST006195_59	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	4.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0006527	smoking status measurement
EFO:0006335	systolic blood pressure

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (6): CHEMBL2094251 (PROTEIN FAMILY), CHEMBL2095203 (PROTEIN FAMILY), CHEMBL2096676 (SELECTIVITY GROUP), CHEMBL2111467 (SELECTIVITY GROUP), CHEMBL229 (SINGLE PROTEIN), CHEMBL2331074 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

537 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 798,827 (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
CHEMBL1112	ARIPIPRAZOLE	4	24,205
CHEMBL12713	SERTINDOLE	4	8,984
CHEMBL134	CLONIDINE	4	97,993
CHEMBL1437	NOREPINEPHRINE	4	108,675
CHEMBL17157	TERFENADINE	4	25,393
CHEMBL1729	CISAPRIDE	4	14,365
CHEMBL1732	DIHYDROERGOTAMINE	4	12,897
CHEMBL2	PRAZOSIN	4	31,107
CHEMBL24	ATENOLOL	4	48,715
CHEMBL279516	INDORAMIN	4	6,216
CHEMBL305660	EBASTINE	4	10,024
CHEMBL3187365	ASENAPINE	4	143
CHEMBL42	CLOZAPINE	4	37,581
CHEMBL429	LABETALOL	4	23,037
CHEMBL434	ISOPROTERENOL	4	40,234
CHEMBL439849	VILAZODONE	4	1,555
CHEMBL49	BUSPIRONE	4	23,063
CHEMBL54	HALOPERIDOL	4	60,883
CHEMBL588	FENOLDOPAM	4	6,729
CHEMBL59	DOPAMINE	4	217,028
CHEMBL597	PHENTOLAMINE	4
CHEMBL611	TERAZOSIN	4
CHEMBL647	APRACLONIDINE	4
CHEMBL707	DOXAZOSIN	4
CHEMBL708	ZIPRASIDONE	4
CHEMBL709	ALFUZOSIN	4
CHEMBL715	OLANZAPINE	4
CHEMBL716	QUETIAPINE	4
CHEMBL770	TOLAZOLINE	4
CHEMBL836	TAMSULOSIN	4

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Adrenoceptors

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

Ligand	Action	Affinity	Parameter
tamsulosin	Antagonist	10.7	pKi
silodosin	Antagonist	10.4	pKi
NAN 190	Antagonist	10.1	pKi
MT-1207	Antagonist	10.0	pIC50
S(+)-niguldipine	Antagonist	9.9	pKi
[125I]HEAT (BE2254)	Antagonist	9.9	pKd
prazosin	Inverse agonist	9.9	pKi
WB 4101	Antagonist	9.8	pKi
SNAP5089	Antagonist	9.7	pKi
upidosin	Antagonist	9.6	pKi
RS-100329	Antagonist	9.6	pKi
oxymetazoline	Full agonist	9.3	pEC50
RS-17053	Antagonist	9.3	pKi
ρ-Da1a	Antagonist	9.3	pKi
doxazosin	Antagonist	9.3	pKi
5-methylurapidil	Antagonist	9.2	pKi
(-)-adrenaline	Full agonist	9.1	pEC50
[3H]prazosin	Inverse agonist	9.1	pKd
(+)-cyclazosin	Antagonist	8.9	pKi
Ro-70-0004	Antagonist	8.9	pKi
BODIPY FL-prazosin	Inverse agonist	8.7	pKi
risperidone	Antagonist	8.7	pKi
HEAT (BE2254)	Antagonist	8.6	pKi
A-119637	Antagonist	8.6	pKi
(-)-noradrenaline	Full agonist	8.6	pEC50

Binding affinities (BindingDB)

121 measured of 160 human assays (187 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
5-[(2R)-2-{[2-(2-ethoxyphenoxy)ethyl]amino}propyl]-2-methoxybenzenesulfonamide	KI	0.029 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_60147	KI	0.19 nM
(S,S)-reboxetine	KI	0.3 nM
(2S,4aR,6aR,7R,9S,10aS,10bR)-9-(acetyloxy)-2-(furan-3-yl)dodecahydro-6a,10b-dimethyl-4,10-dioxo-2H-naphtho-[2,1-c]pyran-7-carboxylic acid methyl ester	EC50	0.3 nM
Urapidil-5-methyl	KI	0.35 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
RS-17053	KI	0.6 nM
Rec 27/0074	KI	0.89 nM
3-(3-{4-[4-Fluoro-2-(2,2,2-trifluoro-ethoxy)-phenyl]-piperazin-1-yl}-propyl)-5-methyl-1H-pyrimidine-2,4-dione	KI	1 nM
Rec 27/0224	KI	1.05 nM
NSC_16041629	KI	1.7 nM
6,7-dimethoxy-2-[4-(tetrahydrofuran-2-ylcarbonyl)piperazin-1-yl]quinazolin-4-amine	KI	1.82 nM
5-[2-(4-Benzo[d]isothiazol-3-yl-piperazin-1-yl)-ethyl]-6-chloro-1,3-dihydro-indol-2-one	KI	1.9 nM
Permax	KI	1.91 nM
4-[4-(4-Chloro-phenyl)-4-hydroxy-piperidin-1-yl]-1-(4-fluoro-phenyl)-butan-1-one;propionate(HCl)	KI	2.92 nM
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
CHEMBL1907861	KI	3 nM
N-{3-[(4-amino-6,7-dimethoxyquinazolin-2-yl)(methyl)amino]propyl}tetrahydrofuran-2-carboxamide	KI	3.16 nM
UK 33,274	KI	3.16 nM
Terguride	KI	3.47 nM
CAS_16041092	KI	3.6 nM
S18616	KI	3.98 nM
2-methyl-4-(4-methylpiperazin-1-yl)-10H-thieno[2,3-b][1,5]benzodiazepine	KI	4 nM
[6-[(2,6-difluorophenyl)methyl-methylamino]-3-pyridinyl]-[4-[(3R)-3-methylpiperidin-1-yl]piperidin-1-yl]methanone	IC50	4.5 nM	US-9624199: Substituted bipiperidinyl derivatives
NSC_16041630	KI	5.3 nM
CHEMBL78986	KI	6.7 nM
[4-(3,4-Dihydroisoquinolin-2(1H)-yl)piperidin-1-yl][6-(morpholin-4-yl)pyridin-3-yl]methanone	IC50	9 nM	US-9624198: Substituted piperidinyltetrahydroquinolines
8-Chloro-11-(4-methyl-piperazin-1-yl)-5H-dibenzo[b,e][1,4]diazepine(Clopazine)	KI	9.6 nM	US-8598119: Methods and compositions for sleep disorders and other disorders
[4-(6-Methoxy-3,4-dihydroisoquinolin-2(1H)-yl)piperidin-1-yl][6-(3-methoxypyrrolidin-1-yl)pyridin-3-yl]methanone	IC50	11 nM	US-9624198: Substituted piperidinyltetrahydroquinolines
[4-(3,4-Dihydroisoquinolin-2(1H)-yl)piperidin-1-yl][6-(2-oxa-6-azaspiro[3.3]hept-6-yl)pyridin-3-yl]methanone	IC50	11 nM	US-9624198: Substituted piperidinyltetrahydroquinolines
[4-(3,4-dihydro-1H-isoquinolin-2-yl)piperidin-1-yl]-[6-(2,6-dimethylmorpholin-4-yl)-3-pyridinyl]methanone	IC50	11 nM	US-9624198: Substituted piperidinyltetrahydroquinolines
[6-[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]-3-pyridinyl]-[4-[(3R)-3-methylpiperidin-1-yl]piperidin-1-yl]methanone	IC50	11 nM	US-9624199: Substituted bipiperidinyl derivatives
CAS_16041091	KI	11 nM
NSC_16041263	KI	11 nM
[6-(3-methoxypyrrolidin-1-yl)-3-pyridinyl]-[4-[(3R)-3-methylpiperidin-1-yl]piperidin-1-yl]methanone	IC50	12 nM	US-9624199: Substituted bipiperidinyl derivatives
Bromocriptine+ (GTP+)	KI	12.9 nM
[4-(7-Fluoro-3,4-dihydroisoquinolin-2(1H)-yl)piperidin-1-yl]{6-[(2-methoxyethyl)amino]pyridin-3-yl}methanone	IC50	13 nM	US-9624198: Substituted piperidinyltetrahydroquinolines
[4-[3-(cyclopropylmethoxy)piperidin-1-yl]piperidin-1-yl]-(6-morpholin-4-yl-3-pyridinyl)methanone	IC50	13 nM	US-9624199: Substituted bipiperidinyl derivatives
[4-[3-(cyclopropylmethoxy)piperidin-1-yl]piperidin-1-yl]-(2-morpholin-4-ylpyrimidin-5-yl)methanone	IC50	14 nM	US-9624199: Substituted bipiperidinyl derivatives
NSC_16041628	KI	14 nM
[6-(1-methoxybutan-2-ylamino)-3-pyridinyl]-[4-[(3R)-3-methylpiperidin-1-yl]piperidin-1-yl]methanone	IC50	16 nM	US-9624199: Substituted bipiperidinyl derivatives
CHEMBL1907669	KI	17 nM
[6-(4,4-difluoropiperidin-1-yl)-3-pyridinyl]-[4-[(3R)-3-methylpiperidin-1-yl]piperidin-1-yl]methanone	IC50	18 nM	US-9624199: Substituted bipiperidinyl derivatives
[6-[[(2S)-1-hydroxybutan-2-yl]amino]-3-pyridinyl]-[4-[(3R)-3-methylpiperidin-1-yl]piperidin-1-yl]methanone	IC50	18 nM	US-9624199: Substituted bipiperidinyl derivatives
[2-(4,4-difluoropiperidin-1-yl)pyrimidin-5-yl]-[4-[(3R)-3-methylpiperidin-1-yl]piperidin-1-yl]methanone	IC50	19 nM	US-9624199: Substituted bipiperidinyl derivatives
NSC_54746	KI	19.9 nM

ChEMBL bioactivities

3392 potent at pChembl≥5 of 3643 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	Ki	0.01	nM	CHEMBL145843
10.70	Ki	0.02	nM	MAZAPERTINE
10.70	Ki	0.02	nM	CHEMBL145547
10.54	Ki	0.029	nM	TAMSULOSIN
10.44	Ki	0.036	nM	SILODOSIN
10.40	Kd	0.03981	nM	TAMSULOSIN
10.40	Ki	0.04	nM	PRAZOSIN
10.40	Ki	0.03981	nM	SILODOSIN
10.40	Ki	0.04	nM	ABANOQUIL
10.40	Ki	0.03981	nM	CHEMBL292189
10.30	Ki	0.05012	nM	CHEMBL42472
10.30	Ki	0.05012	nM	CHEMBL2234441
10.30	Ki	0.05	nM	CHEMBL2234441
10.30	Ki	0.05012	nM	TAMSULOSIN
10.30	Ki	0.05	nM	CHEMBL341849
10.27	Ki	0.054	nM	PRAZOSIN
10.24	Ki	0.057	nM	CHEMBL309518
10.22	Ki	0.06	nM	CHEMBL144933
10.22	Ki	0.06	nM	CHEMBL145894
10.20	Ki	0.063	nM	PRAZOSIN
10.20	Ki	0.0631	nM	CHEMBL56863
10.19	Ki	0.064	nM	CHEMBL83340
10.17	Ki	0.068	nM	CHEMBL90086
10.15	EC50	0.07	nM	TAMSULOSIN
10.15	Ki	0.07	nM	CHEMBL94188
10.11	Ki	0.077	nM	CHEMBL313990
10.10	Ki	0.08	nM	CHEMBL2234443
10.10	Ki	0.08	nM	CHEMBL145190
10.08	Ki	0.084	nM	CHEMBL83272
10.05	Ki	0.08913	nM	CHEMBL43905
10.05	Ki	0.08913	nM	CHEMBL2234443
10.03	Ki	0.094	nM	CHEMBL338029
10.00	Ki	0.1	nM	CHEMBL145411
10.00	Ki	0.1	nM	CHEMBL196961
10.00	Ki	0.1	nM	CHEMBL198462
10.00	Ki	0.1	nM	CHEMBL196958
10.00	Ki	0.1	nM	CHEMBL142743
10.00	Ki	0.1	nM	CHEMBL298713
10.00	Ki	0.1	nM	CHEMBL142981
10.00	Ki	0.1	nM	CHEMBL142929
10.00	Ki	0.099	nM	CHEMBL81006
10.00	Ki	0.1	nM	CHEMBL146654
10.00	Ki	0.1	nM	CHEMBL142236
10.00	Ki	0.1	nM	CHEMBL145072
10.00	Ki	0.1	nM	CHEMBL142251
10.00	Ki	0.1	nM	CHEMBL445577
10.00	Ki	0.1	nM	CHEMBL145190
10.00	Ki	0.1	nM	CHEMBL141322
9.96	EC50	0.1096	nM	CHEMBL72441
9.96	Ki	0.11	nM	CHEMBL304591

PubChem BioAssay actives

1937 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
methyl 4-(3,4-difluorophenyl)-6-methyl-3-[3-[4-(2-nitrophenyl)piperazin-1-yl]propylcarbamoyl]-2-oxo-1,4-dihydropyrimidine-5-carboxylate	36612: In vitro binding affinity against Alpha-1A adrenergic receptor of human liver microsomes.	ki	<0.0001	uM
methyl 4-(3,4-difluorophenyl)-6-methyl-3-[3-[(2S)-2-methyl-4-(2-nitrophenyl)piperazin-1-yl]propylcarbamoyl]-2-oxo-1,4-dihydropyrimidine-5-carboxylate	36612: In vitro binding affinity against Alpha-1A adrenergic receptor of human liver microsomes.	ki	<0.0001	uM
Tamsulosin	36126: Activity against Alpha-1 adrenergic receptor subtypes of human prostate tissue	kd	<0.0001	uM
2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-6,7-dimethoxyquinolin-4-amine	36618: Binding affinity against Alpha-1A adrenergic receptor from human clone	ki	<0.0001	uM
5,6-dimethyl-3-[3-[4-[2-(2,2,2-trifluoroethoxy)phenyl]piperazin-1-yl]propyl]-1H-pyrimidine-2,4-dione	36758: Inhibition of [3H]prazosin binding to CHO-K1 whole cells expressing human cloned Alpha-1A adrenergic receptor	ki	<0.0001	uM
methyl 4-(3,4-difluorophenyl)-2,6-dimethyl-3-[5-[4-(2-methylphenyl)-4-(4-methylphenyl)piperidin-1-yl]pentyl]-4H-pyrimidine-5-carboxylate	36476: Binding affinity against Alpha-1A adrenergic receptor (recombinant human receptor) using [3H]prazosin.	ki	0.0001	uM
methyl 4-(3,4-difluorophenyl)-3-[3-(4-methoxycarbonyl-4-phenylpiperidin-1-yl)propylcarbamoyl]-6-methyl-2-oxo-1,4-dihydropyrimidine-5-carboxylate	36610: In vitro binding affinity against Alpha-1A adrenergic receptor of human liver microsomes.	ki	0.0001	uM
methyl 4-(2,1,3-benzoxadiazol-5-yl)-3-[3-(4-methoxycarbonyl-4-phenylpiperidin-1-yl)propylcarbamoyl]-6-methyl-2-oxo-1,4-dihydropyrimidine-5-carboxylate	36610: In vitro binding affinity against Alpha-1A adrenergic receptor of human liver microsomes.	ki	0.0001	uM
(4R)-N-[3-[4-(2-cyanophenyl)piperidin-1-yl]propyl]-4-(3,4-difluorophenyl)-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	1470592: Displacement of [125I]L-762,459 from recombinant human alpha1a adrenergic receptor expressed in mammalian cells measured after 1 hr	ki	0.0001	uM
2-(4-methoxyphenyl)-1,3-dioxo-N-[3-[4-(2-propan-2-yloxyphenyl)piperazin-1-yl]propyl]isoindole-5-carboxamide	36483: Binding affinity towards cloned human alpha-1A adrenergic receptor was determined using [125]-HEAT as radioligand	ki	0.0001	uM
methyl 3-[3-(4-cyano-4-phenylpiperidin-1-yl)propylcarbamoyl]-4-(3,4-difluorophenyl)-6-(methoxymethyl)-2-oxo-1,4-dihydropyrimidine-5-carboxylate	36611: In vitro binding affinity against alpha-1A adrenergic receptor of human liver microsomes	ki	0.0001	uM
(4R)-4-(3,4-difluorophenyl)-N-[3-[4-(4-fluorophenyl)piperidin-1-yl]propyl]-1,3,6-trimethyl-2-oxo-4H-pyrimidine-5-carboxamide	1470592: Displacement of [125I]L-762,459 from recombinant human alpha1a adrenergic receptor expressed in mammalian cells measured after 1 hr	ki	0.0001	uM
methyl 4-(3,4-difluorophenyl)-3-[3-[4-(2-ethoxyphenyl)piperazin-1-yl]propylcarbamoyl]-6-methyl-2-oxo-1,4-dihydropyrimidine-5-carboxylate	36612: In vitro binding affinity against Alpha-1A adrenergic receptor of human liver microsomes.	ki	0.0001	uM
methyl 3-[3-[4-(2-carbamoylphenyl)piperazin-1-yl]propylcarbamoyl]-4-(3,4-difluorophenyl)-6-(methoxymethyl)-2-oxo-1,4-dihydropyrimidine-5-carboxylate	36612: In vitro binding affinity against Alpha-1A adrenergic receptor of human liver microsomes.	ki	0.0001	uM
methyl 4-(3,4-difluorophenyl)-6-methyl-3-[3-[4-(2-methylphenyl)-4-(4-methylphenyl)piperidin-1-yl]propylcarbamoyl]-2-oxo-1,4-dihydropyrimidine-5-carboxylate	36611: In vitro binding affinity against alpha-1A adrenergic receptor of human liver microsomes	ki	0.0001	uM
(6R)-N-[3-[4-(2-cyano-4-fluorophenyl)piperidin-1-yl]propyl]-6-(3,4-difluorophenyl)-3,4-dimethyl-2-oxo-1,6-dihydropyrimidine-5-carboxamide	36607: Evaluated for the ability to displace [125I]- HEAT from human cloned Alpha-1A adrenergic receptor stably expressed in CHO cells.	ki	0.0001	uM
3-[2-[(3aR,9bR)-6-methoxy-1,3,3a,4,5,9b-hexahydrobenzo[e]isoindol-2-yl]ethyl]-2,4-dioxo-1H-quinazoline-7-carbonitrile	36469: In vitro antagonistic activity against alpha-1A receptor in dog prostate.	kd	0.0001	uM
methyl 4-(3,4-difluorophenyl)-6-methyl-3-[3-[(2R)-2-methyl-4-(2-nitrophenyl)piperazin-1-yl]propylcarbamoyl]-2-oxo-1,4-dihydropyrimidine-5-carboxylate	36612: In vitro binding affinity against Alpha-1A adrenergic receptor of human liver microsomes.	ki	0.0001	uM
methyl 3-[3-[4-(2-cyanophenyl)piperazin-1-yl]propylcarbamoyl]-4-(3,4-difluorophenyl)-6-methyl-2-oxo-1,4-dihydropyrimidine-5-carboxylate	36612: In vitro binding affinity against Alpha-1A adrenergic receptor of human liver microsomes.	ki	0.0001	uM
methyl 4-(3,4-difluorophenyl)-3-[5-(4-methoxycarbonyl-4-phenylpiperidin-1-yl)pentyl]-6-methyl-2-oxo-1,4-dihydropyrimidine-5-carboxylate	36476: Binding affinity against Alpha-1A adrenergic receptor (recombinant human receptor) using [3H]prazosin.	ki	0.0001	uM
methyl 4-(3,4-difluorophenyl)-3-[3-[4-(2-methoxyphenyl)piperazin-1-yl]propylcarbamoyl]-6-methyl-2-oxo-1,4-dihydropyrimidine-5-carboxylate	36612: In vitro binding affinity against Alpha-1A adrenergic receptor of human liver microsomes.	ki	0.0001	uM
methyl 3-[3-[4-(2-carbamoylphenyl)piperazin-1-yl]propylcarbamoyl]-6-(methoxymethyl)-2-oxo-4-(2,4,5-trifluorophenyl)-1,4-dihydropyrimidine-5-carboxylate	36612: In vitro binding affinity against Alpha-1A adrenergic receptor of human liver microsomes.	ki	0.0001	uM
(4R)-N-[3-[4-(2-cyano-4-fluorophenyl)piperidin-1-yl]propyl]-4-(3,4-difluorophenyl)-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	1470592: Displacement of [125I]L-762,459 from recombinant human alpha1a adrenergic receptor expressed in mammalian cells measured after 1 hr	ki	0.0001	uM
(4R)-4-(3,4-difluorophenyl)-N-[3-[4-(4-fluorophenyl)piperidin-1-yl]propyl]-3,6-dimethyl-2-oxo-1,4-dihydropyrimidine-5-carboxamide	36607: Evaluated for the ability to displace [125I]- HEAT from human cloned Alpha-1A adrenergic receptor stably expressed in CHO cells.	ki	0.0001	uM
(6R)-N-[3-[4-cyano-4-(4-fluorophenyl)piperidin-1-yl]propyl]-6-(3,4-difluorophenyl)-3-methyl-2-oxo-1,6-dihydropyrimidine-5-carboxamide	36475: Ability to displace [125I]- HEAT from human cloned Alpha-1A adrenergic receptor stably expressed in CHO cells.	ki	0.0001	uM
methyl 3-[3-[4-cyano-4-(4-fluorophenyl)piperidin-1-yl]propylcarbamoyl]-4-(3,4-difluorophenyl)-6-(methoxymethyl)-2-oxo-1,4-dihydropyrimidine-5-carboxylate	36611: In vitro binding affinity against alpha-1A adrenergic receptor of human liver microsomes	ki	0.0001	uM
(4R)-N-[3-[4-(2-cyano-4-fluorophenyl)piperidin-1-yl]propyl]-4-(3,4-difluorophenyl)-6-(methoxymethyl)-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	36607: Evaluated for the ability to displace [125I]- HEAT from human cloned Alpha-1A adrenergic receptor stably expressed in CHO cells.	ki	0.0001	uM
N-(4,5-dihydro-1H-imidazol-2-ylmethyl)-5-methyl-2-methylsulfanylaniline	36133: Agonist potency at Alpha-1 adrenergic receptor assayed in rat-1 fibroblasts expressing human Alpha-1 adrenergic receptor	ec50	0.0001	uM
3-[2-[4-[3-[(3-methyl-4-oxo-2-phenylchromene-8-carbonyl)amino]propyl]piperazin-1-yl]phenoxy]propyl nitrate	36614: Inhibition of [3H]prazosin binding to cloned human Alpha-1A adrenergic receptor in CHO cells (chinese hamster ovary cells)	ki	0.0001	uM
2-(2,6-dimethoxyphenoxy)-N-[[(2S,4R)-4-phenyl-3,4-dihydro-2H-chromen-2-yl]methyl]ethanamine	36748: Affinity constant on CHO cells expressing Human recombinant Alpha-1A adrenergic receptor	ki	0.0001	uM
methyl 3-[3-[4-(2-carbamoylphenyl)piperazin-1-yl]propylcarbamoyl]-4-(2,4-difluorophenyl)-6-ethyl-2-oxo-1,4-dihydropyrimidine-5-carboxylate	36612: In vitro binding affinity against Alpha-1A adrenergic receptor of human liver microsomes.	ki	0.0001	uM
3-[4-[4-(benzotriazol-1-yl)butyl]piperazin-1-yl]-1,2-benzothiazole;hydrochloride	2128213: Displacement of [3H]prazosin from recombinant human alpha 1A adrenoceptor extracted from CHO cell membrane incubated for 60 mins by radioligand binding assay	ic50	0.0001	uM
3-[1-[4-(5-nitro-1,1,3-trioxo-1,2-benzothiazol-2-yl)butyl]piperidin-4-yl]-1,3-benzoxazol-2-one	35749: Ability to displace beta ([125I]-iodo-4-hydroxyphenyl)-ethylamino methyl tetralone from human cloned Alpha-1a adrenergic receptor stably expressed in Chinese Hamster Ovary (CHO) cells	ki	0.0001	uM
3-[1-[4-(5-methylsulfanyl-1,1,3-trioxo-1,2-benzothiazol-2-yl)butyl]piperidin-4-yl]-1,3-benzoxazol-2-one	35751: Ability to displace beta ([125I]-iodo-4-hydroxyphenyl)-ethylaminomethyl tetralone from human cloned Alpha-1a adrenergic receptor stably expressed in CHO cells	ki	0.0001	uM
3-[1-[4-(1,1,3-trioxo-1,2-benzothiazol-2-yl)butyl]piperidin-4-yl]-1,3-benzoxazol-2-one	35749: Ability to displace beta ([125I]-iodo-4-hydroxyphenyl)-ethylamino methyl tetralone from human cloned Alpha-1a adrenergic receptor stably expressed in Chinese Hamster Ovary (CHO) cells	ki	0.0001	uM
6-fluoro-3-[1-[4-(1,1,3-trioxo-1,2-benzothiazol-2-yl)butyl]piperidin-4-yl]-1,3-benzoxazol-2-one	35749: Ability to displace beta ([125I]-iodo-4-hydroxyphenyl)-ethylamino methyl tetralone from human cloned Alpha-1a adrenergic receptor stably expressed in Chinese Hamster Ovary (CHO) cells	ki	0.0001	uM
3-[1-[4-(5-methoxy-1,1,3-trioxo-1,2-benzothiazol-2-yl)butyl]piperidin-4-yl]-1,3-benzoxazol-2-one	35753: Ability to displace beta ([125I]-iodo-4-hydroxyphenyl)-ethylaminomethyl tetralone from human cloned Alpha-1a adrenergic receptor stably expressed in Chinese Hamster Ovary (CHO) cells	ki	0.0001	uM
3-[1-[4-(5-methyl-1,1,3-trioxo-1,2-benzothiazol-2-yl)butyl]piperidin-4-yl]-1,3-benzoxazol-2-one	35753: Ability to displace beta ([125I]-iodo-4-hydroxyphenyl)-ethylaminomethyl tetralone from human cloned Alpha-1a adrenergic receptor stably expressed in Chinese Hamster Ovary (CHO) cells	ki	0.0001	uM
4-[2-[4-(5-chloro-2-methoxyphenyl)piperazin-1-yl]ethyl]-11-methyl-8-thia-4,6,11-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),5-trien-3-one	257244: Inhibitory activity against Adrenergic alpha-1 receptor	ki	0.0001	uM
4-[2-[4-(2-methoxy-5-phenylphenyl)piperazin-1-yl]ethyl]-11-methyl-8-thia-4,6,11-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),5-trien-3-one	257244: Inhibitory activity against Adrenergic alpha-1 receptor	ki	0.0001	uM
2-(2,6-dimethoxyphenoxy)-N-[(4-phenyl-3,4-dihydro-2H-thiochromen-2-yl)methyl]ethanamine	36748: Affinity constant on CHO cells expressing Human recombinant Alpha-1A adrenergic receptor	ki	0.0001	uM
3-[3-[4-[2-(2,2,2-trifluoroethoxy)phenyl]piperazin-1-yl]propyl]-1H-quinazoline-2,4-dione	36758: Inhibition of [3H]prazosin binding to CHO-K1 whole cells expressing human cloned Alpha-1A adrenergic receptor	ki	0.0001	uM
(6R)-N-[3-[4-(2-cyano-4-fluorophenyl)piperidin-1-yl]propyl]-6-(3,4-difluorophenyl)-3-methyl-2-oxo-1,6-dihydropyrimidine-5-carboxamide	36607: Evaluated for the ability to displace [125I]- HEAT from human cloned Alpha-1A adrenergic receptor stably expressed in CHO cells.	ki	0.0001	uM
11-methyl-4-[2-[4-(2-propan-2-yloxyphenyl)piperazin-1-yl]ethyl]-8-thia-4,6,11-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),5-trien-3-one	257244: Inhibitory activity against Adrenergic alpha-1 receptor	ki	0.0001	uM
4-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethylamino]-2-methyl-6-phenyl-5-propanoylpyridazin-3-one	218797: Binding affinity towards human cloned alpha-1A-adrenoceptor using [3H]prazosin as radioligand	ki	0.0002	uM
4-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethylamino]-2-methyl-5-(2-methylpropanoyl)-6-phenylpyridazin-3-one	218797: Binding affinity towards human cloned alpha-1A-adrenoceptor using [3H]prazosin as radioligand	ki	0.0002	uM
methyl 1-[3-[[5-carbamoyl-4-(3,4-difluorophenyl)-6-ethyl-2-oxo-1,4-dihydropyrimidine-3-carbonyl]amino]propyl]-4-phenylpiperidine-4-carboxylate	239202: Binding constant measured against Alpha-1A adrenergic receptor in human prostate; +++:highly active	ki	0.0002	uM
(4R)-4-(3,4-difluorophenyl)-N-[3-[4-(4-fluorophenyl)piperidin-1-yl]propyl]-6-(methoxymethyl)-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	1470592: Displacement of [125I]L-762,459 from recombinant human alpha1a adrenergic receptor expressed in mammalian cells measured after 1 hr	ki	0.0002	uM
methyl 1-[3-[[5-carbamoyl-4-(2,4-difluorophenyl)-6-ethyl-2-oxo-1,4-dihydropyrimidine-3-carbonyl]amino]propyl]-4-phenylpiperidine-4-carboxylate	36610: In vitro binding affinity against Alpha-1A adrenergic receptor of human liver microsomes.	ki	0.0002	uM
methyl 4-(3,4-difluorophenyl)-6-methyl-2-oxo-3-[3-(3-oxospiro[4H-isochromene-1,4’-piperidine]-1’-yl)propylcarbamoyl]-1,4-dihydropyrimidine-5-carboxylate	36611: In vitro binding affinity against alpha-1A adrenergic receptor of human liver microsomes	ki	0.0002	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Phenylephrine	increases activity, affects reaction, affects transport, decreases activity, decreases reaction (+7 more)	8
Prazosin	affects binding, decreases reaction, decreases activity, decreases transport, increases activity	7
alfuzosin	affects binding, decreases reaction	4
Terazosin	affects binding	3
5-methylurapidil	affects binding, decreases reaction, increases abundance, increases activity, decreases activity	3
Calcium	decreases reaction, increases abundance, increases activity, affects binding	3
Epinephrine	decreases reaction, increases abundance, increases activity, affects binding	3
Oxymetazoline	affects binding, increases activity, increases abundance, decreases reaction	3
Doxazosin	affects binding	3
Tamsulosin	affects binding	2
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	2
Endosulfan	increases expression	2
Indoramin	affects binding	2
Norepinephrine	affects binding, increases activity, increases abundance, decreases reaction	2
Phentolamine	increases abundance, increases activity, affects cotreatment, increases phosphorylation, affects binding (+1 more)	2
Potassium	affects binding, affects cotreatment, affects reaction, affects transport, increases activity (+2 more)	2
Tetrachlorodibenzodioxin	decreases expression	2
methyleugenol	decreases expression	1
xylometazoline	affects binding, decreases reaction	1
(2-(2’,6’-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane	affects binding	1
arsenite	increases methylation	1
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	increases methylation	1
phenethylamine	affects binding, decreases activity	1
2-(beta-(3-iodo-4-hydroxyphenyl)ethylaminomethyl)tetralone	affects binding	1
BMY 7378	affects binding	1
niguldipine	affects binding	1
KT 5720	decreases reaction, decreases transport, increases activity	1
abanoquil	affects binding	1

ChEMBL screening assays

982 unique, capped per target: 787 binding, 179 functional, 16 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1110026	Binding	Binding affinity to human alpha1 adrenergic receptor by radioligand displacement assay	Potent dihydroquinolinone dopamine D2 partial agonist/serotonin reuptake inhibitors for the treatment of schizophrenia. — Bioorg Med Chem Lett
CHEMBL3635163	Functional	Agonist activity at adrenergic a1 receptor (unknown origin) expressed in CHO cells assessed as calcium mobilization at 3 uM	Discovery of dihydroquinazolinone derivatives as potent, selective, and CNS-penetrant M(1) and M(4) muscarinic acetylcholine receptors agonists. — Bioorg Med Chem Lett
CHEMBL4729785	ADMET	Binding affinity to alpha1 adrenergic receptor (unknown origin)	Synthesis and pharmacological evaluation of piperidine (piperazine)-amide substituted derivatives as multi-target antipsychotics. — Bioorg Med Chem Lett

Cellosaurus cell lines

8 cell lines: 4 spontaneously immortalized cell line, 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_DD01	L-alpha-1c L-cells	Spontaneously immortalized cell line	Male
CVCL_H387	CHO-K1/ADRA1A	Spontaneously immortalized cell line	Female
CVCL_KB30	GeneBLAzer ADRA1A-NFAT-bla CHO-K1	Spontaneously immortalized cell line	Female
CVCL_KU49	CHO-K1 ADRA1A Gq	Spontaneously immortalized cell line	Female
CVCL_SB79	HAP1 ADRA1A (-) 1	Cancer cell line	Male
CVCL_SB80	HAP1 ADRA1A (-) 2	Cancer cell line	Male
CVCL_YK26	U2OS ADRA1A DAG-Nomad	Cancer cell line	Female
CVCL_YK27	U2OS ADRA1A HiTSeeker	Cancer cell line	Female

Clinical trials (associated diseases)

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