ADRA1D

Summary

ADRA1D (adrenoceptor alpha 1D, HGNC:280) is a protein-coding gene on chromosome 20p13, encoding Alpha-1D adrenergic receptor (P25100). 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-1D-adrenergic receptor. Similar to alpha-1B-adrenergic receptor gene, this gene comprises 2 exons and a single intron that interrupts the coding region.

Source: NCBI Gene 146 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 120 total
• Druggable target: yes — 125 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000678

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:280
Approved symbol	ADRA1D
Name	adrenoceptor alpha 1D
Location	20p13
Locus type	gene with protein product
Status	Approved
Aliases	ADRA1R, ADRA1A, ADRA1
Ensembl gene	ENSG00000171873
Ensembl biotype	protein_coding
OMIM	104219
Entrez	146

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000379453, ENST00000621688

RefSeq mRNA: 1 — MANE Select: NM_000678 NM_000678

CCDS: CCDS13079

Canonical transcript exons

ENST00000379453 — 2 exons

Exon	Start	End
ENSE00001481103	4220630	4222130
ENSE00001481114	4247847	4249287

Expression profiles

Bgee: expression breadth ubiquitous, 155 present calls, max score 83.71.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0093 / max 123.6952, expressed in 311 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
186193	1.0093	311

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.71	gold quality
endometrium epithelium	UBERON:0004811	74.81	gold quality
descending thoracic aorta	UBERON:0002345	74.68	gold quality
thoracic aorta	UBERON:0001515	73.29	gold quality
ascending aorta	UBERON:0001496	73.02	gold quality
endocervix	UBERON:0000458	72.31	gold quality
ectocervix	UBERON:0012249	70.23	gold quality
stromal cell of endometrium	CL:0002255	69.83	gold quality
diaphragm	UBERON:0001103	69.27	gold quality
pancreatic ductal cell	CL:0002079	68.16	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	68.03	gold quality
olfactory bulb	UBERON:0002264	67.89	gold quality
prefrontal cortex	UBERON:0000451	67.86	gold quality
lateral nuclear group of thalamus	UBERON:0002736	67.72	silver quality
type B pancreatic cell	CL:0000169	66.84	silver quality
tibial nerve	UBERON:0001323	66.81	gold quality
mucosa of stomach	UBERON:0001199	66.61	gold quality
aorta	UBERON:0000947	66.43	gold quality
body of uterus	UBERON:0009853	65.70	gold quality
frontal cortex	UBERON:0001870	64.70	gold quality
upper lobe of left lung	UBERON:0008952	64.46	gold quality
right frontal lobe	UBERON:0002810	64.15	gold quality
sural nerve	UBERON:0015488	64.09	silver quality
dorsolateral prefrontal cortex	UBERON:0009834	63.56	gold quality
substantia nigra pars reticulata	UBERON:0001966	63.48	gold quality
cingulate cortex	UBERON:0003027	63.44	gold quality
neocortex	UBERON:0001950	63.32	gold quality
left uterine tube	UBERON:0001303	63.20	gold quality
upper lobe of lung	UBERON:0008948	63.16	gold quality
anterior cingulate cortex	UBERON:0009835	63.14	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.95

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, AR, CEBPB, CEBPD, CEBPG, CREM, DLX2, FOXC1, HOXA1, KLF6, MYB, MYBL2, MYOD1, NFATC3, NFE2L2, NFIC, NFKB, NR3C2, RELA, SCX, SNAI1, SOX17, SP1, SP7, TBP, TCF3, TP53, ZBTB7A, ZBTB7B, ZNF260

miRNA regulators (miRDB)

64 targeting ADRA1D, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-7845-5P	99.88	64.88	771
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-26A-1-3P	99.64	66.81	788
HSA-MIR-26A-2-3P	99.64	66.82	786
HSA-MIR-451B	99.55	68.28	1380
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-372-5P	99.41	69.11	2299

Literature-anchored findings (GeneRIF, showing 32)

• 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)
• 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)
• cell surface expression of alpha1D-adrenergic receptors is controlled by heterodimerization with alpha1B-adrenergic receptors (PMID:14736874)
• alpha(1A)- and alpha(1D)-adrenergic receptors mediate G(1)-S cell-cycle arrest (PMID:15297446)
• Human ureter was endowed with each alpha1 AR subtype, although alpha1D and alpha1A ARs were prevalent over alpha1B ARs. (PMID:15690361)
• alpha1D-adrenergic receptors are regulated by syntrophins through a PDZ domain-mediated interaction (PMID:16533813)
• Differential methylation of proximal GC boxes in the ADRA1D promoter disrupts Sp1 binding in a cell-specific manner resulting in repression of basal alpha1dAR expression. (PMID:17384146)
• ADRA1D polymorphisms are predictive markers of the response to beta-blockers (PMID:17404580)
• Stimulation of alpha(1D)-ARs by picomolar phenylephrine concentrations devoid of any contractile vascular effects, induces a proangiogenic phenotype in endothelial cells that is enhanced in a hypoxic environment. (PMID:17660397)
• 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 higher than in proximal and mid ureter but not statistically significant (PMID:17973108)
• Investigate role of ADRA1D amino residues in binding of beta-adrenergic antagonists (prazosin/tamulosin). (PMID:18187928)
• ADRA1A expression was decreased in end stage renal disease. Functional receptor changes mediated vascular hypersensitivity to phenylephrine. (PMID:18257748)
• ADRA1D induces vascular smooth muscle apoptosis via a p53-dependent mechanism. (PMID:18628404)
• Our data indicate that carboxyl terminus-truncated alpha(1D)-adrenoceptors are fully functional and subjected to regulation by phosphorylation. The roles of the carboxyl termini differ among alpha(1)-adrenoceptor subtypes. (PMID:19458937)
• Genetic characteristics associated with response to domperidone therapy included polymorphisms in the drug transporter gene ABCB1, the potassium channel KCNH2 gene, and alpha1D–adrenoceptor ADRA1D gene. (PMID:21063774)
• Data show that alpha-dystrobrevin-1 recruits alpha-catulin, which supersensitizes alpha(1D)-AR functional responses by recruiting effector molecules to the signalosome. (PMID:21115837)
• alpha(1)(D)-adrenoceptors in the lower urinary tract might play an important role in the pathophysiology of lower urinary tract disorders. [review] (PMID:23205498)
• Mean alpha-receptor stain rates in renal pelvis were 2.65 +/- 0.74, 1.35 +/- 0.81 and 2.9 +/- 0.30 for alpha 1A, 1B and 1D, respectively. For calyces, the rates are 2.40 +/- 0.82, 1.50 +/- 0.76 and 2.75 +/- 0.44 for alpha 1A, 1B and 1D, respectively. (PMID:23877383)
• alpha1A-adrenergic receptors are stably expressed and stimulate cell migration and TGF-beta1, IGF-1, hyaluronan and PIP production in human skin fibroblasts. (PMID:24844469)
• Cross-talk between alpha1D-adrenoceptors and transient receptor potential vanilloid type 1 triggers prostate cancer cell proliferation. (PMID:25481381)
• This study showed that ADRA1D gene involved in neuronal growth and cerebellum development and associated with neurological and psychological disorders. (PMID:26381449)
• In conclusion, our work clarified some cellular aspects promoted by alpha1D-AR activity modulation and supports a further pharmacological approach in the cure of hormone-refractory PC, by targeting specifically this AR subtype (PMID:26621245)
• Immunoreactivity for ADRA2D was densely distributed in submucosal glands of nasal turbinates. (PMID:26739946)
• expression of carboxyl terminus-truncated alpha1D-adrenoceptors alters ERK and p38 phosphorylation state. (PMID:27146292)
• processing of the ADRA1D NT domain is a physiological mechanism employed by cells to generate a functional ADRA1D isoform with optimal pharmacodynamic properties. (PMID:27382054)
• Hetero-oligomerization of a1B/D-adrenergic receptor with the chemokine (C-X-C motif) receptor 4:atypical chemokine receptor 3 heteromeric complex is required for a1B/Dadrenergic receptor function. (PMID:28862946)
• ADRA1 expression was greater on vascular smooth muscle in burn scars than in unscarred tissue, and greater on dermal nerve fibres, blood vessels and fibroblasts in keloid scars than in either burn scars or unscarred skin. (PMID:29089212)
• The roles of adrenoceptor alpha 1D phosphorylation sites/clusters were investigated. Carboxyl terminus phosphorylation seems to control receptor’s membrane localization. Intracellular loop 3 mutation caused agonist-induced sustained ERK1/2 activation. (PMID:30419287)
• Characterization of heteromeric complexes between chemokine (C-X-C motif) receptor 4 and alpha1-adrenergic receptors utilizing intermolecular bioluminescence resonance energy transfer assays. (PMID:32085899)
• N-glycosylation of alpha1D-adrenergic receptor N-terminal domain is required for correct trafficking, function, and biogenesis. (PMID:32350295)
• Functional Involvement of ADRA1D in Cutaneous Melanoma Progression and Angiogenesis. (PMID:37571902)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	adra1d	ENSDARG00000024101
mus_musculus	Adra1d	ENSMUSG00000027335
rattus_norvegicus	Adra1d	ENSRNOG00000021256
caenorhabditis_elegans	ser-5	WBGENE00008890

Paralogs (18): ADRB1 (ENSG00000043591), ADRA1A (ENSG00000120907), DRD2 (ENSG00000149295), ADRA2A (ENSG00000150594), GPR101 (ENSG00000165370), ADRB2 (ENSG00000169252), ADRA1B (ENSG00000170214), 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-1D adrenergic receptor — P25100 (reviewed: P25100)

Alternative names: Alpha-1A adrenergic receptor, Alpha-1D adrenoreceptor, Alpha-adrenergic receptor 1a

All UniProt accessions (2): P25100, B0ZBE0

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. ADRA1D binds the catecholamine ligands norepinephrine and epinephrine.

Subunit / interactions. Interacts with FLNA (via filamin repeat 21); increases PKA-mediated phosphorylation of FLNA.

Subcellular location. Cell membrane.

Post-translational modifications. Palmitoylated. Palmitoylation by ZDHHC21 may increase the expression of the receptor and regulate downstream signaling.

Similarity. Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRA1D sub-subfamily.

RefSeq proteins (1): NP_000669* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000363	ADRA1D_rcpt	Family
IPR002233	ADR_fam	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (30 total): topological domain 8, transmembrane region 7, sequence conflict 4, compositionally biased region 3, region of interest 2, binding site 2, glycosylation site 2, chain 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P25100-F1	65.88	0.26

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): 176; 258

Post-translational modifications (1): 419

Glycosylation sites (2): 65, 82

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: 378 (showing top): MODULE_92, AP1_01, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_MUSCLE_TISSUE_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, ENK_UV_RESPONSE_KERATINOCYTE_UP, 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

GO Biological Process (12): G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-modulating G protein-coupled receptor signaling pathway (GO:0007188), 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), positive regulation of cell population proliferation (GO:0008284), positive regulation of MAPK cascade (GO:0043410), positive regulation of vasoconstriction (GO:0045907), adenylate cyclase-activating adrenergic receptor signaling pathway (GO:0071880), neuron-glial cell signaling (GO:0150099), signal transduction (GO:0007165), adrenergic receptor signaling pathway (GO:0071875)

GO Molecular Function (5): alpha1-adrenergic receptor activity (GO:0004937), identical protein binding (GO:0042802), G protein-coupled receptor activity (GO:0004930), adrenergic receptor activity (GO:0004935), protein binding (GO:0005515)

GO Cellular Component (2): plasma membrane (GO:0005886), 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
G protein-coupled receptor signaling pathway	4
cell communication	2
signaling	2
adrenergic receptor signaling pathway	2
G protein-coupled receptor activity	1
signal transduction	1
adenylate cyclase activity	1
phospholipase C activator activity	1
regulation of biological quality	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
MAPK cascade	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
regulation of vasoconstriction	1
vasoconstriction	1
positive regulation of multicellular organismal process	1
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1
cell-cell signaling	1
cellular process	1
regulation of cellular process	1
cellular response to stimulus	1
adrenergic receptor activity	1
alpha-adrenergic receptor activity	1
protein binding	1
transmembrane signaling receptor activity	1
G protein-coupled amine receptor activity	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1444 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADRA1D	GNAQ	P50148	831
ADRA1D	TBXA2R	P21731	665
ADRA1D	PAFAH1B2	P68402	647
ADRA1D	AGTR1	P30556	611
ADRA1D	GRIK1	P39086	605
ADRA1D	GNA11	P29992	590
ADRA1D	GNA13	Q14344	589
ADRA1D	GNA12	Q03113	581
ADRA1D	ARHGEF12	Q9NZN5	572
ADRA1D	SUCLG1	P53597	565
ADRA1D	ARRB2	P32121	525
ADRA1D	SLC6A2	P23975	524
ADRA1D	AGT	P01019	523
ADRA1D	OXTR	P30559	514
ADRA1D	NAPA	P54920	498
ADRA1D	ADRA2A	P08913	498

IntAct

169 interactions, top by confidence:

A	B	Type	Score
ADRA1D	SNTA1	psi-mi:“MI:0403”(colocalization)	0.860
ADRA1D	SNTA1	psi-mi:“MI:0914”(association)	0.860
SNTA1	ADRA1D	psi-mi:“MI:0914”(association)	0.860
SNTA1	ADRA1D	psi-mi:“MI:0915”(physical association)	0.860
ADRA1D	SNTA1	psi-mi:“MI:0915”(physical association)	0.860
ADRA1D	SNTA1	psi-mi:“MI:0407”(direct interaction)	0.860
SNTB2	ADRA1D	psi-mi:“MI:0407”(direct interaction)	0.840
ADRA1D	SNTB1	psi-mi:“MI:0407”(direct interaction)	0.840
SCRIB	ADRA1D	psi-mi:“MI:0915”(physical association)	0.820
ADRA1D	SCRIB	psi-mi:“MI:0914”(association)	0.820
ADRA1D	SCRIB	psi-mi:“MI:0915”(physical association)	0.820
SCRIB	ADRA1D	psi-mi:“MI:0914”(association)	0.820
ADRA1D	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.820
ADRA1D	UTRN	psi-mi:“MI:0914”(association)	0.770
ADRA1D	UTRN	psi-mi:“MI:0915”(physical association)	0.770
ADRA1D	ADRA1D	psi-mi:“MI:0914”(association)	0.760
ADRA1D	ADRA1D	psi-mi:“MI:0915”(physical association)	0.760
ADRA1D	CTNNAL1	psi-mi:“MI:0914”(association)	0.710
ADRA1D	LIN7A	psi-mi:“MI:0914”(association)	0.590

BioGRID (19): ADRA1D (Affinity Capture-MS), ADRA1D (Affinity Capture-MS), ADRA1D (Affinity Capture-MS), ADRA1D (Affinity Capture-RNA), ADRA1D (Two-hybrid), ADRA1D (Protein-peptide), ACTA2 (Affinity Capture-MS), AMFR (Affinity Capture-MS), CKAP4 (Affinity Capture-MS), DTNA (Affinity Capture-MS), ERLIN1 (Affinity Capture-MS), ERLIN2 (Affinity Capture-MS), GOPC (Affinity Capture-MS), SNTB2 (Affinity Capture-MS), SNTB1 (Affinity Capture-MS)

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: A0A678XMK4, O02662, O02666, O14804, O19091, O42574, O70528, O77680, O77700, P07700, P11617, P17124, P18089, P21728, P23944, P25021, P25100, P25102, P25115, P28221, P28565, P35405, P35406, P42289, P42290, P42291, P43141, P46626, P47747, P47800, P49145, P50406, P53452, P53454, P60021, P61752, P79400, P97288, P97292, P97714

SIGNOR signaling

18 interactions.

A	Effect	B	Mechanism
8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione	down-regulates	ADRA1D	“chemical inhibition”
ADRA1D	“up-regulates activity”	GNAS	binding
ADRA1D	“up-regulates activity”	GNAL	binding
ADRA1D	“up-regulates activity”	GNAQ	binding
ADRA1D	“up-regulates activity”	GNA14	binding
(R)-noradrenaline	“up-regulates activity”	ADRA1D	“chemical activation”
terazosin	“down-regulates activity”	ADRA1D	“chemical inhibition”
phentolamine	“down-regulates activity”	ADRA1D	“chemical inhibition”
methoxamine	“up-regulates activity”	ADRA1D	“chemical activation”
silodosin	“down-regulates activity”	ADRA1D	“chemical inhibition”
(S)-adrenaline	“up-regulates activity”	ADRA1D	“chemical activation”
(R)-adrenaline	“up-regulates activity”	ADRA1D	“chemical activation”
oxymetazoline	“up-regulates activity”	ADRA1D	“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”	ADRA1D	“chemical inhibition”
N-(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)-2-(2,6-dimethoxyphenoxy)ethanamine	“down-regulates activity”	ADRA1D	“chemical inhibition”
prazosin	“down-regulates activity”	ADRA1D	“chemical inhibition”
tamsulosin	“down-regulates activity”	ADRA1D	“chemical inhibition”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 89 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Formation of the dystrophin-glycoprotein complex (DGC)	7	36.0×	5e-08
Assembly and cell surface presentation of NMDA receptors	8	33.8×	7e-09
Neurexins and neuroligins	10	32.8×	7e-11
Protein-protein interactions at synapses	6	26.6×	5e-06
Non-integrin membrane-ECM interactions	5	12.9×	7e-04

GO biological processes:

GO term	Partners	Fold	FDR
regulation of sodium ion transmembrane transport	5	63.5×	1e-06
protein localization to synapse	6	55.4×	2e-07
establishment or maintenance of epithelial cell apical/basal polarity	7	49.0×	4e-08
receptor clustering	6	45.1×	6e-07
regulation of postsynaptic membrane neurotransmitter receptor levels	6	35.8×	2e-06
Rho protein signal transduction	5	14.9×	8e-04
cell-cell adhesion	8	9.8×	1e-04
protein-containing complex assembly	7	9.6×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	112
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

321 predictions. Top by Δscore:

Variant	Effect	Δscore
20:4247840:CACT:C	donor_loss	1.0000
20:4247841:ACTC:A	donor_loss	1.0000
20:4247842:CTCA:C	donor_loss	1.0000
20:4247843:TCACC:T	donor_loss	1.0000
20:4247844:CAC:C	donor_loss	1.0000
20:4247846:CCGAG:C	donor_gain	1.0000
20:4222126:GGAGC:G	acceptor_gain	0.9900
20:4222127:GAGC:G	acceptor_gain	0.9900
20:4222128:AGCC:A	acceptor_loss	0.9900
20:4222129:GCC:G	acceptor_loss	0.9900
20:4222131:C:CC	acceptor_gain	0.9900
20:4222131:CT:C	acceptor_loss	0.9900
20:4222132:T:A	acceptor_loss	0.9900
20:4247845:A:AC	donor_gain	0.9900
20:4247846:C:CC	donor_gain	0.9900
20:4222128:AGC:A	acceptor_gain	0.9800
20:4222129:GC:G	acceptor_gain	0.9800
20:4222130:CC:C	acceptor_gain	0.9800
20:4247838:GTCAC:G	donor_loss	0.9800
20:4247839:TCAC:T	donor_loss	0.9800
20:4247846:CCGA:C	donor_gain	0.9400
20:4247845:AC:A	donor_gain	0.9300
20:4247846:CC:C	donor_gain	0.9300
20:4222133:G:C	acceptor_gain	0.9000
20:4222128:AGCCT:A	acceptor_gain	0.8900
20:4222129:GCCTG:G	acceptor_gain	0.8900
20:4222130:CCTGT:C	acceptor_gain	0.8900
20:4222127:GAGCC:G	acceptor_gain	0.8800
20:4222131:CTGTA:C	acceptor_gain	0.8800
20:4222133:G:GT	acceptor_gain	0.8800

AlphaMissense

3654 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:4222060:G:C	N394K	1.000
20:4222060:G:T	N394K	1.000
20:4222077:A:G	W389R	1.000
20:4222077:A:T	W389R	1.000
20:4247887:G:C	F357L	1.000
20:4247887:G:T	F357L	1.000
20:4247889:A:G	F357L	1.000
20:4248169:G:C	F263L	1.000
20:4248169:G:T	F263L	1.000
20:4248171:A:G	F263L	1.000
20:4248400:G:C	S186R	1.000
20:4248400:G:T	S186R	1.000
20:4248402:T:G	S186R	1.000
20:4248452:C:T	C169Y	1.000
20:4248545:A:G	L138P	1.000
20:4222040:A:T	I401N	0.999
20:4222046:G:T	P399Q	0.999
20:4222048:G:C	N398K	0.999
20:4222048:G:T	N398K	0.999
20:4222050:T:C	N398D	0.999
20:4222057:G:C	S395R	0.999
20:4222057:G:T	S395R	0.999
20:4222059:T:G	S395R	0.999
20:4222068:A:G	Y392H	0.999
20:4222070:C:T	G391D	0.999
20:4222071:C:G	G391R	0.999
20:4247863:G:C	F365L	0.999
20:4247863:G:T	F365L	0.999
20:4247865:A:G	F365L	0.999
20:4247866:G:C	F364L	0.999

dbSNP variants (sampled 300 via entrez): RS1000010625 (20:4237369 G>A), RS1000050181 (20:4237801 C>G,T), RS1000107007 (20:4248985 C>A,G), RS1000141228 (20:4249188 G>A), RS1000374645 (20:4225515 C>A,T), RS1000595139 (20:4232066 C>T), RS1000733150 (20:4224941 G>A), RS1000874789 (20:4242429 C>T), RS1000929985 (20:4249250 G>T), RS1001006742 (20:4236775 C>T), RS1001016119 (20:4236019 G>A), RS1001246858 (20:4242212 A>T), RS1001303874 (20:4231264 ATTG>A,ATTGTTG), RS1001364095 (20:4227780 CT>C,CTT), RS1001674314 (20:4222201 G>C,T)

Disease associations

OMIM: gene MIM:104219 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001949_8	Preeclampsia	9.000000e-06
GCST003174_18	Sense of smell	7.000000e-06
GCST003174_3	Sense of smell	3.000000e-06
GCST004251_1	Paneth cell defects in Crohn’s disease	3.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007963	abnormal paneth cell measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL2094251 (PROTEIN FAMILY), CHEMBL2095203 (PROTEIN FAMILY), CHEMBL2111467 (SELECTIVITY GROUP), CHEMBL223 (SINGLE PROTEIN), CHEMBL2331074 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

125 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)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1048101	Efficacy	3	nifedipine	Hypertension

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1048101	ADRA1A	3	2.75	1	nifedipine

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Adrenoceptors

Most potent curated ligand interactions (58 total), top 25:

Ligand	Action	Affinity	Parameter
RX18	Antagonist	10.25	pKi
tamsulosin	Antagonist	10.2	pKi
prazosin	Inverse agonist	10.2	pKi
(+)-cyclazosin	Inverse agonist	9.9	pKi
[125I]HEAT (BE2254)	Antagonist	9.9	pKd
WB 4101	Antagonist	9.6	pKi
A-119637	Antagonist	9.6	pKi
(S)-41	Antagonist	9.5	pKi
HEAT (BE2254)	Antagonist	9.5	pKd
A-123189	Antagonist	9.5	pKi
NAN 190	Antagonist	9.2	pKi
doxazosin	Antagonist	9.1	pKi
BMY-7378	Antagonist	9.1	pKi
MT-1207	Antagonist	8.85	pIC50
silodosin	Antagonist	8.7	pKi
[3H]prazosin	Antagonist	8.7	pKi
terazosin	Antagonist	8.6	pKi
alfuzosin	Antagonist	8.4	pKi
dapiprazole	Antagonist	8.4	pKi
phenoxybenzamine	Antagonist	8.4	pKi
spiperone	Antagonist	8.1	pKi
5-methylurapidil	Antagonist	8.0	pKi
spiroxatrine	Antagonist	7.9	pKi
RS-100329	Antagonist	7.9	pKi
RS-17053	Antagonist	7.8	pKi

Binding affinities (BindingDB)

39 measured of 43 human assays (50 total across all organisms); most potent 39 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
Rec 27/0074	KI	0.89 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
Permax	KI	1.91 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
Terguride	KI	3.47 nM
CAS_16041092	KI	3.6 nM
S18616	KI	3.98 nM
NSC_16041630	KI	5.3 nM
CHEMBL78986	KI	6.7 nM
CAS_16041091	KI	11 nM
NSC_16041263	KI	11 nM
Bromocriptine+ (GTP+)	KI	12.9 nM
NSC_16041628	KI	14 nM
CHEMBL1907669	KI	17 nM
NSC_54746	KI	19.9 nM
NSC_16041264	KI	22 nM
CAS_172307	KI	25.1 nM
NSC_16041265	KI	33 nM
CAS_16041449	KI	51 nM
NSC_16041451	KI	101 nM
CAS_16041090	KI	110 nM
CAS_16040907	KI	155 nM
CAS_105182-45-4	KI	158 nM
(R)-5-(1-(2,3-dimethylphenyl)ethyl)-1H-imidazole	KI	200 nM
S32504	KI	257 nM
4-[2-(dipropylamino)ethyl]-1,3-dihydro-2H-indol-2-one	KI	288 nM
NSC_4850	KI	447 nM
CAS_85760-74-3	IC50	462 nM	US-9359372: Hexahydrodibenzo[a,g]quinolizine compound, preparation method thereof, pharmaceutical composition and use thereof
Pramipexole	KI	692 nM
B-HT 920	KI	1700 nM
(6,7-Dihydroxy-1,2,3,4-tetrahydro-naphthalen-2-yl)-dimethyl-ammonium	KI	3800 nM

ChEMBL bioactivities

2172 potent at pChembl≥5 of 2204 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.82	Ki	0.015	nM	DEXMEDETOMIDINE
10.50	Ki	0.03162	nM	CLOPENPHENDIOXAN
10.40	Kd	0.03981	nM	TAMSULOSIN
10.40	Ki	0.03981	nM	CHEMBL4128084
10.40	Ki	0.04	nM	ABANOQUIL
10.30	Ki	0.05012	nM	CHEMBL196817
10.30	Ki	0.05012	nM	CHEMBL198860
10.27	Ki	0.054	nM	PRAZOSIN
10.25	Ki	0.05623	nM	CHEMBL3297829
10.24	Ki	0.058	nM	TAMSULOSIN
10.22	Ki	0.06026	nM	CHEMBL342062
10.20	Ki	0.0631	nM	CHEMBL197442
10.20	Ki	0.0631	nM	CHEMBL200366
10.20	Ki	0.0631	nM	CHEMBL4126860
10.20	Ki	0.063	nM	PRAZOSIN
10.17	Ki	0.06761	nM	CHEMBL43116
10.15	Ki	0.07	nM	CHEMBL1203855
10.15	Ki	0.07	nM	CHEMBL1744288
10.10	Ki	0.08	nM	CHEMBL1788145
10.06	Ki	0.088	nM	CHEMBL1744273
10.05	Ki	0.09	nM	CHEMBL1744270
10.05	Ki	0.08913	nM	CHEMBL42472
10.05	Ki	0.09	nM	CHEMBL243694
10.00	Ki	0.1	nM	CHEMBL1744272
10.00	Ki	0.1	nM	CHEMBL200580
10.00	IC50	0.1	nM	CHEMBL3809093
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	TAMSULOSIN
9.90	Ki	0.1259	nM	CHEMBL382972
9.89	Ki	0.13	nM	CHEMBL80641
9.89	Ki	0.1288	nM	CHEMBL56438
9.85	Ki	0.1413	nM	CHEMBL3298750
9.85	Ki	0.14	nM	CHEMBL232609
9.82	Ki	0.1514	nM	CHEMBL4129461
9.82	IC50	0.15	nM	TAMSULOSIN
9.80	Ki	0.1585	nM	TAMSULOSIN
9.80	Kd	0.1585	nM	TAMSULOSIN
9.78	Ki	0.166	nM	CHEMBL220515
9.77	Ki	0.17	nM	CHEMBL1203846
9.77	IC50	0.17	nM	PRAZOSIN
9.77	Ki	0.17	nM	PRAZOSIN
9.77	Ki	0.1698	nM	CYCLODOXAZOSIN
9.77	Ki	0.1698	nM	CYCLAZOSIN
9.75	Ki	0.1778	nM	CHEMBL1254582
9.74	Ki	0.18	nM	CHEMBL355784
9.74	Ki	0.182	nM	CHEMBL44403
9.74	Ki	0.18	nM	TAMSULOSIN
9.71	Ki	0.195	nM	CHEMBL27013

PubChem BioAssay actives

1965 with measured affinity, of 3302 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[2-[(4-chlorophenyl)methoxy]phenoxy]-N-[2-(2,6-dimethoxyphenoxy)ethyl]ethanamine	257359: Displacement of [3H]prazosin from cloned human ADRA1D expressed in CHO cells	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	35328: Binding affinity against Alpha-1D adrenergic receptor, from human clones.	ki	<0.0001	uM
Dexmedetomidine	36549: In vitro binding affinity against alpha-2D adrenergic receptor of male Wistar rat	ki	<0.0001	uM
benzyl (4aS,8aR)-4-(4-amino-6,7-dimethoxyquinazolin-2-yl)-2,3,4a,5,6,7,8,8a-octahydroquinoxaline-1-carboxylate	1497049: Displacement of [3H]prazosin from human alpha1D adrenergic receptor expressed in CHO cell membranes after 30 mins by rapid filtration method	ki	<0.0001	uM
N-[2-(2,6-dimethoxyphenoxy)ethyl]-2-(2-phenylmethoxyphenoxy)ethanamine	257359: Displacement of [3H]prazosin from cloned human ADRA1D expressed in CHO cells	ki	0.0001	uM
5-acetyl-4-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethylamino]-2-methyl-6-phenylpyridazin-3-one	218801: Binding affinity towards human cloned alpha-1D-adrenoceptor using [3H]prazosin as radioligand	ki	0.0001	uM
N-[2-(2,6-dimethoxyphenoxy)ethyl]-2-[2-[(2-methylphenyl)methoxy]phenoxy]ethanamine	257359: Displacement of [3H]prazosin from cloned human ADRA1D expressed in CHO cells	ki	0.0001	uM
N-[2-(2,6-dimethoxyphenoxy)ethyl]-2-[2-[(4-nitrophenyl)methoxy]phenoxy]ethanamine	257359: Displacement of [3H]prazosin from cloned human ADRA1D expressed in CHO cells	ki	0.0001	uM
N-[2-(2,6-dimethoxyphenoxy)ethyl]-2-[2-[(4-methylphenyl)methoxy]phenoxy]ethanamine	257359: Displacement of [3H]prazosin from cloned human ADRA1D expressed in CHO cells	ki	0.0001	uM
2-[2-[(3-chlorophenyl)methoxy]phenoxy]-N-[2-(2,6-dimethoxyphenoxy)ethyl]ethanamine	257359: Displacement of [3H]prazosin from cloned human ADRA1D expressed in CHO cells	ki	0.0001	uM
N-[2-(2,6-dimethoxyphenoxy)ethyl]-2-[2-[(4-methoxyphenyl)methoxy]phenoxy]ethanamine	257359: Displacement of [3H]prazosin from cloned human ADRA1D expressed in CHO cells	ki	0.0001	uM
N-[2-(2,6-dimethoxyphenoxy)ethyl]-2-[2-[(3-nitrophenyl)methoxy]phenoxy]ethanamine	257359: Displacement of [3H]prazosin from cloned human ADRA1D expressed in CHO cells	ki	0.0001	uM
2-(2,6-dimethoxyphenoxy)-N-[[(2S,4R)-4-phenyl-3,4-dihydro-2H-chromen-2-yl]methyl]ethanamine	35462: Affinity constant on CHO cells expressing Human recombinant Alpha-1D adrenergic receptor	ki	0.0001	uM
4-fluoro-2-[4-[4-(2-propan-2-yloxyphenyl)piperazin-1-yl]cyclohexyl]isoindole-1,3-dione	293843: Displacement of [125]HEAT from human adrenergic alpha-1d receptor expressed in CHO cells	ki	0.0001	uM
1-(3-hydroxypropyl)-5-[2-[2-(2-phenylmethoxyphenoxy)ethylamino]propyl]indole-7-carboxamide	1301978: Antagonist activity at alpha-1D adrenergic receptor (unknown origin) transfected in HEK293 cells assessed as reduction in agonist-induced calcium mobilization after 10 mins	ic50	0.0001	uM
[(4aS,8aR)-4-[4-(dipropylamino)-6,7-dimethoxyquinazolin-2-yl]-2,3,4a,5,6,7,8,8a-octahydroquinoxalin-1-yl]-(furan-2-yl)methanone	1497049: Displacement of [3H]prazosin from human alpha1D adrenergic receptor expressed in CHO cell membranes after 30 mins by rapid filtration method	ki	0.0001	uM
(E)-but-2-enedioic acid;5-[(2,4-dimethylthiophen-3-yl)methyl]-1H-imidazole	36549: In vitro binding affinity against alpha-2D adrenergic receptor of male Wistar rat	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
5-[(3,4-dibromothiophen-2-yl)methyl]-1H-imidazole;hydrochloride	36549: In vitro binding affinity against alpha-2D adrenergic receptor of male Wistar rat	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
5-bromo-6-chloro-N-[4-[4-(2-propan-2-yloxyphenyl)piperazin-1-yl]cyclohexyl]pyridine-3-sulfonamide	296252: Binding affinity to human cloned adrenergic Alpha-1D receptor	ki	0.0001	uM
Prazosin	2198823: Binding affinity to Alpha 1 receptor (unknown origin) assessed as inhibition constant	ki	0.0001	uM
(E)-but-2-enedioic acid;5-[(2,5-dichlorothiophen-3-yl)methyl]-1H-imidazole	36549: In vitro binding affinity against alpha-2D adrenergic receptor of male Wistar rat	ki	0.0001	uM
5-[1-(4-bromothiophen-3-yl)ethyl]-1H-imidazole;(E)-but-2-enedioic acid	36549: In vitro binding affinity against alpha-2D adrenergic receptor of male Wistar rat	ki	0.0001	uM
5-(1-benzothiophen-3-ylmethyl)-1H-imidazole;(E)-but-2-enedioic acid	36549: In vitro binding affinity against alpha-2D adrenergic receptor of male Wistar rat	ki	0.0001	uM
N-benzyl-N’-[3-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-2,4-dioxo-1H-[1]benzothiolo[3,2-d]pyrimidin-8-yl]pentanediamide	1159310: Displacement of [125I]BE2254 from human alpha1d receptor expressed in HEK293 cells	ki	0.0001	uM
N’-benzyl-N-[3-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-2,4-dioxo-1H-[1]benzothiolo[3,2-d]pyrimidin-8-yl]-N’-methylpentanediamide	1159310: Displacement of [125I]BE2254 from human alpha1d receptor expressed in HEK293 cells	ki	0.0001	uM
[(4aS,8aR)-4-(4-amino-6,7-dimethoxyquinazolin-2-yl)-2,3,4a,5,6,7,8,8a-octahydroquinoxalin-1-yl]-(furan-2-yl)methanone	1497049: Displacement of [3H]prazosin from human alpha1D adrenergic receptor expressed in CHO cell membranes after 30 mins by rapid filtration method	ki	0.0001	uM
(E)-but-2-enedioic acid;5-[(2-ethylthiophen-3-yl)methyl]-1H-imidazole	36549: In vitro binding affinity against alpha-2D adrenergic receptor of male Wistar rat	ki	0.0001	uM
8-[2-[4-(2,5-dichlorophenyl)piperazin-1-yl]ethyl]-8-azaspiro[4.5]decane-7,9-dione	603873: Displacement of [125I]BE-2254 from human adrenergic Alpha-1D receptor expressed in HEK293 cells	ki	0.0001	uM
N-[6-[(4-amino-6,7-dimethoxyquinazolin-2-yl)-methylamino]hexyl]-3-[(dimethylamino)methyl]-N-methylbenzamide	35474: Binding affinity at human cloned Alpha-1D adrenergic receptor in chinese hamster ovary cells by [3H]prazosin displacement.	ki	0.0002	uM
1-[(4aS,8aR)-4-(4-amino-6,7-dimethoxyquinazolin-2-yl)-2,3,4a,5,6,7,8,8a-octahydroquinoxalin-1-yl]ethanone	1497049: Displacement of [3H]prazosin from human alpha1D adrenergic receptor expressed in CHO cell membranes after 30 mins by rapid filtration method	ki	0.0002	uM
5-[1-(3-bromothiophen-2-yl)ethyl]-1H-imidazole	36549: In vitro binding affinity against alpha-2D adrenergic receptor of male Wistar rat	ki	0.0002	uM
N-[2-(2,6-dimethoxyphenoxy)ethyl]-2-[2-[(3-methylphenyl)methoxy]phenoxy]ethanamine	257359: Displacement of [3H]prazosin from cloned human ADRA1D expressed in CHO cells	ki	0.0002	uM
[(4aR,8aS)-4-(4-amino-6,7-dimethoxyquinazolin-2-yl)-2,3,4a,5,6,7,8,8a-octahydroquinoxalin-1-yl]-(furan-2-yl)methanone	422826: Displacement of [3H]prazosin from human Alpha-1D adrenoceptor expressed in CHO cells	ki	0.0002	uM
N-[6-[(4-amino-6,7-dimethoxyquinazolin-2-yl)-methylamino]hexyl]-N-methylfuran-2-carboxamide	35474: Binding affinity at human cloned Alpha-1D adrenergic receptor in chinese hamster ovary cells by [3H]prazosin displacement.	ki	0.0002	uM
3-[2-[4-(5-chloro-2-methoxyphenyl)piperazin-1-yl]ethyl]-2-methyl-5H-pyrimido[5,4-b]indol-4-one	277058: Displacement of [125I]BE2254 from human cloned adrenergic alpha 1D receptor expressed in HEK293 cells	ki	0.0002	uM
5-[(3,4-dimethylthiophen-2-yl)methyl]-1H-imidazole;hydrochloride	36549: In vitro binding affinity against alpha-2D adrenergic receptor of male Wistar rat	ki	0.0002	uM
2-[[2-(2,6-dimethoxyphenoxy)ethylamino]methyl]-4-phenyl-3,4-dihydro-2H-naphthalen-1-one	35462: Affinity constant on CHO cells expressing Human recombinant Alpha-1D adrenergic receptor	ki	0.0002	uM
4-[2-[4-[2-(2,2-dimethylpropoxy)phenyl]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	0.0002	uM
4-[2-[4-(2,3-dihydro-1-benzofuran-7-yl)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	0.0002	uM
4-[2-[4-(4,5-dichloro-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	0.0002	uM
2-[4-[4-(2-propan-2-yloxyphenyl)piperazin-1-yl]cyclohexyl]benzo[e]isoindole-1,3-dione	293843: Displacement of [125]HEAT from human adrenergic alpha-1d receptor expressed in CHO cells	ki	0.0002	uM
[(4aR,8aS)-4-(4-amino-6,7-dimethoxyquinazolin-2-yl)-2,3,4a,5,6,7,8,8a-octahydroquinoxalin-1-yl]-(2,3-dihydro-1,4-benzodioxin-3-yl)methanone	422826: Displacement of [3H]prazosin from human Alpha-1D adrenoceptor expressed in CHO cells	ki	0.0002	uM
2-methoxy-5-[(2R)-2-[2-(2-propan-2-yloxyphenoxy)ethylamino]propyl]benzenesulfonamide	545213: Displacement of [3H]prazosin from human Alpha-1D adrenoceptor expressed in CHO cells	ki	0.0002	uM
N-[2-(2,6-dimethoxyphenyl)sulfanylethyl]-2-(2-phenylmethoxyphenoxy)ethanamine	515615: Displacement of [3H]prazosin from human adrenergic Alpha-1D expressed in CHO cells	ki	0.0002	uM
5-[(4-bromothiophen-3-yl)methyl]-1H-imidazole;(E)-but-2-enedioic acid	36549: In vitro binding affinity against alpha-2D adrenergic receptor of male Wistar rat	ki	0.0002	uM
4-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethylamino]-2-methyl-6-phenyl-5-propanoylpyridazin-3-one	218801: Binding affinity towards human cloned alpha-1D-adrenoceptor using [3H]prazosin as radioligand	ki	0.0003	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Phenylephrine	affects binding, affects response to substance, affects cotreatment, decreases reaction, increases phosphorylation (+2 more)	4
Prazosin	affects binding, decreases reaction	4
Epinephrine	increases abundance, increases activity, affects binding, decreases reaction	3
Norepinephrine	increases abundance, decreases reaction, affects binding, increases activity	3
BMY 7378	affects binding	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Calcium	decreases reaction, increases abundance, increases activity, affects binding	2
Oxymetazoline	decreases reaction, affects binding	2
Phentolamine	increases phosphorylation, affects binding, decreases reaction, increases abundance, increases activity (+1 more)	2
Tetrachlorodibenzodioxin	increases expression	2
aristolochic acid I	increases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
xylometazoline	affects binding, decreases reaction	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
zinc chromate	increases abundance, decreases expression	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, affects response to substance, increases expression, affects cotreatment	1
Terazosin	affects binding	1
alfuzosin	affects binding	1
2-(beta-(3-iodo-4-hydroxyphenyl)ethylaminomethyl)tetralone	affects binding	1
5-methylurapidil	affects binding	1
abanoquil	affects binding	1
sarpogrelate	affects binding, decreases reaction	1
SK&F 104856	affects binding	1
chromium hexavalent ion	decreases expression, increases abundance	1
1-(2-(3-methoxyphenyl)ethyl)phenoxy-3-(dimethylamino)-2-propanol	affects binding, decreases reaction	1
RS 17053	affects binding	1
abrine	decreases expression	1
licochalcone B	increases expression	1

ChEMBL screening assays

617 unique, capped per target: 518 binding, 95 functional, 4 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

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

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

Cellosaurus	Name	Category	Sex
CVCL_9111	L-alpha-1a L-cells	Spontaneously immortalized cell line	Male
CVCL_D7JR	Ubigene A-549 ADRA1D KO	Cancer cell line	Male
CVCL_H389	CHO-K1/ADRA1D	Spontaneously immortalized cell line	Female
CVCL_KZ31	PathHunter HEK 293 ADRA1D(82-572) beta-arrestin	Transformed cell line	Female

Clinical trials (associated diseases)

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