DRD1

Summary

DRD1 (dopamine receptor D1, HGNC:3020) is a protein-coding gene on chromosome 5q35.2, encoding D(1A) dopamine receptor (P21728). Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.

This gene encodes the D1 subtype of the dopamine receptor. The D1 subtype is the most abundant dopamine receptor in the central nervous system. This G-protein coupled receptor stimulates adenylyl cyclase and activates cyclic AMP-dependent protein kinases. D1 receptors regulate neuronal growth and development, mediate some behavioral responses, and modulate dopamine receptor D2-mediated events. Alternate transcription initiation sites result in two transcript variants of this gene.

Source: NCBI Gene 1812 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 41 total
• Druggable target: yes — 289 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000794

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3020
Approved symbol	DRD1
Name	dopamine receptor D1
Location	5q35.2
Locus type	gene with protein product
Status	Approved
Aliases	D1R
Ensembl gene	ENSG00000184845
Ensembl biotype	protein_coding
OMIM	126449
Entrez	1812

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000393752, ENST00000950668, ENST00000950669

RefSeq mRNA: 1 — MANE Select: NM_000794 NM_000794

CCDS: CCDS4393

Canonical transcript exons

ENST00000393752 — 2 exons

Exon	Start	End
ENSE00001357078	175440036	175443582
ENSE00001357338	175443699	175444182

Expression profiles

Bgee: expression breadth ubiquitous, 130 present calls, max score 87.12.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5100 / max 110.8001, expressed in 76 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
64986	0.5100	76

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
caudate nucleus	UBERON:0001873	87.12	gold quality
nucleus accumbens	UBERON:0001882	85.87	gold quality
putamen	UBERON:0001874	85.41	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.19	gold quality
prefrontal cortex	UBERON:0000451	73.83	gold quality
Brodmann (1909) area 9	UBERON:0013540	70.97	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	70.39	gold quality
telencephalon	UBERON:0001893	69.42	gold quality
cingulate cortex	UBERON:0003027	68.96	gold quality
anterior cingulate cortex	UBERON:0009835	68.71	gold quality
frontal cortex	UBERON:0001870	68.24	gold quality
neocortex	UBERON:0001950	67.54	gold quality
right frontal lobe	UBERON:0002810	67.46	gold quality
Brodmann (1909) area 46	UBERON:0006483	66.84	silver quality
forebrain	UBERON:0001890	65.56	gold quality
cerebral cortex	UBERON:0000956	64.90	gold quality
amygdala	UBERON:0001876	64.09	gold quality
cortical plate	UBERON:0005343	63.29	gold quality
orbitofrontal cortex	UBERON:0004167	61.89	silver quality
paraflocculus	UBERON:0005351	61.64	gold quality
middle frontal gyrus	UBERON:0002702	61.42	gold quality
brain	UBERON:0000955	61.38	gold quality
central nervous system	UBERON:0001017	60.79	gold quality
endometrium epithelium	UBERON:0004811	60.44	gold quality
postcentral gyrus	UBERON:0002581	59.78	gold quality
superior frontal gyrus	UBERON:0002661	59.48	gold quality
pigmented layer of retina	UBERON:0001782	58.49	gold quality
temporal lobe	UBERON:0001871	58.49	gold quality
parietal lobe	UBERON:0001872	57.29	gold quality
decidua	UBERON:0002450	56.55	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.95

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
SULT1A1	Activation
SULT1A3	Activation

Upstream regulators (CollecTRI, top): FOS, HR, KLF16, MEIS2, POU3F4, SP1, SP3, TCF20, TFAP2A, TFAP2B, TGIF1, ZIC2

miRNA regulators (miRDB)

124 targeting DRD1, 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-5692A	100.00	74.40	6850
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872

Literature-anchored findings (GeneRIF, showing 40)

• peripheral dopamine D1 and D2 receptors are present in the seminal vesicle tissue (PMID:11783439)
• Patterns of cyclic AMP formation by coexpressed D1 and D2L dopamine receptors in HEK 293 cells. (PMID:11918350)
• dopamine depletion does not result in increased neostriatal binding (PMID:11920160)
• critical role of GRK4, relative to GRK2, in the homologous desensitization of D1 receptors in renal proximal tubule cells. (PMID:12164861)
• mechanism of activation as evidenced by molecular interplay between the third extracellular loop and the cytoplasmic tail (PMID:12509438)
• Significant age-related decline was observed for dopamine receptor mRNAs in the hippocampus and entorhinal cortex (PMID:12509874)
• regulation of trafficking and desensitization by oligomerization with glutamate N-methyl-D-aspartate receptors (PMID:12646556)
• D1 dopamine receptors have a role in inducing nitric-oxide synthase activation and cytotoxicity (PMID:12738794)
• Among type 1 alcoholics dopamine transporters are lower in nucleus accumbens and dopamine D(2), but not D(1) or D(3) receptors in nucleus accumbens and amygdala. Lower dopamine receptor density is specific for D(2) receptor and for type 1 alcoholism. (PMID:12781734)
• This is the first report of a male-limited association between the DRD1 gene restriction fragment length polymorphism and sensation-seeking score in alcohol-dependent subjects. (PMID:12966314)
• DRD1 is involved in ADHD. Haplotype 3 contains a potential risk factor for the inattentive symptom dimension of the disorder. The putative DRD1 risk variant for ADHD resides outside of the coding region of the gene. (PMID:14569274)
• stimulation of co-expressed D1 and D2 receptors resulted in an increase of intracellular calcium levels via a signaling pathway not activated by either receptor alone (PMID:15159403)
• have identified a sequence present in the carboxyl-terminal cytoplasmic domain of the human D1 dopamine receptor that is specifically required for the efficient recycling of endocytosed receptors back to the plasma membrane (PMID:15192107)
• role of ERK in the cytotoxicity mediated upon activation of the D1 dopamine receptor. (PMID:15247297)
• the interrelationship between D1 and D2 receptor-mediated control of motor activity, food intake, and gastrointestinal functions (PMID:15272078)
• D1 receptors are mainly localized on smooth muscle cells in corpus cavernosum (PMID:15549138)
• These data suggest that DRD1 gene is not a useful marker for prediction of the susceptibility of Tourette syndrome. (PMID:15564897)
• Heterologously and endogenously expressed D1Rs in renal cells are associated with and regulated by caveolin-2. (PMID:15569306)
• Racial differences may play an important role concerning the association of variants in the dopamine receptor type 1 gene with essential hypertension. (PMID:15607627)
• importance of dopamine D(1) receptors in reward and/or alcoholism. (PMID:15621009)
• Results suggest an association between the DRD1 gene and bipolar I disorder (BP I) in the Sardinian population. (PMID:15704231)
• This study provides support for an association between attention deficit hyperactivity disorder (ADHD) and polymorphisms in dopamine D1 receptor gene. (PMID:15717291)
• GRK4 constitutively phosphorylates the D1 receptor in the absence of agonist activation. (PMID:16338988)
• (11)C-NNC 112 displays a favorable radiation dose profile in humans and would allow multiple PET examinations per year to be performed on the same subject. (PMID:16391193)
• The -48A/G polymorphism of DRD1 was estimated in patients with schizophrenia or bipolar disorder. No association was found with schizophrenia. The G/G genotype and G allele were significantly more frequent in patients with bipolar disorder, type 2. (PMID:16397404)
• dopamine D(1) and D(2) receptors can form hetero-oligomers in the plasma membrane. The degree of receptor protein-protein interaction is significantly enhanced by concomitant addition of D(1) and D(2) receptor subtype-specific agonists. (PMID:16846218)
• dopamine receptor type 1 and Gs protein alpha subunit loci contribute to blood pressure regulation at rest (PMID:16876683)
• The fact that the same haplotype shows a similar trend for association in samples originating from different ethnic backgrounds seems to imply that the -800C/-48G/1403T haplotype may be considered as a risk factor for bipolar type I disorder. (PMID:17066478)
• The association of DRD1 with inattention, but not with reading disabilities, or the other reading and reading-related phenotypes analysed, suggests that DRD1 contributes uniquely to inattention, without overlap for reading ability. (PMID:17310237)
• D1 and D2 dopamine receptor expression is regulated by direct interaction with the chaperone protein calnexin (PMID:17395585)
• The information derived from this study could be valuable for understanding the genetic factors involved in alcoholic phenotypes and genetic distribution of the DRD gene family, and could facilitate further investigation in other ethnic groups. (PMID:17466946)
• The results clearly indicate that D1R-modulated NR1a/NR2B receptor function depends on PSD-95 and is subjected to the regulation of PKA and PKC. (PMID:17506933)
• Single-nucleotide polymorphisms of the dopamine D(1) receptor gene is associated with nicotine dependence (PMID:18092181)
• Discovery of differential regulation by D1and D5 receptors opens new avenues for development of agonists selective to either receptor subtype as targeted antihypertensive agents that can decrease AT(1)R-mediated antinatriuresis. (PMID:18172057)
• Preferential haplotype transmission of markers at the DRD1 locus and an increased frequency of a specific haplotype support the DRD1 gene as a risk gene for core symptoms of autism spectrum disorders in families having only affected males. (PMID:18205172)
• The observation that the hD1R mutations induce significant alterations in pharmacologic properties may have implications both for disease susceptibility and/or therapeutic response to dopaminergic ligands. (PMID:18210231)
• receptor hetero-oligomer complex formed resulted in a significantly enhanced surface expression of mu-opioid receptor. This hetero-oligomer formation involved the interaction of mu-opioid receptor with the dopamine D1 receptor carboxyl tail (PMID:18237729)
• DRD1 is a susceptibility gene in alcohol dependence, specifically haplotype rs686*T-rs4532*G. (PMID:18341651)
• low doses of a selective D1 receptors agonist accelerated the formation of mutant huntingtin protein nuclear aggregates, whereas the number of cytoplasmic aggregates was decreased. (PMID:18403126)
• renal sodium handling and blood pressure were associated with genetic variation in the DRD1 promoter (PMID:18413491)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	drd1b	ENSDARG00000038918
mus_musculus	Drd1	ENSMUSG00000021478
rattus_norvegicus	Drd1	ENSRNOG00000023688

Paralogs (25): DRD4 (ENSG00000069696), HRH3 (ENSG00000101180), HRH2 (ENSG00000113749), CHRM3 (ENSG00000133019), HRH4 (ENSG00000134489), TAAR5 (ENSG00000135569), GPR84 (ENSG00000139572), GPR161 (ENSG00000143147), TAAR2 (ENSG00000146378), TAAR6 (ENSG00000146383), TAAR8 (ENSG00000146385), TAAR1 (ENSG00000146399), DRD3 (ENSG00000151577), HTR4 (ENSG00000164270), CHRM1 (ENSG00000168539), DRD5 (ENSG00000169676), HTR1A (ENSG00000178394), HTR1D (ENSG00000179546), CHRM4 (ENSG00000180720), CHRM2 (ENSG00000181072), CHRM5 (ENSG00000184984), GPR21 (ENSG00000188394), HRH1 (ENSG00000196639), GPR52 (ENSG00000203737), TAAR9 (ENSG00000237110)

Protein

Protein identifiers

D(1A) dopamine receptor — P21728 (reviewed: P21728)

Alternative names: Dopamine D1 receptor

All UniProt accessions (1): P21728

UniProt curated annotations — full annotation on UniProt →

Function. Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase. Forms heterotetramers with DRD3 to potentiate beta-arrestin recruitment and mediate locomotor activity.

Subunit / interactions. Interacts with DNAJC14 via its C-terminus. Interacts with DRD2. Interacts with DORIP1. Interacts with DRD3.

Subcellular location. Cell membrane. Endoplasmic reticulum membrane. Cell projection. Cilium membrane. Dendrite. Dendritic spine.

Tissue specificity. Detected in caudate, nucleus accumbens and in the olfactory tubercle.

Similarity. Belongs to the G-protein coupled receptor 1 family.

RefSeq proteins (1): NP_000785* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000929	Dopamine_rcpt	Family
IPR001413	Dopamine_D1_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (41 total): helix 12, topological domain 8, transmembrane region 7, sequence variant 6, lipid moiety-binding region 2, chain 1, glycosylation site 1, disulfide bond 1, mutagenesis site 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

31 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9LLJ	ELECTRON MICROSCOPY	2.61
9LLF	ELECTRON MICROSCOPY	2.64
9I54	ELECTRON MICROSCOPY	2.72
9LLH	ELECTRON MICROSCOPY	2.73
9LLG	ELECTRON MICROSCOPY	2.77
9I52	ELECTRON MICROSCOPY	2.8
7JVP	ELECTRON MICROSCOPY	2.9
9LLE	ELECTRON MICROSCOPY	2.9
9LWC	ELECTRON MICROSCOPY	2.9
7JV5	ELECTRON MICROSCOPY	3
7JVQ	ELECTRON MICROSCOPY	3
7LJC	ELECTRON MICROSCOPY	3
7X2F	ELECTRON MICROSCOPY	3
8JXS	ELECTRON MICROSCOPY	3
9LLI	ELECTRON MICROSCOPY	3
7CKZ	ELECTRON MICROSCOPY	3.1
7F0T	ELECTRON MICROSCOPY	3.1
7F1O	ELECTRON MICROSCOPY	3.13
7CKY	ELECTRON MICROSCOPY	3.2
7LJD	ELECTRON MICROSCOPY	3.2
7X2C	ELECTRON MICROSCOPY	3.2
8IRR	ELECTRON MICROSCOPY	3.2
7CKW	ELECTRON MICROSCOPY	3.22
7CRH	ELECTRON MICROSCOPY	3.3
7X2D	ELECTRON MICROSCOPY	3.3
7F1Z	ELECTRON MICROSCOPY	3.46
7CKX	ELECTRON MICROSCOPY	3.54
8JXR	ELECTRON MICROSCOPY	3.57
7F23	ELECTRON MICROSCOPY	3.58
7JOZ	X-RAY DIFFRACTION	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P21728-F1	73.23	0.42

Antibody-complex structures (SAbDab): 20 — 7CKW, 7CKX, 7CKY, 7CKZ, 7CRH, 7F0T, 7F1O, 7F23, 7JOZ, 7JV5, 7JVP, 7JVQ, 7LJC, 7LJD, 7X2C, 7X2D, 7X2F, 8IRR, 8JXR, 8JXS

Functional residue map

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

Post-translational modifications (2): 347, 351

Disulfide bonds (1): 96–186

Glycosylation sites (1): 5

Mutagenesis-validated functional residues (1):

Position	Phenotype
381–395	reduced localization to ciliary membrane.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-390651	Dopamine receptors
R-HSA-418555	G alpha (s) signalling events

MSigDB gene sets: 361 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, GOBP_FOREBRAIN_NEURON_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, GOBP_MEMORY, RNGTGGGC_UNKNOWN, GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_DENTATE_GYRUS_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_CARBOHYDRATE_TRANSPORT, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_RESPONSE_TO_COCAINE, MODULE_571

GO Biological Process (61): temperature homeostasis (GO:0001659), conditioned taste aversion (GO:0001661), behavioral fear response (GO:0001662), response to amphetamine (GO:0001975), protein import into nucleus (GO:0006606), G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger (GO:0007187), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), adenylate cyclase-activating dopamine receptor signaling pathway (GO:0007191), G protein-coupled dopamine receptor signaling pathway (GO:0007212), synapse assembly (GO:0007416), memory (GO:0007613), mating behavior (GO:0007617), grooming behavior (GO:0007625), adult walking behavior (GO:0007628), visual learning (GO:0008542), response to xenobiotic stimulus (GO:0009410), astrocyte development (GO:0014002), obsolete dopamine transport (GO:0015872), transmission of nerve impulse (GO:0019226), neuronal action potential (GO:0019228), dentate gyrus development (GO:0021542), striatum development (GO:0021756), cerebral cortex GABAergic interneuron migration (GO:0021853), positive regulation of cell migration (GO:0030335), peristalsis (GO:0030432), operant conditioning (GO:0035106), synaptic transmission, glutamatergic (GO:0035249), regulation of dopamine metabolic process (GO:0042053), vasodilation (GO:0042311), dopamine metabolic process (GO:0042417), maternal behavior (GO:0042711), positive regulation of potassium ion transport (GO:0043268), positive regulation of MAPK cascade (GO:0043410), obsolete D-glucose import (GO:0046323), habituation (GO:0046959), sensitization (GO:0046960), behavioral response to cocaine (GO:0048148), positive regulation of release of sequestered calcium ion into cytosol (GO:0051281), regulation of dopamine uptake involved in synaptic transmission (GO:0051584), positive regulation of synaptic transmission, glutamatergic (GO:0051968)

GO Molecular Function (8): dopamine neurotransmitter receptor activity, coupled via Gs (GO:0001588), G-protein alpha-subunit binding (GO:0001965), G protein-coupled receptor activity (GO:0004930), dopamine neurotransmitter receptor activity (GO:0004952), heterotrimeric G-protein binding (GO:0032795), dopamine binding (GO:0035240), arrestin family protein binding (GO:1990763), protein binding (GO:0005515)

GO Cellular Component (18): nucleus (GO:0005634), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), cilium (GO:0005929), presynaptic membrane (GO:0042734), dendritic spine (GO:0043197), postsynaptic membrane (GO:0045211), ciliary membrane (GO:0060170), G protein-coupled receptor complex (GO:0097648), non-motile cilium (GO:0097730), glutamatergic synapse (GO:0098978), GABA-ergic synapse (GO:0098982), endoplasmic reticulum (GO:0005783), endomembrane system (GO:0012505), membrane (GO:0016020), dendrite (GO:0030425), cell projection (GO:0042995), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Amine ligand-binding receptors	1
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	3
cellular anatomical structure	3
associative learning	2
G protein-coupled dopamine receptor signaling pathway	2
synaptic transmission, dopaminergic	2
action potential	2
protein binding	2
intracellular membrane-bounded organelle	2
synaptic membrane	2
postsynapse	2
cilium	2
synapse	2
multicellular organismal-level homeostasis	1
feeding behavior	1
behavioral defense response	1
fear response	1
response to amine	1
intracellular protein transport	1
protein localization to nucleus	1
import into nucleus	1
establishment of protein localization to organelle	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1
cellular response to dopamine	1
nervous system development	1
cell junction assembly	1
synapse organization	1
learning or memory	1
reproductive behavior	1
behavior	1
adult locomotory behavior	1
walking behavior	1
visual behavior	1
response to chemical	1
glial cell development	1
astrocyte differentiation	1
cell communication	1
chemical synaptic transmission	1
nervous system process	1

Protein interactions and networks

STRING

1880 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DRD1	TMTC1	Q8IUR5	920
DRD1	SLC6A3	Q01959	906
DRD1	PPP1R1B	Q9UD71	822
DRD1	GNAL	P38405	796
DRD1	BDNF	P23560	790
DRD1	RDM1	Q8NG50	780
DRD1	ARRB2	P32121	770
DRD1	SLC6A4	P31645	763
DRD1	GRIN2A	Q12879	741
DRD1	DNAJC14	Q6Y2X3	717
DRD1	COMT	P21964	716
DRD1	GRIA1	P42261	715
DRD1	DRD3	P35462	697
DRD1	CHRNA4	P43681	679
DRD1	TH	P07101	662

IntAct

30 interactions, top by confidence:

A	B	Type	Score
PRKCA	DRD1	psi-mi:“MI:0915”(physical association)	0.560
YWHAG	DRD1	psi-mi:“MI:0915”(physical association)	0.560
SETDB1	DRD1	psi-mi:“MI:0915”(physical association)	0.560
KAT5	DRD1	psi-mi:“MI:0915”(physical association)	0.560
LMO3	DRD1	psi-mi:“MI:0915”(physical association)	0.560
ADORA1	DRD1	psi-mi:“MI:0915”(physical association)	0.460
ADORA1	DRD1	psi-mi:“MI:0403”(colocalization)	0.460
DRD1	CRHR2	psi-mi:“MI:0915”(physical association)	0.460
DRD1	CRHR2	psi-mi:“MI:0403”(colocalization)	0.460
	DRD1	psi-mi:“MI:0915”(physical association)	0.400
DRD1	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
RAMP1	DRD1	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	DRD1	psi-mi:“MI:0915”(physical association)	0.400
DRD1	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
DRD1	GHSR	psi-mi:“MI:2364”(proximity)	0.270
EGFR	DRD1	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (26): DRD1 (Biochemical Activity), DRD3 (Affinity Capture-Western), DRD1 (Affinity Capture-Western), DRD3 (FRET), GHSR (FRET), PDCD6IP (Two-hybrid), PDCD6IP (Reconstituted Complex), DRD1 (Affinity Capture-Western), DRD1 (Reconstituted Complex), VPS35 (Affinity Capture-Western), DRD1 (Affinity Capture-Western), DRD1 (Co-localization), DLG4 (Affinity Capture-Western), DLG4 (Reconstituted Complex), DRD1 (Affinity Capture-Western)

ESM2 similar proteins: A0A678XMK4, A6QLE7, O17899, O42384, O42574, O70528, O77680, P04274, P07550, P0C5J4, P10608, P17124, P18762, P18901, P21728, P25102, P30728, P42288, P42289, P42290, P42291, P47898, P49285, P49288, P50130, P51046, P53452, P54833, P70585, P97288, Q09638, Q13639, Q15760, Q16950, Q16951, Q28044, Q28509, Q28997, Q4KWL2, Q61121

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

8 interactions.

A	Effect	B	Mechanism
DRD1	“up-regulates activity”	GNAS	binding
DRD1	“up-regulates activity”	GNAL	binding
DRD1	“up-regulates activity”	GNAI1	binding
DRD1	“up-regulates activity”	GNAI3	binding
DRD1	“up-regulates activity”	GNAZ	binding
DRD1	“up-regulates activity”	GNAQ	binding
DRD1	“up-regulates activity”	GNA14	binding
dopamine	“up-regulates activity”	DRD1	“chemical activation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 12 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.

GO biological processes:

GO term	Partners	Fold	FDR
G protein-coupled receptor signaling pathway	5	15.1×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	3
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

238 predictions. Top by Δscore:

Variant	Effect	Δscore
5:175443694:CCTA:C	donor_loss	0.9800
5:175443695:CTA:C	donor_loss	0.9800
5:175443698:C:CT	donor_loss	0.9800
5:175443702:G:A	donor_gain	0.9700
5:175443521:G:C	donor_gain	0.9600
5:175443584:T:C	acceptor_gain	0.9600
5:175443582:CCT:C	acceptor_gain	0.9200
5:175440436:ACTC:A	acceptor_gain	0.9100
5:175440435:GACT:G	acceptor_gain	0.9000
5:175443697:A:AC	donor_gain	0.9000
5:175443698:C:CC	donor_gain	0.9000
5:175443584:T:TC	acceptor_gain	0.8800
5:175443698:CCTTG:C	donor_gain	0.8700
5:175443506:C:A	donor_gain	0.8600
5:175443580:CGC:C	acceptor_gain	0.8600
5:175443907:T:TA	donor_gain	0.8600
5:175443583:C:CC	acceptor_gain	0.8500
5:175443579:ACGCC:A	acceptor_loss	0.8200
5:175443581:GCC:G	acceptor_loss	0.8200
5:175443582:CC:C	acceptor_loss	0.8200
5:175443584:T:A	acceptor_loss	0.8200
5:175443580:CGCCT:C	acceptor_gain	0.8100
5:175440317:GATTC:G	acceptor_gain	0.8000
5:175440318:ATTCC:A	acceptor_gain	0.8000
5:175443583:C:T	acceptor_gain	0.7700
5:175443592:C:CT	acceptor_gain	0.7500
5:175443581:GC:G	acceptor_gain	0.7400
5:175443976:T:TA	donor_gain	0.7300
5:175444001:CTGG:C	donor_gain	0.7300
5:175444002:TGGT:T	donor_gain	0.7300

AlphaMissense

2928 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:175442257:A:C	F281L	1.000
5:175442257:A:T	F281L	1.000
5:175442259:A:G	F281L	1.000
5:175442438:G:T	A221D	1.000
5:175442738:C:A	R121M	1.000
5:175442746:G:C	S118R	1.000
5:175442746:G:T	S118R	1.000
5:175442748:T:G	S118R	1.000
5:175442087:C:G	R338P	0.999
5:175442089:A:C	F337L	0.999
5:175442089:A:T	F337L	0.999
5:175442090:A:G	F337S	0.999
5:175442091:A:G	F337L	0.999
5:175442117:G:C	P328R	0.999
5:175442117:G:T	P328H	0.999
5:175442119:G:C	N327K	0.999
5:175442119:G:T	N327K	0.999
5:175442139:A:G	W321R	0.999
5:175442139:A:T	W321R	0.999
5:175442141:C:T	G320E	0.999
5:175442233:G:C	F289L	0.999
5:175442233:G:T	F289L	0.999
5:175442235:A:G	F289L	0.999
5:175442236:G:C	F288L	0.999
5:175442236:G:T	F288L	0.999
5:175442238:A:G	F288L	0.999
5:175442247:A:G	W285R	0.999
5:175442247:A:T	W285R	0.999
5:175442483:G:C	P206R	0.999
5:175442483:G:T	P206H	0.999

dbSNP variants (sampled 300 via entrez): RS1000465307 (5:175440599 G>A,T), RS1000583674 (5:175440736 A>G), RS1000649587 (5:175445406 T>A), RS1001943086 (5:175445764 G>A), RS1001998450 (5:175445435 A>G), RS1002724380 (5:175444409 A>G), RS1003030214 (5:175443365 C>T), RS1003622125 (5:175444651 G>A), RS1003674500 (5:175444387 C>A), RS1004306564 (5:175441378 C>A,T), RS1004765130 (5:175441008 C>T), RS1005122894 (5:175445877 G>T), RS1005420812 (5:175444830 G>C), RS1005453269 (5:175444690 G>C), RS1006031473 (5:175439612 A>T)

Disease associations

OMIM: gene MIM:126449 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST001402_7	Treatment response for severe sepsis	8.000000e-06
GCST001762_825	Obesity-related traits	5.000000e-06
GCST002936_13	Cadmium levels	9.000000e-06
GCST003542_45	Night sleep phenotypes	5.000000e-06
GCST003989_23	Chin dimples	7.000000e-14
GCST004068_37	Venous thromboembolism adjusted for sickle cell variant rs77121243-T	8.000000e-06
GCST006291_19	Spherical equivalent or myopia (age of diagnosis)	4.000000e-08
GCST010002_44	Refractive error	5.000000e-16
GCST90012857_9	Falling risk	2.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004627	IGF-1 measurement
EFO:0004847	age at onset

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2056 (SINGLE PROTEIN), CHEMBL2096905 (PROTEIN FAMILY), CHEMBL2111341 (SELECTIVITY GROUP)

Molecules with ChEMBL bioactivity

289 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 637,260 (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
CHEMBL1023	BEXAROTENE	4	40,951
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1064	SIMVASTATIN	4	123,163
CHEMBL1065	METHYSERGIDE	4	8,455
CHEMBL1085	ACETOPHENAZINE	4	5,134
CHEMBL1088	MESORIDAZINE	4	12,814
CHEMBL11	IMIPRAMINE	4	48,893
CHEMBL1106	EPINASTINE	4	8,530
CHEMBL1108	DROPERIDOL	4	16,888
CHEMBL111	RIMONABANT	4	15,726
CHEMBL1112	ARIPIPRAZOLE	4	24,205
CHEMBL1113	AMOXAPINE	4	20,128
CHEMBL1123	DICYCLOMINE	4	8,691
CHEMBL1138	EZETIMIBE	4	29,509
CHEMBL1171837	PONATINIB	4	8,955
CHEMBL1172	DESLORATADINE	4	19,720
CHEMBL118	CELECOXIB	4	112,844
CHEMBL119	TRIMETREXATE	4	57,002
CHEMBL1198857	VILANTEROL	4	2,552
CHEMBL1200490	CETRORELIX	4	16,775
CHEMBL1200492	NEFAZODONE HYDROCHLORIDE	4
CHEMBL1200809	AZELASTINE HYDROCHLORIDE	4
CHEMBL1201	THIOTHIXENE	4
CHEMBL1201087	CABERGOLINE	4
CHEMBL1201196	SERTACONAZOLE	4
CHEMBL1201203	BENZTROPINE	4
CHEMBL1201245	BROMODIPHENHYDRAMINE	4
CHEMBL1201287	DEXBROMPHENIRAMINE	4
CHEMBL1201304	INDOCYANINE GREEN ACID FORM	4
CHEMBL1201342	METHIXENE	4

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

PharmGKB clinical annotations

9 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs11746641	Efficacy	3	bupropion;nicotine
rs11749035	Efficacy	3	bupropion;nicotine
rs2168631	Efficacy	3	bupropion;nicotine
rs265976	Efficacy	3	clozapine	Schizophrenia
rs4532	Efficacy	3	lithium	Bipolar Disorder
rs4532	Toxicity	3	dextroamphetamine;methylphenidate	Attention Deficit Disorder with Hyperactivity
rs4532	Other	3	nicotine	Tobacco Use Disorder
rs5326	Dosage	3	methadone	Heroin Dependence
rs686	Other	3	nicotine	Tobacco Use Disorder

PharmGKB variants

10 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs686	DRD1	3	3.00	1	nicotine
rs4532	DRD1	3	4.50	3	lithium;dextroamphetamine;methylphenidate;nicotine
rs5326	DRD1	3	2.50	1	methadone
rs265976	DRD1	3	0.25	1	clozapine
rs265981	DRD1		0.00	0
rs2168631	DRD1	3	3.50	1	bupropion;nicotine
rs4867798	DRD1		0.00	0
rs7725278	DRD1		0.00	0
rs11746641	DRD1	3	3.50	1	bupropion;nicotine
rs11749035	DRD1	3	3.50	1	bupropion;nicotine

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Dopamine receptors

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

Ligand	Action	Affinity	Parameter
SKF-83959	Biased agonist	9.7	pEC50
SCH-23390	Antagonist	9.5	pKi
SKF-83566	Antagonist	9.5	pKi
[125I]SCH23982	Antagonist	9.5	pKd
[3H]SCH-23390	Antagonist	9.5	pKd
(R)-SCH-23390	Antagonist	9.0	pKi
A77636	Full agonist	8.74	pKi
SKF-75670	Full agonist	8.7	pKi
SKF-81297	Full agonist	8.7	pKi
mevidalen	Positive	8.64	pEC50
(+)-butaclamol	Antagonist	8.5	pKi
flupentixol	Antagonist	8.4	pKi
ecopipam	Antagonist	8.3	pKi
(-)-stepholidine	Antagonist	8.29	pKi
haloperidol	Antagonist	8.2	pKi
tavapadon	Partial agonist	8.07	pKi
periciazine	Antagonist	8.0	pKi
dihydrexidine	Full agonist	8.0	pKi
LY3154885	Positive	7.93	pEC50
fenoldopam	Full agonist	7.9	pKi
fluphenazine	Antagonist	7.7	pKi
(+)-SKF-82526	Full agonist	7.55	pKi
N-propylnorapomorphine	Full agonist	7.4	pKi
UCM-1306	Positive	7.22	pEC50
lisuride	Partial agonist	7.2	pKi

Binding affinities (BindingDB)

724 measured of 782 human assays (807 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
2-[2-[3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazol-5-yl]ethyl]isoindole-1,3-dione	EC50	0.000309 nM
3,4-dimethoxy-N-[5-(2-thenyl)-1,3,4-thiadiazol-2-yl]benzamide	EC50	0.000313 nM
6-cyclohexyl-3-(1,4,5,6-tetrahydrocyclopenta[c]pyrazol-3-yl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole	EC50	0.00114 nM
2-(allylamino)-4-amino-5-(2,2-dimethylpropanoyl)-3-thiophenecarbonitrile	EC50	0.00114 nM
4-amino-2,6-diphenyl-5-pyrimidinecarbonitrile	EC50	0.00117 nM
(5Z)-2-(1-azepanyl)-5-(7-bromo-5-methyl-2-oxo-1H-indol-3-ylidene)-4-thiazolone	EC50	0.00135 nM
2-methylpropyl 6-(furan-2-yl)-3-methyl-4-oxidanylidene-1,5,6,7-tetrahydroindole-2-carboxylate	EC50	0.00157 nM
2-[5-(furan-2-yl)-4-oxidanylidene-3-phenyl-thieno[2,3-d]pyrimidin-2-yl]sulfanylethanamide	EC50	0.00163 nM
4-[5-(3-carbomethoxy-5-keto-2-methyl-1,4-dihydroindeno[1,2-b]pyridin-4-yl)-2-furyl]benzoic acid	EC50	0.00174 nM
4-hydroxy-6-(4-isopropylphenyl)-2-piperidin-1-ylpyrimidine-5-carbonitrile	EC50	0.00175 nM
2-[(2,5-dimethoxybenzylidene)amino]-4,5-bis(2-furyl)-3-furonitrile	EC50	0.00197 nM
1-butyl-5-keto-2-nicotinoylimino-dipyrido[1,2-d:3’,4’-f]pyrimidine-3-carboxylic acid ethyl ester	EC50	0.00202 nM
1-(3-amino-7-methoxy-1-pyrazolo[3,4-b]quinolinyl)-2-(2-methoxyphenyl)ethanone	EC50	0.00201 nM
3-methyl-5-[[1-oxo-2-(1,3,4-thiadiazol-2-ylthio)ethyl]amino]thiophene-2,4-dicarboxylic acid diethyl ester	EC50	0.00223 nM
5-acetyl-2-methyl-6-(methylamino)-4-phenyl-3-pyridinecarbonitrile	EC50	0.00233 nM
7-(4-carbomethoxyphenyl)-5-methyl-2-(methylthio)-1,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidine-6-carboxylic acid ethyl ester	EC50	0.00231 nM
1-[6-(4-ethoxy-3-methoxy-phenyl)-3-(methylthio)-6H-[1,2,4]triazino[5,6-d][3,1]benzoxazepin-7-yl]ethanone	EC50	0.00238 nM
1-(5-bromanylpyridin-2-yl)-3-butyl-urea	EC50	0.00243 nM
5-[[[1-(4-fluorophenyl)-4-keto-2H-pyrazolo[3,4-d]pyrimidin-6-yl]thio]methyl]furan-2-carboxylic acid methyl ester	EC50	0.00249 nM
6-(cyclohexylamino)-8-(2-furanyl)-3,3-dimethyl-1,4-dihydropyrano[3,4-c]pyridine-5-carbonitrile	EC50	0.0026 nM
1-[1-(3-chlorophenyl)-4-(2-furoyl)-1H-pyrazol-3-yl]ethanone	EC50	0.00279 nM
MLS000092489	EC50	0.00289 nM
(E)-3-amino-2-[2-[[5-[(4-chlorobenzyl)thio]-1,3,4-thiadiazol-2-yl]thio]acetyl]but-2-enenitrile	EC50	0.00314 nM
5-methyl-2-(2-pyridin-3-ylquinazolin-4-yl)pyrazol-3-amine	EC50	0.00314 nM
2-[(2-isopropyl-3-keto-2H-imidazo[1,2-c]quinazolin-5-yl)thio]acetonitrile	EC50	0.00314 nM
1-methoxypropan-2-yl 2-amino-1-(3-methoxypropyl)pyrrolo[3,2-b]quinoxaline-3-carboxylate	EC50	0.00352 nM
(1-benzylbenzimidazol-2-yl)-(2-furfuryl)amine	EC50	0.0035 nM
2-[3-(2-Chloro-benzyl)-5-cyclopropyl-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-ylamino]-ethanol	EC50	0.00365 nM
4,5-diphenyl-1H-imidazole	EC50	0.0037 nM
MLS000098496	EC50	0.00366 nM
1-Phenylbenzimidazole deriv. 76	EC50	0.00399 nM
4-methoxy-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidine	EC50	0.00401 nM
4-(phenylcarbonyl)-N-pyridin-2-yl-1H-imidazole-5-carboxamide	EC50	0.00411 nM
2-[[7-(2-furanylmethyl)-5,6-diphenyl-4-pyrrolo[2,3-d]pyrimidinyl]amino]ethanol	EC50	0.00424 nM
3,6-diphenyl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole	EC50	0.00431 nM
3-amino-5-phenyl-2-thiophenecarboxylic acid ethyl ester	EC50	0.00428 nM
3-cyclopentyl-6,7-dimethoxy-2-sulfanylidene-1H-quinazolin-4-one	EC50	0.00446 nM
1-(1,3-benzodioxol-5-yl)-5-[(2-fluorobenzyl)thio]-1H-tetrazole	EC50	0.00446 nM
6-phenyl-2-(1-piperidinyl)-1H-pyrimidin-4-one	EC50	0.00455 nM
1-(3-methoxypropyl)-5-oxo-2-[oxo(3-pyridinyl)methyl]imino-3-dipyrido[1,2-d:3’,4’-f]pyrimidinecarboxylic acid ethyl ester	EC50	0.00475 nM
MLS000089039	EC50	0.0047 nM
5-acetyl-4-methyl-2-[(5-propylisoxazole-3-carbonyl)amino]thiophene-3-carboxylic acid ethyl ester	EC50	0.00468 nM
4-(3,4-dihydro-2H-quinolin-1-yl)-[1,2,4]triazolo[4,3-a]quinoxaline	EC50	0.00483 nM
4-(4-bromophenyl)-4,10-dihydro-[1,3,5]triazino[1,2-a]benzimidazol-2-amine;ethanoic acid	EC50	0.0048 nM
3-[(6,6-dimethyl-2-methylsulfanyl-1,4,5,8-tetrahydropyrano[2,3]thieno[2,4-d]pyrimidin-4-yl)amino]propan-1-ol	EC50	0.00522 nM
2-(6-indolo[3,2-b]quinoxalinyl)acetic acid ethyl ester	EC50	0.00538 nM
(4-chlorobenzyl)-(4,6-dimethoxy-s-triazin-2-yl)amine	EC50	0.00551 nM
6-(butylthio)-1-(4-fluorophenyl)-2H-pyrazolo[3,4-d]pyrimidin-4-one	EC50	0.00602 nM
2-acetoxypropyl(trimethyl)ammonium;chloride	EC50	0.0062 nM
(1-amylbenzimidazol-2-yl)-(2-furfuryl)amine	EC50	0.00618 nM

ChEMBL bioactivities

2683 potent at pChembl≥5 of 2836 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.00	Ki	0.1	nM	CHEMBL1814790
9.96	Ki	0.11	nM	CHEMBL1814790
9.96	Ki	0.11	nM	SCH-23390
9.92	EC50	0.12	nM	CHEMBL1196161
9.89	Ki	0.13	nM	ZICRONAPINE
9.82	Ki	0.15	nM	SCH-23390
9.82	Kd	0.15	nM	CHEMBL434215
9.77	Ki	0.17	nM	CHEMBL1256645
9.70	EC50	0.2	nM	CHEMBL574558
9.70	Ki	0.2	nM	SCH-23390
9.70	Ki	0.2	nM	CHEMBL4758723
9.70	AC50	0.2	nM	FENOLDOPAM
9.70	Ki	0.2	nM	CHEMBL596824
9.70	Ki	0.2	nM	CHEMBL599135
9.70	Ki	0.2	nM	CHEMBL599528
9.68	IC50	0.21	nM	CHEMBL4128926
9.66	IC50	0.22	nM	CHEMBL1814790
9.64	EC50	0.23	nM	CHEMBL4465393
9.64	EC50	0.2291	nM	CHEMBL4465393
9.64	Kd	0.23	nM	CHEMBL5207281
9.64	Kd	0.23	nM	CHEMBL5206565
9.64	Kd	0.23	nM	CHEMBL5201074
9.64	Kd	0.23	nM	CHEMBL4860528
9.61	EC50	0.2455	nM	CHEMBL4277264
9.60	EC50	0.25	nM	CHEMBL4277264
9.60	IC50	0.25	nM	CHEMBL1814790
9.57	IC50	0.27	nM	CHEMBL1814790
9.55	Kd	0.28	nM	CHEMBL150800
9.52	Ki	0.3	nM	SCH-23390
9.52	Ki	0.3	nM	CHEMBL300647
9.52	EC50	0.3	nM	CHEMBL4472022
9.52	EC50	0.3	nM	CHEMBL4453318
9.52	Ki	0.3	nM	CHEMBL605127
9.52	Ki	0.3	nM	CHEMBL324017
9.51	IC50	0.31	nM	CHEMBL13668
9.48	Ki	0.33	nM	CHEMBL45491
9.47	Ki	0.34	nM	LISURIDE
9.45	Ki	0.3548	nM	CHEMBL201170
9.43	IC50	0.37	nM	SCH-23390
9.42	Kd	0.38	nM	SCH-23390
9.42	EC50	0.3802	nM	CHEMBL4437552
9.42	EC50	0.38	nM	CHEMBL4437552
9.42	Ki	0.38	nM	SCH-23390
9.41	Ki	0.39	nM	CHEMBL1204122
9.41	Ki	0.39	nM	CHEMBL201170
9.40	Ki	0.4	nM	CHEMBL201170
9.40	Ki	0.4	nM	CHEMBL598104
9.40	Ki	0.4	nM	CHEMBL304535
9.37	Ki	0.4266	nM	SCH-23390
9.35	EC50	0.45	nM	CHEMBL1193571

PubChem BioAssay actives

1593 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
9-chloro-5-(3-methylphenyl)-3-prop-2-enyl-1,2,4,5-tetrahydro-3-benzazepine-7,8-diol	1573447: Agonist activity at human dopamine D1 receptor expressed in CHOK1 cells assessed as reversal of Ro 20-1724 mediated decrease in cAMP accumulation after 60 mins by luminescence assay	ec50	0.0001	uM
4-[(1R,3S)-6-chloro-3-phenyl-2,3-dihydro-1H-inden-1-yl]-1,2,2-trimethylpiperazine	1677162: Binding affinity to human dopamine D1 receptor	ki	0.0001	uM
(5R)-8-chloro-3-methyl-5-phenyl-1,2,4,5-tetrahydro-3-benzazepin-7-ol	611929: Displacement of [3H]SCH23390 from human dopamine D1 receptor	ki	0.0001	uM
5-(4-azidophenyl)-8-iodo-3-methyl-1,2,4,5-tetrahydro-3-benzazepin-7-ol	63206: Ability to inhibit the binding of [3H]-SCH- 23390 to canine striatal membrane	kd	0.0001	uM
(Z)-but-2-enedioic acid;(5R)-8-chloro-3-methyl-5-phenyl-1,2,4,5-tetrahydro-3-benzazepin-7-ol	1152688: Displacement of [3H]SCH23390 from human recombinant D1 receptor expressed in CHO cells	ki	0.0001	uM
N-[[4-[(5R)-8-chloro-7-hydroxy-3-methyl-1,2,4,5-tetrahydro-3-benzazepin-5-yl]phenyl]methyl]-N-cyclobutylacetamide	458496: Binding affinity to dopamine D1 receptor	ki	0.0002	uM
(5R)-8-chloro-3-methyl-5-phenyl-1,2,4,5-tetrahydro-3-benzazepin-7-ol;hydrochloride	63208: Inhibition of [3H]-SCH- 23390 binding to Dopamine receptor D1 from canine striatum	ki	0.0002	uM
9-chloro-3-methyl-5-(3-methylphenyl)-1,2,4,5-tetrahydro-3-benzazepine-7,8-diol	1573447: Agonist activity at human dopamine D1 receptor expressed in CHOK1 cells assessed as reversal of Ro 20-1724 mediated decrease in cAMP accumulation after 60 mins by luminescence assay	ec50	0.0002	uM
7-[3-methyl-4-(6-methylimidazo[1,2-a]pyrazin-5-yl)phenoxy]thieno[2,3-c]pyridine	1593403: Agonist activity at recombinant human D1 receptor expressed in HEK29T cells assessed as induction of stimulatory G-protein-mediated cAMP accumulation measured after 15 mins by Glosensor-based FLIPR assay	ec50	0.0002	uM
3-chloro-6-[(6S)-1,6-dimethyl-3,6-dihydro-2H-pyridin-4-yl]-8-fluoro-11H-benzo[b][1,4]benzodiazepine	1677162: Binding affinity to human dopamine D1 receptor	ki	0.0002	uM
1-[N’-[3-(2-amino-4-methyl-1,3-thiazol-5-yl)propyl]carbamimidoyl]-3-pentylurea	1895223: Displacement of [3H]SCH23390 from human D1 receptor stably expressed in HEK293T cells co-expressing luciferase and CEK incubated for 60 mins by scintillation counting analysis	kd	0.0002	uM
1-[(1R)-1-phenylethyl]-3-[N’-[3-(1H-1,2,4-triazol-5-yl)propyl]carbamimidoyl]urea;dihydrochloride	1895223: Displacement of [3H]SCH23390 from human D1 receptor stably expressed in HEK293T cells co-expressing luciferase and CEK incubated for 60 mins by scintillation counting analysis	kd	0.0002	uM
1-[N’-[3-(5-amino-1,3,4-thiadiazol-2-yl)propyl]carbamimidoyl]-3-pentylurea;bis(2,2,2-trifluoroacetic acid)	1895223: Displacement of [3H]SCH23390 from human D1 receptor stably expressed in HEK293T cells co-expressing luciferase and CEK incubated for 60 mins by scintillation counting analysis	kd	0.0002	uM
1-[N’-[3-(5-amino-1,3,4-thiadiazol-2-yl)propyl]carbamimidoyl]-3-benzylurea;bis(2,2,2-trifluoroacetic acid)	1895223: Displacement of [3H]SCH23390 from human D1 receptor stably expressed in HEK293T cells co-expressing luciferase and CEK incubated for 60 mins by scintillation counting analysis	kd	0.0002	uM
(6aS,13bS)-11-chloro-7-methyl-4-[(E)-phenylmethoxyiminomethyl]-5,6,6a,8,9,13b-hexahydronaphtho[1,2-a][3]benzazepin-12-ol	458849: Displacement of [3H]SCh23390 from dopamine D1 receptor expressed in mouse LTK cells by scintillation counting	ki	0.0002	uM
(6aS,13bS)-11-chloro-7-methyl-4-phenyl-5,6,6a,8,9,13b-hexahydronaphtho[1,2-a][3]benzazepin-12-ol	458849: Displacement of [3H]SCh23390 from dopamine D1 receptor expressed in mouse LTK cells by scintillation counting	ki	0.0002	uM
(6aS,13bS)-11-chloro-7-methyl-4-pyridin-4-yl-5,6,6a,8,9,13b-hexahydronaphtho[1,2-a][3]benzazepin-12-ol	458849: Displacement of [3H]SCh23390 from dopamine D1 receptor expressed in mouse LTK cells by scintillation counting	ki	0.0003	uM
8-bromo-3-methyl-5-phenyl-1,2,4,5-tetrahydro-3-benzazepin-7-ol	63038: Binding affinity against dopamine receptor D1 by using [3H]-SCH- 23390 as radioligand in caudate-putamen of monkey	ki	0.0003	uM
(5R)-9-chloro-3-methyl-5-phenyl-1,2,4,5-tetrahydro-3-benzazepine-7,8-diol	1573447: Agonist activity at human dopamine D1 receptor expressed in CHOK1 cells assessed as reversal of Ro 20-1724 mediated decrease in cAMP accumulation after 60 mins by luminescence assay	ec50	0.0003	uM
3-[(6aR,9S)-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinolin-9-yl]-1,1-diethylurea	1993619: Binding affinity to dopamine D1 receptor (unknown origin) assessed as inhibition constant	ki	0.0003	uM
5’-chloro-N,N-dimethylspiro[cyclohex-2-ene-4,2’-tricyclo[9.4.0.03,8]pentadeca-1(15),3(8),4,6,9,11,13-heptaene]-1-amine	61821: Binding affinity determined in radioreceptor binding assay by using [3H]SCH-23390 radioligand against dopamine receptor D1	ki	0.0003	uM
5’-chloro-N,N-dimethylspiro[cyclohex-2-ene-4,2’-tricyclo[9.4.0.03,8]pentadeca-1(15),3(8),4,6,11,13-hexaene]-1-amine	61821: Binding affinity determined in radioreceptor binding assay by using [3H]SCH-23390 radioligand against dopamine receptor D1	ki	0.0003	uM
(5S)-5-(4-azidophenyl)-8-iodo-3-methyl-1,2,4,5-tetrahydro-3-benzazepin-7-ol	63205: Ability to inhibit [3H]-SCH- 23390 binding to Dopamine receptor D1 of canine striatal membranes	kd	0.0003	uM
8-chloro-3-methyl-5-phenyl-1,2,4,5-tetrahydro-3-benzazepin-7-ol	1285624: Displacement of [3H]SCH23390 from human recombinant Dopamine D1 receptor expressed in CHO cells	ic50	0.0003	uM
11-methyl-11-azatricyclo[12.4.0.03,8]octadeca-1(18),3(8),4,6,14,16-hexaen-6-ol	261570: Displacement of [3H]SCH 23390 from D1 dopamine receptor	ki	0.0004	uM
[(6aR)-11-acetyloxy-9-ethyl-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinolin-10-yl] acetate	1547936: Agonist activity at C-terminal RLuc8-fused D1R (unknown origin) transfected in human HEK293T cells co-expressing N-terminal Venus-tagged beta-arrestin2 assessed as increase in beta-arrestin2 recruitment measured after 5 mins in presence of coelenterazine H by BRET assay	ec50	0.0004	uM
(5R)-8-chloro-3-methyl-5-(3-methylphenyl)-1,2,4,5-tetrahydro-3-benzazepin-7-ol	61822: Binding affinity to displace [3H]- SCH 23390 against Dopamine receptor D1	ki	0.0004	uM
3-methyl-5-phenyl-1,2,4,5-tetrahydro-3-benzazepine-7,8-diol	1573447: Agonist activity at human dopamine D1 receptor expressed in CHOK1 cells assessed as reversal of Ro 20-1724 mediated decrease in cAMP accumulation after 60 mins by luminescence assay	ec50	0.0004	uM
(6aS,13bS)-11-chloro-4-(3-fluorophenyl)-7-methyl-5,6,6a,8,9,13b-hexahydronaphtho[1,2-a][3]benzazepin-12-ol	458849: Displacement of [3H]SCh23390 from dopamine D1 receptor expressed in mouse LTK cells by scintillation counting	ki	0.0004	uM
11-methyl-11-azatricyclo[12.4.0.03,8]octadeca-1(18),3(8),4,6,14,16-hexaen-6-ol;hydrobromide	257774: Inhibition of binding to human D1 receptor expressed in HEK 293 cells by radioligand binding assay	ki	0.0004	uM
N-[(6aS,13bR)-11-chloro-12-hydroxy-7-methyl-5,6,6a,8,9,13b-hexahydronaphtho[1,2-a][3]benzazepin-3-yl]methanesulfonamide	458496: Binding affinity to dopamine D1 receptor	ki	0.0005	uM
N-[[4-[(5R)-8-chloro-7-hydroxy-3-methyl-1,2,4,5-tetrahydro-3-benzazepin-5-yl]phenyl]methyl]-N-cyclobutylmethanesulfonamide	458496: Binding affinity to dopamine D1 receptor	ki	0.0005	uM
4-chloro-11-methyl-11-azatricyclo[12.4.0.03,8]octadeca-1(18),3(8),4,6,14,16-hexaen-5-ol	261570: Displacement of [3H]SCH 23390 from D1 dopamine receptor	ki	0.0005	uM
7-chloro-11-methyl-11-azatricyclo[12.4.0.03,8]octadeca-1(18),3(8),4,6,14,16-hexaen-6-ol	261575: Inhibition of D1 dopamine receptor in HEK 293 cells by intracellular calcium assay	ki	0.0005	uM
8-chloro-6-[(6S)-1,6-dimethyl-3,6-dihydro-2H-pyridin-4-yl]-3-methyl-11H-benzo[b][1,4]benzodiazepine	1677162: Binding affinity to human dopamine D1 receptor	ki	0.0005	uM
N-[[4-[(5R)-8-chloro-7-hydroxy-3-methyl-1,2,4,5-tetrahydro-3-benzazepin-5-yl]phenyl]methyl]-N-methylmethanesulfonamide	458496: Binding affinity to dopamine D1 receptor	ki	0.0005	uM
(6aR)-2-(3-fluoropropoxy)-6-propyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinolin-11-ol	2086631: Binding affinity to D1 receptor (unknown origin) assessed as inhibition constant	ki	0.0005	uM
N-[[4-[(5R)-8-chloro-7-hydroxy-3-methyl-1,2,4,5-tetrahydro-3-benzazepin-5-yl]phenyl]methyl]-N-methylbenzenesulfonamide	458496: Binding affinity to dopamine D1 receptor	ki	0.0006	uM
11-methyl-11,21-diazatetracyclo[12.7.0.03,8.015,20]henicosa-1(14),3,5,7,15(20),16,18-heptaen-17-ol	305858: Displacement of [3H]SCH 23390 from human cloned dopamine D1 receptor expressed in HEK 293 cells	ki	0.0006	uM
(6aS,13bS)-11-chloro-7-methyl-5,6,6a,8,9,13b-hexahydronaphtho[1,2-a][3]benzazepine-4,12-diol	458849: Displacement of [3H]SCh23390 from dopamine D1 receptor expressed in mouse LTK cells by scintillation counting	ki	0.0006	uM
3-[(6aS,13bS)-11-chloro-12-hydroxy-7-methyl-5,6,6a,8,9,13b-hexahydronaphtho[1,2-a][3]benzazepin-4-yl]benzonitrile	458849: Displacement of [3H]SCh23390 from dopamine D1 receptor expressed in mouse LTK cells by scintillation counting	ki	0.0006	uM
(6aS,13bS)-11-chloro-7-methyl-4-(3-nitrophenyl)-5,6,6a,8,9,13b-hexahydronaphtho[1,2-a][3]benzazepin-12-ol	458849: Displacement of [3H]SCh23390 from dopamine D1 receptor expressed in mouse LTK cells by scintillation counting	ki	0.0006	uM
(6aS,13bS)-11-chloro-4-(1H-indol-5-yl)-7-methyl-5,6,6a,8,9,13b-hexahydronaphtho[1,2-a][3]benzazepin-12-ol	458849: Displacement of [3H]SCh23390 from dopamine D1 receptor expressed in mouse LTK cells by scintillation counting	ki	0.0006	uM
(4aS,5R,10bR)-5-phenyl-1,2,3,4,4a,5,6,10b-octahydrobenzo[h]isoquinoline-7,8-diol	502879: Agonist activity at human D1 receptor assessed as cAMP accumulation	ec50	0.0006	uM
(5R)-8-bromo-3-methyl-5-phenyl-1,2,4,5-tetrahydro-3-benzazepin-7-ol;hydrochloride	63208: Inhibition of [3H]-SCH- 23390 binding to Dopamine receptor D1 from canine striatum	ki	0.0006	uM
N-[(6aS,13bR)-11-chloro-12-hydroxy-7-methyl-5,6,6a,8,9,13b-hexahydronaphtho[1,2-a][3]benzazepin-3-yl]ethanesulfonamide	458496: Binding affinity to dopamine D1 receptor	ki	0.0007	uM
9-chloro-5-phenyl-3-prop-2-enyl-1,2,4,5-tetrahydro-3-benzazepine-7,8-diol	1573447: Agonist activity at human dopamine D1 receptor expressed in CHOK1 cells assessed as reversal of Ro 20-1724 mediated decrease in cAMP accumulation after 60 mins by luminescence assay	ec50	0.0007	uM
(5R)-5-[4-[(N-benzyl-2,4-difluoroanilino)methyl]phenyl]-8-chloro-3-methyl-1,2,4,5-tetrahydro-3-benzazepin-7-ol	458496: Binding affinity to dopamine D1 receptor	ki	0.0007	uM
1-[(6aS,13bR)-11-chloro-12-hydroxy-7-methyl-5,6,6a,8,9,13b-hexahydronaphtho[1,2-a][3]benzazepin-3-yl]-3-(2,6-dichlorophenyl)urea	458496: Binding affinity to dopamine D1 receptor	ki	0.0007	uM
(6aS,13bS)-11-chloro-4-(4-methoxyphenyl)-7-methyl-5,6,6a,8,9,13b-hexahydronaphtho[1,2-a][3]benzazepin-12-ol	458849: Displacement of [3H]SCh23390 from dopamine D1 receptor expressed in mouse LTK cells by scintillation counting	ki	0.0007	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
SCH 23390	affects binding, affects localization, decreases reaction, increases activity, increases phosphorylation (+1 more)	6
7-methyl-6,7,8,9,14,15-hexahydro-5H-benz(d)indolo(2,3-g)azecine	affects binding, decreases activity	3
Clozapine	affects binding, affects response to substance	3
Dopamine	increases activity, decreases reaction, affects localization, affects binding	3
SK&F 81297	increases phosphorylation, increases reaction, affects localization, affects binding, decreases reaction (+1 more)	2
A 86929	affects binding, increases activity, increases chemical synthesis, increases reaction, decreases reaction (+1 more)	2
Resveratrol	affects cotreatment, decreases expression	2
Haloperidol	affects binding, affects activity	2
bisphenol A	affects binding	1
terbufos	increases methylation	1
tetrahydropalmatine	affects binding, decreases activity	1
afimoxifene	increases expression	1
butyraldehyde	decreases expression	1
dihydrexidine	increases activity, decreases reaction, affects binding	1
A 68930	affects localization, affects binding, increases activity, decreases reaction	1
SK&F 77434	affects binding, increases activity	1
SK&F 82958	affects localization, decreases reaction, affects binding, increases activity	1
A 77636	affects binding, increases activity, decreases reaction, affects localization	1
SK&F 83959	affects binding, increases activity	1
dinapsoline	decreases reaction, affects localization, affects binding, increases activity	1
SKF 82957	affects binding, increases activity	1
1-propyl-5-(3-p-tolylisoxazol-5-yl)-1,2,3,6-tetrahydropyridine	increases activity, increases phosphorylation, increases reaction, affects binding, decreases reaction	1
7-fluoro-2-oxo-4-(2-(4-(thieno(3,2-c)pyridin-4-yl)piperazin-1-yl)ethyl)-1,2-dihydroquinoline-1-acetamide	affects activity	1
bardoxolone methyl	decreases activity	1
Sunitinib	decreases expression	1
Cyclic AMP	increases chemical synthesis, increases reaction	1
Apomorphine	affects binding, increases activity, decreases reaction	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Chlorpromazine	decreases activity	1
Cocaine	affects localization, affects folding, affects binding, decreases reaction, increases activity (+2 more)	1

ChEMBL screening assays

902 unique, capped per target: 710 binding, 179 functional, 12 admet, 1 unclassified

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000166	Binding	Binding affinity to dopamine D1 receptor	Synthesis and evaluation of dibenzothiazepines: a novel class of selective cannabinoid-1 receptor inverse agonists. — J Med Chem
CHEMBL1038857	Functional	Antagonist activity at human dopamine D1 receptor expressed in HEK293 cells assessed as SKF-38393-induced intracellular calcium by fluorescence microplate reader	Dibenzazecine scaffold rebuilding–is the flexibility always essential for high dopamine receptor affinities? — Bioorg Med Chem
CHEMBL4337838	Unclassified	Ratio of EC50 for agonist activity at human D1 receptor stably expressed in HEK293 cells assessed as induction of cAMP accumulation incubated for 60 mins by HTRF assay to EC50 for positive allosteric modulator activity at human D1 receptor	Synthesis and Pharmacological Characterization of 2-(2,6-Dichlorophenyl)-1-((1S,3R)-5-(3-hydroxy-3-methylbutyl)-3-(hydroxymethyl)-1-methyl-3,4-dihydroisoquinolin-2(1H)-yl)ethan-1-one (LY3154207), a Potent, Subtype Selective, and Orally Available Positive Allosteric Modulator of the Human Dopamine D1 Receptor. — J Med Chem

Cellosaurus cell lines

12 cell lines: 5 transformed cell line, 4 spontaneously immortalized cell line, 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_9867	D1-HEK-293	Transformed cell line	Female
CVCL_C0SI	ACTOne DRD1	Transformed cell line	Female
CVCL_D1S6	Abcam U-87MG DRD1 KO	Cancer cell line	Male
CVCL_E1GS	HEK293 D1	Transformed cell line	Female
CVCL_H420	CHO-K1/D1	Spontaneously immortalized cell line	Female
CVCL_KV06	cAMP Hunter CHO-K1 DRD1 Gs	Spontaneously immortalized cell line	Female
CVCL_KW85	PathHunter CHO-K1 DRD1 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_LA19	PathHunter U2OS DRD1 Total GPCR Internalization	Cancer cell line	Female
CVCL_YK11	HEK293 DRD1 cAMP-Nomad	Transformed cell line	Female
CVCL_YK12	HEK293 DRD1 HiTSeeker	Transformed cell line	Female

Clinical trials (associated diseases)

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