DRD5

Summary

DRD5 (dopamine receptor D5, HGNC:3026) is a protein-coding gene on chromosome 4p16.1, encoding D(1B) dopamine receptor (P21918). Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.

This gene encodes the D5 subtype of the dopamine receptor. The D5 subtype is a G-protein coupled receptor which stimulates adenylyl cyclase. This receptor is expressed in neurons in the limbic regions of the brain. It has a 10-fold higher affinity for dopamine than the D1 subtype. Pseudogenes related to this gene reside on chromosomes 1 and 2.

Source: NCBI Gene 1816 — RefSeq curated summary.

At a glance

• Gene–disease (curated): attention deficit-hyperactivity disorder (No Known Disease Relationship, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 111 total
• Phenotypes (HPO): 6
• Druggable target: yes — 36 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_000798

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3026
Approved symbol	DRD5
Name	dopamine receptor D5
Location	4p16.1
Locus type	gene with protein product
Status	Approved
Aliases	DRD1B
Ensembl gene	ENSG00000169676
Ensembl biotype	protein_coding
OMIM	126453
Entrez	1816

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000304374, ENST00000888644, ENST00000953045

RefSeq mRNA: 1 — MANE Select: NM_000798 NM_000798

CCDS: CCDS3405

Canonical transcript exons

ENST00000304374 — 1 exons

Exon	Start	End
ENSE00001130832	9781634	9784009

Expression profiles

Bgee: expression breadth broad, 64 present calls, max score 78.31.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0306 / max 4.5424, expressed in 16 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
46907	0.0306	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	78.31	gold quality
tibialis anterior	UBERON:0001385	72.70	silver quality
ileal mucosa	UBERON:0000331	71.75	gold quality
buccal mucosa cell	CL:0002336	69.61	gold quality
prefrontal cortex	UBERON:0000451	66.56	gold quality
triceps brachii	UBERON:0001509	65.04	gold quality
gluteal muscle	UBERON:0002000	64.92	gold quality
anterior cingulate cortex	UBERON:0009835	64.73	gold quality
cingulate cortex	UBERON:0003027	64.67	gold quality
deltoid	UBERON:0001476	62.88	silver quality
Brodmann (1909) area 9	UBERON:0013540	60.71	gold quality
neocortex	UBERON:0001950	59.41	gold quality
frontal cortex	UBERON:0001870	59.22	gold quality
vermiform appendix	UBERON:0001154	59.14	gold quality
hypothalamus	UBERON:0001898	58.17	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	57.46	gold quality
upper leg skin	UBERON:0004262	57.41	gold quality
right frontal lobe	UBERON:0002810	57.39	gold quality
diaphragm	UBERON:0001103	56.72	gold quality
decidua	UBERON:0002450	56.55	gold quality
caecum	UBERON:0001153	56.31	gold quality
putamen	UBERON:0001874	56.15	gold quality
skin of hip	UBERON:0001554	56.10	silver quality
cerebral cortex	UBERON:0000956	55.78	gold quality
epithelial cell of pancreas	CL:0000083	54.37	silver quality
cortical plate	UBERON:0005343	54.13	silver quality
telencephalon	UBERON:0001893	53.95	gold quality
caudate nucleus	UBERON:0001873	53.32	gold quality
forebrain	UBERON:0001890	53.03	gold quality
hair follicle	UBERON:0002073	52.43	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.81

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting DRD5, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-4477B	99.23	70.49	1733
HSA-MIR-4727-5P	99.23	67.55	1154
HSA-MIR-1253	99.12	67.08	1688
HSA-MIR-6737-3P	98.95	68.56	1577
HSA-MIR-7157-3P	98.95	68.70	1582
HSA-MIR-6889-3P	98.84	67.35	1198
HSA-MIR-5008-3P	98.73	67.50	1433
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-3136-5P	98.53	67.68	793
HSA-MIR-4439	98.53	67.53	793
HSA-MIR-6764-3P	98.44	67.64	1153
HSA-MIR-6824-3P	98.44	67.62	1154
HSA-MIR-6819-5P	97.96	66.59	1071
HSA-MIR-6893-3P	97.79	64.91	1238
HSA-MIR-6737-5P	97.75	66.54	1044
HSA-MIR-6812-5P	97.56	65.39	1059
HSA-MIR-370-3P	97.09	64.92	1221
HSA-MIR-6857-3P	96.70	65.43	915
HSA-MIR-6816-3P	95.05	66.08	459

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Significant age-related decline was observed for dopamine receptor mRNAs in the hippocampus and entorhinal cortex (PMID:12509874)
• susceptibility loci for attention deficit disorder with hyperactivity at DRD5 (PMID:12660802)
• these results suggest that there may be a functional variant of dopamine d5 receptor that conders susceptibility to developing focal dystonia in later life. (PMID:14509667)
• DRD5 146-bp (DRD5.146) allele and the DRD4 240-bp (DRD4.240) allele of the promoter polymorphism emerge as the two DNA variants showing a significant association in this large sample of predominantly multiplex families with attention deficit disorder (PMID:14699430)
• There is no association of DRD5 polymorphism with ADHD. (PMID:14755441)
• The ability of D5 receptor stimulation to decrease ROS production may explain, in part, the antihypertensive action of D5 receptor activation. (PMID:16352863)
• Preferential transmission of paternal alleles at risk genes for ADHD is established. (PMID:16380908)
• seven consecutive SNPs surrounding the D5 dopamine receptor gene (DRD5), were associated with the age at onset for attention deficit hyperactivity disorder (PMID:17501935)
• Genetic analyses of dopamine related genes in adult ADHD patients suggest an association with the DRD5-microsatellite repeat, but not with DRD4 or SLC6A3 VNTRs. (PMID:18081165)
• DRD5 (CA)(n) repeat has a modest effect in modulating susceptibility to adult attention deficit hyperactivity disorder (PMID:18164132)
• 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)
• Dopamine 5 receptor mediates Ang II type 1 receptor degradation via a ubiquitin-proteasome pathway in mice and human cells (PMID:18464932)
• DRD5 protein is associated with ADHD. (PMID:18563476)
• co-localizes with dopamine D2 receptor (together, they activate a calcium signal); a robust calcium signal is also seen with dopamine D5 alone. (PMID:19171671)
• Levels of mRNA for DRD3 and DRD5 were similar in cells from healthy subjects and from Alzheimer disease patients (PMID:19266703)
• study reports the haplotype structure of the DRD5 coding region; analysis of the DRD5 coding region reveals two highly polymorphic SNPs in weak linkage disequilibrium and a low frequency of rare variants (PMID:19397556)
• results using chimerical receptors support the notion that amino terminus and transmembrane 1 regions may be important in controlling structural changes involved in subtype-specific ligand binding and activation properties of D1R and D5R. (PMID:19786093)
• The DRD5 expression in the temporal lobe of Alzheimer’s disease patients is decressed. (PMID:20164562)
• Data show that indolo[4,3a,3-fg]benzazacycloundecene 3 showed antagonistic properties with nanomolar affinities for all dopamine receptor subtypes. (PMID:20180564)
• These results identify a role of DISC1 in regulating the formation and/or maintenance of primary cilia, and establish subtype-specific targeting of dopamine receptors to the ciliary surface. (PMID:20531939)
• Thirty-six tag single nucleotide polymorphisms (SNPs) and one variable-number tandem repeat, spanning the five dopamine receptor genes (DRD1-DRD5) were analyzed as possible causes for antipsychotic induced weight gain (PMID:20714340)
• These findings suggest that the conflicting findings obtained in association studies between ADRA2A polymorphisms and ADHD might be related to temperament profiles, and support additional studies addressing these effects in larger samples. (PMID:20864182)
• selective activation of D1/D5 receptors could protect synapses from the deleterious action of Abeta oligomers; a selective D1/D5 receptor agonist, prevented the reduction in surface levels of AMPA and NMDA receptors induced by AbetaOs in hippocampal neurons (PMID:21115476)
• Data show that the D5 receptor shows a trafficking profile distinct from that of any of the other dopamine receptors. (PMID:21348911)
• intracellular loop 3 is the critical determinant underlying the subtype-specific regulation of human D5-dopaminergic receptor responsiveness by protein kinase C (PMID:21893192)
• The concentrations of DRD4-mRNA in the whole blood were significantly lower in ADHD and ASD children (19 of 26 comorbid with ADHD) compared to healthy controls. ASD patients revealed a significantly decreased DRD5 mRNA expression. (PMID:21906006)
• Tests of a DRD5 microsatellite and four DRD5 single nucleotide polymorphism variants do not support a significant deviation from the Hardy-Weinberg equilibrium in either Caucasian or African American patients. (PMID:22203087)
• For the first time we report a significant association between nicotine dependence and DRD5, NPY1R MAP3K4 single nucleotide polymorphism. (PMID:22309839)
• confirmed at protein level the previously reported increased expression of DRD5 and the variably aberrant expression of ADORA2A, in Lesch-Nyhan disease lymphocytes (PMID:22403020)
• Dopamine and angiotensin type 2 receptors cooperatively inhibit sodium transport in human renal proximal tubule cells. (PMID:22710646)
• SNX1 has a crucial role in D(5)R trafficking and SNX1 depletion results in D(5)R dysfunction and thus may represent a novel mechanism for the pathogenesis of essential hypertension (PMID:23152498)
• in this report, the specific amino acids in the cytoplasmic regions of D5 and D2 receptors involved in heteromer interactions were determined. (PMID:23318175)
• Its signaling regulates human osteoclastogenesis. (review) (PMID:23445730)
• D1R and D5R colocalize in renal proximal tubule cells and physically interact in second messenger coupling pathways and heterologous receptor interaction between the two receptors. (PMID:24552847)
• We found significant negative correlations regarding the expression of the genes COMT, MAOB, DRD4, DRD5 and FOS, indicating that increased schizotypy coincides with higher levels of dopaminergic dysregulation on the mRNA-level. (PMID:24630741)
• Our find-ings suggest that common genetic variations of DRD5 are likely to con-tribute to genetic susceptibility to paranoid schizophrenia in Han Chinese (PMID:24668635)
• LRs are essential not only for the proper membrane distribution and maintenance of AC5/6 activity but also for the regulation of D1R- and D5R-mediated AC signaling. (PMID:25049074)
• Constitutive D5R signalling up-regulated expression of Na,K-ATPase-alpha2 and NHE-2, increasing glucose metabolism. Agonist treatment increased this and also upregulated NHE-3. (PMID:25154512)
• This study demonistrated that Lymphocyte DR D5 is reduced in MS and IFN-beta restores their expression and responsiveness. (PMID:25468276)
• This study shown DRD5 to be the risk factor for attention deficit/hyperactivity disorder. (PMID:25840828)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	DRD5	ENSDARG00000037576
mus_musculus	Drd5	ENSMUSG00000039358
rattus_norvegicus	Drd5	ENSRNOG00000005338

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), HTR1A (ENSG00000178394), HTR1D (ENSG00000179546), CHRM4 (ENSG00000180720), CHRM2 (ENSG00000181072), DRD1 (ENSG00000184845), CHRM5 (ENSG00000184984), GPR21 (ENSG00000188394), HRH1 (ENSG00000196639), GPR52 (ENSG00000203737), TAAR9 (ENSG00000237110)

Protein

Protein identifiers

D(1B) dopamine receptor — P21918 (reviewed: P21918)

Alternative names: D(5) dopamine receptor, D1beta dopamine receptor, Dopamine D5 receptor

All UniProt accessions (1): P21918

UniProt curated annotations — full annotation on UniProt →

Function. Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.

Subcellular location. Cell membrane.

Tissue specificity. Neuron-specific, localized primarily within limbic regions of the brain.

Disease relevance. Benign essential blepharospasm (BEB) [MIM:606798] A primary focal dystonia affecting the orbicularis oculi muscles. Dystonia is defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. BEB usually begins in middle age. Initial symptoms include eye irritation and frequent blinking, progressing to involuntary spasms of eyelid closure. Patients have normal eyes. The visual disturbance is due solely to the forced closure of the eyelids. In severe cases, this can lead to functional blindness. Disease susceptibility may be associated with variants affecting the gene represented in this entry.

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

RefSeq proteins (1): NP_000789* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000497	Dopamine_D5_rcpt	Family
IPR000929	Dopamine_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (45 total): sequence variant 12, helix 12, topological domain 8, transmembrane region 7, glycosylation site 2, chain 1, lipid moiety-binding region 1, disulfide bond 1, mutagenesis site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8IRV	ELECTRON MICROSCOPY	3.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P21918-F1	69.45	0.31

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 (1): 375

Disulfide bonds (1): 113–217

Glycosylation sites (2): 7, 222

Mutagenesis-validated functional residues (1):

Position	Phenotype
7	impairs subcellular location.

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: 159 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, BENPORATH_ES_WITH_H3K27ME3, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_RESPONSE_TO_COCAINE, GOBP_RESPONSE_TO_AMINE, XU_GH1_AUTOCRINE_TARGETS_UP, GOBP_ASSOCIATIVE_LEARNING, GOBP_REGULATION_OF_SYSTEMIC_ARTERIAL_BLOOD_PRESSURE, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_POSITIVE_REGULATION_OF_LYASE_ACTIVITY, DARWICHE_SKIN_TUMOR_PROMOTER_UP

GO Biological Process (27): synaptic transmission, dopaminergic (GO:0001963), response to amphetamine (GO:0001975), regulation of systemic arterial blood pressure by vasopressin (GO:0001992), norepinephrine-epinephrine vasoconstriction involved in regulation of systemic arterial blood pressure (GO:0001994), intracellular calcium ion homeostasis (GO:0006874), 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), chemical synaptic transmission (GO:0007268), associative learning (GO:0008306), transmission of nerve impulse (GO:0019226), obsolete negative regulation of NAD(P)H oxidase activity (GO:0033861), wound healing (GO:0042060), response to cocaine (GO:0042220), positive regulation of MAPK cascade (GO:0043410), positive regulation of adenylate cyclase activity (GO:0045762), negative regulation of blood pressure (GO:0045776), regulation of female receptivity (GO:0045924), sensitization (GO:0046960), phospholipase C-activating dopamine receptor signaling pathway (GO:0060158), long-term synaptic depression (GO:0060292), cellular response to catecholamine stimulus (GO:0071870), adenylate cyclase-activating adrenergic receptor signaling pathway (GO:0071880), reactive oxygen species metabolic process (GO:0072593), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), mating behavior (GO:0007617)

GO Molecular Function (5): dopamine neurotransmitter receptor activity, coupled via Gs (GO:0001588), G protein-coupled receptor activity (GO:0004930), dopamine neurotransmitter receptor activity (GO:0004952), dopamine binding (GO:0035240), protein binding (GO:0005515)

GO Cellular Component (7): plasma membrane (GO:0005886), cilium (GO:0005929), brush border membrane (GO:0031526), synapse (GO:0045202), ciliary membrane (GO:0060170), non-motile cilium (GO:0097730), membrane (GO:0016020)

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 dopamine receptor signaling pathway	3
chemical synaptic transmission	2
synaptic transmission, dopaminergic	2
G protein-coupled receptor signaling pathway	2
cell projection membrane	2
cilium	2
response to amine	1
regulation of systemic arterial blood pressure by hormone	1
positive regulation of blood pressure by epinephrine-norepinephrine	1
vasoconstriction	1
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	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
anterograde trans-synaptic signaling	1
learning	1
action potential	1
cell communication	1
nervous system process	1
response to wounding	1
tissue regeneration	1
response to alkaloid	1
response to oxygen-containing compound	1
MAPK cascade	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
adenylate cyclase activity	1
positive regulation of cyclase activity	1
regulation of adenylate cyclase activity	1
positive regulation of lyase activity	1
regulation of blood pressure	1
female mating behavior	1
regulation of biological quality	1
nonassociative learning	1
phospholipase C-activating G protein-coupled receptor signaling pathway	1
dopamine neurotransmitter receptor activity	1
transmembrane signaling receptor activity	1
dopamine binding	1

Protein interactions and networks

STRING

1062 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DRD5	SLC6A3	Q01959	841
DRD5	GPRIN2	O60269	834
DRD5	HYDIN	Q4G0P3	830
DRD5	NBPF1	Q3BBV0	812
DRD5	NPEPPS	P55786	811
DRD5	UGT2B17	O75795	810
DRD5	SRGAP2	O75044	772
DRD5	SRGAP3	O43295	770
DRD5	GTF2I	P78347	761
DRD5	COMT	P21964	659
DRD5	SLC6A4	P31645	644
DRD5	DBH	P09172	636
DRD5	MAOA	P21397	610
DRD5	SNAP25	P13795	582
DRD5	DRD4	P21917	555

IntAct

14 interactions, top by confidence:

A	B	Type	Score
NOTCH2NLC	DRD5	psi-mi:“MI:0915”(physical association)	0.560
DRD5	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
RAMP1	DRD5	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	DRD5	psi-mi:“MI:0915”(physical association)	0.400
DRD5	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
DRD5	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	DRD5	psi-mi:“MI:0915”(physical association)	0.400
DRD5	NOTCH2NLC	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (10): GNA13 (Affinity Capture-Western), GNA12 (Affinity Capture-Western), NOTCH2NL (Two-hybrid), NBPF19 (Two-hybrid), DRD5 (Reconstituted Complex), DRD5 (Reconstituted Complex), DRD5 (Affinity Capture-Western), DRD5 (Reconstituted Complex), DRD5 (Two-hybrid), MDH2 (Cross-Linking-MS (XL-MS))

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

Diamond homologs: G3M4F8, O02662, O02666, O02824, O08890, O42384, O42385, O42574, O70528, O77680, P04274, P07550, P07700, P08908, P10608, P15823, P17124, P18090, P18130, P18762, P18841, P18901, P19327, P21728, P21918, P23944, P25021, P25100, P25102, P25115, P25962, P26255, P28565, P30939, P32304, P32305, P34969, P35348, P35368, P35406

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
DRD5	“up-regulates activity”	GNAS	binding
DRD5	“up-regulates activity”	GNAL	binding
DRD5	“up-regulates activity”	GNAI1	binding
DRD5	“up-regulates activity”	GNAI3	binding
DRD5	“up-regulates activity”	GNAO1	binding
DRD5	“up-regulates activity”	GNAZ	binding
DRD5	“up-regulates activity”	GNAQ	binding
DRD5	“up-regulates activity”	GNA14	binding
dopamine	“up-regulates activity”	DRD5	“chemical activation”

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	96
Likely benign	8
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

136 predictions. Top by Δscore:

Variant	Effect	Δscore
4:9782996:A:AG	acceptor_gain	0.9200
4:9782997:G:GG	acceptor_gain	0.9200
4:9782196:T:A	acceptor_gain	0.9000
4:9782186:T:TA	acceptor_gain	0.8900
4:9782910:TTCTC:T	donor_gain	0.8800
4:9781855:C:T	donor_gain	0.7800
4:9782996:AGT:A	acceptor_gain	0.7800
4:9782997:GT:G	acceptor_gain	0.7800
4:9782997:GTG:G	acceptor_gain	0.7800
4:9782930:A:AG	donor_gain	0.7700
4:9782911:TCTCA:T	donor_gain	0.6900
4:9782277:T:TA	acceptor_gain	0.6500
4:9782912:C:CG	donor_gain	0.6400
4:9782931:T:G	donor_gain	0.6400
4:9782896:G:GT	donor_gain	0.6300
4:9781851:G:GT	donor_gain	0.6200
4:9782900:G:GT	donor_gain	0.5600
4:9782925:C:CA	donor_gain	0.5500
4:9782187:G:A	acceptor_gain	0.5100
4:9782176:A:AG	acceptor_gain	0.4800
4:9782996:AGTG:A	acceptor_gain	0.4600
4:9782997:GTGG:G	acceptor_gain	0.4600
4:9782997:GTGGA:G	acceptor_gain	0.4400
4:9782943:T:TG	donor_gain	0.4300
4:9782197:G:A	acceptor_gain	0.4100
4:9781893:TCATG:T	donor_loss	0.4000
4:9781894:CATGG:C	donor_loss	0.4000
4:9781895:ATGG:A	donor_loss	0.4000
4:9781896:TG:T	donor_loss	0.4000
4:9781897:GGTGA:G	donor_loss	0.4000

AlphaMissense

3144 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:9782726:A:C	S233R	0.998
4:9782728:C:A	S233R	0.998
4:9782728:C:G	S233R	0.998
4:9782963:T:C	F312L	0.998
4:9782965:C:A	F312L	0.998
4:9782965:C:G	F312L	0.998
4:9782367:G:A	C113Y	0.997
4:9782966:T:C	F313L	0.996
4:9782968:C:A	F313L	0.996
4:9782968:C:G	F313L	0.996
4:9782350:G:C	W107C	0.995
4:9782350:G:T	W107C	0.995
4:9782432:A:C	S135R	0.995
4:9782434:C:A	S135R	0.995
4:9782434:C:G	S135R	0.995
4:9782942:T:C	F305L	0.995
4:9782944:C:A	F305L	0.995
4:9782944:C:G	F305L	0.995
4:9782367:G:T	C113F	0.994
4:9782729:T:C	F234L	0.994
4:9782731:C:A	F234L	0.994
4:9782731:C:G	F234L	0.994
4:9782366:T:A	C113S	0.993
4:9782367:G:C	C113S	0.993
4:9782368:C:G	C113W	0.993
4:9783065:T:A	W346R	0.993
4:9783065:T:C	W346R	0.993
4:9782706:C:A	A226D	0.991
4:9782289:A:C	D87A	0.990
4:9782388:A:T	D120V	0.990

dbSNP variants (sampled 300 via entrez): RS1000448412 (4:9780068 G>A,C), RS1000776213 (4:9784375 T>C), RS1003356627 (4:9781381 A>C), RS1004658201 (4:9781758 C>A), RS1004925094 (4:9781595 G>A,T), RS1005601977 (4:9783655 C>T), RS1006668679 (4:9779940 G>C), RS1006942343 (4:9779746 C>T), RS1007928569 (4:9783054 A>T), RS1009144888 (4:9784345 A>G), RS1009371318 (4:9780909 A>G), RS1009919216 (4:9781138 C>G), RS1010511590 (4:9780086 A>C,T), RS1011181846 (4:9782086 GCAGCT>G), RS1011465129 (4:9781877 C>A,T)

Disease associations

OMIM: gene MIM:126453 | disease phenotypes: MIM:143465, MIM:181500, MIM:613003, MIM:203100

GenCC curated gene-disease

Disease	Classification	Inheritance
attention deficit-hyperactivity disorder	No Known Disease Relationship	Unknown

Mondo (5): hereditary attention deficit-hyperactivity disorder (MONDO:0100518), schizophrenia (MONDO:0005090), attention deficit-hyperactivity disorder, susceptibility to, 7 (MONDO:0013076), oculocutaneous albinism type 1A (MONDO:0008745), attention deficit-hyperactivity disorder (MONDO:0007743)

Orphanet (3): Oculocutaneous albinism type 1 (Orphanet:352731), Oculocutaneous albinism type 1A (Orphanet:79431), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

6 total (7 of 6 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000643	Blepharospasm
HP:0000752	Hyperactivity
HP:0003596	Middle age onset
HP:0003745	Sporadic
HP:0007018	Attention deficit hyperactivity disorder
HP:0100753	Schizophrenia

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002932_12	Manganese levels	6.000000e-06
GCST003875_45	Gut microbiota (bacterial taxa)	3.000000e-09
GCST004748_43	Lung cancer	4.000000e-06
GCST007628_1	Impulsivity (motor)	3.000000e-07
GCST009391_1251	Metabolite levels	9.000000e-07

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement
EFO:0007883	taxonomic microbiome measurement
EFO:0006946	behavioural disinhibition measurement
EFO:0004761	uric acid measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1850 (SINGLE PROTEIN), CHEMBL2096905 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

36 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 622,271 (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
CHEMBL11	IMIPRAMINE	4	48,893
CHEMBL1112	ARIPIPRAZOLE	4	24,205
CHEMBL1113	AMOXAPINE	4	20,128
CHEMBL1200517	DIHYDROERGOTAMINE MESYLATE	4	2,704
CHEMBL1516474	TEGASEROD MALEATE	4	1,823
CHEMBL1557	DOPAMINE HYDROCHLORIDE	4	42,025
CHEMBL1621	PALIPERIDONE	4	1,701
CHEMBL1628227	DOXEPIN	4	28,171
CHEMBL1633	KETOTIFEN FUMARATE	4	3,954
CHEMBL2028019	CARIPRAZINE	4	1,576
CHEMBL2105760	BREXPIPRAZOLE	4	1,755
CHEMBL21731	MAPROTILINE	4	19,686
CHEMBL3039520	LASMIDITAN	4	550
CHEMBL42	CLOZAPINE	4	37,581
CHEMBL53	APOMORPHINE	4	25,813
CHEMBL54	HALOPERIDOL	4	60,883
CHEMBL564	PROMAZINE	4	9,707
CHEMBL589	ROPINIROLE	4	21,493
CHEMBL59	DOPAMINE	4	217,028
CHEMBL629	AMITRIPTYLINE	4	52,595
CHEMBL71	CHLORPROMAZINE	4
CHEMBL715	OLANZAPINE	4
CHEMBL726	FLUPHENAZINE	4
CHEMBL831	LOXAPINE	4
CHEMBL85	RISPERIDONE	4
CHEMBL908	CHLORPROTHIXENE	4
CHEMBL1201087	CABERGOLINE	4
CHEMBL298406	ECOPIPAM	3
CHEMBL186720	PHENYLTOLOXAMINE	2
CHEMBL263881	LYSERGIDE	2

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Dopamine receptors

Most potent curated ligand interactions (32 total), top 25:

Ligand	Action	Affinity	Parameter
SCH-23390	Antagonist	9.5	pKi
SKF-83566	Antagonist	9.4	pKi
[3H]SCH-23390	Antagonist	9.2	pKd
[125I]SCH23982	Antagonist	9.1	pKd
lisuride	Partial agonist	8.5	pKi
ecopipam	Antagonist	8.3	pKi
(-)-stepholidine	Antagonist	8.24	pKi
flupentixol	Antagonist	8.1	pKi
fluphenazine	Antagonist	7.9	pKi
apomorphine	Partial agonist	7.8	pKi
(+)-SKF-82526	Full agonist	7.8	pKi
cabergoline	Full agonist	7.7	pKi
(+)-butaclamol	Antagonist	7.6	pKi
pergolide	Full agonist	7.5	pKi
SKF-38393	Partial agonist	7.0	pKi
chlorpromazine	Antagonist	6.9	pKi
beta-ergocriptine	Full agonist	6.9	pKi
clozapine	Antagonist	6.6	pKi
A68930	Agonist	6.6	pEC50
dopamine	Full agonist	6.6	pKi
bromocriptine	Full agonist	6.3	pKi
haloperidol	Antagonist	6.3	pKi
SKF-76783	Full agonist	6.3	pKi
(-)-SKF-82526	Full agonist	6.1	pKi
(+)-ADTN	Full agonist	6.0	pKi

Binding affinities (BindingDB)

142 measured of 174 human assays (196 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
2-N-(4-methoxyphenyl)-6-[(1-methyltetrazol-5-yl)sulfanylmethyl]-1,3,5-triazine-2,4-diamine	EC50	0.000516 nM
2-(4-fluorophenyl)-5-[(phenylmethyl)amino]-1,3-oxazole-4-carbonitrile	EC50	0.00105 nM
2-[4-[[3-(3,5-dimethyl-1-pyrazolyl)-2-quinoxalinyl]amino]phenyl]acetic acid	EC50	0.00111 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
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
5-phenyl-[1,2,4]triazolo[4,3-c]quinazoline	EC50	0.00172 nM
4-hydroxy-6-(4-isopropylphenyl)-2-piperidin-1-ylpyrimidine-5-carbonitrile	EC50	0.00175 nM
MLS000042779	EC50	0.0019 nM
2-(2-chlorophenyl)-5-(dimethylamino)-1,3-oxazole-4-carbonitrile	EC50	0.00186 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
MLS000116276	EC50	0.00207 nM
MLS000092489	EC50	0.00289 nM
2-amino-4-(3-thienyl)thiophene-3-carboxylic acid ethyl ester	EC50	0.00302 nM
5,7-dihydroxy-3-(4-methoxyphenyl)-4H-chromen-4-one	EC50	0.00334 nM
MLS000044676	EC50	0.00361 nM
2-(butylthio)-3-ethyl-6-methyl-6,7-dihydrothieno[3,2-d]pyrimidin-4-one	EC50	0.00374 nM
1-Phenylbenzimidazole deriv. 76	EC50	0.00399 nM
2-ethyl-4-(1-piperidinyl)benzofuro[3,2-d]pyrimidine;hydrochloride	EC50	0.00455 nM
4-(4-bromophenyl)-4,10-dihydro-[1,3,5]triazino[1,2-a]benzimidazol-2-amine;ethanoic acid	EC50	0.0048 nM
3-(4-morpholinyl)-1-propyl-5,6,7,8-tetrahydroisoquinoline-4-carbonitrile	EC50	0.00492 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
MLS000116693	EC50	0.00545 nM
3,5-Bis-propylsulfanyl-isothiazole-4-carboxylic acid amide	EC50	0.00566 nM
2-acetoxypropyl(trimethyl)ammonium;chloride	EC50	0.0062 nM
3-[(2-fluorophenyl)methyl]-5-propyl-N-(pyridin-4-ylmethyl)-7-triazolo[4,5-d]pyrimidinamine	EC50	0.00655 nM
1’-{[4-(3-chlorophenyl)piperazin-1-yl]methyl}spiro[1,3-dioxane-2,3’-indol]-2’(1’H)-one	EC50	0.00712 nM
2-[(3-ethyl-4-keto-6-methyl-6,7-dihydrothieno[3,2-d]pyrimidin-2-yl)thio]-N-(5-methylisoxazol-3-yl)acetamide	EC50	0.00738 nM
1-[2-(2-allylphenoxy)ethyl]-1H-imidazole	EC50	0.00743 nM
4-[4-chloro-3-(phenylsulfamoyl)benzoyl]piperazine-1-carboxylic acid ethyl ester	EC50	0.00778 nM
9-(2-thienyl)-2,3,8,9-tetrahydro[1,4]dioxino[2,3-g]quinolin-7(6H)-one	EC50	0.00785 nM
4-(4-chlorophenyl)-4,10-dihydro-[1,3,5]triazino[1,2-a]benzimidazol-2-amine	EC50	0.00797 nM
2,5-bis(methylthio)-3-thiophenecarboxaldehyde oxime	EC50	0.00798 nM
2-sulfanylidene-1,3-dithiole-4,5-dicarboxylic acid dimethyl ester	EC50	0.00847 nM
3-[3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazol-5-yl]-N-(3-pyridinyl)propanamide	EC50	0.00869 nM
4-(4-Methylamino-6-methylsulfanyl-[1,3,5]triazin-2-yloxy)-benzoic acid ethyl ester	EC50	0.00918 nM
MLS000103371	EC50	0.00942 nM
MLS000088295	EC50	0.00953 nM
2,2-diketo-6-phenyl-3,4-dihydrothiazolo[2,3-c][1,2,4]thiadiazine-7-carboxylic acid ethyl ester	EC50	0.00961 nM
5-[[2-[2-(1-benzimidazolyl)-1-oxoethoxy]-1-oxoethyl]amino]-3-methylthiophene-2,4-dicarboxylic acid diethyl ester	EC50	0.00966 nM
1-benzyl-5-(morpholin-4-ylmethylideneamino)pyrazole-4-carbonitrile	EC50	0.00965 nM
2-[5-(4-Fluoro-phenyl)-thiazolo[2,3-c][1,2,4]triazol-3-ylsulfanyl]-N-furan-2-ylmethyl-acetamide	EC50	0.0101 nM
2-[(4-methyl-1,2,4-triazol-3-yl)sulfanyl]-1-(4,4,8-trimethyl-1-sulfanylidene-[1,2]dithiolo[3,4-c]quinolin-5-yl)ethanone	EC50	0.0101 nM
3-[3-(3-ethoxy-4-methoxy-phenyl)-1,2,4-oxadiazol-5-yl]-1-morpholin-4-yl-propan-1-one	EC50	0.0108 nM
MLS000056567	EC50	0.0113 nM
2-amino-4-(4-pyridyl)thiophene-3-carboxylic acid ethyl ester	EC50	0.0117 nM
1-[(3-phenyl[1,3]thiazolo[2,3-c][1,2,4]triazol-6-yl)methyl]indoline	EC50	0.0118 nM
MLS000082582	EC50	0.0119 nM

ChEMBL bioactivities

522 potent at pChembl≥5 of 558 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.28	Ki	0.053	nM	CHEMBL203637
10.24	Ki	0.057	nM	CHEMBL203637
9.82	IC50	0.15	nM	CHEMBL1814790
9.77	Ki	0.17	nM	CHEMBL1814790
9.64	Ki	0.23	nM	CHEMBL245764
9.62	Kd	0.24	nM	CHEMBL4860528
9.62	Kd	0.24	nM	CHEMBL5207281
9.62	Kd	0.24	nM	CHEMBL5206565
9.62	Kd	0.24	nM	CHEMBL5201074
9.52	Ki	0.3	nM	SCH-23390
9.43	IC50	0.37	nM	CHEMBL1814790
9.43	Ki	0.37	nM	CHEMBL5191141
9.41	Ki	0.39	nM	CHEMBL245570
9.32	Ki	0.48	nM	SCH-23390
9.30	Ki	0.5	nM	(R)-SKF-38393
9.27	Ki	0.54	nM	CHEMBL381936
9.25	IC50	0.56	nM	CHEMBL13668
9.24	Ki	0.57	nM	CHEMBL184050
9.21	Ki	0.61	nM	CHEMBL216258
9.17	Ki	0.67	nM	CHEMBL5201983
9.01	Ki	0.98	nM	CHEMBL380464
8.96	IC50	1.1	nM	SCH-23390
8.92	Ki	1.2	nM	CHEMBL383451
8.92	Ki	1.2	nM	CHEMBL599487
8.85	EC50	1.4	nM	CHEMBL353335
8.85	Ki	1.4	nM	CHEMBL604314
8.82	Ki	1.5	nM	CHEMBL201170
8.82	Ki	1.5	nM	CHEMBL1204122
8.80	Ki	1.6	nM	CHEMBL380464
8.78	Ki	1.68	nM	CHEMBL381936
8.77	Ki	1.69	nM	CHEMBL1204122
8.77	Ki	1.69	nM	CHEMBL201170
8.76	Ki	1.75	nM	CHEMBL324017
8.74	Ki	1.8	nM	CHEMBL184049
8.74	EC50	1.8	nM	SKF-89124A
8.72	Ki	1.9	nM	CHEMBL3753266
8.72	Ki	1.9	nM	CHEMBL597900
8.71	Ki	1.95	nM	CHEMBL1489369
8.70	EC50	2	nM	DOPAMINE
8.70	Ki	2	nM	ECOPIPAM
8.68	Ki	2.1	nM	CHEMBL605354
8.64	Ki	2.3	nM	CHEMBL324017
8.63	Ki	2.32	nM	CHEMBL1202298
8.60	Ki	2.5	nM	CHEMBL599135
8.60	Ki	2.5	nM	CHEMBL1087300
8.55	Ki	2.8	nM	CHEMBL216258
8.55	Ki	2.8	nM	SCH-23390
8.52	Ki	3	nM	CHEMBL3752512
8.52	Ki	3.02	nM	CHEMBL1256876
8.51	Ki	3.09	nM	CHEMBL201525

PubChem BioAssay actives

468 with measured affinity, of 1573 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
7-chloro-11-methyl-11-azatricyclo[12.4.0.03,8]octadeca-1(18),3(8),4,6,14,16-hexaen-6-ol	261573: Binding affinity to D5 dopamine receptor by radioligand binding assay	ki	0.0001	uM
(Z)-but-2-enedioic acid;(5R)-8-chloro-3-methyl-5-phenyl-1,2,4,5-tetrahydro-3-benzazepin-7-ol	752248: Binding affinity to human dopamine D5 receptor by radioligand displacement assay	ic50	0.0001	uM
1-[N’-[3-(2-amino-4-methyl-1,3-thiazol-5-yl)propyl]carbamimidoyl]-3-pentylurea	1895225: Displacement of [3H]SCH23390 from human D5 receptor stably expressed in HEK293T cells co-expressing luciferase and CEK incubated for 60 mins by scintillation counting analysis	kd	0.0002	uM
17-methoxy-11,21-dimethyl-11,21-diazatetracyclo[12.7.0.03,8.015,20]henicosa-1(14),3,5,7,15(20),16,18-heptaene	305862: Binding affinity to human cloned dopamine D5 receptor expressed in HEK 293 cells	ki	0.0002	uM
1-[(1R)-1-phenylethyl]-3-[N’-[3-(1H-1,2,4-triazol-5-yl)propyl]carbamimidoyl]urea;dihydrochloride	1895225: Displacement of [3H]SCH23390 from human D5 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)	1895225: Displacement of [3H]SCH23390 from human D5 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)	1895225: Displacement of [3H]SCH23390 from human D5 receptor stably expressed in HEK293T cells co-expressing luciferase and CEK incubated for 60 mins by scintillation counting analysis	kd	0.0002	uM
(5R)-8-chloro-3-methyl-5-phenyl-1,2,4,5-tetrahydro-3-benzazepin-7-ol	1664375: Antagonist activity at dopamine D5 receptor (unknown origin)	ki	0.0003	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	305862: Binding affinity to human cloned dopamine D5 receptor expressed in HEK 293 cells	ki	0.0004	uM
4-[(1R,3S)-6-chloro-3-(2,3,4,5,6-pentadeuteriophenyl)-2,3-dihydro-1H-inden-1-yl]-2,2-dimethyl-1-(trideuteriomethyl)piperazine	1862826: Displacement of [3H]SCH 23390 from recombinant human D5 receptor measured after 60 mins by scintillation counting analysis	ki	0.0004	uM
11-methyl-11-azatricyclo[12.4.0.03,8]octadeca-1(14),3(8),4,6,15,17-hexaene-6,16-diol	261578: Inhibition of D5 dopamine receptor in HEK 293 cells by intracellular calcium assay	ki	0.0005	uM
(5R)-5-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol	1664377: Agonist activity at dopamine D5 receptor (unknown origin)	ki	0.0005	uM
12-methyl-9-oxa-12-azatricyclo[13.4.0.03,8]nonadeca-1(19),3(8),4,6,15,17-hexaen-6-ol	238492: Binding affinity for human recombinant dopamine receptor D5	ki	0.0006	uM
12-methyl-12,22-diazatetracyclo[13.7.0.03,8.016,21]docosa-1(15),3,5,7,16,18,20-heptaene	273263: Displacement of [3H]SCH 23390 from human D5 dopamine receptor expressed in HEK293 cells	ki	0.0006	uM
8-chloro-3-methyl-5-phenyl-1,2,4,5-tetrahydro-3-benzazepin-7-ol	1285628: Displacement of [3H]SCH23390 from human recombinant Dopamine D5 receptor expressed in GH4 cells	ic50	0.0006	uM
1-[(1R,3S)-6-chloro-3-(2,3,4,5,6-pentadeuteriophenyl)-2,3-dihydro-1H-inden-1-yl]-3,3-dimethylpiperazine	1862826: Displacement of [3H]SCH 23390 from recombinant human D5 receptor measured after 60 mins by scintillation counting analysis	ki	0.0007	uM
4-chloro-11-methyl-11-azatricyclo[12.4.0.03,8]octadeca-1(18),3(8),4,6,14,16-hexaen-5-ol	261573: Binding affinity to D5 dopamine receptor by radioligand binding assay	ki	0.0010	uM
N-[[4-[(5R)-8-chloro-7-hydroxy-3-methyl-1,2,4,5-tetrahydro-3-benzazepin-5-yl]phenyl]methyl]-N-methylbenzenesulfonamide	458497: Binding affinity to dopamine D5 receptor	ki	0.0012	uM
5,7-dichloro-11-methyl-11-azatricyclo[12.4.0.03,8]octadeca-1(18),3,5,7,14,16-hexaen-6-ol	261578: Inhibition of D5 dopamine receptor in HEK 293 cells by intracellular calcium assay	ki	0.0012	uM
9-chloro-5-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol	1633736: Agonist activity at D5R (unknown origin) expressed in HEK293 cells assessed as effect on cAMP accumulation incubated for 10 mins by Gs-cAMP Glosensor assay	ec50	0.0014	uM
(6aS,13bS)-11-chloro-7-methyl-5,6,6a,8,9,13b-hexahydronaphtho[1,2-a][3]benzazepine-4,12-diol	458850: Displacement of radioligand from dopamine D5 receptor expressed in mouse LTK cells by scintillation counting	ki	0.0014	uM
11-methyl-11-azatricyclo[12.4.0.03,8]octadeca-1(18),3(8),4,6,14,16-hexaen-6-ol	261573: Binding affinity to D5 dopamine receptor by radioligand binding assay	ki	0.0015	uM
11-methyl-11-azatricyclo[12.4.0.03,8]octadeca-1(18),3(8),4,6,14,16-hexaen-6-ol;hydrobromide	257777: Inhibition of binding to human D5 receptor expressed in HEK 293 cells by radioligand binding assay	ki	0.0015	uM
6-methoxy-12-methyl-9-oxa-12-azatricyclo[13.4.0.03,8]nonadeca-1(19),3(8),4,6,15,17-hexaene	238492: Binding affinity for human recombinant dopamine receptor D5	ki	0.0018	uM
8-bromo-3-methyl-5-phenyl-1,2,4,5-tetrahydro-3-benzazepin-7-ol	1763014: Displacement of [3H]SCH23390 from dopamine D5 receptor (unknown origin)	ki	0.0018	uM
4-[2-(dipropylamino)ethyl]-7-hydroxy-1,3-dihydroindol-2-one	62577: Inhibitory activity against constrictor response to electrical stimulation in the isolated perfused rabbit ear artery(REA) expressing dopamine receptor	ec50	0.0018	uM
(6aS,13bS)-11-chloro-7-methyl-4-thiophen-2-yl-5,6,6a,8,9,13b-hexahydronaphtho[1,2-a][3]benzazepin-12-ol	458850: Displacement of radioligand from dopamine D5 receptor expressed in mouse LTK cells by scintillation counting	ki	0.0019	uM
(6aS,13bR)-11-chloro-7-methyl-5,6,6a,8,9,13b-hexahydronaphtho[1,2-a][3]benzazepin-12-ol	458497: Binding affinity to dopamine D5 receptor	ki	0.0020	uM
Dopamine	1633736: Agonist activity at D5R (unknown origin) expressed in HEK293 cells assessed as effect on cAMP accumulation incubated for 10 mins by Gs-cAMP Glosensor assay	ec50	0.0020	uM
(6aS,13bS)-11-chloro-7-methyl-4-[(E)-phenoxyiminomethyl]-5,6,6a,8,9,13b-hexahydronaphtho[1,2-a][3]benzazepin-12-ol	458850: Displacement of radioligand from dopamine D5 receptor expressed in mouse LTK cells by scintillation counting	ki	0.0021	uM
11-methyl-11-azatricyclo[12.4.0.03,8]octadeca-1(18),3,5,7,14,16-hexaene-5,6-diol;hydrobromide	257773: Inhibition of binding to human D5 receptor expressed in HEK 293 cells by functional calcium assay	ki	0.0023	uM
11-methyl-11,19-diazatetracyclo[12.6.1.03,8.018,21]henicosa-1(20),3,5,7,14(21),15,17-heptaene	464635: Displacement of [3H]radioligand from human recombinant dopamine D5 receptor expressed in HEK293 cells by microplate scintillation counting	ki	0.0025	uM
(6aS,13bS)-11-chloro-7-methyl-4-[(E)-phenylmethoxyiminomethyl]-5,6,6a,8,9,13b-hexahydronaphtho[1,2-a][3]benzazepin-12-ol	458850: Displacement of radioligand from dopamine D5 receptor expressed in mouse LTK cells by scintillation counting	ki	0.0025	uM
6-chloro-11-methyl-11-azatricyclo[12.4.0.03,8]octadeca-1(18),3,5,7,14,16-hexaen-5-ol	261578: Inhibition of D5 dopamine receptor in HEK 293 cells by intracellular calcium assay	ki	0.0031	uM
11-methyl-11-azatricyclo[12.4.0.03,8]octadeca-1(18),3,5,7,14,16-hexaene	257773: Inhibition of binding to human D5 receptor expressed in HEK 293 cells by functional calcium assay	ki	0.0031	uM
ethyl N-[(6aS,13bR)-11-chloro-12-hydroxy-7-methyl-5,6,6a,8,9,13b-hexahydronaphtho[1,2-a][3]benzazepin-3-yl]carbamate	458497: Binding affinity to dopamine D5 receptor	ki	0.0033	uM
(6aS,13bS)-11-chloro-12-hydroxy-7-methyl-5,6,6a,8,9,13b-hexahydronaphtho[1,2-a][3]benzazepine-4-carbaldehyde	458850: Displacement of radioligand from dopamine D5 receptor expressed in mouse LTK cells by scintillation counting	ki	0.0033	uM
(6aS,13bS)-11-chloro-4-[(E)-hydroxyiminomethyl]-7-methyl-5,6,6a,8,9,13b-hexahydronaphtho[1,2-a][3]benzazepin-12-ol	458850: Displacement of radioligand from dopamine D5 receptor expressed in mouse LTK cells by scintillation counting	ki	0.0033	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	458850: Displacement of radioligand from dopamine D5 receptor expressed in mouse LTK cells by scintillation counting	ki	0.0034	uM
17-methoxy-11-methyl-11,21-diazatetracyclo[12.7.0.03,8.015,20]henicosa-1(14),3,5,7,15(20),16,18-heptaene	305862: Binding affinity to human cloned dopamine D5 receptor expressed in HEK 293 cells	ki	0.0036	uM
methyl (6aS,13bS)-11-chloro-12-hydroxy-7-methyl-5,6,6a,8,9,13b-hexahydronaphtho[1,2-a][3]benzazepine-4-carboxylate	458850: Displacement of radioligand from dopamine D5 receptor expressed in mouse LTK cells by scintillation counting	ki	0.0037	uM
(5R)-8-chloro-5-[4-[(cyclobutylamino)methyl]phenyl]-3-methyl-1,2,4,5-tetrahydro-3-benzazepin-7-ol	458497: Binding affinity to dopamine D5 receptor	ki	0.0039	uM
(12S)-11,12-dimethyl-11,21-diazatetracyclo[12.7.0.03,8.015,20]henicosa-1(14),3,5,7,15,17,19-heptaene	646501: Displacement of [3H]SCH23390 from human dopamine D5 receptor expressed in human HEK293 cells	ki	0.0044	uM
(13aS)-3,9-dimethoxy-6,8,13,13a-tetrahydro-5H-isoquinolino[2,1-b]isoquinoline-2,10-diol	452076: Displacement of [3H]SCH23390 from human dopamine D5 receptor expressed in CHO cells by scintillation counting	ki	0.0044	uM
6-(4-furo[3,2-c]pyridin-4-yloxy-2-methylphenyl)-1,5-dimethylpyrimidine-2,4-dione	1633736: Agonist activity at D5R (unknown origin) expressed in HEK293 cells assessed as effect on cAMP accumulation incubated for 10 mins by Gs-cAMP Glosensor assay	ec50	0.0044	uM
6-methoxy-11-methyl-11-azatricyclo[13.4.0.03,8]nonadeca-1(19),3(8),4,6,15,17-hexaene	297409: Displacement of [3H]SCH 23390 from human dopamine D5 receptor expressed in HEK293 cells	ki	0.0046	uM
(6aS,13bS)-11-chloro-7-methyl-4-(3-nitrophenyl)-5,6,6a,8,9,13b-hexahydronaphtho[1,2-a][3]benzazepin-12-ol	458850: Displacement of radioligand from dopamine D5 receptor expressed in mouse LTK cells by scintillation counting	ki	0.0047	uM
4-[3-methyl-4-(6-methylimidazo[1,2-a]pyrazin-5-yl)phenoxy]furo[3,2-c]pyridine	1414734: Agonist activity at dopamine D5 receptor (unknown origin)	ki	0.0048	uM
Haloperidol	62573: The IC50 value was reported as apparent, since [3H]NCA was purported to be irreversible. Result indicates the mean of two separate experiments, each performed in triplicate.	ic50	0.0050	uM
3,5-dichloro-N-[[(2S)-1-ethylpyrrolidin-2-yl]methyl]-2-hydroxy-6-methoxybenzamide	62004: In vitro inhibition of [3H]-Spiperone binding to Dopamine receptor D2 in Macaca nemestrina striatal membranes (using L-tartrate salt of authentic raclopride)	ki	0.0051	uM

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
7-methyl-6,7,8,9,14,15-hexahydro-5H-benz(d)indolo(2,3-g)azecine	decreases activity, affects binding	3
Tamoxifen	affects expression, increases expression	2
Valproic Acid	affects expression, increases methylation	2
Aflatoxin B1	increases methylation, increases expression	2
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
A 86929	affects binding, increases activity	1
perfluoro-n-nonanoic acid	increases expression	1
perfluorohexanesulfonic acid	increases expression	1
Irinotecan	affects cotreatment, increases response to substance	1
Resveratrol	affects cotreatment, decreases expression	1
Leflunomide	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression	1
Leucovorin	increases response to substance, affects cotreatment	1
Diethylhexyl Phthalate	decreases expression	1
Fluorouracil	increases response to substance, affects cotreatment	1
Lipopolysaccharides	increases expression, affects cotreatment, affects response to substance	1
Phenethylamines	affects binding	1
Plant Extracts	affects cotreatment, decreases expression	1
Sarin	increases expression	1
Silicon Dioxide	decreases expression	1
Theophylline	increases expression	1
Antirheumatic Agents	decreases expression	1
Copper Sulfate	increases expression	1
Raloxifene Hydrochloride	increases expression	1

ChEMBL screening assays

313 unique, capped per target: 280 binding, 28 functional, 5 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1026446	Binding	Displacement of [3H]SCH23390 from human dopamine D5 receptor at 10 uM	Synthesis and evaluation of [N-methyl-11C]N-desmethyl-loperamide as a new and improved PET radiotracer for imaging P-gp function. — J Med Chem
CHEMBL3562072	Functional	PubChem BioAssay. Counterscreening of D4 Antagonists against Dopamine 5 DRD5 (Human), Confirmatory Assay. (Class of assay: confirmatory)	PubChem BioAssay data set
CHEMBL4406535	ADMET	Agonist activity at Gs-coupled human D5R expressed in CHOK1 cells assessed as induction of beta-arrestin recruitment measured after 90 mins by beta-galactosidase based PathHunter assay	Discovery, Optimization, and Characterization of ML417: A Novel and Highly Selective D3 Dopamine Receptor Agonist. — J Med Chem

Cellosaurus cell lines

6 cell lines: 4 spontaneously immortalized cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C0SK	ACTOne DRD5	Transformed cell line	Female
CVCL_H423	CHO-K1/D5/Galpha15	Spontaneously immortalized cell line	Female
CVCL_KV10	cAMP Hunter CHO-K1 DRD5 Gs	Spontaneously immortalized cell line	Female
CVCL_KW90	PathHunter CHO-K1 DRD5 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_YK13	HEK293 DRD5 HiTSeeker	Transformed cell line	Female
CVCL_YR49	GeneBLAzer D5-CRE-bla CHO-K1	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00152750	PHASE4	UNKNOWN	Study of Clonidine on Sleep Architecture in Children With Tourette’s Syndrome (TS) and Comorbid ADHD
NCT00181571	PHASE4	COMPLETED	A Double-Blind Comparison of Concerta and Placebo in Adults With Attention Deficit Hyperactivity Disorder
NCT00181675	PHASE4	COMPLETED	A Double-Blind Comparison of Galantamine HBr and Placebo in Adults With Attention Deficit Hyperactivity Disorder
NCT00181714	PHASE4	COMPLETED	Prevention of Cigarette Smoking in Attention Deficit Hyperactivity Disorder (ADHD) Youth With Concerta
NCT00181948	PHASE4	COMPLETED	Strattera Treatment in Children With ADHD Who Have Poor Response to Stimulant Therapy
NCT00181987	PHASE4	COMPLETED	Concerta in the Treatment of ADHD in Youth and Adults With Bipolar Disorder
NCT00190736	PHASE4	COMPLETED	Efficacy and Safety of Once-Daily Atomoxetine Hydrochloride in Adults With ADHD Over an Extended Period of Time (6 Months)
NCT00190775	PHASE4	COMPLETED	A Randomized, Double-Blind Comparison of Placebo and Atomoxetine Hydrochloride Given Once a Day in Adults With Attention-Deficit/Hyperactivity Disorder (ADHD)
NCT00190879	PHASE4	COMPLETED	Placebo-Controlled Study of Atomoxetine Hydrochloride in the Treatment of Adults With ADHD and Comorbid Social Anxiety Disorder
NCT00190957	PHASE4	COMPLETED	Atomoxetine Treatment of Adults With ADHD and Comorbid Alcohol Abuse
NCT00191035	PHASE4	COMPLETED	Maintenance of Benefit With Atomoxetine Hydrochloride in Adolescents With ADHD
NCT00191048	PHASE4	COMPLETED	Treatment With Atomoxetine Hydrochloride in Children and Adolescents With ADHD
NCT00191633	PHASE4	COMPLETED	Study of Atomoxetine in Children With ADHD to Assess Symptomatic and Functional Outcomes
NCT00191906	PHASE4	COMPLETED	Comparison of Atomoxetine and Placebo in Children With Attention-Deficit/Hyperactivity Disorder (ADHD) and/or Reading Disorder (RD)
NCT00216918	PHASE4	COMPLETED	Neuropsychological Functioning in Children With Attention-Deficit/Hyperactivity Disorder.
NCT00221962	PHASE4	COMPLETED	Study of Aripiprazole (Abilify) in Children With ADHD (Attention Deficit Hyperactivity Disorder)
NCT00223561	PHASE4	COMPLETED	Methylphenidate and Driving Ability in Adult Patients With Attention-Deficit Hyperactivity Disorder
NCT00299234	PHASE4	TERMINATED	Atomoxetine for Children With Acquired Attentional Disorders Following Completion of Chemotherapy for ALL
NCT00302406	PHASE4	COMPLETED	Naturalistic Substitution of Concerta in Adult Subject With ADHD Receiving Immediate Release Methylphenidate
NCT00305370	PHASE4	COMPLETED	Aripiprazole Associated With Methylphenidate in Children and Adolescents With Bipolar Disorder and ADHD
NCT00381758	PHASE4	COMPLETED	The COMACS Study: A Comparison of Methylphenidates in an Analog Classroom Setting
NCT00406354	PHASE4	COMPLETED	Comparison of Atomoxetine Versus Placebo in Children and Adolescents With ADHD and Comorbid ODD in Germany
NCT00434213	PHASE4	COMPLETED	Characterization of Dermal Reactions in Pediatric Patients With ADHD Using DAYTRANA
NCT00468143	PHASE4	COMPLETED	A Within-Subject Cross-Over Comparison Between Immediate Release and Extended Release Adderall
NCT00471354	PHASE4	COMPLETED	A Study for Patients With Attention-Deficit/Hyperactivity Disorder Treated With Atomoxetine
NCT00483106	PHASE4	COMPLETED	Clinical and Pharmacogenetic Study of Attention Deficit With Hyperactivity Disorder (ADHD)
NCT00485849	PHASE4	COMPLETED	A Study of Atomoxetine for Attention Deficit and Hyperactive/Impulsive Behaviour Problems in Children With ASD
NCT00485875	PHASE4	COMPLETED	Safety and Efficacy of Switching From a Stimulant Medication to Atomoxetine in Children and Adolescents With ADHD
NCT00486122	PHASE4	COMPLETED	Evaluation of Continuous Symptom Treatment of ADHD
NCT00500071	PHASE4	COMPLETED	Dose-Optimization Study Evaluating the Efficacy, Safety and Tolerability of Vyvanse (Lisdexamfetamine Dimesylate) in Children Aged 6-12 Diagnosed With ADHD
NCT00506727	PHASE4	COMPLETED	Analog Classroom Study Comparison of ADDERALL XR With STRATTERA in Children Aged 6-12 With ADHD
NCT00510276	PHASE4	COMPLETED	Treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) With Atomoxetine in Young Adults and Its Effects on Functional Outcomes
NCT00517504	PHASE4	COMPLETED	Methylphenidate Study in Young Children With Developmental Disorders
NCT00517647	PHASE4	COMPLETED	Atomoxetine Pilot Study in Preschool Children With ADHD
NCT00518232	PHASE4	COMPLETED	A Study to Determine Effective and Tolerable Titration Scheme for OROS-Methylphenidate in Children With Attention-deficit Hyperactivity Disorder
NCT00530257	PHASE4	COMPLETED	Study of the Effects of Osmotic-Release Oral System (OROS) Methylphenidate (Concerta) on Attention and Memory
NCT00536419	PHASE4	UNKNOWN	Impact of Attention Deficit/Hyperactivity Disorder and Substance Use Disorder on Motorcycle Traffic Accidents
NCT00546910	PHASE4	COMPLETED	Comparison of Atomoxetine Versus Placebo in Children With Attention-Deficit/Hyperactivity Disorder (ADHD)
NCT00552266	PHASE4	UNKNOWN	Methylphenidate in ADHD With Trichotillomania
NCT00564954	PHASE4	COMPLETED	A Study of Dex-methylphenidate Extended Release in Children (6-12 Years) With Attention-Deficit/Hyperactivity Disorder (ADHD)