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DRD4

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Summary

DRD4 (dopamine receptor D4, HGNC:3025) is a protein-coding gene on chromosome 11p15.5, encoding D(4) dopamine receptor (P21917). Dopamine receptor responsible for neuronal signaling in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior.

This gene encodes the D4 subtype of the dopamine receptor. The D4 subtype is a G-protein coupled receptor which inhibits adenylyl cyclase. It is a target for drugs which treat schizophrenia and Parkinson disease. Mutations in this gene have been associated with various behavioral phenotypes, including autonomic nervous system dysfunction, attention deficit/hyperactivity disorder, and the personality trait of novelty seeking. This gene contains a polymorphic number (2-10 copies) of tandem 48 nt repeats; the sequence shown contains four repeats.

Source: NCBI Gene 1815 — RefSeq curated summary.

At a glance

  • Clinical variants (ClinVar): 208 total — 1 likely-pathogenic
  • Phenotypes (HPO): 3
  • Druggable target: yes — 119 molecules with ChEMBL bioactivity
  • MANE Select transcript: NM_000797

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:3025
Approved symbolDRD4
Namedopamine receptor D4
Location11p15.5
Locus typegene with protein product
StatusApproved
Ensembl geneENSG00000069696
Ensembl biotypeprotein_coding
OMIM126452
Entrez1815

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000176183, ENST00000528733

RefSeq mRNA: 1 — MANE Select: NM_000797 NM_000797

CCDS: CCDS7710

Canonical transcript exons

ENST00000176183 — 4 exons

ExonStartEnd
ENSE00000438635637269637589
ENSE00001318101640401640706
ENSE00001325621639648640306
ENSE00003462140639433639545

Expression profiles

Bgee: expression breadth ubiquitous, 130 present calls, max score 82.96.

FANTOM5 (CAGE): breadth broad, TPM avg 3.7003 / max 368.9632, expressed in 257 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter IDTPM avgSamples expressed
1122243.3669251
1122270.148644
1122260.118541
1122250.066431

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047382.96gold quality
lower esophagus mucosaUBERON:003583476.73gold quality
right uterine tubeUBERON:000130275.62gold quality
pituitary glandUBERON:000000774.89gold quality
right hemisphere of cerebellumUBERON:001489074.69gold quality
left ovaryUBERON:000211974.46gold quality
cerebellumUBERON:000203773.80gold quality
cerebellar hemisphereUBERON:000224573.65gold quality
adenohypophysisUBERON:000219673.64gold quality
cerebellar cortexUBERON:000212973.63gold quality
right ovaryUBERON:000211872.95gold quality
primary visual cortexUBERON:000243672.50gold quality
sural nerveUBERON:001548871.98gold quality
lower esophagusUBERON:001347371.75gold quality
lower esophagus muscularis layerUBERON:003583371.74gold quality
ovaryUBERON:000099271.71gold quality
body of uterusUBERON:000985371.18gold quality
esophagogastric junction muscularis propriaUBERON:003584170.94gold quality
endocervixUBERON:000045870.91gold quality
right frontal lobeUBERON:000281070.61gold quality
muscle layer of sigmoid colonUBERON:003580570.53gold quality
tibial nerveUBERON:000132370.28gold quality
ectocervixUBERON:001224969.96gold quality
putamenUBERON:000187469.58gold quality
myometriumUBERON:000129669.36gold quality
skin of abdomenUBERON:000141669.11gold quality
right lobe of liverUBERON:000111469.03gold quality
Ammon’s hornUBERON:000195469.02gold quality
nucleus accumbensUBERON:000188268.88gold quality
uterine cervixUBERON:000000268.45gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

ExperimentMarker?Max mean expression
E-ANND-3no1.15
E-CURD-10no0.64

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

4 targeting DRD4, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-4747-5P100.0067.902681
HSA-MIR-5196-5P100.0067.982761
HSA-MIR-4533100.0069.482758
HSA-MIR-1252-5P100.0069.802774

Literature-anchored findings (GeneRIF, showing 40)

  • we propose that this allele originated as a rare mutational event that nevertheless increased to high frequency in human populations by positive selection. (PMID:11756666)
  • No association between dopamine D4 receptor gene variants and novelty seeking was found in Swedish adults. (PMID:11803441)
  • The DRD4 gene plays a role in the development of attachment behavior in low-risk, non-clinical populations. (PMID:11803443)
  • no association of polymorphism and methampheteamine abuse in Chinese males (PMID:11901357)
  • DRD4 VNTR polymorphism moderates craving after alcohol comsumption (PMID:11950104)
  • The dopamine D4 receptor and the hyperactivity phenotype: no evidence to support this association. (PMID:11986982)
  • study did not support the involvement of 5-HTTLPR, TPH, MAO-A, or DRD4 polymorphisms in mood disorders (PMID:11992558)
  • possible influence of monoamine oxydase A (MAO-A), catechol-O-methyltransferase (COMT), serotonin receptor 2A (5-HT2A), dopamine receptor D2 (DRD2), and dopamine receptor D4 (DRD4) gene variants on timing of recurrence in mood disorders (PMID:11992560)
  • no association between gene exon III and -521C/T polymorphism and novelty seeking (PMID:12140774)
  • on average, there is no association between DRD4 polymorphism and novelty seeking (PMID:12192615)
  • genetic variation within the DRD4 promoter and gender differences contribute to variation in Novelty Seeking behaviors such as Extraversion. (PMID:12192624)
  • the relationship between the DRD4 receptor and ADHD is complex and may be reflecting linkage disequilibrium between the 7 or long DRD4 exon III repeats and a ’true’ risk allele in this gene or a neighboring locus. (PMID:12192625)
  • Ethnic heterogeneity in allele variation in the DRD4 gene in schizophrenia in Asians and Caucasians (PMID:12223255)
  • the fact that DRD4 exhibit parent of orgin effect and is located in close proximity to a cluster of imprinted genes, suggests that genomic imprinting may be operating in bipolar disorder. (PMID:12232779)
  • dopamine receptor D4 mRNA levels were significantly decreased in untreated depressed patients as compared to controls (PMID:12452539)
  • Significant age-related decline was observed for dopamine receptor mRNAs in the hippocampus and entorhinal cortex (PMID:12509874)
  • both temperament and attachment behavior were affected by the DRD4 repeat polymorphism (PMID:12556912)
  • An association analysis for dopamine D4 receptor polymorphism and p300 component in normal young women is negative. (PMID:12605102)
  • link between the DRD4 gene and human temperament in 3 year old infants. (PMID:12687422)
  • no significant association was found between the DRD4 genotype and clinical response to risperidone in schizophrenics (PMID:12729944)
  • variation in exon III in novelty seeking behavior (PMID:12740593)
  • A 48-bp repeat polymorphism in the DRD4 gene was studied. The odds ratios for any 2- or 5-repeat allele vs. 0 was 2.41 for total novelty-seeking, 2.94 for exploratory excitability & 2.74 for impulsiveness but not for other components. of novelty seeking. (PMID:12764221)
  • genotyped 16 subjects for the DRD4 and MAOA genes who had been scanned during the Attention Network Test (PMID:12773616)
  • allelic heterogeneity at the DRD4 locus may also contribute to the observed association with attention deficit disorder with hyperactivity (PMID:12808433)
  • a haplotype of markers in the 5’ promoter region of the dopamine D4 receptor gene may confer susceptibility to attention-deficit hyperactivity disorder (PMID:12960764)
  • 7-repeat allele (7R) of the dopamine-4 receptor gene (DRD4) carriers reported significantly greater inattention and dysphoria in childhood (p=0.01 and 0.001, respectively) and a higher maximal lifetime BMI (p=0.007) than did probands without this allele. (PMID:14560322)
  • Participants carrying any two- or five-repeat alleles of the DRD4 gene had a significantly greater risk of exhibiting novelty seeking bsehaviors. (PMID:14569271)
  • Placement of the three repeat variants of dopamine D4 receptor downstream from the luciferase gene in the expression vector, shows that the D4.7 repeat sequence has significantly suppressed expression of the reporter compared to the D4.2 and D4.4 repeats. (PMID:14581929)
  • Schizophrenia and polymorphisms including -616C>G, -603T>del, -602G>del, 600G>C, -521C>T, -376C>T and a 120 bp tandem duplication polymorphism (120 bp repeat) in 1.2 kb upstream from the initiation codon in the promoter region of the DRD4 gene. (PMID:14623368)
  • 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)
  • drd4 gene is associated with neuropsychological test performance in children with ADHD (PMID:14702261)
  • Polymorphisms (-C616G, -C521T, and 48 bp repeat) at the DRD4 gene do not have a minor effect in the susceptibility to schizophrenia (PMID:14755438)
  • the associations between DRD4 duplication genotype and novelty seeking were not significant in these groups. (PMID:15048656)
  • The personality dimension of persistence is associated with the third-exon VNTR of the DRD4 gene among Caucasian males. (PMID:15048658)
  • Association of ADHD to genetic variation in or near to DRD4 and replicate the previously reported association between ADHD and the 7R allele. (PMID:15094785)
  • Findings provide additional evidence for the role of the dopamine D4 receptor in attention-deficit/hyperactivity disorder during the course of child development. (PMID:15206004)
  • long-repeat alleles of DRD4 (ranging from 4 to 6 repeats) and DAT1 (ranging from 11 to 12 repeats), were present more frequently in attention deficit hyperactivity disorder probands than controls (PMID:15211638)
  • no association was demonstrated between this dopamine receptor D4 polymorphism and novelty seeking in our young Chinese female sample population (PMID:15292670)
  • The “Social Problem” scale was weakly associated with the number of risk alleles of DRD2 and DRD4. (PMID:15319572)
  • An association between DRD4 exon 3 long allele variants and delusional symptomatology could not be confirmed in an independent sample from Germany. (PMID:15364409)

Cross-species orthologs

4 orthologs

OrganismSymbolGene ID
danio_reriodrd4bENSDARG00000035820
danio_reriodrd4aENSDARG00000038363
mus_musculusDrd4ENSMUSG00000025496
rattus_norvegicusDrd4ENSRNOG00000017927

Paralogs (25): 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), DRD1 (ENSG00000184845), CHRM5 (ENSG00000184984), GPR21 (ENSG00000188394), HRH1 (ENSG00000196639), GPR52 (ENSG00000203737), TAAR9 (ENSG00000237110)

Protein

Protein identifiers

D(4) dopamine receptor — P21917 (reviewed: P21917)

Alternative names: D(2C) dopamine receptor, Dopamine D4 receptor

All UniProt accessions (1): P21917

UniProt curated annotations — full annotation on UniProt →

Function. Dopamine receptor responsible for neuronal signaling in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior. Activated by dopamine, but also by epinephrine and norepinephrine, and by numerous synthetic agonists and drugs. Agonist binding triggers signaling via G proteins that inhibit adenylyl cyclase. Modulates the circadian rhythm of contrast sensitivity by regulating the rhythmic expression of NPAS2 in the retinal ganglion cells.

Subunit / interactions. Forms homo- and heterooligomers with DRD2. D4.7 allele exhibits higher affinity for homodimers compared to DRD2 heterodimers, while alleles D42. and 4.4 have similar affinities for both. The interaction with DRD2 may modulate agonist-induced downstream signaling. Interacts with CLIC6. Interacts with GPRASP1. May interact with ADORA2A. Interacts with KLHL12.

Subcellular location. Cell membrane.

Tissue specificity. Highly expressed in retina. Detected at much lower levels in brain, in amygdala, thalamus, hypothalamus, cerebellum and pituitary.

Post-translational modifications. Polyubiquitinated by the BCR(KLHL12) E3 ubiquitin ligase complex: polyubiquitination does not lead to degradation of DRD4 protein. Palmitoylated. Palmitoylation of the C-terminal Cys is important for normal expression at the cell membrane.

Activity regulation. Signaling in response to agonists such as dopamine, epinephrine and norepinephrine is modulated by Na(+); lower Na(+) levels result in higher receptor activity (in vitro).

Polymorphism. The number of repeats of 16 amino acids in the third cytoplasmic loop is highly polymorphic and varies among different alleles. Alleles corresponding in size to a 2 (D4.2), 3 (D4.3), 4 (D4.4), 5 (D4.5), 6 (D4.6), 7 (D4.7) and 9 (D4.9) repeats have been described. The sequence shown is that of allele D4.4. The polymorphic repeat sequence has little influence on DRD4-binding profiles and might not be essential for G protein interaction.

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

RefSeq proteins (1): NP_000788* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000276GPCR_RhodpsnFamily
IPR000929Dopamine_rcptFamily
IPR002185Dopamine_D4_rcptFamily
IPR017452GPCR_Rhodpsn_7TMDomain

Pfam: PF00001

UniProt features (54 total): helix 12, topological domain 8, transmembrane region 7, repeat 4, binding site 4, region of interest 3, sequence variant 3, mutagenesis site 3, disulfide bond 2, turn 2, chain 1, compositionally biased region 1, lipid moiety-binding region 1, glycosylation site 1, sequence conflict 1, strand 1

Structure

Experimental structures (PDB)

2 structures.

PDBMethodResolution (Å)
5WIUX-RAY DIFFRACTION1.96
5WIVX-RAY DIFFRACTION2.14

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P21917-F178.060.47

Functional residue map

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

Ligand- & substrate-binding residues (4): 80; 115; 122; 196

Post-translational modifications (1): 419

Disulfide bonds (2): 108–185, 372–375

Glycosylation sites (1): 3

Mutagenesis-validated functional residues (3):

PositionPhenotype
382increased basal level of g protein-mediated signaling.
418no effect on palmitoylation.
419loss of palmitoylation.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

IDPathway
R-HSA-390651Dopamine receptors
R-HSA-418594G alpha (i) signalling events

MSigDB gene sets: 210 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GSE45365_NK_CELL_VS_CD11B_DC_UP, GOBP_CIRCADIAN_RHYTHM, GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ETHANOL, GOMF_G_PROTEIN_COUPLED_SEROTONIN_RECEPTOR_ACTIVITY, BENPORATH_ES_WITH_H3K27ME3, MODULE_274, GOBP_BEHAVIOR, GOBP_RESPONSE_TO_COCAINE, GOBP_RESPONSE_TO_AMINE, GOBP_NEUROTRANSMITTER_UPTAKE, GOBP_ADULT_BEHAVIOR, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE

GO Biological Process (30): behavioral fear response (GO:0001662), response to amphetamine (GO:0001975), intracellular calcium ion homeostasis (GO:0006874), G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger (GO:0007187), adenylate cyclase-modulating G protein-coupled receptor signaling pathway (GO:0007188), adenylate cyclase-inhibiting dopamine receptor signaling pathway (GO:0007195), chemical synaptic transmission (GO:0007268), adult locomotory behavior (GO:0008344), response to histamine (GO:0034776), social behavior (GO:0035176), regulation of dopamine metabolic process (GO:0042053), fear response (GO:0042596), regulation of circadian rhythm (GO:0042752), positive regulation of MAPK cascade (GO:0043410), behavioral response to cocaine (GO:0048148), behavioral response to ethanol (GO:0048149), rhythmic process (GO:0048511), arachidonate secretion (GO:0050482), negative regulation of protein secretion (GO:0050709), positive regulation of dopamine uptake involved in synaptic transmission (GO:0051586), inhibitory postsynaptic potential (GO:0060080), phospholipase C-activating dopamine receptor signaling pathway (GO:0060158), regulation of postsynaptic neurotransmitter receptor internalization (GO:0099149), synaptic transmission, dopaminergic (GO:0001963), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), adult behavior (GO:0030534), regulation of transport (GO:0051049), regulation of primary metabolic process (GO:0080090), G protein-coupled serotonin receptor signaling pathway (GO:0098664)

GO Molecular Function (13): dopamine neurotransmitter receptor activity, coupled via Gi/Go (GO:0001591), dopamine neurotransmitter receptor activity (GO:0004952), G protein-coupled serotonin receptor activity (GO:0004993), potassium channel regulator activity (GO:0015459), SH3 domain binding (GO:0017124), neurotransmitter receptor activity (GO:0030594), dopamine binding (GO:0035240), identical protein binding (GO:0042802), metal ion binding (GO:0046872), epinephrine binding (GO:0051379), norepinephrine binding (GO:0051380), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

GO Cellular Component (6): centrosome (GO:0005813), plasma membrane (GO:0005886), membrane (GO:0016020), dendrite (GO:0030425), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978)

Reactome top-level categories

Rollup of top-2 pathways:

CategoryPathways
Amine ligand-binding receptors1
GPCR downstream signalling1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cation binding4
G protein-coupled receptor signaling pathway3
adult behavior3
catecholamine binding3
G protein-coupled dopamine receptor signaling pathway2
cellular anatomical structure2
synapse2
behavioral defense response1
fear response1
response to amine1
intracellular monoatomic cation homeostasis1
calcium ion homeostasis1
adenylate cyclase activity1
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway1
anterograde trans-synaptic signaling1
locomotory behavior1
response to nitrogen compound1
behavior1
biological process involved in intraspecies interaction between organisms1
regulation of catecholamine metabolic process1
dopamine metabolic process1
multicellular organismal response to stress1
circadian rhythm1
regulation of biological process1
MAPK cascade1
regulation of MAPK cascade1
positive regulation of intracellular signal transduction1
response to cocaine1
response to ethanol1
biological_process1
icosanoid secretion1
arachidonate transport1
protein secretion1
regulation of protein secretion1
negative regulation of protein transport1
negative regulation of secretion by cell1
positive regulation of neurotransmitter uptake1
dopamine uptake involved in synaptic transmission1
regulation of dopamine uptake involved in synaptic transmission1
dopamine neurotransmitter receptor activity1

Protein interactions and networks

STRING

1412 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
DRD4SLC6A4P31645978
DRD4SLC6A3Q01959960
DRD4COMTP21964943
DRD4MAOAP21397893
DRD4BDNFP23560814
DRD4TPH1P17752798
DRD4MAOBP27338786
DRD4ANKK1Q8NFD2779
DRD4DBHP09172775
DRD4DRD2P14416741
DRD4CHRNA4P43681723
DRD4THP07101704
DRD4TOMTQ8WZ04699
DRD4TPH2Q8IWU9669
DRD4OXTRP30559658

IntAct

35 interactions, top by confidence:

ABTypeScore
DRD4DRD4psi-mi:“MI:2364”(proximity)0.580
DRD4DRD4psi-mi:“MI:0915”(physical association)0.580
GAP43DRD4psi-mi:“MI:0915”(physical association)0.560
STXBP1DRD4psi-mi:“MI:0915”(physical association)0.560
DRD4METAP2psi-mi:“MI:0915”(physical association)0.560
DRD4NECAB3psi-mi:“MI:0915”(physical association)0.560
APPDRD4psi-mi:“MI:0915”(physical association)0.560
DRD4ADRA1Bpsi-mi:“MI:0915”(physical association)0.470
DRD4ADRA1Bpsi-mi:“MI:2364”(proximity)0.470
DRD4ADRB1psi-mi:“MI:0915”(physical association)0.470
DRD4ADRB1psi-mi:“MI:2364”(proximity)0.470
DRD2DRD4psi-mi:“MI:0915”(physical association)0.400
DRD4RAMP2psi-mi:“MI:0915”(physical association)0.400
DRD4RAMP3psi-mi:“MI:0915”(physical association)0.400
DRD4DRD2psi-mi:“MI:2364”(proximity)0.350

BioGRID (33): DRD4 (Affinity Capture-Western), KLHL12 (Affinity Capture-Western), KLHL12 (Affinity Capture-Western), CUL3 (Affinity Capture-Western), DRD4 (Affinity Capture-Western), DRD4 (Affinity Capture-Western), KLHL12 (Affinity Capture-Western), ARRB2 (Affinity Capture-Western), CLIC6 (Two-hybrid), DRD4 (Affinity Capture-Western), ADRB2 (Affinity Capture-Western), DRD4 (FRET), DRD4 (FRET), DRD4 (FRET), KCNJ3 (Affinity Capture-Western)

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

Diamond homologs: A5A4K9, A5A4L1, C3ZQF9, O08725, O17239, O42179, O43193, O55040, O88319, O93603, P19020, P20789, P20905, P21917, P24628, P30989, P35367, P49683, P58826, P79291, Q09388, Q25188, Q28553, Q58CW4, Q5QD24, Q63384, Q7JQF1, Q8BZ39, Q8ITC7, Q90WY4, Q923Y8, Q92847, Q93126, Q95254, Q99P50, Q9ESQ4, Q9GZQ4, Q9HB89, Q9JJI5, Q9JJS7

SIGNOR signaling

7 interactions.

AEffectBMechanism
DRD4“up-regulates activity”GNAI1binding
DRD4“up-regulates activity”GNAI3binding
DRD4“up-regulates activity”GNAO1binding
DRD4“up-regulates activity”GNAZbinding
dopamine“up-regulates activity”DRD4“chemical activation”
DRD4“up-regulates activity”GNB5binding
zotepine“down-regulates activity”DRD4“chemical inhibition”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic1
Uncertain significance161
Likely benign28
Benign9

Top pathogenic / likely-pathogenic (1)

Variant IDHGVSClassification
3065214NM_000797.4(DRD4):c.155dup (p.Asn52fs)Likely pathogenic

SpliceAI

502 predictions. Top by Δscore:

VariantEffectΔscore
11:637586:CGAGG:Cdonor_loss1.0000
11:637590:GTGAG:Gdonor_loss1.0000
11:637591:T:Gdonor_loss1.0000
11:637587:GAG:Gdonor_gain0.9900
11:639916:G:Tdonor_gain0.9900
11:640395:CCCCA:Cacceptor_loss0.9900
11:640396:CCCAG:Cacceptor_loss0.9900
11:640397:CCA:Cacceptor_loss0.9900
11:640398:CA:Cacceptor_loss0.9900
11:640399:A:AGacceptor_gain0.9900
11:640399:A:Tacceptor_loss0.9900
11:640399:AGG:Aacceptor_gain0.9900
11:640400:G:Cacceptor_loss0.9900
11:640400:G:GGacceptor_gain0.9900
11:640400:GGG:Gacceptor_gain0.9900
11:637590:G:GGdonor_gain0.9800
11:639916:G:GTdonor_gain0.9800
11:640279:GCCA:Gdonor_gain0.9800
11:640298:T:TAdonor_gain0.9800
11:640299:G:GAdonor_gain0.9800
11:640399:AG:Aacceptor_gain0.9800
11:640400:GG:Gacceptor_gain0.9800
11:639431:A:Tacceptor_loss0.9700
11:639920:TGGC:Tdonor_gain0.9700
11:639921:G:GAdonor_gain0.9700
11:640269:G:GTdonor_gain0.9700
11:640375:GCTAA:Gacceptor_loss0.9700
11:640376:CTAA:Cacceptor_loss0.9700
11:640377:TAAC:Tacceptor_loss0.9700
11:640399:AGGG:Aacceptor_gain0.9700

AlphaMissense

2646 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
11:637527:A:CS75R0.999
11:637529:C:AS75R0.999
11:637529:C:GS75R0.999
11:637543:A:CD80A0.999
11:637543:A:TD80V0.999
11:639535:A:CS130R0.999
11:639537:C:AS130R0.999
11:639537:C:GS130R0.999
11:640406:T:CF355L0.999
11:640408:C:AF355L0.999
11:640408:C:GF355L0.999
11:640519:C:AN392K0.999
11:640519:C:GN392K0.999
11:637543:A:GD80G0.998
11:639545:G:TR133M0.998
11:640418:T:AW359R0.998
11:640418:T:CW359R0.998
11:640427:T:CF362L0.998
11:640429:C:AF362L0.998
11:640429:C:GF362L0.998
11:640430:T:CF363L0.998
11:640432:C:AF363L0.998
11:640432:C:GF363L0.998
11:640520:A:CS393R0.998
11:640522:C:AS393R0.998
11:640522:C:GS393R0.998
11:640531:C:AN396K0.998
11:640531:C:GN396K0.998
11:637542:G:CD80H0.997
11:637544:C:AD80E0.997

dbSNP variants (sampled 300 via entrez): RS1000155908 (11:638474 C>T), RS1000497897 (11:639910 C>T), RS1000610892 (11:636031 C>T), RS1000649443 (11:636021 C>T), RS1001158081 (11:639367 G>A), RS1001855770 (11:638354 G>A,C,T), RS1001992806 (11:635614 G>A), RS1002000516 (11:639169 C>A,T), RS1002968488 (11:637507 C>A,T), RS1003315598 (11:639959 G>A,C), RS1003414791 (11:637100 C>T), RS1004060100 (11:638290 C>A), RS1004366239 (11:637747 C>T), RS1004471672 (11:637353 G>A,T), RS1005192041 (11:639869 T>A,C)

Disease associations

OMIM: gene MIM:126452 | disease phenotypes: MIM:143465

GenCC curated gene-disease

Mondo (1): hereditary attention deficit-hyperactivity disorder (MONDO:0100518)

Orphanet (0):

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPOTerm
HP:0000006Autosomal dominant inheritance
HP:0000752Hyperactivity
HP:0007018Attention deficit hyperactivity disorder

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL2095396 (SELECTIVITY GROUP), CHEMBL2096905 (PROTEIN FAMILY), CHEMBL2097165 (SELECTIVITY GROUP), CHEMBL219 (SINGLE PROTEIN), CHEMBL2331075 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

119 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 591,472 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL1201087CABERGOLINE412,778
CHEMBL53APOMORPHINE425,813
CHEMBL54HALOPERIDOL460,883
CHEMBL589ROPINIROLE421,493
CHEMBL59DOPAMINE4217,028
CHEMBL104CLOTRIMAZOLE456,325
CHEMBL11IMIPRAMINE448,893
CHEMBL1112ARIPIPRAZOLE424,205
CHEMBL1113AMOXAPINE420,128
CHEMBL1172DESLORATADINE419,720
CHEMBL1200492NEFAZODONE HYDROCHLORIDE45,428
CHEMBL1200517DIHYDROERGOTAMINE MESYLATE42,704
CHEMBL1200986HALOPERIDOL DECANOATE4591
CHEMBL1201THIOTHIXENE413,101
CHEMBL1201217DYCLONINE47,785
CHEMBL126224IPRINDOLE44,398
CHEMBL1263SALMETEROL440,383
CHEMBL12713SERTINDOLE48,984
CHEMBL1303ROTIGOTINE4832
CHEMBL1366AURANOFIN4
CHEMBL1423PIMOZIDE4
CHEMBL14376ILOPERIDONE4
CHEMBL1516474TEGASEROD MALEATE4
CHEMBL1557DOPAMINE HYDROCHLORIDE4
CHEMBL1615374VILAZODONE HYDROCHLORIDE4
CHEMBL1621PALIPERIDONE4
CHEMBL1623MECLIZINE4
CHEMBL1628227DOXEPIN4
CHEMBL1707LOPERAMIDE HYDROCHLORIDE4
CHEMBL2PRAZOSIN4

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

PharmGKB variants

6 variants.

VariantGenesLevelScore#Clin annotsDrugs
rs11246226DRD40.000
rs3758653DRD40.000
rs1800955DRD40.000
rs2133251840DRD40.000
rs762502DRD40.000
rs747302DRD40.000

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Dopamine receptors

Most potent curated ligand interactions (53 total), top 25:

LigandActionAffinityParameter
benperidolAntagonist10.18pKi
perospironeAntagonist10.05pKi
L-750,667Antagonist10.0pKi
nemonaprideAntagonist10.0pKd
[125I]L750667Antagonist9.8pKd
RBI257Antagonist9.6pKi
[3H]N-methylspiperoneAntagonist9.5pKi
[3H]spiperoneAntagonist9.5pKd
CP-293019Antagonist9.5pKi
NGD 94-1Antagonist9.5pKi
L745870Antagonist9.41pKi
CP-226269Partial agonist9.4pKi
spiperoneAntagonist9.3pKi
sertindoleAntagonist9.07pKi
FAUC213Partial agonist9.0pKi
sonepiprazoleAntagonist8.9pKi
U101958Antagonist8.9pKi
A-381393Antagonist8.82pKi
haloperidolAntagonist8.8pKi
PD168,077Partial agonist8.8pKi
L741742Antagonist8.5pKi
apomorphinePartial agonist8.4pKi
[3H]NGD941Antagonist8.3pKd
lisuridePartial agonist8.3pKi
roxindolePartial agonist8.2pKi

Binding affinities (BindingDB)

97 measured of 112 human assays (150 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValuePatent
NSC_104911KI0.1 nM
roxindoleKI0.11 nM
(2,3-Dimethoxy-phenyl)-{1-[2-(4-fluoro-phenyl)-ethyl]-piperidin-4-yl}-methanol(MDL 100907)KI0.14 nM
3,3-diethyl-1-[(4R,7R)-6-methyl-6,11-diazatetracyclo[7.6.1.0^{2,7}.0^{12,16}]hexadeca-1(15),2,9,12(16),13-pentaen-4-yl]ureaKI0.15 nM
CAS_53772-85-3KI0.2 nM
(trans) 2-{4-[3-(4-Fluoro-phenyl)-6-trifluoromethyl-indan-1-yl]-piperazin-1-yl}-ethanolKI0.3 nM
CAS_51152-91-1KI0.3 nM
2-Chlor-11-(2-dimethylaminoaethoxy)-dibenzo(b,f)-thiepinKI0.5 nM
N-((S)-1-Bicyclo[3.3.1]non-9-yl-pyrrolidin-3-yl)-5-chloro-2-methoxy-4-methylamino-benzamideKI0.67 nM
SDZ-208-912KI0.9 nM
ISOCLOZAPINEKI1.45 nM
CAS_62865KI1.5 nM
1-(8-chloro-10,11-dihydrodibenzo[b,f]thiepin-10-yl)-4-methylpiperazineKI1.8 nM
5-[2-(4-Benzo[d]isothiazol-3-yl-piperazin-1-yl)-ethyl]-6-chloro-1,3-dihydro-indol-2-oneKI1.9 nM
PermaxKI1.91 nM
(-)-1-Propyl-2,3,10,10a-tetrahydro-1H,4aH-4,9-dioxa-1-aza-phenanthren-6-olKI2.14 nM
NSC_188942KI2.5 nM
4-[4-(4-Chloro-phenyl)-4-hydroxy-piperidin-1-yl]-1-(4-fluoro-phenyl)-butan-1-one;propionate(HCl)KI2.92 nM
8-[4-(4-fluorophenyl)-4-keto-butyl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-oneKI2.94 nMUS-9359372: Hexahydrodibenzo[a,g]quinolizine compound, preparation method thereof, pharmaceutical composition and use thereof
TergurideKI3.47 nM
IsoloxapineKI3.7 nM
Glaxo 1192U90KI4 nM
LecozotanKI4.5 nM
CAS_84-01-5KI10 nM
BUSPARKI12 nM
Bromocriptine+ (GTP+)KI12.9 nM
PerlapineKI13 nM
CAS_129029-23-8KI13.9 nM
NemonaprideKI15 nM
NSC_54746KI19.9 nM
CAS_62421-17-4KI25 nM
CAS_5311190KI29.4 nM
1-(4-{3-[4-(6-Fluoro-benzo[d]isoxazol-3-yl)-piperidin-1-yl]-propoxy}-3-methoxy-phenyl)-ethanoneKI33 nM
cid_3396KI56 nM
CAS_132-66-1KI68 nM
N-[2-[2-[[(2S,5S)-2-(6-amino-3-pyridinyl)-5-methylmorpholin-4-yl]methyl]cyclopropyl]ethyl]-1H-indole-2-carboxamideKI106 nMUS-12479838: D3 receptor agonist compounds; methods of preparation; intermediates thereof; and methods of use thereof
7-[4-[(5S)-2-(6-amino-3-pyridinyl)-5-methylmorpholin-4-yl]butoxy]-3,4-dihydro-1H-quinolin-2-oneKI113 nMUS-12479838: D3 receptor agonist compounds; methods of preparation; intermediates thereof; and methods of use thereof
(5-Methoxy-1-methyl-1,2,3,4-tetrahydro-naphthalen-2-yl)-propyl-amineKI120 nM
N-[4-[(2S,5S)-2-(6-amino-3-pyridinyl)-5-methylmorpholin-4-yl]butyl]-1H-indole-2-carboxamideKI134 nMUS-12479838: D3 receptor agonist compounds; methods of preparation; intermediates thereof; and methods of use thereof
2-[4-[3-[2-(trifluoromethyl)phenothiazin-10-yl]propyl]piperazin-1-yl]ethanol;hydrochlorideKI146 nM
PHNO,(+)KI147 nM
2-{3-[Bis-(4-fluoro-phenyl)-methoxy]-8-aza-bicyclo[3.2.1]oct-8-ylmethyl}-1H-indoleKI172 nM
Isoindoline, 15KI188 nM
CAS_51012-32-9KI226 nM
7-Dipropylamino-5,6,7,8-tetrahydro-naphthalen-2-ol (DP-7-ADTN)KI265 nM
4-[2-(dipropylamino)ethyl]-1,3-dihydro-2H-indol-2-oneKI288 nM
Isoindoline, 14KI302 nM
CHEMBL5171398KI319 nM
NSC_3853KI343 nM
S32504 (+)KI355 nM

ChEMBL bioactivities

4476 potent at pChembl≥5 of 4536 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
10.74Ki0.018nMCHEMBL156599
10.60Ki0.025nMCHEMBL156845
10.52Ki0.03nMCHEMBL2420894
10.52Ki0.03nMMOSAPRAMINE
10.40Ki0.04nMCHEMBL157322
10.40Ki0.04nMCHEMBL93403
10.24IC500.057nMCHEMBL93403
10.18Ki0.066nMBENPERIDOL
10.11Kd0.078nMCHEMBL4860528
10.11Kd0.078nMCHEMBL5207281
10.11Kd0.078nMCHEMBL5206565
10.11Kd0.078nMCHEMBL5201074
9.80EC500.1585nMCHEMBL4085780
9.78EC500.166nMCHEMBL6167299
9.74EC500.18nMCHEMBL5290993
9.70Ki0.2nMSPIPERONE
9.70EC500.2nMUCSF924
9.70Ki0.2nMUCSF924
9.68Kd0.21nMNEMONAPRIDE
9.68Ki0.21nMCHEMBL345848
9.64Ki0.23nMCHEMBL326454
9.60Ki0.25nMCHEMBL211164
9.60Ki0.25nMCHEMBL4442460
9.59Ki0.26nMCHEMBL157388
9.55Ki0.28nMCHEMBL379602
9.51Ki0.309nMCHEMBL129534
9.51Ki0.31nMCHEMBL129534
9.48Ki0.33nMSPIPERONE
9.48Ki0.33nMCHEMBL379125
9.48Ki0.33nMCHEMBL4096543
9.48Ki0.3311nMCHEMBL4096543
9.48Ki0.33nMCHEMBL92859
9.46Ki0.3467nMCHEMBL129927
9.46Ki0.35nMCHEMBL129927
9.43Ki0.37nMN-{4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl}-1-ruthena-1,1’-spirobi[pentacyclo[2.2.0.0^{1,3}.0^{1,5}.0^{2,6}]hexane]-2,2’,4,4’-tetraene-6-carboxamide
9.41Ki0.39nMCHEMBL279247
9.40Ki0.4nMCHEMBL2207643
9.40Ki0.4nML-745870
9.39Ki0.4074nMCHEMBL5198170
9.37Ki0.43nML-745870
9.37Ki0.43nMCHEMBL555670
9.36Ki0.44nMCHEMBL210404
9.36Ki0.4365nMCHEMBL210404
9.35Ki0.45nMSPIPERONE
9.35Ki0.45nMCHEMBL394473
9.34Ki0.4571nMCHEMBL128232
9.34Ki0.46nMCHEMBL128232
9.34Ki0.46nMCHEMBL93832
9.32Kd0.48nMMESPIPERONE
9.32Kd0.4786nMMESPIPERONE

PubChem BioAssay actives

3824 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.

CompoundAssayTypeValueUnit
N-[2-[4-(2-chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide63533: Binding affinity towards human Dopamine receptor D4 using [3H]spiroperidol as radioligandki<0.0001uM
3-methoxy-N-[2-[4-(4-methylphenyl)piperazin-1-yl]ethyl]benzamide63533: Binding affinity towards human Dopamine receptor D4 using [3H]spiroperidol as radioligandki<0.0001uM
N-[2-[4-(2,3-dichlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide63533: Binding affinity towards human Dopamine receptor D4 using [3H]spiroperidol as radioligandki<0.0001uM
3-[[4-(2-ethoxyphenyl)piperazin-1-yl]methyl]-1H-indole767064: Binding affinity to human dopamine D4 receptor by radioligand binding assayki<0.0001uM
N-[2-[4-(4-chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide63533: Binding affinity towards human Dopamine receptor D4 using [3H]spiroperidol as radioligandki<0.0001uM
1’-[3-(2-chloro-5,6-dihydrobenzo[b][1]benzazepin-11-yl)propyl]spiro[1,5,6,7,8,8a-hexahydroimidazo[1,2-a]pyridine-3,4’-piperidine]-2-one1615608: Agonist activity at dopamine D4 receptor (unknown origin)ki<0.0001uM
3-[1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl]-1H-benzimidazol-2-one1309485: Binding affinity to human dopamine D4 receptor by radioligand displacement assayki0.0001uM
1-[N’-[3-(2-amino-4-methyl-1,3-thiazol-5-yl)propyl]carbamimidoyl]-3-pentylurea1895224: Displacement of [3H]N-methylspiperone from human D4.4 receptor stably expressed in HEK293T cells co-expressing ElucN-betaarr2 hD4.4R-ELuc incubated for 60 mins by scintillation counting analysiskd0.0001uM
1-[(1R)-1-phenylethyl]-3-[N’-[3-(1H-1,2,4-triazol-5-yl)propyl]carbamimidoyl]urea;dihydrochloride1895224: Displacement of [3H]N-methylspiperone from human D4.4 receptor stably expressed in HEK293T cells co-expressing ElucN-betaarr2 hD4.4R-ELuc incubated for 60 mins by scintillation counting analysiskd0.0001uM
1-[N’-[3-(5-amino-1,3,4-thiadiazol-2-yl)propyl]carbamimidoyl]-3-pentylurea;bis(2,2,2-trifluoroacetic acid)1895224: Displacement of [3H]N-methylspiperone from human D4.4 receptor stably expressed in HEK293T cells co-expressing ElucN-betaarr2 hD4.4R-ELuc incubated for 60 mins by scintillation counting analysiskd0.0001uM
1-[N’-[3-(5-amino-1,3,4-thiadiazol-2-yl)propyl]carbamimidoyl]-3-benzylurea;bis(2,2,2-trifluoroacetic acid)1895224: Displacement of [3H]N-methylspiperone from human D4.4 receptor stably expressed in HEK293T cells co-expressing ElucN-betaarr2 hD4.4R-ELuc incubated for 60 mins by scintillation counting analysiskd0.0001uM
3-methoxy-N-[2-(4-naphthalen-1-ylpiperazin-1-yl)ethyl]benzamide63533: Binding affinity towards human Dopamine receptor D4 using [3H]spiroperidol as radioligandki0.0002uM
1-[3-(4-phenylpiperazin-1-yl)propyl]-3,4-dihydroquinolin-2-one1479887: Agonist activity at human SP/Myc epitope-tagged dopamine D4 receptor expressed in HEK293T cells assessed as RLuc8-fused Galphai1 activation after 2 mins by BRET assayec500.0002uM
(1S)-1-methyl-N-[(3R,4S)-4-methyl-1-propan-2-ylpyrrolidin-3-yl]-1,3-dihydroisoindole-2-carboxamide1932168: Agonist activity at D4R (unknown origin) by camp reporter assayec500.0002uM
N-(1-benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-(methylamino)benzamide65945: Binding Affinity to Human Dopamine receptor D4 expressed in CHO cells was determined using [3H]- nemonapride as radioligandkd0.0002uM
8-[4-(4-fluorophenyl)-4-oxobutyl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one751684: Displacement of [3H]Spiperone from human recombinant dopamine D4 receptor expressed in CHOK1 cells after 2 hrski0.0002uM
4-methyl-3-[1-[(3-methylphenyl)methyl]piperidin-4-yl]-5-phenyl-1H-imidazol-2-one63511: Affinity to displace [3H]spiperone from cloned human Dopamine receptor D4 stably expressed in HEK393 cell lineski0.0003uM
N-[2-(3-chlorophenoxy)ethyl]-3-phenoxypropan-1-amine243282: Binding affinity to displace [3H]spiperone from cloned human dopamine receptor D4 was determinedki0.0003uM
N-[2-(3,4-dimethylphenoxy)ethyl]-3-phenoxypropan-1-amine243282: Binding affinity to displace [3H]spiperone from cloned human dopamine receptor D4 was determinedki0.0003uM
N-[2-[4-(3-chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide63533: Binding affinity towards human Dopamine receptor D4 using [3H]spiroperidol as radioligandki0.0003uM
6-bromo-2-[[4-(2-methoxyphenyl)piperazin-1-yl]methyl]imidazo[1,2-a]pyridine1615608: Agonist activity at dopamine D4 receptor (unknown origin)ki0.0003uM
6-iodo-2-[[4-(2-methoxyphenyl)piperazin-1-yl]methyl]imidazo[1,2-a]pyridine1615608: Agonist activity at dopamine D4 receptor (unknown origin)ki0.0003uM
1-(N-benzylanilino)-3-[3-[4-(2-methoxyphenyl)piperazin-1-yl]propyl]urea1526878: Displacement of [3H] Spiperone from human D4.4 receptor expressed in CHO cells by competitive radioligand binding assayki0.0003uM
1-(2-methoxyphenyl)-4-[(1-phenylpyrazol-4-yl)methyl]piperazine265126: Displacement of [3H]spiperone from human cloned dopamine D4 receptor expressed in CHO cellski0.0003uM
N-[1-[(4-iodophenyl)methyl]piperidin-4-yl]-N-methyl-3-propan-2-yloxypyridin-2-amine1456755: Inhibition of human dopamine D4 receptorki0.0003uM
3-[[4-(4-chlorophenyl)piperazin-1-yl]methyl]-1H-pyrrolo[2,3-b]pyridine;hydrochloride238524: Binding affinity for dopamine D4 receptorki0.0004uM
1-[3-[4-(2-nitrophenyl)piperazin-1-yl]propyl]-3,4-dihydroquinolin-2-one;oxalic acid1851862: Displacement of [3H]N-methylspiperone from human D4.4 receptor expressed in HEK293T cell membrane incubated for 1 hr by MicroBeta scintillation counting methodki0.0004uM
1-benzyl-4-(3-methyl-4-phenylpyrazol-1-yl)piperidine63525: Binding affinity of compound towards human Dopamine receptor D4 by displacing [125I]-iodosulpiride expressed in CHO cellski0.0004uM
1-(azulen-1-ylmethyl)-4-(2-methoxyphenyl)piperazine1932146: Displacement of [3H]-spiperone from human D4 receptor expressed in CHO cells assessed as inhibition constantki0.0004uM
1-(2-methoxyphenyl)-4-[(1-pyridin-2-ylpyrazol-4-yl)methyl]piperazine265126: Displacement of [3H]spiperone from human cloned dopamine D4 receptor expressed in CHO cellski0.0004uM
N-[2-[4-(2,3-dichlorophenyl)piperazin-1-yl]ethyl]-3-ethynylbenzamide301658: Displacement of [3H]spiperone from human cloned dopamine D4.4 receptor expressed in CHO cell membraneski0.0004uM
3-[[4-(4-chlorophenyl)piperazin-1-yl]methyl]-1H-pyrrolo[2,3-b]pyridine1456755: Inhibition of human dopamine D4 receptorki0.0004uM
N-[2-(4-chlorophenoxy)ethyl]-3-phenoxypropan-1-amine243282: Binding affinity to displace [3H]spiperone from cloned human dopamine receptor D4 was determinedki0.0005uM
N-[2-(3-chloro-4-methylphenoxy)ethyl]-3-phenoxypropan-1-amine243282: Binding affinity to displace [3H]spiperone from cloned human dopamine receptor D4 was determinedki0.0005uM
N-[2-(3-methylphenoxy)ethyl]-3-phenoxypropan-1-amine243282: Binding affinity to displace [3H]spiperone from cloned human dopamine receptor D4 was determinedki0.0005uM
3-[1-[(3-chlorophenyl)methyl]piperidin-4-yl]-4-methyl-5-phenyl-1H-imidazol-2-one63511: Affinity to displace [3H]spiperone from cloned human Dopamine receptor D4 stably expressed in HEK393 cell lineski0.0005uM
N-[2-(4-methylphenoxy)ethyl]-3-phenoxypropan-1-amine243282: Binding affinity to displace [3H]spiperone from cloned human dopamine receptor D4 was determinedki0.0005uM
8-iodo-2-[[4-(2-methoxyphenyl)piperazin-1-yl]methyl]-6-methylimidazo[1,2-a]pyridine266776: Displacement of [3H]spiperone from human dopamine receptor D4.4 in CHO cell membraneki0.0005uM
8-[4-(4-fluorophenyl)-4-oxobutyl]-3-methyl-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one2198856: Binding affinity to DRD4 in human HEK293T cells membrane assessed as dissociation constant incubated for 2 hrs by radioligand saturation assaykd0.0005uM
Pramipexole63685: in vitro high binding affinity was determined on human Dopamine receptor D4 expressed in chinese hamster ovary(CHO) K-1 cells using [3H]spiperone as radioligand.ki0.0005uM
1-[3-[4-(2-chlorophenyl)piperazin-1-yl]propyl]-3,4-dihydroquinolin-2-one;oxalic acid1851877: Displacement of [3H]7-OH-DPAT from human D4.4 receptor expressed in HEK293T cell membrane incubated for 1.5 hrs by MicroBeta scintillation counting methodki0.0005uM
(NE)-N-[[2-[(4-phenylpiperazin-1-yl)methyl]-1H-indol-3-yl]methylidene]hydroxylamine1932146: Displacement of [3H]-spiperone from human D4 receptor expressed in CHO cells assessed as inhibition constantki0.0005uM
1-[3-[4-(2-methoxyphenyl)piperazin-1-yl]propyl]-3-[(2-phenylphenyl)methyl]urea1998321: Displacement of [3H]-N-methylspiperone from human dopmaine D4.4 receptor expressed in HEK293T cells assessed as inhibition constant by competition binding assayki0.0005uM
1-(3-chlorobenzo[b][1]benzoxepin-5-yl)-4-methylpiperazine64202: Affinity was evaluated by inhibition of [3H]-spiperone binding to COS cells transfected with human dopamine D-4 receptorki0.0005uM
3-(1,3-dihydroisoindol-2-yl)-2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]propan-1-ol1799610: Binding Assay from Article 10.1002/1439-7633(20021004)3:10: “Synthesis and structure-activity relationship of the isoindolinyl benzisoxazolpiperidines as potent, selective, and orally active human dopamine D4 receptor antagonists.”ki0.0005uM
2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]-3-(4-fluoro-1,3-dihydroisoindol-2-yl)propan-1-ol1799610: Binding Assay from Article 10.1002/1439-7633(20021004)3:10: “Synthesis and structure-activity relationship of the isoindolinyl benzisoxazolpiperidines as potent, selective, and orally active human dopamine D4 receptor antagonists.”ki0.0005uM
3-[[4-(4-iodophenyl)piperazin-1-yl]methyl]-1H-pyrrolo[2,3-b]pyridine63531: Binding affinity towards cloned human Dopamine receptor D4 stably expressed in CHO cells was evaluated using [3H]spiperone as radioligandki0.0005uM
4-methyl-5-phenyl-3-[1-(2-phenylethyl)piperidin-4-yl]-1H-imidazol-2-one63511: Affinity to displace [3H]spiperone from cloned human Dopamine receptor D4 stably expressed in HEK393 cell lineski0.0006uM
3-[1-[(3-methoxyphenyl)methyl]piperidin-4-yl]-4-methyl-5-phenyl-1H-imidazol-2-one63511: Affinity to displace [3H]spiperone from cloned human Dopamine receptor D4 stably expressed in HEK393 cell lineski0.0006uM
3-methoxy-N-[2-(4-pyridin-2-ylpiperazin-1-yl)ethyl]benzamide63533: Binding affinity towards human Dopamine receptor D4 using [3H]spiroperidol as radioligandki0.0006uM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
Valproic Acidaffects cotreatment, increases expression, decreases expression, increases methylation7
trichostatin Aaffects cotreatment, decreases expression3
Clozapinedecreases reaction, increases activity, affects response to substance, affects binding3
mercuric bromideaffects cotreatment, decreases expression2
Benzo(a)pyrenedecreases expression, decreases methylation, increases methylation2
Dopamineincreases activity, affects binding, decreases reaction2
Methamphetamineaffects response to substance, increases response to substance2
Phenylmercuric Acetateaffects cotreatment, decreases expression2
Spiperoneaffects binding, decreases reaction2
aristolochic acid Iincreases expression1
GSK-J4increases expression1
methylmercuric chloridedecreases expression1
dimethyl phosphateaffects response to substance1
fucoxanthinincreases activity1
nemonaprideaffects binding1
ropiniroleaffects binding, increases activity1
di-n-butylphosphoric acidaffects expression1
A 86929affects binding1
NRA 0045affects binding1
NRA 0160decreases activity, affects binding1
7-methyl-6,7,8,9,14,15-hexahydro-5H-benz(d)indolo(2,3-g)azecineaffects binding, decreases activity1
7-fluoro-2-oxo-4-(2-(4-(thieno(3,2-c)pyridin-4-yl)piperazin-1-yl)ethyl)-1,2-dihydroquinoline-1-acetamideaffects activity1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideaffects cotreatment, decreases expression1
dorsomorphinaffects cotreatment, decreases expression1
bisphenol Sdecreases expression1
jinfukangaffects cotreatment, decreases expression1
1-(2,3-dihydrobenzo(b)(1,4)dioxin-6-yl)-4-((6-fluoropyridin-3-yl)methyl)piperazineaffects binding1
Resveratrolaffects cotreatment, decreases expression1
Temozolomideincreases expression1
Cisplatinaffects cotreatment, decreases expression1

ChEMBL screening assays

951 unique, capped per target: 787 binding, 154 functional, 9 admet, 1 unclassified

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL5232013BindingBinding affinity to human D2/D4 receptor assessed as inhibition constantA review: Biologically active 3,4-heterocycle-fused coumarins. — Eur J Med Chem
CHEMBL661208FunctionalAntagonism of apomorphine induced inhibition of the tachycardia produced by stimulation of the right cardioaccelerator nerve in cat.Assessment of a potential dopaminergic prodrug moiety in several ring systems. — J Med Chem
CHEMBL4048887UnclassifiedSelectivity ratio of Ki for human dopamine D3 receptor to Ki for human dopamine D4 receptor1-[3-(4-Butylpiperidin-1-yl)propyl]-1,2,3,4-tetrahydroquinolin-2-one (77-LH-28-1) as a Model for the Rational Design of a Novel Class of Brain Penetrant Ligands with High Affinity and Selectivity for Dopamine D4 Receptor. — J Med Chem

Cellosaurus cell lines

5 cell lines: 2 transformed cell line, 2 spontaneously immortalized cell line, 1 undefined cell line type

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

CellosaurusNameCategorySex
CVCL_E7HLHEK293 hD4.4Transformed cell lineFemale
CVCL_H365293 c18/DRD4Transformed cell lineFemale
CVCL_KS83Chem-5 DRD4Undefined cell line type
CVCL_KV09cAMP Hunter CHO-K1 DRD4 GiSpontaneously immortalized cell lineFemale
CVCL_KW89PathHunter CHO-K1 DRD4 beta-arrestinSpontaneously immortalized cell lineFemale

Clinical trials (associated diseases)

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

About this page

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

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 81

This page pulls from 81 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgtopdb_interactiongwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot