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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. [provided by RefSeq, Jul 2008]
DRD4 (Dopamine Receptor D4) is a Protein Coding gene. Diseases associated with DRD4 include Attention Deficit-Hyperactivity Disorder and Autonomic Nervous System Disease. Among its related pathways are Signaling by GPCR and GPCRs, Other. Gene Ontology (GO) annotations related to this gene include G protein-coupled receptor activity and SH3 domain binding. An important paralog of this gene is DRD3.
D4 receptors are members of the dopamine receptor G-protein-coupled receptor family that also includes D1, D2, D3 and D5. They are located primarily in the frontal cortex, midbrain, amygdala and the cardiovascular system. A role in cognition and emotion has been proposed.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0001591 | dopamine neurotransmitter receptor activity, coupled via Gi/Go | IMP,ISS | -- |
GO:0004930 | G protein-coupled receptor activity | IBA | 21873635 |
GO:0004952 | dopamine neurotransmitter receptor activity | IDA | 8413587 |
GO:0004993 | G protein-coupled serotonin receptor activity | IBA | 21873635 |
GO:0005515 | protein binding | IPI | 12297500 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005623 | cell | IEA | -- |
GO:0005886 | plasma membrane | IDA,TAS | -- |
GO:0005887 | integral component of plasma membrane | IBA,IDA | 8413587 |
GO:0016020 | membrane | IDA | 7512953 |
GO:0016021 | integral component of membrane | IEA | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Peptide ligand-binding receptors | ||
2 | Signaling by GPCR | ||
3 | Methylphenidate Pathway, Pharmacodynamics | ||
4 | Nicotine Pathway (Dopaminergic Neuron), Pharmacodynamics | ||
5 | Monoamine GPCRs |
.75
|
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000187 | activation of MAPK activity | IDA | 9843378 |
GO:0001662 | behavioral fear response | NAS | 12860355 |
GO:0001963 | synaptic transmission, dopaminergic | IEA | -- |
GO:0001975 | response to amphetamine | IEA,ISS | -- |
GO:0006874 | cellular calcium ion homeostasis | IC | 7921596 |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Dopamine | Approved | Pharma | Agonist, Full agonist, Target, agonist | 3978 | ||
Clozapine | Approved | Pharma | Antagonist, Allosteric regulator, Positive, Agonist, Full agonist, Inverse agonist, Target, antagonist | Antipsychotic medication | 136 | |
Apomorphine | Approved, Investigational | Pharma | Agonist, Partial agonist, Antagonist, Full agonist, Activator, Activation, Target, agonist | 48 | ||
Pramipexole | Approved, Investigational | Pharma | Agonist, Full agonist, Target, agonist | Dopamine agonist | 157 | |
Bromocriptine | Approved, Investigational | Pharma | Antagonist, Agonist, Partial agonist, Full agonist, Target, antagonist, agonist | 44 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
SKF-82526 |
|
Agonist, Full agonist |
|
|||
Promazine 5-sulfoxide |
|
Compound | Action | Cas Number |
---|---|---|
A 412997 dihydrochloride | Selective D4 agonist | 1347744-96-0 |
ABT 724 trihydrochloride | Potent, selective D4 partial agonist; proerectile | 587870-77-7 |
PD 168077 maleate | High affinity, selective D4 agonist | 630117-19-0 |
PNU 96415E | D4 and 5-HT2A antagonist; antipsychotic | 170856-41-4 |
Ro 10-5824 dihydrochloride | Selective D4 receptor partial agonist | 189744-94-3 |
Compound | Action | Cas Number |
---|---|---|
(-)-Quinpirole hydrochloride | 85798-08-9 | |
(+)-AJ 76 hydrochloride | Dopamine receptor antagonist | 85378-82-1 |
(+)-UH 232 maleate | 1217473-50-1 | |
(R)-(-)-Apomorphine hydrochloride | 314-19-2 | |
(RS)-(±)-Sulpiride | 15676-16-1 | |
2-CMDO | 24140-98-5 | |
3-CPMT | 14008-79-8 | |
3'-Fluorobenzylspiperone maleate | 1135278-61-3 | |
6-Hydroxydopamine hydrobromide | 636-00-0 | |
7-Hydroxy-DPAT hydrobromide | 76135-30-3 | |
A 412997 dihydrochloride | Selective D4 agonist | 1347744-96-0 |
ABT 724 trihydrochloride | Dopamine D4 receptor agonist,potent and selective | 587870-77-7 |
Alizapride HCl | 59338-87-3 | |
Amantadine HCl | 665-66-7 | |
Ambrisentan | ETA-receptor antagonist | 177036-94-1 |
Amisulpride | Dopamine D2/D3 receptor antagonist | 71675-85-9 |
Aripiprazole | Antipsychotic | 129722-12-9 |
Bromocriptine mesylate | 22260-51-1 | |
Bupropion hydrochloride | Dopamine/norepinephrine inhibitor | 31677-93-7 |
Carmoxirole hydrochloride | 115092-85-8 | |
Chlorpromazine HCl | 69-09-0 | |
Chlorprothixene | 113-59-7 | |
Clozapine | Antipsychotic medication | 5786-21-0 |
CY 208-243 | 100999-26-6 | |
Dihydrexidine hydrochloride | 158704-02-0 | |
Domperidone | Drug for gastroparesis | 57808-66-9 |
Dopamine HCl | 62-31-7 | |
Eticlopride hydrochloride | 97612-24-3 | |
Flupenthixol dihydrochloride | Antipsychotic drug,exhibits antagonistic activity at dopamine D1-5 receptors | 2413-38-9 |
GBR 12783 dihydrochloride | 67469-75-4 | |
GBR 12935 dihydrochloride | 67469-81-2 | |
GBR 13069 dihydrochloride | 67469-45-8 | |
GSK 789472 hydrochloride | 1257326-24-1 | |
Haloperidol | Antipsychotic drug | 52-86-8 |
JHW 007 hydrochloride | 202645-74-7 | |
L-741,626 | 81226-60-0 | |
L-741,742 hydrochloride | 874882-93-6 | |
L-745,870 trihydrochloride | 866021-03-6 | |
LE 300 | 274694-98-3 | |
Levodapa | 59-92-7 | |
Levosulpiride | Antipsychotic drug | 23672-07-3 |
Loxapine Succinate | 27833-64-3 | |
LY404039 | MGlu2 and mGlu3 receptors agonist | 635318-11-5 |
Mesoridazine | 0 | 5588-33-0 |
Mesoridazine Besylate | 0 | 32672-69-8 |
Metoclopramide | Dopamine receptor antagonist | 364-62-5 |
Nemonapride | 75272-39-8 | |
NGB 2904 | 189061-11-8 | |
NGD 94-1 | 178928-68-2 | |
Nomifensine | 32795-47-4 | |
NPEC-caged-dopamine | 1257326-23-0 | |
OSU 6162 hydrochloride | 156907-84-5 | |
Paliperidone | 144598-75-4 | |
PAOPA | 114200-31-6 | |
PD 168077 maleate | 630117-19-0 | |
PD 168568 dihydrochloride | 210688-56-5 | |
PD128907 HCl | 112960-16-4 | |
Penfluridol | 26864-56-2 | |
Pergolide mesylate | 66104-23-2 | |
PG 01037 dihydrochloride | 675599-62-9 | |
Piribedil dihydrochloride | 1451048-94-4 | |
PNU 177864 hydrochloride | 250266-51-4 | |
PNU 96415E | 170856-41-4 | |
Pramipexole | Dopamine agonist | 104632-26-0 |
Pramipexole 2HCl Monohydrate | 191217-81-9 | |
Pramipexole dihydrochloride | Dopamine receptor agonist | 104632-25-9 |
Quetiapine | 111974-69-7 | |
Quetiapine Fumarate | 111974-72-2 | |
Quinelorane hydrochloride | 97548-97-5 | |
Raclopride | 84225-95-6 | |
Remoxipride hydrochloride | 73220-03-8 | |
Ro 10-5824 dihydrochloride | 189744-94-3 | |
Rotundine | Dopamine D1 receptor antagonist,potent and selective | 483-14-7 |
Roxindole hydrochloride | 108050-82-4 | |
RuBi-Dopa | ||
SCH 23390 hydrochloride | 125941-87-9 | |
Sitaxentan sodium | 210421-74-2 | |
SKF 38393 hydrobromide | 20012-10-6 | |
SKF 77434 hydrobromide | 300561-58-4 | |
SKF 81297 hydrobromide | 67287-39-2 | |
SKF 83566 hydrobromide | 108179-91-5 | |
SKF 83822 hydrobromide | 74115-10-9 | |
SKF 83959 hydrobromide | 67287-95-0 | |
Sonepiprazole | 170858-33-0 | |
U 99194 maleate | 234757-41-6 |
This gene was present in the common ancestor of animals.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | DRD4 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | Drd4 30 17 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Drd4 30 |
|
||
Oppossum (Monodelphis domestica) |
Mammalia | DRD4 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | DRD4 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | DRD4 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | drd4 30 |
|
||
African clawed frog (Xenopus laevis) |
Amphibia | Xl.6249 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | drd4a 30 31 |
|
OneToMany | |
drd4b 31 |
|
OneToMany | |||
drd4-rs 31 |
|
OneToMany | |||
African malaria mosquito (Anopheles gambiae) |
Insecta | GPRDOP3 30 |
|
||
Fruit Fly (Drosophila melanogaster) |
Insecta | D2R 31 |
|
OneToMany | |
Worm (Caenorhabditis elegans) |
Secernentea | dop-3 31 |
|
ManyToMany | |
dop-2 31 |
|
ManyToMany |
SNP ID | Clinical significance and condition | Chr 11 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
714338 | Benign: not provided | 637,526(+) | G/A | SYNONYMOUS_VARIANT | |
738977 | Likely Benign: not provided | 637,355(+) | G/A | SYNONYMOUS_VARIANT | |
745612 | Likely Benign: not provided | 639,426(+) | C/T | INTRON_VARIANT | |
745613 | Likely Benign: not provided | 640,453(+) | G/A | SYNONYMOUS_VARIANT | |
752181 | Likely Benign: not provided | 637,553(+) | C/T | SYNONYMOUS_VARIANT |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
dgv1522n54 | CNV | loss | 21841781 |
dgv1523n54 | CNV | gain | 21841781 |
dgv182e199 | CNV | deletion | 23128226 |
esv2743857 | CNV | deletion | 23290073 |
esv2759794 | CNV | loss | 17122850 |
esv2762889 | CNV | loss | 21179565 |
nsv1039558 | CNV | gain | 25217958 |
nsv1053964 | CNV | gain | 25217958 |
nsv1069992 | CNV | deletion | 25765185 |
nsv1159791 | CNV | deletion | 26073780 |
nsv467635 | CNV | loss | 19166990 |
nsv469923 | CNV | loss | 18288195 |
nsv552861 | CNV | loss | 21841781 |
nsv552866 | CNV | loss | 21841781 |
nsv832043 | CNV | loss | 17160897 |
nsv951271 | CNV | deletion | 24416366 |
Disorder | Aliases | PubMed IDs |
---|---|---|
attention deficit-hyperactivity disorder |
|
|
autonomic nervous system disease |
|
|
oppositional defiant disorder |
|
|
novelty seeking personality trait |
|
|
conduct disorder |
|