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DRD4 Gene(Protein Coding)

Dopamine Receptor D4

GCID:
GC11P000647
GIFtS:
67
Genes Participants
UDN Logo

Aliases for DRD4 Gene

Aliases for DRD4 Gene

  • Dopamine Receptor D4 2 3 5
  • D(2C) Dopamine Receptor 3 4
  • Dopamine D4 Receptor 3 4
  • Seven Transmembrane Helix Receptor 3
  • D4DR 3

External Ids for DRD4 Gene

Previous GeneCards Identifiers for DRD4 Gene

  • GC11P001092
  • GC11M000923
  • GC11M000559
  • GC11P000627
  • GC11P000452
  • GC11P000638
  • GC11P000646
  • GC11P000653
  • GC11P000656
  • GC11P000644
  • GC11P000645

Summaries for DRD4 Gene

Entrez Gene Summary for DRD4 Gene

  • 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]

GeneCards Summary for DRD4 Gene

DRD4 (Dopamine Receptor D4) is a Protein Coding gene. Diseases associated with DRD4 include Attention Deficit-Hyperactivity Disorder and Oppositional Defiant Disorder. Among its related pathways are Peptide ligand-binding receptors and Signaling by GPCR. GO annotations related to this gene include G-protein coupled receptor activity and SH3 domain binding. An important paralog of this gene is HTR1F.

UniProtKB/Swiss-Prot for DRD4 Gene

  • Dopamine receptor responsible for neuronal signaling in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior. Its activity is mediated by G proteins which inhibit adenylyl cyclase. Modulates the circadian rhythm of contrast sensitivity by regulating the rhythmic expression of NPAS2 in the retinal ganglion cells (By similarity).

Tocris Summary for DRD4 Gene

  • 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.

Gene Wiki entry for DRD4 Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for DRD4 Gene

Genomics for DRD4 Gene

Products:

  1. Regulatory Element

Regulatory Elements for DRD4 Gene

Enhancers for DRD4 Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around DRD4 on UCSC Golden Path with GeneCards custom track

Transcription factor binding sites by QIAGEN in the DRD4 gene promoter:

Genomic Location for DRD4 Gene

Chromosome:
11
Start:
637,293 bp from pter
End:
640,706 bp from pter
Size:
3,414 bases
Orientation:
Plus strand

Genomic View for DRD4 Gene

Genes around DRD4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
DRD4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for DRD4 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for DRD4 Gene

Proteins for DRD4 Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

  • Protein details for DRD4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P21917-DRD4_HUMAN
    Recommended name:
    D(4) dopamine receptor
    Protein Accession:
    P21917
    Secondary Accessions:
    • B0M0J7
    • Q7Z7Q5
    • Q8NGM5

    Protein attributes for DRD4 Gene

    Size:
    467 amino acids
    Molecular mass:
    48361 Da
    Quaternary structure:
    • 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 (By similarity) and GPRASP1. May interact with ADORA2A. Interacts with KLHL12.
    SequenceCaution:
    • Sequence=AAL58637.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};

neXtProt entry for DRD4 Gene

Proteomics data for DRD4 Gene at MOPED

Protein Expression for DRD4 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for DRD4 Gene

  • Polyubiquitinated by the BCR(KLHL12) E3 ubiquitin ligase complex: polyubiquitination does not lead to degradation of DRD4 protein.
  • Glycosylation at Asn 3
  • Modification sites at PhosphoSitePlus

Other Protein References for DRD4 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for DRD4 Gene

Domains & Families for DRD4 Gene

Gene Families for DRD4 Gene

HGNC:
IUPHAR :

Protein Domains for DRD4 Gene

InterPro:
Blocks:
ProtoNet:

Suggested Antigen Peptide Sequences for DRD4 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

P21917

UniProtKB/Swiss-Prot:

DRD4_HUMAN :
  • Belongs to the G-protein coupled receptor 1 family.
Family:
  • Belongs to the G-protein coupled receptor 1 family.
genes like me logo Genes that share domains with DRD4: view

Function for DRD4 Gene

Products:

  1. Animal Model
  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line
  7. Flow Cytometry

Molecular function for DRD4 Gene

GENATLAS Biochemistry:
dopamine receptor D4,with high affinity for antagonist clozapine,G protein coupled receptor superfamily,not imprinted in the human brain (putatively involved in the susceptibility to Gilles de la Tourette syndrome),and a wide range of neuropsychiatric disorders and normal behavioural variation
UniProtKB/Swiss-Prot 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. Its activity is mediated by G proteins which inhibit adenylyl cyclase. Modulates the circadian rhythm of contrast sensitivity by regulating the rhythmic expression of NPAS2 in the retinal ganglion cells (By similarity).

Gene Ontology (GO) - Molecular Function for DRD4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IEA,IPI 12297500
GO:0008144 drug binding IEA,IDA 1319557
genes like me logo Genes that share ontologies with DRD4: view

Phenotypes for DRD4 Gene

MGI mutant phenotypes for DRD4:
inferred from 2 alleles
GenomeRNAi human phenotypes for DRD4:
genes like me logo Genes that share phenotypes with DRD4: view

Animal Models for DRD4 Gene

MGI Knock Outs for DRD4:

Animal Model Products

miRNA for DRD4 Gene

miRTarBase miRNAs that target DRD4

Inhibitory RNA Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for DRD4 Gene

Localization for DRD4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for DRD4 Gene

Cell membrane; Multi-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for DRD4 Gene COMPARTMENTS Subcellular localization image for DRD4 gene
Compartment Confidence
plasma membrane 5
extracellular 1
nucleus 1

Gene Ontology (GO) - Cellular Components for DRD4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005887 integral component of plasma membrane IDA 8413587
GO:0016021 integral component of membrane IEA --
GO:0030425 dendrite IEA --
genes like me logo Genes that share ontologies with DRD4: view

Pathways & Interactions for DRD4 Gene

genes like me logo Genes that share pathways with DRD4: view

Gene Ontology (GO) - Biological Process for DRD4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001975 response to amphetamine IEA,ISS --
GO:0008306 associative learning IEA --
GO:0008344 adult locomotory behavior IEA,ISS --
GO:0008355 olfactory learning IEA --
GO:0009648 photoperiodism IEA --
genes like me logo Genes that share ontologies with DRD4: view

No data available for SIGNOR curated interactions for DRD4 Gene

Drugs & Compounds for DRD4 Gene

Products:

  1. Drug

(111) Drugs for DRD4 Gene - From: DrugBank, ClinicalTrials, ApexBio, DGIdb, IUPHAR, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Dopamine Approved Pharma Full agonist, Agonist, agonist, Target 3636
Clozapine Approved Pharma Antagonist, antagonist, Target Antipsychotic medication, Dopamine antagonist with some D4 selectivity. Also 5-HT2A/2C antagonist 113
Apomorphine Approved, Investigational Pharma Partial agonist, Agonist, agonist, Target 34
Pramipexole Approved, Investigational Pharma Full agonist, Agonist, agonist, Target Dopamine agonist 137
Bromocriptine Approved, Investigational Pharma Antagonist, agonist, Target, antagonist 29

(30) Additional Compounds for DRD4 Gene - From: Novoseek, IUPHAR, Tocris, and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
SKF-82526
Full agonist, Agonist
Promazine 5-sulfoxide
A 412997 dihydrochloride
1347744-96-0
ABT 724 trihydrochloride
587870-77-7
PD 168077 maleate
630117-19-0

(5) Tocris Compounds for DRD4 Gene

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
Ro 10-5824 dihydrochloride Selective D4 receptor partial agonist 189744-94-3
WAY 100635 maleate Potent, 5-HT1A silent antagonist. Also D4 agonist 634908-75-1

(28) ApexBio Compounds for DRD4 Gene

Compound Action Cas Number
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
Bupropion hydrochloride Dopamine/norepinephrine inhibitor 31677-93-7
Chlorpromazine HCl 69-09-0
Chlorprothixene 113-59-7
Clozapine Antipsychotic medication 5786-21-0
Domperidone Drug for gastroparesis 57808-66-9
Dopamine HCl 62-31-7
Haloperidol Antipsychotic drug 52-86-8
Levodapa 59-92-7
Levosulpiride Antipsychotic drug 23672-07-3
Loxapine Succinate 27833-64-3
LY404039 MGlu2 and mGlu3 receptors agonist 635318-11-5
Metoclopramide Dopamine receptor antagonist 364-62-5
Paliperidone 144598-75-4
PD128907 HCl 112960-16-4
Penfluridol 26864-56-2
Pergolide mesylate 66104-23-2
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
Rotundine Dopamine D1 receptor antagonist,potent and selective 483-14-7
Sitaxentan sodium 210421-74-2
genes like me logo Genes that share compounds with DRD4: view

Drug Products

Transcripts for DRD4 Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone
  5. Flow Cytometry

mRNA/cDNA for DRD4 Gene

(1) REFSEQ mRNAs :
(3) Additional mRNA sequences :
(22) Selected AceView cDNA sequences:
(2) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for DRD4 Gene

Dopamine receptor D4:
Representative Sequences:

Inhibitory RNA Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for DRD4 Gene

No ASD Table

Relevant External Links for DRD4 Gene

GeneLoc Exon Structure for
DRD4
ECgene alternative splicing isoforms for
DRD4

Expression for DRD4 Gene

Products:

  1. Primer

mRNA expression in normal human tissues for DRD4 Gene

mRNA expression in normal human tissues for DRD4 Gene
mRNA expression by BioGPS for DRD4 GenemRNA expression by GTEx for DRD4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for DRD4 Gene

This gene is overexpressed in Retina (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for DRD4 Gene



SOURCE GeneReport for Unigene cluster for DRD4 Gene Hs.99922

genes like me logo Genes that share expression patterns with DRD4: view

Protein tissue co-expression partners for DRD4 Gene

- Elite partner

Primer Products

No data available for mRNA differential expression in normal tissues and mRNA Expression by UniProt/SwissProt for DRD4 Gene

Orthologs for DRD4 Gene

This gene was present in the common ancestor of animals.

Orthologs for DRD4 Gene

Organism Taxonomy Gene Similarity Type Details
mouse
(Mus musculus)
 Mammalia Drd4 35
  • 82.34 (n)
  • 79.32 (a)
Drd4 16
Drd4 36
  • 78 (a)
 OneToOne
rat
(Rattus norvegicus)
 Mammalia Drd4 35
  • 81.77 (n)
  • 78.35 (a)
oppossum
(Monodelphis domestica)
 Mammalia DRD4 36
  • 61 (a)
 OneToOne
chimpanzee
(Pan troglodytes)
 Mammalia DRD4 36
  • 95 (a)
 OneToOne
chicken
(Gallus gallus)
 Aves DRD4 35
  • 66.38 (n)
  • 60.98 (a)
DRD4 36
  • 57 (a)
 OneToOne
lizard
(Anolis carolinensis)
 Reptilia DRD4 36
  • 58 (a)
 OneToOne
tropical clawed frog
(Silurana tropicalis)
 Amphibia drd4 35
  • 66.67 (n)
  • 69.4 (a)
African clawed frog
(Xenopus laevis)
 Amphibia Xl.6249 35
zebrafish
(Danio rerio)
 Actinopterygii drd4a 35
  • 61.93 (n)
  • 59.71 (a)
drd4-rs 36
  • 50 (a)
 OneToMany
drd4a 36
  • 51 (a)
 OneToMany
drd4b 36
  • 54 (a)
 OneToMany
African malaria mosquito
(Anopheles gambiae)
 Insecta GPRDOP3 35
  • 51.62 (n)
  • 48.64 (a)
fruit fly
(Drosophila melanogaster)
 Insecta D2R 36
  • 23 (a)
 OneToMany
worm
(Caenorhabditis elegans)
 Secernentea dop-2 36
  • 15 (a)
 ManyToMany
dop-3 36
  • 20 (a)
 ManyToMany
Species with no ortholog for DRD4:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • cow (Bos Taurus)
  • dog (Canis familiaris)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for DRD4 Gene

ENSEMBL:
Gene Tree for DRD4 (if available)
TreeFam:
Gene Tree for DRD4 (if available)

Paralogs for DRD4 Gene

Paralogs for DRD4 Gene

(1) SIMAP similar genes for DRD4 Gene using alignment to 81 proteins:

genes like me logo Genes that share paralogs with DRD4: view

Variants for DRD4 Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for DRD4 Gene

DRD4_HUMAN-P21917
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 D4.7. The polymorphic repeat sequence has little influence on DRD4-binding profiles and might not be essential for G protein interaction.

Sequence variations from dbSNP and Humsavar for DRD4 Gene

SNP ID Clin Chr 11 pos Sequence Context AA Info Type
rs1800443 - 639,830(+) CGTGG(G/T)CTACT reference, missense
VAR_003467 -
VAR_003468 -
rs3889692 - 640,090(+) CGCCC(C/G)CCGCG reference, missense
rs747302 -- 636,689(+) CTGAG(A/C/G)GCCAG upstream-variant-2KB

Structural Variations from Database of Genomic Variants (DGV) for DRD4 Gene

Variant ID Type Subtype PubMed ID
dgv182e199 CNV Deletion 23128226
dgv920n71 CNV Loss 21882294
dgv921n71 CNV Loss 21882294
dgv922n71 CNV Loss 21882294
nsv469923 CNV Loss 18288195
essv23843 CNV CNV 17122850
nsv896545 CNV Loss 21882294
dgv935n71 CNV Loss 21882294
dgv936n71 CNV Loss 21882294
nsv467635 CNV Loss 19166990
dgv940n71 CNV Loss 21882294
dgv941n71 CNV Loss 21882294
nsv896570 CNV Loss 21882294
dgv942n71 CNV Loss 21882294
nsv832043 CNV Loss 17160897
esv2743857 CNV Deletion 23290073

Variation tolerance for DRD4 Gene

Gene Damage Index Score: 6.52; 77.71% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for DRD4 Gene

Human Gene Mutation Database (HGMD)
DRD4

Disorders for DRD4 Gene

MalaCards: The human disease database

(29) MalaCards diseases for DRD4 Gene - From: OMIM, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
attention deficit-hyperactivity disorder
  • attention deficit hyperactivity disorder
oppositional defiant disorder
tic disorder
chronic tic disorder
  • chronic motor or vocal tic disorder
separation anxiety disorder
  • separation anxiety disorder of childhood
- elite association - COSMIC cancer census association via MalaCards
Search DRD4 in MalaCards View complete list of genes associated with diseases

Relevant External Links for DRD4

Genetic Association Database (GAD)
DRD4
Human Genome Epidemiology (HuGE) Navigator
DRD4
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
DRD4
genes like me logo Genes that share disorders with DRD4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for DRD4 Gene

Publications for DRD4 Gene

  1. Associations of the dopamine D4 receptor gene VNTR polymorphism with drug use in adolescent psychiatric inpatients. (PMID: 17175015) McGeary J.E. … Monti P.M. (Pharmacol. Biochem. Behav. 2007) 3 23 48 67
  2. Schizophrenia is not associated with DRD4 48-base-pair-repeat length or individual alleles: results of a meta-analysis. (PMID: 13129658) Glatt S.J. … Tsuang M.T. (Biol. Psychiatry 2003) 3 23 25
  3. Atypical neuroleptics have low affinity for dopamine D2 receptors or are selective for D4 receptors. (PMID: 9015795) Seeman P. … Van Tol H.H. (Neuropsychopharmacology 1997) 23 25 26
  4. Dopamine receptor D4 polymorphism predicts the effect of L-DOPA on gambling behavior. (PMID: 19914604) Eisenegger C. … Fehr E. (Biol. Psychiatry 2010) 3 23
  5. Polymorphisms in dopamine system genes are associated with individual differences in attention in infancy. (PMID: 20210499) Holmboe K. … Johnson M.H. (Dev Psychol 2010) 3 23

Products for DRD4 Gene

  • Addgene plasmids for DRD4

Sources for DRD4 Gene

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