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DRD4 Gene

protein-coding GIFtS: 68
GCID: GC11P000656

Dopamine Receptor D4

See DRD4-related diseases
at

MalaCards

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, ¹⁰fRNAdb, ¹²H-InvDB, ¹³NCBI, ¹⁴NONCODE, and/or ¹⁵RNAdb)
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Aliases
Dopamine Receptor D4¹ ²
Dopamine D4 Receptor² ³
D(2C) Dopamine Receptor² ³
D4DR²
D(4) Dopamine Receptor²
Seven Transmembrane Helix Receptor²

External Ids:	HGNC: 3025¹	Entrez Gene: 1815²	Ensembl: ENSG00000069696⁷	OMIM: 126452⁵	UniProtKB: P21917³

Export aliases for DRD4 gene to outside databases

Previous GC identifers: GC11P001092 GC11M000923 GC11M000559 GC11P000627 GC11P000452 GC11P000638 GC11P000646 GC11P000653

(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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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 separation anxiety disorder, and chronic tic disorder. GO annotations related to this gene include drug binding and identical protein binding. An important paralog of this gene is HTR2A.

UniProtKB/Swiss-Prot: DRD4_HUMAN, P21917

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

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. The function of the D4 receptor is unknown, although a role in cognition and emotion has been

proposed. The human D4 receptor gene has been localized to chromosome 11 (11q15.5).

Gene Wiki entry for DRD4 (Dopamine receptor D4) Gene

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:

NC_000011.9 NC_018922.2 NT_009237.19 NT_187586.1

Regulatory elements:

Regulatory transcription factor binding sites in the DRD4 gene promoter:
Sp1 p300 C/EBPalpha
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: DRD4 promoter sequence

Search Chromatin IP Primers for DRD4

Epigenetics:

DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat DRD4

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 11p15.5 Ensembl cytogenetic band: 11p15.5 HGNC cytogenetic band: 11p15.5

DRD4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
DRD4 gene location

GeneLoc information about chromosome 11 GeneLoc Exon Structure

GeneLoc location for GC11P000656: view genomic region (about GC identifiers)

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

(According to ¹UniProtKB, HORDE, ²neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: DRD4_HUMAN, P21917 (See protein sequence)

Recommended Name: D(4) dopamine receptor

Size: 467 amino acids; 48361 Da

Subunit: 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

Sequence caution: Sequence=AAL58637.1; Type=Erroneous gene model prediction;

Secondary accessions: B0M0J7 Q7Z7Q5 Q8NGM5

Explore the universe of human proteins at neXtProt for DRD4: NX_P21917

Explore proteomics data for DRD4 at MOPED

Post-translational modifications:

Polyubiquitinated by the BCR(KLHL12) E3 ubiquitin ligase complex: polyubiquitination does not lead to degradation

of DRD4 protein¹

Glycosylation² at Asn3

Modification sites at PhosphoSitePlus

See DRD4 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

REFSEQ proteins: NP_000788.2

ENSEMBL proteins:

ENSP00000176183

Reactome Protein details: P21917

DRD4 Human Recombinant Protein Products:

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	antibodies-online peptides for DRD4

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(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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HGNC Gene Families:

DRD: GPCR / Class A : Dopamine receptors

IUPHAR Guide to PHARMACOLOGY protein family classification: D₄ receptor

Dopamine receptors

4 InterPro protein domains:

IPR017452 GPCR_Rhodpsn_7TM

IPR000929 Dopamine_rcpt

IPR000276 GPCR_Rhodpsn

IPR002185 Dopamine_D4_rcpt

Graphical View of Domain Structure for InterPro Entry P21917

ProtoNet protein and cluster: P21917

2 Blocks protein domains:

IPB000929 Dopamine receptor signature

IPB002185 Dopamine D4 receptor signature

UniProtKB/Swiss-Prot: DRD4_HUMAN, P21917

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

Find genes that share domains with DRD4 About GenesLikeMe

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, genOway,
transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Molecular Function:

UniProtKB/Swiss-Prot Summary: DRD4_HUMAN, P21917

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

Genatlas biochemistry entry for DRD4:

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

Gene Ontology (GO): Selected molecular function terms (see all 9): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0001591	dopamine neurotransmitter receptor activity, coupled via Gi/Go	ISS	--
GO:0004930	G-protein coupled receptor activity	--	--
GO:0004952	dopamine neurotransmitter receptor activity	IDA	8413587
GO:0005515	protein binding	IPI	12297500
GO:0008144	drug binding	IDA	1319557

Find genes that share ontologies with DRD4 About GenesLikeMe

Phenotypes:
4 MGI mutant phenotypes (inferred from 2 alleles) (MGI details for Drd4):

behavior/neurological

homeostasis/metabolism

nervous system

vision/eye

Find genes that share phenotypes with DRD4 About GenesLikeMe

Animal Models:
MGI mouse knock-outs for DRD4: Drd4^tm1Dkg Drd4^{tm1(IL2RA)Tao}

genOway: Develop your customized and physiologically relevant rodent model for DRD4

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Gene Editing
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DNA2.0 Custom Protein Engineering Service for DRD4

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		Browse ESI BIO Cell Lines and PureStem Progenitors for DRD4

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for DRD4

(According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Subcellular locations from UniProtKB/Swiss-Prot

DRD4_HUMAN, P21917: Cell membrane; Multi-pass membrane protein

Subcellular locations from COMPARTMENTS:

Compartment	Confidence
plasma membrane	5
nucleus	2
extracellular	1

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Gene Ontology (GO): Selected cellular component terms (see all 13): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005737	cytoplasm	--	--
GO:0005886	plasma membrane	TAS	--
GO:0005887	integral component of plasma membrane	IDA	15755724
GO:0005938	cell cortex	IEA	--
GO:0012506	vesicle membrane	IEA	--

Find genes that share ontologies with DRD4 About GenesLikeMe

(SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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SuperPaths for DRD4 About (see all 9)

See pathways by source

Powered
by

SuperPath

Contained pathways About

Peptide ligand-binding receptors

Class A/1 (Rhodopsin-like receptors)	0.71	GPCRs, Class A Rhodopsin-like	0.43
GPCR ligand binding	0.71	Neuroactive ligand-receptor interaction	0.36
G alpha (i) signalling events	0.44

Monoamine GPCRs

	Monoamine GPCRs	0.79			Dopamine receptors	0.00
	Amine ligand-binding receptors	0.79

Nicotine Pathway (Dopaminergic Neuron), Pharmacodynamics

Nicotine Pathway (Dopaminergic Neuron), Pharmacodynamics

0.44

Nicotine Activity on Dopaminergic Neurons

0.44

Signaling by GPCR

	Signaling by GPCR	0.90			Signal Transduction	0.58
	GPCR downstream signaling	0.90

Circadian entrainment

Dopaminergic synapse

0.37

Find genes that share SuperPaths with DRD4 About GenesLikeMe

Pathways by source See SuperPaths
Show all pathways

2 Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for DRD4

	CDK5 Pathway
	Dopamine-DARPP32 Feedback onto cAMP Pathway

5 BioSystems Pathways for DRD4

	Hypothetical Network for Drug Addiction
	Nicotine Activity on Dopaminergic Neurons
	GPCRs, Other
	GPCRs, Class A Rhodopsin-like
	Monoamine GPCRs

2 Reactome Pathways for DRD4

	Dopamine receptors
	G alpha (i) signalling events

1 PharmGKB Pathway for DRD4

Nicotine Pathway (Dopaminergic Neuron), Pharmacodynamics

2 Kegg Pathways (Kegg details for DRD4):

	Neuroactive ligand-receptor interaction
	Dopaminergic synapse

Pathway & Disease-focused RT² Profiler PCR Array including DRD4:

G Protein Coupled Receptors 384HT in human mouse rat

Interactions:

GeneGlobe Interaction Network for DRD4

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

Selected Interacting proteins for DRD4 (P21917^{1, 2, 3} ENSP00000176183⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 159)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
DRD4	P21917¹^,²	EBI-8592297,EBI-8592297 MINT-8090346 MINT-8090371 MINT-8090394
KCNJ9	Q92806³, ENSP00000357067⁴	I2D: score=2 STRING: ENSP00000357067
KLHL12	Q53G59³, ENSP00000356230⁴	I2D: score=2 STRING: ENSP00000356230
KCNJ3	P48549³, ENSP00000295101⁴	I2D: score=1 STRING: ENSP00000295101
KCNJ5	P48544³, ENSP00000339960⁴	I2D: score=1 STRING: ENSP00000339960

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Gene Ontology (GO): Selected biological process terms (see all 37): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000187	activation of MAPK activity	IDA	15755724
GO:0001662	behavioral fear response	NAS	12860355
GO:0001963	synaptic transmission, dopaminergic	IEA	--
GO:0001975	response to amphetamine	ISS	--
GO:0006874	cellular calcium ion homeostasis	IC	7921596

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(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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Browse Small Molecules at EMD Millipore

Enzo Life Sciences drugs & compounds for DRD4

Browse compounds at ApexBio

Compounds for DRD4 available from Tocris Bioscience About this table

Compound	Action	CAS #
A 412997 dihydrochloride	Selective D4 agonist	[1347744-96-0]
PD 168077 maleate	High affinity, selective D4 agonist	[630117-19-0]
L-745,870 trihydrochloride	Highly selective D4 antagonist	[158985-00-3]
PNU 96415E	D4 and 5-HT2A antagonist; antipsychotic	[170856-41-4]
L-741,742 hydrochloride	Highly selective D4 antagonist	[156337-32-5]

2 HMDB Compounds for DRD4 About this table

Compound	Synonyms	CAS #	PubMed Ids
Dopamine	2-(3,4-Dihydroxyphenyl)ethylamine (see all 22)	62-31-7	--
Olanzapine	Lanzac (see all 5)	132539-06-1	--

Selected DrugBank Compounds for DRD4 (see all 24) About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
Apomorphine	Apomorfin (see all 9)	41372-20-7	target	agonist	9497025 17067298 15007532 11752352 17164075 9871530 18691132
Clozapine	--	5786-21-0	target	antagonist	13129658 16223700 11752352 15886414 12763097 15992586
Asenapine	--	65576-45-6	target	antagonist	21655346 18308814 10592235
Levodopa	3,4-dihydroxyphenylalanine (see all 4)	59-92-7	target	agonist	11978145 18549347 9633680
Cabergoline	Cabergolina [Spanish] (see all 2)	81409-90-7	target	agonist	18691132 12388667
Olanzapine	--	132539-06-1	target	antagonist	16237394 11752352
Paliperidone	--	144598-75-4	target	antagonist	7520908 7531353
Pramipexole	--	104632-26-0	target	agonist	11752352 18691132
Promazine	Promazin (see all 2)	58-40-2	target	antagonist	17139284 17016423
Propiomazine	--	362-29-8	target	antagonist	17139284 17016423

Selected IUPHAR Ligands for DRD4 (D₄ receptor) (see all 26) About this table

Ligand	Type	Action	Affinity	Pubmed IDs
nemonapride	Antagonist	Antagonist	10	8248849
[¹²⁵I]L750667	Antagonist	Antagonist	9.8	8967990
[³H]spiperone	Antagonist	Antagonist	9.5	7777184 1840645
L745870	Antagonist	Antagonist	9.4	8642550
spiperone	Antagonist	Antagonist	9.3	7475902
U101958	Antagonist	Antagonist	8.9	9098699
haloperidol	Antagonist	Antagonist	8.7	8102973 7862709
L741742	Antagonist	Antagonist	8.5	8642551
apomorphine	Agonist	Partial agonist	8.4	12388666
[³H]NGD941	Antagonist	Antagonist	8.3	9262371

Selected Novoseek inferred chemical compound relationships for DRD4 gene (see all 56) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
dopamine	87.9	471	12587848 (3), 10050966 (2), 10412189 (2), 10490700 (2) (see all 99)
maoa	78.3	24	20218801 (3), 12773616 (2), 17918108 (2), 18239643 (1) (see all 16)
clozapine	75.9	57	7944879 (7), 8693618 (4), 7737323 (3), 8866760 (2) (see all 29)
fananserin	67.5	3	8957240 (3)
raclopride	62.9	2	8248849 (1), 9765336 (1)
melperone	62.7	1	8102973 (1)
spiperone	59.6	4	9042615 (1), 9353380 (1), 7873121 (1), 9843378 (1)
methylphenidate	55.4	24	17077808 (5), 10596245 (1), 10889550 (1), 17955457 (1) (see all 7)
haloperidol	47.2	3	16288878 (1), 9042615 (1), 7873121 (1)
apomorphine	42.6	2	8097160 (1), 10832611 (1)

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(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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REFSEQ mRNAs for DRD4 gene:

NM_000797.3

Unigene Cluster for DRD4:

Dopamine receptor D4

Hs.99922 [show with all ESTs]

Unigene Representative Sequence: L12398

2 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000176183(uc001lqp.2) ENST00000528733

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		GenScript: all cDNA clones in your preferred vector: DRD4 (NM_000797)
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for DRD4
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		Addgene plasmids for DRD4

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		QuantiTect SYBR Green Assays in human, mouse, rat DRD4
		QuantiFast Probe-based Assays in human, mouse, rat DRD4

Additional mRNA sequence:

EU432112.1 L12398.1 S76942.1

3 DOTS entries:

DT.97854770 DT.97854768 DT.100748281

22 AceView cDNA sequences:

BM725264 NM_000797 BM674709 BM931265 BQ187919 CA418876 BF224406 BQ187417

BM929293 AI628607 BX282376 BQ188490 BE222894 H46232 BM694620 L12398

BM727107 BM713372 BM722840 BM929265 AA419163 BQ186689

GeneLoc Exon Structure

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE ¹MOPED, ²PaxDb, and ³MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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DRD4 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>^2/3
CGAP TAG: AGGGTCCTGC

About this image

DRD4 expression in embryonic tissues and stem cells About this table

Data from LifeMap, the Embryonic Development and Stem Cells Database
selected tissues (see all 9) fully expand


Eye (Sensory Organs) fully expand to see all 3 entries
Mature Rod Cells Outer Nuclear Layer

Neurons
Mature Rod Cells Outer Nuclear Layer

Brain (Nervous System) fully expand to see all 2 entries
Midbrain tegmentum
N2/LSB induced-cells

Ovary (Reproductive System) fully expand to see all 2 entries
Pre-Granulosa Cells Primordial Follicle

Bone (Muscoskeletal System)
TGFbeta3+BMP7-induced chondrocytes

DRD4 Protein expression data from MOPED¹, PaxDb² and MaxQB³:

About this image

DRD4 Protein Expression

SOURCE GeneReport for Unigene cluster: Hs.99922

Pathway & Disease-focused RT² Profiler PCR Array including DRD4:

G Protein Coupled Receptors 384HT in human mouse rat

Primer Products:		OriGene qPCR primer pairs and template standards for DRD4 OriGene qSTAR qPCR primer pairs in human, mouse for DRD4
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		QuantiFast Probe-based Assays in human, mouse, rat DRD4

In Situ
Assay Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for DRD4

(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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This gene was present in the common ancestor of animals.

Orthologs for DRD4 gene from Selected species (see all 12) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Drd4^{1 , 5}	dopamine receptor D4^{1, 5}	82.34(n)¹ 79.32(a)¹		7 (86.60 cM)⁵ 13491¹ NM_007878.2¹ NP_031904.1¹ 141292006⁵
chicken (Gallus gallus)	Aves	DRD4¹	dopamine receptor D4	66.38(n) 60.98(a)		423016 NM_001142849.1 NP_001136321.1
lizard (Anolis carolinensis)	Reptilia	DRD4⁶	dopamine receptor D4	58(a)	1 ↔ 1	1(74190534-74256891)
African clawed frog (Xenopus laevis)	Amphibia	Xl.6249²	Xenopus laevis transcribed sequence with moderate similarity to protein spP21917 (H.sapiens) D4DR_HUMAN D(4) dopamine receptor (D(2C) dopamine receptor) less	77.6(n)		CD362987.1
zebrafish (Danio rerio)	Actinopterygii	drd4a¹	dopamine receptor D4a	61.93(n) 59.71(a)		503564 NM_001012616.2 NP_001012634.1
fruit fly (Drosophila melanogaster)	Insecta	D2R⁶	Dopamine 2-like receptor	23(a)	1 → many	X(19898715-19922226)
worm (Caenorhabditis elegans)	Secernentea	dop-3⁶ dop-2⁶	Protein DOP-3, isoform d (dop-3) mRNA, complete cd... Protein DOP-2, isoform c (dop-2) mRNA, complete cd...	20(a) 15(a)	many ↔ many many ↔ many	X(6564175-6569518) WBGene00020506 V(9608562-9614942) WBGene00001053

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

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
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Paralogs for DRD4 gene

HTR2A² DRD2² CHRM1² CHRM2² HRH3² HTR2B² HRH4² HTR2C²

HRH1² CHRM5² DRD3² CHRM4² CHRM3²

1 SIMAP similar gene for DRD4 using alignment to 81 protein entries: DRD4_HUMAN (see all proteins):

DRD3

Find genes that share paralogs with DRD4 About GenesLikeMe

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, ⁴UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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Polymorphic Variants from UniProtKB/Swiss-Prot

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

SNP ID	Valid	Clinical significance	Chr 11 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs1800443^1,2,,4	C,F,H	non-pathogenic¹	639830(+)	`CGTGGT/GCTACT`	2	/G /V	mis¹ ese³		16		MN NS EA NA EU	6915
rs183430024^1,2		--	635342(+)	`GAGTTC/TGAGAC`	1	--	us2k¹		0	--	--	--	--
rs188367813^1,2		--	635356(+)	`CCTGGC/GCAATA`	1	--	us2k¹		0	--	--	--	--
rs35383378^1,2	C	--	635548(+)	`ATCTC-/AAAAAAA`	1	--	us2k¹		1		NA	2
rs12788170^1,2	F	--	635569(+)	`AAAAAC/ACAAAT`	1	--	us2k¹ tfbs³ trp³		1		CSA	2
rs73402953^1,2	C,F	--	635637(+)	`TGTGTG/ACTGCA`	1	--	us2k¹		1		WA	2
rs115480982^1,2	C,F	--	635796(+)	`TCCATC/ACTGGG`	1	--	us2k¹		2		WA NA	238
rs147540639^1,2		--	636047(+)	`GCCTGC/TGCACA`	1	--	us2k¹		0	--	--	--	--
rs202018472^1,2		--	636086(+)	`AGCCC-/TCGTGA`	1	--	us2k¹		0	--	--	--	--
rs66971635^1,2	C	--	636087(+)	`GCCCCG/-GTGAC`	1	--	us2k¹		1		NA	2

HapMap Linkage Disequilibrium report for DRD4 (637293 - 640706 bp)

Structural Variations
Database of Genomic Variants (DGV) Selected variations for DRD4 (see all 16): About this table

Variant ID	Type	Subtype	PubMed ID
dgv182e199	CNV	Deletion	23128226
esv2743857	CNV	Deletion	23290073
dgv920n71	CNV	Loss	21882294
nsv896545	CNV	Loss	21882294
nsv469923	CNV	Loss	18288195
dgv921n71	CNV	Loss	21882294
dgv936n71	CNV	Loss	21882294
dgv940n71	CNV	Loss	21882294
dgv935n71	CNV	Loss	21882294
nsv467635	CNV	Loss	19166990

Human Gene Mutation Database (HGMD): DRD4

Site Specific Mutation Identification with PCR Assays

SeqTarget long-range PCR primers for resequencing DRD4

DNA2.0 Custom Variant and Variant Library Synthesis for DRD4

(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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OMIM gene information: 126452
OMIM disorders: 601696  143465
20 diseases for DRD4:
About MalaCards

separation anxiety disorder chronic tic disorder oppositional defiant disorder tic disorder

attention deficit hyperactivity disorder autonomic nervous system disease seasonal affective disorder pathological gambling

conduct disorder delusional disorder schizophrenia heroin dependence

parkinson's disease obsessive-compulsive disorder hyperprolactinemia migraine without aura

substance dependence schizoaffective disorder tardive dyskinesia obesity

12 inferred disease relationships from the University of Copenhagen DISEASES database for DRD4:

Attention deficit hyperactivity disorder Schizophrenia Conduct disorder Pathological gambling

Delusional disorder Heroin dependence Substance abuse Gilles de la Tourette syndrome

Chronic tic disorder Alcohol dependence Nicotine dependence Autistic disorder

Find genes that share disorders with DRD4 About GenesLikeMe

Selected Novoseek inferred disease relationships for DRD4 gene (see all 36) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
novelty seeking personality trait	88.4	8	15292670 (1), 9723153 (1), 9152990 (1), 10898899 (1) (see all 6)
attention-deficit hyperactivity disorder	88.3	103	16917940 (2), 20410729 (2), 9491811 (2), 15206004 (2) (see all 67)
schizophrenia	68	127	9353244 (4), 8135305 (4), 11496369 (3), 8546161 (3) (see all 70)
psychotic	52.5	37	10050966 (5), 10490703 (4), 17822780 (3), 10478793 (3) (see all 14)
bipolar disorder	51.2	14	10490710 (3), 7914460 (2), 7853381 (1), 10646829 (1) (see all 11)
heroin addiction	50.3	10	20218801 (3), 16167465 (1), 18991844 (1), 10673776 (1)
psychiatric disorder	50.1	22	15981960 (3), 14581929 (1), 15985158 (1), 20305304 (1) (see all 13)
tourette syndrome	48.4	6	10402503 (2), 9246007 (1), 7881421 (1), 8751866 (1) (see all 5)
conduct disorder	42.5	4	15288435 (1), 11443528 (1), 17587443 (1)
obsessive-compulsive disorder	41.7	4	12497615 (1), 9280153 (1)

Genetic Association Database (GAD): DRD4
Human Genome Epidemiology (HuGE) Navigator: DRD4 (410 documents)

Export disorders for DRD4 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
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PubMed articles for DRD4 gene, integrated from 10 sources (see all 883):
(articles sorted by number of sources associating them with DRD4)

Utopia: connect your pdf to the dynamic
world of online information

Schizophrenia is not associated with DRD4 48-base-pair-repeat length or individual alleles: results of a meta-analysis. (PubMed id 13129658)^{1, 4, 7, 9} Glatt S.J....Tsuang M.T. (Biol. Psychiatry 2003)
Dopamine D4 receptor gene exon III polymorphism and interindividual variation in response to clozapine. (PubMed id 16223700)^{1, 4, 7} Zhao A.L....Chen X.G. (Int. J. Neurosci. 2005)
Associations of the dopamine D4 receptor gene VNTR polymorphism with drug use in adolescent psychiatric inpatients. (PubMed id 17175015)^{1, 4, 9} McGeary J.E....Monti P.M. (Pharmacol. Biochem. Behav. 2007)
Exon 3 polymorphisms of dopamine D4 receptor (DRD4) gene and attention deficit hyperactivity disorder in Chinese children. (PubMed id 16917940)^{1, 4, 9} Cheuk D.K....Wong V. (Am. J. Med. Genet. B Neuropsychiatr. Genet. 2006)
No association of the dopamine D4 receptor (DRD4) and -521 C/T promoter polymorphisms with infant attachment disorganization. (PubMed id 15513263)^{1, 4, 9} Bakermans-Kranenburg M.J. and Van Ijzendoorn M.H. (amp 2004)
Association of dopamine D4 receptor (DRD4) exon III repeat polymorphism with temperament in 3-year-old infants. (PubMed id 12687422)^{1, 4, 9} De Luca A....Dallapiccola B. (Neurogenetics 2003)
Interaction between serotonin transporter promoter and dopamine receptor D4 polymorphisms on decision making. (PubMed id 19615421)^{1, 4, 9} Ha R.Y....Kim S.J. (amp 2009)
Dopamine D4 receptor (DRD4) gene polymorphism in the first psychotic episode. (PubMed id 11282178)^{1, 4, 9} Rinetti G....Nicolini H. (Arch. Med. Res. 2001)
Relations between multi-informant assessments of ADHD symptoms, DAT1, and DRD4. (PubMed id 19025233)^{1, 4, 9} Gizer I.R....Rowe D.C. (J Abnorm Psychol 2008)
Association of the dopamine D4 receptor (DRD4) gene and approach-related personality traits: meta-analysis and new data. (PubMed id 17574217)^{1, 4, 9} MunafA^ M.R....Flint J. (Biol. Psychiatry 2008)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 1815	HGNC: 3025	AceView: DRD4	Ensembl:ENSG00000069696	euGenes: HUgn1815
ECgene: DRD4	Kegg: 1815	H-InvDB: DRD4

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for DRD4	Pharmacogenomics, SNPs, Pathways

Intellectual Property for DRD4 gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

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Patent Information for DRD4 gene:
Search GeneIP for patents involving DRD4

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

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