Tchem D(4) dopamine receptor

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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).

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]

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Property Summary

Ligand Count	1,332
NCBI Gene PubMed Count	641
PubMed Score	745.02

PubTator Score	1219.26

Knowledge Summary

Patent (10,275)

TINX Plot

Disease (7)

Disease	Target Count	Z-score	Confidence
Amphetamine-Related Disorders	74	0.0	0.0
Anxiety, Separation	1	0.0	0.0
Attention Deficit Disorder with Hyperactivity	21	0.0	0.0
Attention Deficit and Disruptive Behavior Disorders	2	0.0	0.0
Child Development Disorders, Pervasive	3	0.0	0.0
NOVELTY SEEKING PERSONALITY TRAIT	1	0.0	0.0
Tic Disorders	2	0.0	0.0

Disease	Target Count
Seasonal affective disorder	28
Alcohol abuse	50
Alcoholic Intoxication	34
Alcoholic Intoxication, Chronic	289
Cannabis use	6
Dysphoric mood	7
Marijuana Abuse	31
Mental Depression	333
Mood Disorders	184
PARKINSON DISEASE, LATE-ONSET	20
Separation anxiety disorder	5
Tic disorder	8
Unipolar Depression	250

Disease	Target Count
Schizophrenia	1160
Bipolar Disorder	666
Major Depressive Disorder	301
Acromegaly	51
Amenorrhea	58
Bruxism (teeth grinding)	1
Chronic schizophrenia	16
Chronic thromboembolic pulmonary hypertension	4
Depressive disorder	409
Gilles de la Tourette's syndrome	2
Hyperprolactinemia	27
Hypertensive disorder	56
Lack or loss of sexual desire	3
Migraine	83
Parkinson's disease	392
Psychotic disorder	6
Restless legs	4
pulmonary arterial hypertension	75

Disease	Target Count	P-value
psoriasis	6694	1.1e-17
atypical teratoid / rhabdoid tumor	5112	8.0e-03

Disease	Target Count	Z-score	Confidence
Opiate dependence	29	0.0	5.0

Disease	Target Count	Z-score	Confidence
Conduct disorder	33	5.153	2.6
Oppositional defiant disorder	17	5.018	2.5
Alcohol dependence	107	4.769	2.4
Substance abuse	59	4.516	2.3
Pathological gambling	15	4.503	2.3
Delusional disorder	13	4.463	2.2
Heroin dependence	30	4.419	2.2
Gilles de la Tourette syndrome	47	3.927	2.0
Chronic tic disorder	8	3.903	2.0
obsessive-compulsive disorder	61	3.899	1.9
Nicotine dependence	54	3.699	1.8
Personality disorder	25	3.476	1.7
Schizoaffective Disorder	55	3.317	1.7
Autistic Disorder	364	3.293	1.6
Eating disorder	26	3.285	1.6

Disease	Target Count
Attention deficit hyperactivity disorder	278

Differential Expression (2)

Disease	log2 FC	p
atypical teratoid / rhabdoid tumor	1.100	8.0e-03
psoriasis	-1.500	1.1e-17

Uterus 17,618

Ovary 17,971

Pituitary 18,147

Testis 18,518

Brain - Cerebellum 17,983

Prostate 18,213

Vagina 17,834

Brain - Cerebellar Hemisphere 18,015

Esophagus - Muscularis 18,017

Esophagus - Gastroesophageal Junction 18,000

Thyroid 18,024

Artery - Aorta 17,896

Colon - Sigmoid 18,089

Nerve - Tibial 18,007

Artery - Coronary 17,949

Small Intestine - Terminal Ileum 17,954

Skin - Not Sun Exposed (Suprapubic) 18,081

Brain - Cortex 18,039

Lung 18,057

Esophagus - Mucosa 18,076

Brain - Spinal cord (cervical c-1) 17,973

Brain - Hypothalamus 18,169

Stomach 17,879

Adipose - Visceral (Omentum) 17,937

Artery - Tibial 17,631

Brain - Nucleus accumbens (basal ganglia... 18,024

Skin - Sun Exposed (Lower leg) 17,968

Breast - Mammary Tissue 18,103

Brain - Caudate (basal ganglia) 18,001

Adipose - Subcutaneous 18,110

Colon - Transverse 17,825

Brain - Frontal Cortex (BA9) 18,069

Adrenal Gland 18,071

Brain - Putamen (basal ganglia) 17,863

Brain - Hippocampus 18,011

Brain - Amygdala 18,006

Brain - Anterior cingulate cortex (BA24) 17,989

Brain - Substantia nigra 17,981

Liver 18,071

Pancreas 18,123

Kidney - Cortex 17,329

Spleen 17,614

Minor Salivary Gland 18,005

Heart - Atrial Appendage 17,896

Muscle - Skeletal 17,778

Heart - Left Ventricle 18,006

Cells - Transformed fibroblasts 17,577

Cells - EBV-transformed lymphocytes 18,186

Whole Blood 17,439

Adult Prostate 8,952

Adult Rectum 8,022

Adult Ovary 10,192

Adult Gallbladder 7,612

Adult Retina 10,115

Adult Urinary Bladder 7,592

Gall bladder

Ovary

Prostate gland

Rectum

Retina

Urinary bladder

endometrium 16,349

lymph node 15,833

ovary 15,408

skin 16,206

small intestine 16,154

testis 17,936

Endocrine System 18,159

Female tissues 17,400

Digestive Tract 17,369

Skin and soft tissues 17,230

Blood and immune system 16,909

Brain 7,346

Dopaminergic system 43

Brain 1,516

Adult 1,013

Saliva 87

Ganglion 334

sknf1 3

Synonym

Accession	P21917 B0M0J7 Q7Z7Q5 Q8NGM5
Symbols	D4DR

Gene

DRD4

PANTHER Protein Class (2)

receptor 400

G-protein coupled receptor 221

Ortholog (8)

Species	Source	Disease
Rat 15,117	Inparanoid OMA EggNOG
Pig 10,168	OMA EggNOG
Anole lizard 10,588	Inparanoid OMA EggNOG
Xenopus 10,468	OMA EggNOG
Zebrafish 9,726	Inparanoid OMA
Chimp 14,140	OMA EggNOG
Macaque 12,761	Inparanoid OMA
Mouse 16,570	Inparanoid OMA EggNOG

UniProt Keyword (16)

Complete proteome 20,231

Polymorphism 12,194

Reference proteome 20,231

Repeat 4,916

Ubl conjugation 2,439

Cell membrane 3,390

Disulfide bond 3,599

G-protein coupled receptor 830

Glycoprotein 4,623

Membrane 7,361

See all...

GO Function (7)

identical protein binding 1,084

SH3 domain binding 125

potassium channel regulator activity 39

drug binding 75

dopamine binding 13

dopamine neurotransmitter receptor activ... 8

dopamine neurotransmitter receptor activ... 3

GO Component (4)

membrane 1,917

plasma membrane 4,414

integral component of plasma membrane 1,418

postsynapse 38

GO Process (26)

G-protein coupled receptor signaling pat... 1,053

regulation of circadian rhythm 48

rhythmic process 53

dopamine receptor signaling pathway 14

response to amphetamine 25

activation of MAPK activity 107

negative regulation of protein secretion 12

negative regulation of adenylate cyclase... 34

social behavior 54

cellular calcium ion homeostasis 85

See all...

Compartment GO Term (12)

Cell 16,178

Cell part 16,177

Cell periphery 5,382

Integral component of membrane 5,331

Integral component of plasma membrane 1,693

Intrinsic component of membrane 5,458

Intrinsic component of plasma membrane 1,749

Membrane 8,531

Membrane part 6,554

Plasma membrane 5,830

Plasma membrane part 2,594

cellular_component 18,320

OMIM Phenotype (1)

Attention deficit-hyperactivity disorder 1

MGI Phenotype (4)

homeostasis-metabolism phenotype 4,747

vision-eye phenotype 1,622

nervous system phenotype 3,447

behavior-neurological phenotype 3,401

HCA RNA Cell Line (43)

A-431 16,131

A549 15,174

AN3-CA 15,648

BJ 15,448

BJ hTERT+ SV40 Large T+ RasG12V 15,493

CACO-2 15,436

CAPAN-2 16,102

Daudi 15,753

EFO-21 17,301

HaCaT 16,515

See all...

Pathway (31)

Neuroactive ligand-receptor interaction 276

Dopaminergic synapse 135

http://pathwaycommons.org/pc2/Pathway_27... 235

http://pathwaycommons.org/pc2/Pathway_b5... 233

http://pathwaycommons.org/pc2/Pathway_db... 223

http://pathwaycommons.org/pc2/Pathway_ea... 224

http://pathwaycommons.org/pc2/Pathway_f3... 224

http://pathwaycommons.org/pc2/Pathway_f7... 223

http://pathwaycommons.org/pc2/Pathway_0c... 35

http://pathwaycommons.org/pc2/Pathway_69... 36

See all...

PDB (2)

...
More...

Drug (13)

aripiprazole lauroxil
pKi 7.36

flibanserin
pKi 8.40

pramipexole
pKi 9.31

clebopride
pKi 8.49

tandospirone
pKi 8.14

nemonapride
pKd 9.68

haloperidol decanoate
pKi 8.24

dopamine
pKi 7.01

rotigotine
pKi 7.26

haloperidol
pKi 7.38

chlorpromazine
pKi 7.50

loxapine
pIC50 7.85

ropinirole
pKi 8.11

Ligand (1,307)

brexpiprazole
pKi 8.20

cabergoline
pKi 7.30

terguride
pKi 8.10

apomorphine
pKi 8.05

amoxapine
pKi 7.47

rotigotine
pKi 7.26

Lysergide
pKi 7.25

loxapine
pKi 8.31

zotepine
pKi 7.41

ketanserin
pKi 8.46

spiperone
pKi 9.70

haloperidol
pKd 9.42

lisuride
pKi 8.30

perospirone
pKi 10.05

sertindole
pKi 7.96

CHEMBL294394
pKi 7.00

CHEMBL20729
pKi 7.00

CHEMBL85
pKi 7.00

CHEMBL484203
pKi 7.00

CHEMBL163239
pKi 7.00

See all 1307 ligands...

Gene RIF (776)

AA Sequence

MGNRSTADADGLLAGRGPAAGASAGASAGLAGQGAAALVGGVLLIGAVLAGNSLVCVSVATERALQTPTN      1 - 70
SFIVSLAAADLLLALLVLPLFVYSEVQGGAWLLSPRLCDALMAMDVMLCTASIFNLCAISVDRFVAVAVP     71 - 140
LRYNRQGGSRRQLLLIGATWLLSAAVAAPVLCGLNDVRGRDPAVCRLEDRDYVVYSSVCSFFLPCPLMLL    141 - 210
LYWATFRGLQRWEVARRAKLHGRAPRRPSGPGPPSPTPPAPRLPQDPCGPDCAPPAPGLPRGPCGPDCAP    211 - 280
AAPGLPPDPCGPDCAPPAPGLPQDPCGPDCAPPAPGLPRGPCGPDCAPPAPGLPQDPCGPDCAPPAPGLP    281 - 350
PDPCGSNCAPPDAVRAAALPPQTPPQTRRRRRAKITGRERKAMRVLPVVVGAFLLCWTPFFVVHITQALC    351 - 420
PACSVPPRLVSAVTWLGYVNSALNPVIYTVFNAEFRNVFRKALRACC                           421 - 467
//

Text Mined References (646)

Summary
Details

	PMID	Year	Title

Tchem D(4) dopamine receptor Add to cart View Collections Empty Collection

Property Summary

Knowledge Summary

Patent (10,275)

TINX Plot

Disease (7)

Expression

Differential Expression (2)

Synonym

Gene

PANTHER Protein Class (2)

Ortholog (8)

UniProt Keyword (16)

GO Function (7)

GO Component (4)

GO Process (26)

Compartment GO Term (12)

OMIM Phenotype (1)

MGI Phenotype (4)

HCA RNA Cell Line (43)

Pathway (31)

PDB (2)

Drug (13)

Ligand (1,307)

Gene RIF (776)

AA Sequence

Text Mined References (646)

Tchem D(4) dopamine receptor

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