DRD4 [The Human Chemical-Genetic Interaction Map Project]

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======= DRD4 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: DRD4
  * **<color #00a2e8>Official Name</color>**: dopamine receptor D4
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=1815|1815]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P21917|P21917]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=DRD4&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20DRD4|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/126452|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  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]. 
  * **<color #00a2e8>UniProt Summary</color>**:  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 (PubMed:9003072, PubMed:16423344, PubMed:27659709, PubMed:29051383). Agonist binding triggers signaling via G proteins that inhibit adenylyl cyclase (PubMed:7512953, PubMed:7643093, PubMed:16423344, PubMed:27659709, PubMed:29051383). Modulates the circadian rhythm of contrast sensitivity by regulating the rhythmic expression of NPAS2 in the retinal ganglion cells (By similarity). {ECO:0000250|UniProtKB:P51436, ECO:0000269|PubMed:16423344, ECO:0000269|PubMed:1840645, ECO:0000269|PubMed:27659709, ECO:0000269|PubMed:29051383, ECO:0000269|PubMed:7512953, ECO:0000269|PubMed:7643093, ECO:0000269|PubMed:8078498, ECO:0000269|PubMed:9003072}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|7TM GPCR Srsx|
|7tm 1|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|dopamine neurotransmitter receptor activity|
|positive regulation of catecholamine uptake involved in synaptic transmission|
|positive regulation of dopamine uptake involved in synaptic transmission|
|positive regulation of sodium:proton antiporter activity|
|norepinephrine binding|
|regulation of sodium:proton antiporter activity|
|positive regulation of neurotransmitter uptake|
|positive regulation of synaptic transmission, dopaminergic|
|epinephrine binding|
|regulation of catecholamine uptake involved in synaptic transmission|
|dopamine neurotransmitter receptor activity, coupled via Gi/Go|
|regulation of dopamine uptake involved in synaptic transmission|
|inhibitory postsynaptic potential|
|adenylate cyclase-inhibiting dopamine receptor signaling pathway|
|behavioral response to ethanol|
|response to histamine|
|regulation of postsynaptic neurotransmitter receptor internalization|
|dopamine binding|
|negative regulation of voltage-gated calcium channel activity|
|regulation of synaptic transmission, dopaminergic|
|positive regulation of sodium ion transmembrane transporter activity|
|regulation of dopamine metabolic process|
|regulation of neurotransmitter uptake|
|regulation of catecholamine metabolic process|
|behavioral response to cocaine|
|positive regulation of sodium ion transmembrane transport|
|regulation of proton transport|
|arachidonate transport|
|arachidonic acid secretion|
|icosanoid secretion|
|dopamine metabolic process|
|behavioral fear response|
|fatty acid derivative transport|
|icosanoid transport|
|positive regulation of response to drug|
|behavioral defense response|
|response to amphetamine|
|fear response|
|G protein-coupled serotonin receptor signaling pathway|
|G protein-coupled serotonin receptor activity|
|positive regulation of sodium ion transport|
|dopamine receptor signaling pathway|
|positive regulation of amine transport|
|regulation of voltage-gated calcium channel activity|
|negative regulation of calcium ion transmembrane transporter activity|
|neurotransmitter receptor activity|
|positive regulation of neurotransmitter transport|
|serotonin receptor signaling pathway|
|negative regulation of calcium ion transmembrane transport|
|potassium channel regulator activity|
|negative regulation of cation channel activity|
|catechol-containing compound metabolic process|
|catecholamine metabolic process|
|response to amine|
|response to bronchodilator|
|social behavior|
|intraspecies interaction between organisms|
|regulation of sodium ion transmembrane transporter activity|
|regulation of receptor internalization|
|response to cocaine|
|drug binding|
|long-chain fatty acid transport|
|negative regulation of calcium ion transport|
|regulation of sodium ion transmembrane transport|
|chemical synaptic transmission, postsynaptic|
|multi-organism behavior|
|multicellular organismal response to stress|
|negative regulation of ion transmembrane transporter activity|
|fatty acid transport|
|adult locomotory behavior|
|response to anesthetic|
|negative regulation of transporter activity|
|regulation of cellular amine metabolic process|
|acid secretion|
|negative regulation of cation transmembrane transport|
|postsynapse|
|phenol-containing compound metabolic process|
|adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway|
|cellular response to dopamine|
|response to dopamine|
|regulation of sodium ion transport|
|regulation of calcium ion transmembrane transporter activity|
|signal transduction involved in cellular response to ammonium ion|
|regulation of amine transport|
|negative regulation of ion transmembrane transport|
|regulation of response to drug|
|regulation of postsynaptic membrane potential|
|regulation of receptor-mediated endocytosis|
|cellular response to catecholamine stimulus|
|cellular response to monoamine stimulus|
|positive regulation of ion transmembrane transporter activity|
|response to catecholamine|
|response to monoamine|
|positive regulation of transporter activity|
|response to alkaloid|
|regulation of circadian rhythm|
|negative regulation of transmembrane transport|
|response to ethanol|
|cellular response to ammonium ion|
|SH3 domain binding|
|negative regulation of protein secretion|
|monocarboxylic acid transport|
|negative regulation of peptide secretion|
|positive regulation of cation transmembrane transport|
|regulation of neurotransmitter transport|
|adult behavior|
|negative regulation of ion transport|
|regulation of calcium ion transmembrane transport|
|positive regulation of synaptic transmission|
|activation of MAPK activity|
|positive regulation of ion transmembrane transport|
|regulation of cation channel activity|
|negative regulation of protein transport|
|response to ammonium ion|
|negative regulation of establishment of protein localization|
|ammonium ion metabolic process|
|locomotory behavior|
|positive regulation of transmembrane transport|
|negative regulation of secretion by cell|
|regulation of endocytosis|
|adenylate cyclase-modulating G protein-coupled receptor signaling pathway|
|negative regulation of secretion|
|response to alcohol|
|G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger|
|regulation of calcium ion transport|
|regulation of ion transmembrane transporter activity|
|positive regulation of MAP kinase activity|
|regulation of transmembrane transporter activity|
|positive regulation of ion transport|
|rhythmic process|
|regulation of transporter activity|
|organic acid transport|
|carboxylic acid transport|
|lipid transport|
|response to xenobiotic stimulus|
|response to antibiotic|
|lipid localization|
|activation of protein kinase activity|
|regulation of cation transmembrane transport|
|positive regulation of protein serine/threonine kinase activity|
|regulation of MAP kinase activity|
|glutamatergic synapse|
|regulation of neurotransmitter levels|
|regulation of metal ion transport|
|cellular response to drug|
|anterograde trans-synaptic signaling|
|dendrite|
|chemical synaptic transmission|
|cell surface receptor signaling pathway involved in cell-cell signaling|
|regulation of membrane potential|
|cellular calcium ion homeostasis|
|trans-synaptic signaling|
|modulation of chemical synaptic transmission|
|regulation of trans-synaptic signaling|
|calcium ion homeostasis|
|organic hydroxy compound metabolic process|
|organic anion transport|
|synaptic signaling|
|regulation of protein secretion|
|cellular divalent inorganic cation homeostasis|
|regulation of ion transmembrane transport|
|negative regulation of transport|
|divalent inorganic cation homeostasis|
|regulation of peptide secretion|
|drug metabolic process|
|response to toxic substance|
|regulation of protein serine/threonine kinase activity|
|positive regulation of protein kinase activity|
|regulation of cellular protein localization|
|cellular response to organic cyclic compound|
|positive regulation of MAPK cascade|
|regulation of vesicle-mediated transport|
|cellular metal ion homeostasis|
|regulation of transmembrane transport|
|behavior|
|positive regulation of kinase activity|
|anion transport|
|cellular response to organonitrogen compound|
|metal ion homeostasis|
|cellular cation homeostasis|
|cellular ion homeostasis|
|positive regulation of transferase activity|
|cellular response to nitrogen compound|
|regulation of ion transport|
|regulation of protein transport|
|cation homeostasis|
|inorganic ion homeostasis|
|G protein-coupled receptor activity|
|regulation of peptide transport|
|cellular chemical homeostasis|
|regulation of establishment of protein localization|
|regulation of secretion by cell|
|regulation of MAPK cascade|
|ion homeostasis|
|regulation of protein kinase activity|
|regulation of secretion|
|regulation of kinase activity|
|cellular homeostasis|
|regulation of cellular localization|
|response to organic cyclic compound|
|regulation of transferase activity|
|positive regulation of transport|
|response to organonitrogen compound|
|positive regulation of protein phosphorylation|
|positive regulation of intracellular signal transduction|
|response to drug|
|regulation of protein localization|
|cellular response to oxygen-containing compound|
|positive regulation of phosphorylation|
|identical protein binding|
|response to nitrogen compound|
|chemical homeostasis|
|cell-cell signaling|
|secretion|
|positive regulation of phosphate metabolic process|
|positive regulation of phosphorus metabolic process|
|negative regulation of molecular function|
|cellular response to endogenous stimulus|
|positive regulation of protein modification process|
|G protein-coupled receptor signaling pathway|
|defense response|
|ion transport|
|nervous system process|
|integral component of plasma membrane|
|positive regulation of catalytic activity|
|regulation of protein phosphorylation|
|response to endogenous stimulus|
|response to oxygen-containing compound|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|homeostatic process|
|positive regulation of signal transduction|
|positive regulation of protein metabolic process|
|positive regulation of molecular function|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|regulation of protein modification process|
|regulation of transport|
|system process|
|membrane|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp419|Tunicamycin 0.04 to 0.075μM  on day4 R07 exp419]]|-2.44|
|[[:results:exp415|Trichostatin-A 0.06μM R07 exp415]]|-1.89|
|[[:results:exp341|BRD2 inhibitor II 20μM R07 exp341]]|-1.88|
|[[:results:exp500|LY2090314 0.003μM R08 exp500 no dilution day6]]|1.72|
|[[:results:exp231|Epothilone-B 0.0015μM R05 exp231]]|2.08|
|[[:results:exp513|ONC212 0.15μM R08 exp513]]|2.17|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 11989
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: -0.74 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='DRD4 Expression in NALM6 Cells: -0.74'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>