Protein / target
D(4) dopamine receptor
Protein at a glance
Biological role
Dopamine neurotransmitter receptor activity, coupled via Gi/Go
Primary system
Nervous system
Strongest disease association
schizophrenia
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
30 approved · 2 in clinical development
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
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. Activated by dopamine, but also by epinephrine and norepinephrine, and by numerous synthetic agonists and drugs (PubMed:16423344, PubMed:27659709, PubMed:29051383, PubMed:9003072). Agonist binding triggers signaling via G proteins that inhibit adenylyl cyclase (PubMed:16423344, PubMed:27659709, PubMed:29051383, PubMed:7512953, PubMed:7643093). Modulates the circadian rhythm of contrast sensitivity by regulating the rhythmic expression of NPAS2 in the retinal ganglion cells (By similarity)
Subcellular location
Domains and Gene Ontology detail (39)Hide
Gene Ontology
- Cdendrite
- Cglutamatergic synapse
- Cmembrane
- Cplasma membrane
- Cpostsynapse
- Fdopamine binding
- Fdopamine neurotransmitter receptor activity
- Fdopamine neurotransmitter receptor activity, coupled via Gi/Go
- Fepinephrine binding
- FG protein-coupled serotonin receptor activity
- Fidentical protein binding
- Fmetal ion binding
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
Synaptic signalling
- ·glutamatergic synapse
- ·postsynapse
- ·dopamine neurotransmitter receptor activity
- ·dopamine neurotransmitter receptor activity, coupled via Gi/Go
G protein-coupled signalling
- ·G protein-coupled serotonin receptor activity
- ·adenylate cyclase-modulating G protein-coupled receptor signaling pathway
- ·G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messen…
Inhibitory neurotransmission
- ·inhibitory postsynaptic potential
Excitatory neurotransmission
- ·glutamatergic synapse
Metabolic enzyme activity
- ·regulation of dopamine metabolic process
Motor control
- ·adult locomotory behavior
View underlying pathways (2)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Drugs targeting this protein
Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.
D2-like dopamine receptor antagonist
Appears in clinical studies involving bipolar disorder, schizophrenia, major depressive disorder, Agitation
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Highest overall evidence
Remaining associations by Open Targets' aggregated evidence score.
Show all associationsHide all associations
Open Targets ranks 524 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.
Known drugs · 33 total
schizophrenia · anxiety disorder · mental disorder
bipolar disorder · psychotic disorder · psychotic disorder
Parkinson disease · movement disorder · Rett syndrome
schizophrenia · psychotic disorder · acute myeloid leukemia
major depressive disorder
Nausea and vomiting · Nausea · psychotic disorder
bipolar I disorder · schizophrenia · Agitation
schizophrenia
Parkinson disease · erectile dysfunction · epilepsy
Tractability
Safety liabilities
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.
Show remaining trials (24)Hide
ClinicalTrials.gov via the drug-target graph.
Related literature
Papers indexed under “Receptors, Dopamine D4” — a subject heading that covers this protein without being specific to it. Shown as context; not counted as this protein's own research activity.
Europe PMC literature, reached through a MeSH descriptor linked to this protein.
Forefront confidence
Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.
The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.
What's happening now
Recent activity around this target, drawn from one canonical event stream. Every item is reached through a drug that targets this protein, so each event is news about that drug rather than about the protein directly.
- Withdrawn from market
Market withdrawal: Olanzapine Apotex (EMA)
- New publicationOlanzapine for the Prevention of Postdischarge Nausea and Vomiting after Ambulatory Surgery: A Randomized Controlled Trial.
- New publicationMitigation of Olanzapine-Induced Weight Gain With Samidorphan, an Opioid Antagonist: A Randomized Double-Blind Phase 2 Study in Patients With Schizophrenia.
- New publicationCanadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder.
- New publicationOlanzapine for prevention of chemotherapy-induced nausea and vomiting in children and adolescents: a multi-center, feasibility study.
- Regulatory approval
Approval: Olazax (EMA)
- Regulatory approval
Approval: Olazax Disperzi (EMA)
- Regulatory approval
Approval: Olanzapine Glenmark (EMA)
- Regulatory approval
Approval: Olanzapine Glenmark Europe (EMA)
- Regulatory approval
Approval: Zypadhera (EMA)
- Regulatory approval
Approval: Olanzapine Viatris (previously Olanzapine Mylan) (EMA)
- Regulatory approval
Approval: Olanzapine Teva (EMA)
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.