Protein / target
Orexin/Hypocretin receptor type 1
Protein at a glance
Biological role
G protein-coupled receptor activity
Primary system
Nervous system
Strongest disease association
intelligence
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
4 approved · 4 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
G protein-coupled receptor that binds the neuropeptide orexin-A with high affinity, and orexin-B with lower affinity, two peptides derived from a common precursor, prepro-orexin (PubMed:32669442, PubMed:9491897). Its activity is mediated via a G(q)-protein-coupled pathway, which activates the phosphatidylinositol-calcium second messenger system in response to orexin-A binding (PubMed:32669442). In addition to G(q)-mediated signaling, orexin-A stimulation also promotes beta-arrestin recruitment, leading to receptor internalization (PubMed:15683363, PubMed:32669442). Plays a significant role in the regulation of food intake (By similarity)
Subcellular location
Domains and Gene Ontology detail (11)Hide
Gene Ontology
- Cplasma membrane
- Csynapse
- FG protein-coupled receptor activity
- Forexin receptor activity
- Fpeptide hormone binding
- Pcellular response to hormone stimulus
- Pchemical synaptic transmission
- Pfeeding behavior
- Pneuropeptide signaling pathway
- Pphospholipase C-activating G protein-coupled receptor signaling pathway
- Pregulation of cytosolic calcium ion concentration
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
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G protein-coupled signalling
- ·G protein-coupled receptor that binds the neuropeptide orexin-A with high affinity, and…
- ·G protein-coupled receptor activity
- ·phospholipase C-activating G protein-coupled receptor signaling pathway
Synaptic signalling
- ·synapse
- ·chemical synaptic transmission
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.
Orexin receptor antagonist
Appears in clinical studies involving insomnia, Alzheimer disease, cocaine use disorder, restless legs syndrome
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.
Strongest genetic associations
Human genetic evidence — the most direct causal link between this target and a disease.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Show all associationsHide all associations
Open Targets ranks 227 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 · 8 total
insomnia · insomnia · post-traumatic stress disorder
insomnia · insomnia · alcohol dependence
insomnia
insomnia · insomnia · sleep-wake disorder
insomnia
diabetic neuropathy · insomnia · major depressive disorder
insomnia · Alzheimer disease · cocaine use disorder
insomnia
Tractability
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.
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.
- New publicationOrexin receptor antagonists in the treatment of insomnia associated with psychiatric disorders: a systematic review.
- New publicationSuvorexant for Reduction of Delirium in Older Adults After Hospitalization: A Randomized Clinical Trial.
- New publicationEffects of Suvorexant, an Orexin Receptor Antagonist, on Respiration during Sleep In Patients with Obstructive Sleep Apnea.
- New publicationEffects of suvorexant, an orexin receptor antagonist, on breathing during sleep in patients with chronic obstructive pulmonary disease.
- New publicationOrexin receptor antagonism for treatment of insomnia: a randomized clinical trial of suvorexant.
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.