Protein / target
5-hydroxytryptamine receptor 1A
Protein at a glance
Biological role
G protein-coupled serotonin receptor activity
Primary system
Nervous system
Strongest disease association
bipolar disorder
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
17 approved · 16 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 for 5-hydroxytryptamine (serotonin) (PubMed:22957663, PubMed:3138543, PubMed:33762731, PubMed:37935376, PubMed:37935377, PubMed:8138923, PubMed:8393041). Also functions as a receptor for various drugs and psychoactive substances (PubMed:22957663, PubMed:3138543, PubMed:33762731, PubMed:38552625, PubMed:8138923, PubMed:8393041). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase (PubMed:22957663, PubMed:3138543, PubMed:33762731, PubMed:8138923, PubMed:8393041). HTR1A is coupled to G(i)/G(o) G alpha proteins and mediates inhibitory neurotransmission: signaling inhibits adenylate cyclase activity and activates a phosphatidylinositol-calcium second messenger system that regulates the release of Ca(2+) ions from intracellular stores (PubMed:33762731, PubMed:35610220). Beta-arrestin family members regulate signaling by mediating both receptor desensitization and resensitization processes (PubMed:18476671, PubMed:20363322, PubMed:20945968). Plays a role in the regulation of 5-hydroxytryptamine release and in the regulation of dopamine and 5-hydroxytryptamine metabolism (PubMed:18476671, PubMed:20363322, PubMed:20945968). Plays a role in the regulation of dopamine and 5-hydroxytryptamine levels in the brain, and thereby affects neural activity, mood and behavior (PubMed:18476671, PubMed:20363322, PubMed:20945968). Plays a role in the response to anxiogenic stimuli (PubMed:18476671, PubMed:20363322, PubMed:20945968)
Subcellular location
Domains and Gene Ontology detail (23)Hide
Gene Ontology
- Cdendrite
- Cplasma membrane
- Csynapse
- FG protein-coupled serotonin receptor activity
- FGi/o-coupled serotonin receptor activity
- Fneurotransmitter receptor activity
- Freceptor-receptor interaction
- Fserotonin binding
- Fserotonin receptor activity
- Padenylate cyclase-inhibiting serotonin receptor signaling pathway
- Pbehavioral fear response
- Pchemical synaptic transmission
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
G protein-coupled signalling
- ·G protein-coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:22957663, PubMed:…
- ·G protein-coupled serotonin receptor activity
- ·G protein-coupled receptor signaling pathway
- ·G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messen…
Synaptic signalling
- ·synapse
- ·neurotransmitter receptor activity
- ·chemical synaptic transmission
Metabolic enzyme activity
- ·regulation of dopamine metabolic process
- ·serotonin metabolic process
Inhibitory neurotransmission
- ·G protein-coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:22957663, PubMed:…
View underlying pathways (1)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.
Serotonin 1a (5-HT1a) receptor partial agonist
Appears in clinical studies involving schizophrenia, major depressive disorder, bipolar 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.
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.
Highest overall evidence
Remaining associations by Open Targets' aggregated evidence score.
Show all associationsHide all associations
Open Targets ranks 489 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 · 35 total
Parkinson disease
obesity disorder · Obesity
major depressive disorder
schizophrenia · major depressive disorder · bipolar disorder
anxiety disorder
major depressive disorder · depressive disorder
major depressive disorder · generalized anxiety disorder · depressive disorder
major depressive disorder · major depressive disorder · mood disorder
Parkinson disease · movement disorder
Cognitive impairment · Alzheimer disease
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.
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.
- Product recall
Recall (Class II): ARIPIPRAZOLE
- New publicationLong-Acting Injectable Antipsychotic Initiation in Child and Adolescent Patients with Psychiatric Disorders.
- Safety communication
Drug Safety Update: Aripiprazole (Abilify and generic brands): risk of pathological gambling
- New publicationCariprazine in acute exacerbation of schizophrenia: a fixed-dose, phase 3, randomized, double-blind, placebo- and active-controlled trial.
- Regulatory approval
Approval: Aripiprazole Accord (EMA)
- Regulatory approval
Approval: Aripiprazole Sandoz (EMA)
- Regulatory approval
Approval: Aripiprazole Mylan Pharma (previously Aripiprazole Pharmathen) (EMA)
- Regulatory approval
Approval: Aripiprazole Zentiva (EMA)
- Regulatory approval
Approval: Abilify Maintena (EMA)
- New publicationAripiprazole for the treatment of methamphetamine dependence: a randomized, double-blind, placebo-controlled trial.
- New publicationDouble-blind, randomized, placebo-controlled long-term maintenance study of aripiprazole in children with bipolar disorder.
- New publicationAn open-label trial of aripiprazole in the treatment of aggression in male adolescents diagnosed with conduct disorder.
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.