Protein / target
5-hydroxytryptamine receptor 1A
Protein at a glance
Biological role
G protein-coupled serotonin receptor
Strongest disease association
Bipolar Disorder
Therapeutic position
Established drug target
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function overview
G protein-coupled receptor for 5-hydroxytryptamine (serotonin).
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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.
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Inhibitory neurotransmission
- ·G protein-coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:22957663, PubMed:…
Cell proliferation & survival
- ·positive regulation of cell population proliferation
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…
Metabolic enzyme activity
- ·regulation of dopamine metabolic process
- ·serotonin metabolic process
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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.
Approved medicines with mapped indications
Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.
17 medicines meet Open Targets' target-level approved-medicine definition; the 2 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.
Drugs targeting this protein
How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.
Serotonin 1a (5-HT1a) receptor partial agonist
Indicated for Autistic Disorder, Bipolar Disorder, Depressive Disorder, Psychomotor Agitation
Serotonin 1a (5-HT1a) receptor partial agonist
Indicated for Psychotic Disorders, Schizophrenia
ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.
Translational evidence
Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.
Strongest disease associations · via encoding gene HTR1A
Gene-level evidence surfaced through the gene HTR1Athat encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.
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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 per-type scores above show the calculation.
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Drug development
35 compounds recorded · 17 approved · 16 in clinical development · 2 earlier-stage
View all recorded compounds (10)Hide
Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.
Tractability
Small molecules — Strong
Antibodies — Emerging
Protein degraders — Emerging
Other modalities — Strong
View underlying tractability evidence (10)Hide
Raw Open Targets tractability assessment buckets, by modality.
Safety-related annotations
Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.
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. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.
View all trials (26)Hide
ClinicalTrials.gov via the drug-target graph.
What's happening now
Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for a drug that targets this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.
- 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.
- Regulatory approval
Approval: Abilify (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.