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Protein / target

5-hydroxytryptamine receptor 2C

Encoded byHTR2CP28335Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
37
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding

Strongest disease association

Autistic Disorder

Via encoding gene HTR2C · Clinical evidence · score 0.61

Therapeutic position

Established drug target

Small molecules

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

G protein-coupled receptor for 5-hydroxytryptamine (serotonin).

View complete UniProt function annotation

G protein-coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:12970106, PubMed:18703043, PubMed:19057895, PubMed:29398112, PubMed:7895773). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-iodophenyl-2-aminopropane (DOI) and lysergic acid diethylamide (LSD) (PubMed:19057895, PubMed:29398112). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors (PubMed:18703043, PubMed:29398112). HTR2C is coupled to G(q)/G(11) G alpha proteins and activates phospholipase C-beta, releasing diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) second messengers that modulate the activity of phosphatidylinositol 3-kinase and promote the release of Ca(2+) ions from intracellular stores, respectively (PubMed:18703043, PubMed:29398112). Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways (PubMed:29398112). Regulates neuronal activity via the activation of short transient receptor potential calcium channels in the brain, and thereby modulates the activation of pro-opiomelanocortin neurons and the release of CRH that then regulates the release of corticosterone (By similarity). Plays a role in the regulation of appetite and eating behavior, responses to anxiogenic stimuli and stress (By similarity). Plays a role in insulin sensitivity and glucose homeostasis (By similarity)

Subcellular location

Cell membrane
Domains and Gene Ontology detail (27)

Gene Ontology

  • Cdendrite
  • CG protein-coupled serotonin receptor complex
  • Cplasma membrane
  • Csynapse
  • F1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding
  • FG protein-coupled serotonin receptor activity
  • FGq/11-coupled serotonin receptor activity
  • Fidentical protein binding
  • Fneurotransmitter receptor activity
  • Fserotonin binding
  • Fserotonin receptor activity
  • Pbehavioral fear response

458 aa · 52 kDa · 2 isoforms

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Synaptic signallingGOG protein-coupled signallingUniProt · GO
View supporting evidence

Synaptic signalling

  • ·synapse
  • ·neurotransmitter receptor activity
  • ·chemical synaptic transmission

G protein-coupled signalling

  • ·G protein-coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:12970106, PubMed:…
  • ·G protein-coupled serotonin receptor complex
  • ·G protein-coupled serotonin receptor activity
  • ·G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messen…
View underlying pathways (2)

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

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.

GNAQHTR2AHTR2BGNASGNB1GNG2CACNA1DCACNA1CGNA11SLC6A4HTR2C

10 strongest partners — larger node and heavier line mean higher confidence

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

6 medicines · 8 areas

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.

Psychotic Disorders3 medicines
Depressive Disorder2 medicines
Mental Disorders2 medicines
Psychomotor Agitation2 medicines
Autistic Disorder1 medicine
Sleep Initiation and Maintenance Disorders1 medicine

37 medicines meet Open Targets' target-level approved-medicine definition; the 6 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

6

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.

Risperidone
Narrow target profileApprovedAntagonist

Serotonin 2c (5-HT2c) receptor antagonist

Indicated for Autistic Disorder, Bipolar Disorder, Psychotic Disorders, Schizophrenia

Direct interaction with this protein · 1 of 3 recorded protein targets — narrow recorded profile

Quetiapine Fumarate
Narrow target profileApprovedAntagonist

Serotonin 2c (5-HT2c) receptor antagonist

Indicated for Bipolar Disorder, Schizophrenia

Direct interaction with this protein · 1 of 3 recorded protein targets — narrow recorded profile

agomelatine
Narrow target profileApprovedAntagonist

Serotonin 2c (5-HT2c) receptor antagonist

Indicated for Depressive Disorder

Direct interaction with this protein · 1 of 3 recorded protein targets — narrow recorded profile

olanzapine
ApprovedAntagonist

Serotonin 2c (5-HT2c) receptor antagonist

Indicated for Bipolar Disorder, Mental Disorders, Psychomotor Agitation, Psychotic Disorders

Direct interaction with this protein · 1 of 5 recorded protein targets

mirtazapine
ApprovedAntagonist

Serotonin 2c (5-HT2c) receptor antagonist

Indicated for Depressive Disorder, Sleep Initiation and Maintenance Disorders

Direct interaction with this protein · 1 of 5 recorded protein targets

loxapine
ApprovedAntagonist

Serotonin 2c (5-HT2c) receptor antagonist

Indicated for Bipolar Disorder, Mental Disorders, Psychomotor Agitation, Psychotic Disorders

Direct interaction with this protein · 1 of 5 recorded protein targets

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

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 HTR2C

Gene-level evidence surfaced through the gene HTR2Cthat 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.

Autistic Disorder
0.78Well supported

Clinical evidence dominant · Open Targets 0.61

Schizophrenia
0.76Well supported

Clinical evidence dominant · Open Targets 0.61

Bipolar Disorder
0.75Well supported

Clinical evidence dominant · Open Targets 0.61

Major depressive disorder
0.75Well supported

Clinical evidence dominant · Open Targets 0.61

Psychotic disorder
0.74Moderately supported

Clinical evidence dominant · Open Targets 0.60

View evidence synthesis (5)
Autistic DisorderWell supported
0.78
agreement 0.660.90
Clinical85%Animal model13%RNA expression1%Literature1%

Open Targets aggregate 0.61 · 4 independent evidence families

SchizophreniaWell supported
0.76
agreement 0.600.91
Clinical96%Literature4%

Open Targets aggregate 0.61 · 2 independent evidence families

Bipolar DisorderWell supported
0.75
agreement 0.600.91
Clinical97%Literature3%

Open Targets aggregate 0.61 · 2 independent evidence families

Major depressive disorderWell supported
0.75
agreement 0.600.91
Clinical97%Literature3%

Open Targets aggregate 0.61 · 2 independent evidence families

Psychotic disorderModerately supported
0.74
agreement 0.590.90
Clinical98%Literature2%

Open Targets aggregate 0.60 · 2 independent evidence families

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.

Show all associations
Autistic Disorder0.61
Schizophrenia0.61
Bipolar Disorder0.61
Major depressive disorder0.61
Psychotic disorder0.60
bipolar I disorder0.60
Depressive Disorder0.59
Epilepsies, Myoclonic0.58

Drug development

44 compounds recorded · 37 approved · 4 in clinical development · 3 earlier-stage

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 6 drugs that target this protein in Forefront's canonical graph (6 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
FENFLURAMINE HYDROCHLORIDEApproval
CHLORPROTHIXENEApproval
LORCASERINApproval
DEXFENFLURAMINE HYDROCHLORIDEUnknown
VABICASERINPhase 2
QUETIAPINEApproval
TRIMIPRAMINEApproval
CLOTHIAPINEApproval
TEDATIOXETINEPhase 2
ZIPRASIDONE HYDROCHLORIDEApproval

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 moleculesStrong

Approved Drug and Structure with Ligand support this modality.

AntibodiesEmerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

Feasibility evidence (small molecule binder) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (8)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

increased convulsionsLynch et al. (2017)metabolic syndromeClinPGxdecreased locomotor activityLynch et al. (2017)increased memoryLynch et al. (2017)abnormal mouth movementsLynch et al. (2017)antipsychotic-induced weight gainClinPGxpenile erectionLynch et al. (2017)decreased convulsionsLynch et al. (2017)decreased eatingLynch et al. (2017)Increased, Kidney FailureAOP-Wikiweight gainClinPGxdecreased memoryLynch et al. (2017)

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

30

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)

NOT_YET_RECRUITING · via Risperidone · NCT07503002

ClinicalTrials.gov via the drug-target graph.

What's happening now

12

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 4 drugs that target 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.

  1. Label change2026-08-10

    Label change: OLANZAPINE (ANDA076133)

    fda · regulatory · fda · via olanzapine

  2. Label change2026-08-10

    Label change: OLANZAPINE (ANDA076255)

    fda · regulatory · fda · via olanzapine

  3. Label change2026-07-01

    Label change: RISPERIDONE (ANDA076996)

    fda · regulatory · fda · via Risperidone

  4. Label change2026-06-08

    Label change: RISPERIDONE (ANDA077494)

    fda · regulatory · fda · via Risperidone

  5. Label change2026-02-09

    Label change: OLANZAPINE (ANDA076133)

    fda · regulatory · fda · via olanzapine

  6. Label change2026-02-09

    Label change: OLANZAPINE (ANDA076255)

    fda · regulatory · fda · via olanzapine

  7. New publication2024-06-08
    Effects of PDE10A inhibitor MK-8189 in people with an acute episode of schizophrenia: A randomized proof-of-concept clinical trial.

    Schizophrenia research · 2024 · 13 citations · Europe PMC · via Risperidone

  8. New publication2018-03-14
    Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder.

    Bipolar disorders · 2018 · 1,126 citations · Europe PMC · via Quetiapine Fumarate

  9. Safety communication2014-12-11

    Drug Safety Update: Agomelatine (Valdoxan): risk of liver toxicity

    mhra · safety · mhra · via agomelatine

  10. Safety communication2014-12-11

    Drug Safety Update: Agomelatine (Valdoxan/ Thymanax): risk of dose-related hepatotoxicity and liver failure

    mhra · safety · mhra · via agomelatine

  11. New publication2013-11-01
    Cognitive-behavioral therapy vs risperidone for augmenting serotonin reuptake inhibitors in obsessive-compulsive disorder: a randomized clinical trial.

    JAMA psychiatry · 2013 · 143 citations · Europe PMC · via Risperidone

  12. New publication2005-09-19
    Effectiveness of antipsychotic drugs in patients with chronic schizophrenia.

    The New England journal of medicine · 2005 · 3,569 citations · Europe PMC · via Quetiapine Fumarate

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.