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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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HTR3A
5-hydroxytryptamine receptor 3A
Chromosome 11 · 11q23.2
NCBI Gene: 3359Ensembl: ENSG00000166736.13HGNC: HGNC:5297UniProt: B4E398
150PubMed Papers
20Diseases
29Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelReceptorTransporter
CLINICAL
FDA Approved Target
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
transmembrane transportserotonin-gated cation-selective signaling pathwayplasma membranecleavage furrowChemotherapy-induced nausea and vomitingpost operative nausea and vomitingNauseamajor depressive disorder
✦AI Summary

HTR3A encodes the 5-hydroxytryptamine receptor 3A subunit, which forms serotonin-activated cation-selective ion channels that mediate fast depolarizing responses in neurons. The HTR3A receptor functions as a ligand-gated calcium channel, where serotonin binding leads to calcium influx and downstream signaling cascades 1. Mechanistically, HTR3A activation triggers Ca2+ influx, followed by CaMKIIα phosphorylation and NLRP3 inflammasome activation, demonstrating its role in inflammatory signaling pathways 1. The receptor shows significant disease relevance across multiple conditions. HTR3A polymorphisms are associated with psychiatric disorders, including bipolar disorder in Chinese populations and personality traits like harm avoidance in women 23. The gene also plays a role in gastrointestinal disorders, with specific polymorphisms linked to diarrhea-predominant irritable bowel syndrome 4. Additionally, HTR3A variants affect dopamine receptor availability in fibromyalgia patients, suggesting involvement in pain modulation 5. Clinically, HTR3A represents a therapeutic target, with antagonists used to treat emesis and IBS 6. The gene's polymorphisms may serve as biomarkers for psychotherapy response and are being investigated as predictors of treatment outcomes in psychiatric conditions 7.

Sources cited
1
HTR3A functions as a serotonin-activated calcium channel that triggers CaMKIIα phosphorylation and NLRP3 inflammasome activation
PMID: 34285037
2
HTR3A polymorphisms are associated with bipolar disorder in Chinese populations
PMID: 27706728
3
HTR3A C178T polymorphism is associated with harm avoidance personality trait in women
PMID: 14557147
4
HTR3A polymorphisms are linked to diarrhea-predominant irritable bowel syndrome
PMID: 24257177
5
HTR3A variants affect dopamine receptor availability in fibromyalgia patients
PMID: 31868947
6
HTR3A antagonists are used therapeutically for treating emesis and IBS
PMID: 27763704
7
HTR3A DNA methylation may serve as a biomarker for psychotherapy response
PMID: 40454823
Disease Associationsⓘ20
Chemotherapy-induced nausea and vomitingOpen Targets
0.61Moderate
post operative nausea and vomitingOpen Targets
0.60Moderate
NauseaOpen Targets
0.60Moderate
major depressive disorderOpen Targets
0.60Moderate
cancerOpen Targets
0.60Moderate
VomitingOpen Targets
0.59Moderate
schizophreniaOpen Targets
0.59Moderate
Nausea and vomitingOpen Targets
0.59Moderate
irritable bowel syndromeOpen Targets
0.58Moderate
gastrointestinal diseaseOpen Targets
0.53Moderate
neoplasmOpen Targets
0.52Moderate
depressive disorderOpen Targets
0.51Moderate
gastroparesisOpen Targets
0.47Moderate
obesityOpen Targets
0.47Moderate
psychosisOpen Targets
0.46Moderate
fibromyalgiaOpen Targets
0.44Moderate
gastroenteritisOpen Targets
0.38Weak
generalized anxiety disorderOpen Targets
0.38Weak
alcohol dependenceOpen Targets
0.38Weak
migraine disorderOpen Targets
0.37Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets29
ALOSETRONApproved
Serotonin 3a (5-HT3a) receptor antagonist
gastrointestinal disease
ALOSETRON HYDROCHLORIDEApproved
Serotonin 3a (5-HT3a) receptor antagonist
irritable bowel syndrome
AMISULPRIDEApproved
Serotonin (5-HT) receptor antagonist
Nausea and vomiting
CILANSETRONApproved
Serotonin 3 (5-HT3) receptor antagonist
gastrointestinal disease
CLOTHIAPINEApproved
Dopamine D4 receptor antagonist
schizophrenia
DEXFENFLURAMINEApproved
Serotonin (5-HT) receptor agonist
obesity
DEXFENFLURAMINE HYDROCHLORIDEUNKNOWN
Serotonin (5-HT) receptor agonist
DOLASETRONApproved
Serotonin 3a (5-HT3a) receptor antagonist
Nausea
DOLASETRON MESYLATEApproved
Serotonin 3a (5-HT3a) receptor antagonist
cancer
FACINICLINE HYDROCHLORIDEPhase II
Serotonin 3 (5-HT3) receptor antagonist
schizophrenia
GRANISETRONApproved
Serotonin 3a (5-HT3a) receptor antagonist
Nausea and vomiting
GRANISETRON HYDROCHLORIDEApproved
Serotonin 3a (5-HT3a) receptor antagonist
Chemotherapy-induced nausea and vomiting
METOCLOPRAMIDEApproved
Dopamine D2 receptor antagonist
gastrointestinal disease
METOCLOPRAMIDE HYDROCHLORIDEApproved
Dopamine D2 receptor antagonist
MOSAPRIDEApproved
Serotonin 4 (5-HT4) receptor agonist
gastrointestinal disease
ONDANSETRONApproved
Serotonin 3a (5-HT3a) receptor antagonist
post operative nausea and vomiting
ONDANSETRON HYDROCHLORIDEApproved
Serotonin 3a (5-HT3a) receptor antagonist
Chemotherapy-induced nausea and vomiting
PALONOSETRONApproved
Serotonin 3a (5-HT3a) receptor antagonist
Nausea
PALONOSETRON HYDROCHLORIDEApproved
Serotonin 3a (5-HT3a) receptor antagonist
post operative nausea and vomiting
PUMOSETRAGPhase II/III
Serotonin 3 (5-HT3) receptor partial agonist
irritable bowel syndrome
RAMOSETRONApproved
Serotonin 3 (5-HT3) receptor antagonist
Nausea and vomiting
RAMOSETRON HYDROCHLORIDEApproved
Serotonin 3 (5-HT3) receptor antagonist
irritable bowel syndrome
RENZAPRIDEPhase III
Serotonin 4 (5-HT4) receptor agonist
irritable bowel syndrome
TEDATIOXETINEPhase II
Serotonin 2c (5-HT2c) receptor antagonist
major depressive disorder
TROPISETRONApproved
Serotonin 3 (5-HT3) receptor antagonist
Nausea
VORTIOXETINEApproved
Serotonin 1a (5-HT1a) receptor agonist
major depressive disorder
VORTIOXETINE HYDROBROMIDEApproved
Serotonin 1a (5-HT1a) receptor agonist
ZIMELDINEApproved
Serotonin (5-HT) receptor antagonist
major depressive disorder
ZIMELDINE HYDROCHLORIDEUNKNOWN
Serotonin (5-HT) receptor antagonist
Related Genes
HTR1EProtein interaction100%CACNG7Protein interaction94%HTR3BProtein interaction94%HTR3DProtein interaction93%HTR3CProtein interaction93%CACNG8Protein interaction91%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
86%
Lung
3%
Liver
0%
Heart
0%
Ovary
0%
Gene Interaction Network
Click a node to explore
HTR3AHTR1ECACNG7HTR3BHTR3DHTR3CCACNG8
PROTEIN STRUCTURE
Preparing viewer…
PDB8AXD · 2.98 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.03LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.80 [0.62–1.03]
RankingsWhere HTR3A stands among ~20K protein-coding genes
  • #3,019of 20,598
    Most Researched150 · top quartile
  • #72of 1,025
    FDA-Approved Drug Targets23 · top 10%
  • #10,254of 17,882
    Most Constrained (LOEUF)1.03
Genes detectedHTR3A
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Overproduction of Gastrointestinal 5-HT Promotes Colitis-Associated Colorectal Cancer Progression via Enhancing NLRP3 Inflammasome Activation.
PMID: 34285037
Cancer Immunol Res · 2021
1.00
2
Associations of serotonin receptor gene HTR3A, HTR3B, and HTR3A haplotypes with bipolar disorder in Chinese patients.
PMID: 27706728
Genet Mol Res · 2016
0.90
3
The Human Serotonin Type 3 Receptor Gene (HTR3A-E) Allelic Variant Database.
PMID: 27763704
Hum Mutat · 2017
0.80
4
β-Cell adaptation in pregnancy.
PMID: 27615133
Diabetes Obes Metab · 2016
0.70
5
A polymorphism in the serotonin receptor 3A (HTR3A) gene and its association with harm avoidance in women.
PMID: 14557147
Arch Gen Psychiatry · 2003
0.60