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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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TAAR1
trace amine associated receptor 1
Chromosome 6 · 6q23.2
NCBI Gene: 134864Ensembl: ENSG00000146399.3HGNC: HGNC:17734UniProt: Q96RJ0
52PubMed Papers
20Diseases
1Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Receptor
CLINICAL
Clinical Trials
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
trace-amine receptor activityG protein-coupled receptor activityprotein bindingG protein-coupled receptor signaling pathwayschizophreniageneralized anxiety disorderneoplasmParkinson disease
✦AI Summary

TAAR1 is a G-protein coupled receptor that recognizes diverse endogenous trace amines including β-phenylethylamine, 3-iodothyronamine, and various other metabolites, as well as psychoactive substances like amphetamine and methamphetamine 12. Unlike classical biogenic amine receptors, TAAR1 is unresponsive to epinephrine and histamine 3. The receptor employs a primary amine recognition pocket with a conserved acidic residue (D3.32) for ligand binding, complemented by extended binding pockets enabling diverse ligand selectivity 13. Mechanistically, TAAR1 displays ligand-dependent G-protein coupling: cadaverine activates Gi/o proteins inhibiting adenylate cyclase, β-PEA and T1AM activate Gs proteins stimulating adenylate cyclase, while cyclohexylamine and isoamylamine couple to Gq/G11 proteins activating phospholipase C 13. In neurons, TAAR1 activation decreases basal firing rates and reduces neurotransmitter receptor sensitivity 1. Clinically, TAAR1 agonists show therapeutic potential for schizophrenia and psychostimulant addiction by negatively regulating dopaminergic transmission in the mesocorticolimbic system 45. However, recent clinical trials demonstrate that TAAR1 agonists (ulotaront and ralmitaront) show modest efficacy compared to placebo in acute schizophrenia and reduced effectiveness versus dopamine D2 antagonists 6, though they present a relatively benign side-effect profile 6.

Sources cited
1
TAAR1 recognizes endogenous trace amines and amphetamine; primary amine recognition pocket structure; ligand-dependent G-protein coupling
PMID: 37935376
2
TAAR1 recognition of methamphetamine and β-PEA; molecular basis of ligand selectivity; binding pocket architecture
PMID: 37935377
3
TAAR1 signaling profile; ligand-dependent G-protein coupling specifics; unresponsiveness to classical biogenic amines
PMID: 37963465
4
TAAR1 negatively regulates dopamine transmission; TAAR1 agonists in psychostimulant addiction models
PMID: 31974906
5
TAAR1 distribution in monoaminergic system; role in psychiatric disorders including schizophrenia and substance use disorders
PMID: 38142862
6
Clinical trial data on ulotaront and ralmitaront efficacy; comparison with dopamine antagonists; side-effect profile
PMID: 39036710
Disease Associationsⓘ20
schizophreniaOpen Targets
0.42Moderate
generalized anxiety disorderOpen Targets
0.19Weak
neoplasmOpen Targets
0.11Weak
Parkinson diseaseOpen Targets
0.11Weak
cancerOpen Targets
0.09Suggestive
major depressive disorderOpen Targets
0.09Suggestive
myeloid sarcomaOpen Targets
0.08Suggestive
posterior cortical atrophyOpen Targets
0.07Suggestive
non-small cell lung carcinomaOpen Targets
0.07Suggestive
breast cancerOpen Targets
0.07Suggestive
melanomaOpen Targets
0.06Suggestive
psychosisOpen Targets
0.06Suggestive
ovarian cancerOpen Targets
0.05Suggestive
colitisOpen Targets
0.05Suggestive
cystic fibrosisOpen Targets
0.05Suggestive
infectionOpen Targets
0.05Suggestive
SepsisOpen Targets
0.04Suggestive
narcolepsyOpen Targets
0.04Suggestive
post-traumatic stress disorderOpen Targets
0.04Suggestive
COVID-19Open Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets1
ULOTARONTPhase III
Serotonin 1a (5-HT1a) receptor agonist
schizophrenia
Related Genes
EPB41L4BProtein interaction85%EPB41L4AProtein interaction81%PTPN4Protein interaction76%MRGPRDShared pathway50%GPR157Shared pathway40%PTGER3Shared pathway33%
Tissue Expression6 tissues
Ovary
0%
Brain
0%
Lung
0%
Heart
0%
Bone Marrow
0%
Liver
0%
Gene Interaction Network
Click a node to explore
TAAR1EPB41L4BEPB41L4APTPN4MRGPRDGPR157PTGER3
PROTEIN STRUCTURE
Preparing viewer…
PDB8W88 · 2.60 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.95LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.64 [0.97–1.95]
RankingsWhere TAAR1 stands among ~20K protein-coding genes
  • #8,619of 20,598
    Most Researched52
  • #17,651of 17,882
    Most Constrained (LOEUF)1.95
Genes detectedTAAR1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Structural and signaling mechanisms of TAAR1 enabled preferential agonist design.
PMID: 37963465
Cell · 2023
1.00
2
Negative symptoms in schizophrenia: Newly emerging measurements, pathways, and treatments.
PMID: 37517366
Schizophr Res · 2023
0.90
3
Ligand recognition and G-protein coupling of trace amine receptor TAAR1.
PMID: 37935376
Nature · 2023
0.80
4
Update on novel antipsychotics and pharmacological strategies for treatment-resistant schizophrenia.
PMID: 36368055
Expert Opin Pharmacother · 2022
0.70
5
TAAR1 and Psychostimulant Addiction.
PMID: 31974906
Cell Mol Neurobiol · 2020
0.60