HTR2A Gene: Serotonin 2A Receptor
Key mediator of serotonergic signaling in the CNS and periphery; implicated in neuropsychiatric disorders and drug response.
Gene Information Card
| Symbol | HTR2A |
|---|---|
| Full Name | 5-hydroxytryptamine receptor 2A |
| Gene Type | protein coding |
| Chromosomal Location | 13q14.2 |
| NCBI Gene ID | 3356 ncbi.nlm.nih.gov/gene/3356 |
| Ensembl ID | ENSG00000147246 |
| UniProt ID | P28223 |
| OMIM ID | 182135 |
| HGNC ID | 5293 |
| Aliases | 5-HT2A, HTR2, 5-HT-2A |
Description
The HTR2A gene encodes the serotonin 2A receptor, a G protein-coupled receptor (GPCR) that mediates excitatory neurotransmission via activation of phospholipase C and inositol phosphate signaling. It is widely expressed in the central nervous system, particularly in cortical and limbic regions, and also in peripheral tissues such as platelets and smooth muscle. HTR2A is a major target for atypical antipsychotics, antidepressants, and hallucinogens like LSD, and is involved in mood regulation, cognition, and perception.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Schizophrenia | Altered receptor density and signaling; genetic variants affect antipsychotic response | Association studies; pharmacogenetic studies (ClinVar, PubMed) |
| Major Depressive Disorder | Dysregulation of serotonergic signaling; receptor downregulation in depression | Postmortem brain studies; PET imaging; genetic association |
| Obsessive-Compulsive Disorder | Serotonergic dysfunction; receptor binding changes | Imaging studies; genetic association |
| Alzheimer's Disease | Reduced cortical HTR2A binding correlates with cognitive decline | PET studies; postmortem analysis |
| Substance Dependence | Modulation of reward pathways; variants influence addiction risk | Genetic association studies |
| Suicidal Behavior | Altered receptor expression in prefrontal cortex | Postmortem studies; genetic association |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Cerebral Cortex | High | nTPM ~ 20-30 |
| Hippocampus | Moderate | nTPM ~ 10-15 |
| Cerebellum | Low | nTPM ~ 2-5 |
| Platelets | High (protein) | nTPM not applicable |
| Smooth Muscle | Moderate | nTPM ~ 5-10 |
| Lung | Low | nTPM ~ 1-3 |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | Moderate | Neuronal-like expression |
| U87 (glioblastoma) | Low | Glial expression |
| HEK293 (embryonic kidney) | Low | Transfected for studies |
| A549 (lung carcinoma) | Low | Peripheral expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs6311 (A-1438G) | SNP (promoter) | ~50% in populations | Alters promoter activity; associated with psychiatric disorders and antipsychotic response |
| rs6313 (T102C) | SNP (synonymous) | ~50% in populations | Linked to rs6311; affects mRNA stability; associated with schizophrenia and depression |
| His452Tyr (rs6314) | Missense | ~10% in populations | Reduced receptor signaling; associated with altered drug response |
| Thr25Asn | Missense | Rare | Potential functional impact; not well characterized |
Mutation functional classification
Loss of Function (LOF)
Rare variants causing reduced receptor expression or signaling (e.g., His452Tyr) may lead to loss of function, contributing to depressive or cognitive symptoms.
Gain of Function (GOF)
Some promoter variants (e.g., rs6311) may increase receptor expression, potentially enhancing serotonergic signaling and affecting drug response.
Dominant Negative (DN)
No clear dominant-negative mutations reported for HTR2A.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor activity | • serotonin binding |
| • phospholipase C-activating G protein-coupled receptor signaling pathway | • chemical synaptic transmission |
| • response to xenobiotic stimulus | • positive regulation of cytosolic calcium ion concentration |
| • cell surface receptor signaling pathway | • integral component of plasma membrane |
Pathways
• Serotonergic synapse
• Neuroactive ligand-receptor interaction
• Calcium signaling pathway
• cAMP signaling pathway (via Gq/11)
Protein Summary
The serotonin 2A receptor (5-HT2A) is a 471-amino acid GPCR with seven transmembrane domains. It couples primarily to Gq/11 proteins, activating phospholipase C and increasing intracellular calcium. It is a key excitatory receptor in the cortex, modulating pyramidal neuron activity and influencing mood, cognition, and perception. It is the primary target for hallucinogens (e.g., LSD, psilocybin) and a major site for atypical antipsychotics (e.g., clozapine, risperidone). Post-translational modifications include N-glycosylation and phosphorylation, which regulate receptor trafficking and desensitization.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HTR2A Knockout HEK293 Cell Line | EDJ-KQ1591 | Human | 3356 | Details Get a Quote |
| HTR2A Knockout HeLa Cell Line | EDJ-KQ53591 | Human | 3356 | Details Get a Quote |
| HTR2A Knockout A-549 Cell Line | EDJ-KQ62059 | Human | 3356 | Details Get a Quote |
| HTR2A Knockout HCT 116 Cell Line | EDJ-KQ70541 | Human | 3356 | Details Get a Quote |
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