HTR1A (5-Hydroxytryptamine Receptor 1A)
Serotonin 1A Receptor: A Key Regulator of Mood, Anxiety, and Neurotransmission
Gene Information Card
| Symbol | HTR1A |
|---|---|
| Full Name | 5-Hydroxytryptamine Receptor 1A |
| Gene Type | protein-coding |
| Chromosomal Location | 5q12.3 |
| NCBI Gene ID | 3350 ncbi.nlm.nih.gov/gene/3350 |
| Ensembl ID | ENSG00000178394 |
| UniProt ID | P08908 |
| OMIM ID | 109760 |
| HGNC ID | 5286 |
| Aliases | 5-HT1A, 5-HT-1A, ADRBRL1, G-21, PFMCD |
Description
The HTR1A gene encodes the serotonin 1A receptor (5-HT1A), a G protein-coupled receptor (GPCR) for the neurotransmitter serotonin. It is widely expressed in the brain, particularly in the raphe nuclei, hippocampus, and cortex, where it modulates neuronal excitability, serotonin release, and stress responses. The receptor is a major target for anxiolytic and antidepressant drugs, such as buspirone and vilazodone.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Major Depressive Disorder | Reduced receptor binding and altered signaling in limbic regions; HTR1A polymorphisms affect treatment response | ClinVar, OMIM |
| Generalized Anxiety Disorder | Decreased 5-HT1A autoreceptor function leads to dysregulated serotonin release | ClinVar, PubMed |
| Panic Disorder | Association with rs6295 (C-1019G) promoter polymorphism affecting gene expression | ClinVar, OMIM |
| Obsessive-Compulsive Disorder | Altered 5-HT1A binding in cortical-striatal circuits | ClinVar |
| Alzheimer's Disease | Reduced 5-HT1A receptor density in hippocampus correlates with cognitive decline | PubMed |
| Schizophrenia | Dysregulation of 5-HT1A in prefrontal cortex; potential therapeutic target | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 5.2 | Medium |
| Hippocampus | 8.1 | High |
| Amygdala | 6.7 | High |
| Raphe nuclei | 12.3 | High |
| Cerebellum | 1.4 | Low |
| Spinal cord | 2.0 | Low |
| Heart | 0.3 | Not detected |
| Liver | 0.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 4.5 | Endogenous expression |
| HEK293 (embryonic kidney) | 0.2 | Low; often used for recombinant expression |
| U87MG (glioblastoma) | 1.8 | Moderate |
| HMC3 (microglia) | 3.1 | Detectable |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs6295 (C-1019G) | Promoter SNP | ~30% (global) | Alters transcription factor binding; associated with anxiety and depression |
| rs878567 (Ile28Val) | Missense | <1% | Reduced receptor signaling in vitro |
| rs1800044 (Gly22Ser) | Missense | <0.5% | Impaired cell surface expression |
| rs1799817 (Arg219Leu) | Missense | <0.1% | Loss of G protein coupling |
Mutation functional classification
Loss of Function (LOF)
rs1800044 (Gly22Ser) and rs1799817 (Arg219Leu) reduce receptor expression or signaling.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported.
Dominant Negative (DN)
Not described for HTR1A.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor activity | • serotonin binding |
| • serotonin receptor activity | • adenylate cyclase inhibiting G protein-coupled receptor signaling pathway |
| • regulation of serotonin secretion | • nervous system development |
| • synaptic transmission | • serotonergic |
| • response to drug |
Pathways
• Serotonergic synapse (KEGG: hsa04726)
• Neuroactive ligand-receptor interaction (KEGG: hsa04080)
• GPCR downstream signaling (Reactome: R-HSA-388396)
Protein Summary
The 5-HT1A receptor is a 422-amino acid transmembrane protein with seven alpha-helical domains. It couples primarily to Gi/o proteins, inhibiting adenylyl cyclase and modulating ion channels. The receptor exists as both presynaptic autoreceptors (in raphe nuclei) and postsynaptic heteroreceptors (in forebrain). Its activation reduces neuronal firing and neurotransmitter release, playing a central role in mood regulation, stress resilience, and cognition.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HTR1A Knockout HEK293 Cell Line | EDJ-KQ1784 | Human | 3350 | Details Get a Quote |
| HTR1A Knockout HeLa Cell Line | EDJ-KQ53586 | Human | 3350 | Details Get a Quote |
| HTR1A Knockout A-549 Cell Line | EDJ-KQ62054 | Human | 3350 | Details Get a Quote |
| HTR1A Knockout HCT 116 Cell Line | EDJ-KQ70536 | Human | 3350 | Details Get a Quote |
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