HTR2A
5-HT2A serotonin receptor
Gene Number: 3356
Location: 13q14.2
Key Functions: Serotonin signaling, mood regulation, cognitive function, sleep regulation, sensory perception
HTR2A encodes the 5-hydroxytryptamine receptor 2A (5-HT₂A), a G protein–coupled receptor (GPCR) primarily coupled to the Gq/11 signaling pathway. It plays a pivotal role in mediating the effects of serotonin (5-HT) on neuronal excitability, synaptic plasticity, and cortical integration. The receptor is widely distributed in the central nervous system (CNS)—particularly in the prefrontal cortex, anterior cingulate cortex, hippocampus, amygdala, and thalamus—where it influences mood, cognition, perception, and consciousness.
Upon serotonin binding, 5-HT₂A receptors activate phospholipase C (PLC), resulting in the generation of inositol triphosphate (IP₃) and diacylglycerol (DAG), leading to intracellular Ca²⁺ release and protein kinase C (PKC) activation. This signaling cascade modulates neuronal firing, synaptic strength, and neurotransmitter release, thus impacting affective, cognitive, and perceptual processes.
Interaction with other neurotransmitter systems: HTR2A signaling modulates and is modulated by dopaminergic and glutamatergic transmission. In cortical networks, its activation enhances NMDA receptor–mediated excitatory postsynaptic potentials, while in subcortical circuits, HTR2A antagonism indirectly increases dopamine release in the prefrontal cortex, a mechanism believed to underlie the pro-cognitive and antipsychotic effects of certain serotonergic drugs.
SNP ID | Your Genotype | Alternative Alleles | Interpretation |
|---|---|---|---|
rs6313 | Analyze your DNA to see your genotype | A | Analyze your DNA to see a personalized result. |
rs6311 | Analyze your DNA to see your genotype | A,T | Analyze your DNA to see a personalized result. |
rs6313
AA – Normal risk for rheumatoid arthritis (R).
AG – Higher risk for rheumatoid arthritis based on haplotype data (R).
GG – Higher risk for rheumatoid arthritis (R).
Functional effect: The G allele is part of an HTR2A haplotype (rs6311-rs1328674-rs6313-rs6314) associated with approximately 1.68× increased RA risk.
rs6311
TT – Normal (lower) risk of sexual dysfunction when treated with SSRI antidepressants (R).
CT – Normal risk of SSRI-related sexual dysfunction (R).
CC – ~3.6× increased risk of sexual dysfunction under SSRI treatment (R).
Functional effect: The C allele in the promoter region may influence mRNA expression and SSRI side-effect susceptibility, particularly sexual dysfunction.
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