HTR2A rs6314: Understanding the His452Tyr Genetic Variant
The rs6314 variant is a genetic change in the HTR2A gene that alters the structure of the serotonin 2A receptor. Research has explored its potential associations with memory performance, sleep patterns, and responses to certain antidepressant medications.
What each genotype means
Typical Serotonin Receptor Signaling
You have two copies of the standard C allele encoding the typical histidine at position 452 of the 5-HT2A receptor. In population studies, this baseline genotype is associated with standard slow-wave sleep architecture, conventional long-term memory performance, and expected receptor signaling efficiency. Because this is the most widely studied reference genotype, it generally exhibits average response profiles across clinical investigations.
Found in approximately 80% to 85% of individuals of European ancestry and over 90% of individuals in East Asian and African populations.
Altered Receptor Function Carrier
You carry one copy of the T allele (encoding the Tyr452 missense change), which has been linked in preliminary functional studies to altered 5-HT2A receptor expression and downstream intracellular signaling. Research has associated this carrier status with subtle variations in slow-wave sleep duration, subjective sleep maintenance, and variable memory performance, though overall scientific evidence remains limited and mixed across populations. If you are taking psychiatric medications such as atypical antipsychotics or antidepressants that interact with serotonin pathways, discuss any medication management or dosing considerations directly with your clinician or pharmacist.
Carried by roughly 15% to 18% of individuals of European ancestry and approximately 5% to 10% of individuals of East Asian ancestry.
Atypical Serotonin Receptor Function
You carry two copies of the uncommon T allele encoding the Tyr452 variant in the 5-HT2A serotonin receptor. Laboratory and association models suggest this genotype may be associated with modified downstream signaling, reduced receptor expression, and potential shifts in sleep patterns, though dedicated research in TT homozygotes is sparse due to low frequency. Because this genetic variant can influence serotonergic drug targets, consult your clinician or pharmacist if you have questions regarding the response or dosing of serotonergic medications.
Very rare across global populations, occurring in fewer than 1% of individuals worldwide.
What is rs6314?
The variant rs6314 is a single nucleotide polymorphism (SNP) located in the HTR2A gene on chromosome 13. Specifically, it is a missense variant found in exon 3 of the gene. This genetic change involves a substitution of a cytosine (C) for a thymine (T) at a specific position in the DNA sequence. This alteration results in a change at the protein level, where the amino acid histidine is replaced by tyrosine at the 452nd position of the serotonin 2A receptor protein. Because this change occurs within the coding region of the gene, it is often referred to as His452Tyr or H452Y. Scientists study this variant because such structural changes in receptors can potentially influence how cells receive and process chemical signals in the brain.
The Role of the HTR2A Gene
The HTR2A gene provides instructions for creating the serotonin 2A receptor, a protein found on the surface of nerve cells in the brain. This receptor is a critical component of the serotonin system, which helps regulate mood, sleep, memory, and various cognitive functions. When serotonin binds to this receptor, it triggers a cascade of intracellular signaling events that influence how neurons communicate. Because the receptor is involved in such fundamental brain processes, researchers have long investigated whether variations in the HTR2A gene might contribute to differences in human behavior or susceptibility to psychiatric conditions. The His452Tyr change is of particular interest because it has been hypothesized to lead to blunted or altered intracellular signaling, potentially affecting how the receptor functions in response to serotonin.
Research Associations and Evidence
Research into rs6314 has produced mixed and sometimes conflicting results, leading to a classification of limited evidence. Some studies have suggested an association between this variant and differences in episodic memory performance, with certain genotypes potentially performing better than others. Other research has explored its role in sleep maintenance and subjective sleep quality. Additionally, some pharmacogenetic studies have investigated whether this variant influences how patients respond to antidepressants like paroxetine or citalopram, though findings have not been consistently replicated across all populations. It is important to note that many of these associations are statistical in nature and do not imply a direct cause-and-effect relationship. Because psychiatric and cognitive traits are complex and influenced by many genes and environmental factors, the impact of a single variant like rs6314 is generally considered to be small.
What This Information Means for You
If you have received information about your rs6314 genotype, it is important to view it within the context of current scientific understanding. This variant is a common genetic difference, and having a particular genotype does not mean you will experience specific cognitive or health outcomes. The evidence linking this SNP to clinical traits remains limited and is not used in routine medical practice to predict health or guide treatment. If you are curious about how your genetics might relate to medication response, you should discuss this with your clinician or pharmacist. They can provide guidance based on your full medical history and established clinical guidelines rather than relying on a single genetic marker. Genetic information should never be used to self-diagnose or make changes to prescribed treatments without professional medical supervision.
How common is this variant?
The Tyr452 (T) allele frequency is approximately 0.09 in European populations and ranges between 0.03 and 0.05 in East Asian populations.
Frequently asked questions
Is rs6314 a diagnostic test for depression?
No, rs6314 is not a diagnostic test for depression or any other psychiatric condition. Genetic variants like this are studied for research purposes and do not provide a clinical diagnosis.
Can I use my rs6314 result to choose an antidepressant?
You should not use this genetic information to choose or change your medication. Always consult with your doctor or pharmacist, as they consider many factors beyond a single genetic variant when determining the best treatment plan.
Does the rs6314 variant cause memory loss?
There is no evidence that this variant causes memory loss. Some research has explored its potential influence on memory performance, but these findings are not definitive and do not indicate a clinical disorder.
How common is the T allele?
The T allele is relatively uncommon, with frequencies typically ranging from 3% to 9% depending on your ancestral background. It is much less frequent than the C allele.
Sources & further reading
Educational information only, last refreshed 10/12/2026. Not medical advice — these associations describe population statistics, not individual predictions.
Curious what your genotype is for rs6314?
Upload a raw DNA file from 23andMe, AncestryDNA, MyHeritage, or FamilyTreeDNA and see this variant — plus thousands more — interpreted in your full report.
Get my report — $29Related variants in HTR2A
Recent clinical reviews indicate that HTR2A variants do not currently support actionable clinical antidepressant guidance.
Promoter variant in HTR2A associated with sleep architecture and mood resilience.
HTR2A serotonin-receptor variant associated with sleep architecture and mood regulation.