FKBP5 rs3800374: Understanding Your Genetic Variant
The rs3800374 variant is a genetic change located within the FKBP5 gene, which plays a critical role in regulating the body's stress response system. Research suggests this variant may influence how the glucocorticoid receptor functions, potentially impacting the negative feedback loop of the HPA axis.
What each genotype means
Typical cortisol feedback regulation
You carry two copies of the common C allele. Research suggests this genotype is typically associated with baseline glucocorticoid receptor sensitivity and typical hypothalamic-pituitary-adrenal (HPA) axis regulation following acute stress. However, published associations for this single marker remain limited and may vary depending on biological sex and broader genetic haplotypes.
Carried by approximately 45% to 50% of individuals of European ancestry and roughly 35% of individuals of African ancestry.
Moderately altered stress reactivity
You carry one copy of the minor T allele. Some studies associate the T allele with altered FKBP5 expression, leading to differences in glucocorticoid receptor sensitivity and acute cortisol response following psychosocial stress, particularly in males. Because clinical evidence is limited and complex environmental interactions exist, this genotype alone does not determine your stress resilience or mental health risk.
Carried by approximately 40% to 45% of individuals of European ancestry and up to 48% of individuals of African ancestry.
Altered stress response profile
You carry two copies of the minor T allele. In published literature, carrying two copies of this variant has been linked to differences in HPA-axis negative feedback and modified cortisol response dynamics during stress tests, with effects often reported as sex-specific. Evidence for this specific variant is limited and largely exploratory, meaning it confers only a statistical association rather than a certain physiological outcome.
Carried by roughly 8% to 10% of individuals of European ancestry and approximately 16% of individuals of African ancestry.
What is the rs3800374 Variant?
The rs3800374 variant is a single nucleotide polymorphism (SNP) located within the FKBP5 gene. In genetics, a SNP represents a variation at a single position in the DNA sequence among individuals. This specific variant involves a change between the nucleotides cytosine (C) and thymine (T). It is categorized as a trait-associated variant, meaning researchers study it to understand how it might correlate with specific physiological or behavioral characteristics. Because it sits within a gene involved in complex hormonal pathways, scientists are interested in whether this specific change alters the efficiency or expression of the protein produced by the FKBP5 gene. It is important to note that the presence of this variant does not determine a specific health outcome, but rather serves as a point of interest in studies exploring the biological underpinnings of stress regulation and hormonal sensitivity.
The Role of the FKBP5 Gene
The FKBP5 gene provides instructions for making a protein known as FK506-binding protein 5. This protein functions as a co-chaperone, a type of molecule that assists other proteins in folding correctly and maintaining their proper shape. Specifically, FKBP5 interacts with the glucocorticoid receptor, which is the primary receptor for cortisol, the body's main stress hormone. By binding to this receptor complex, FKBP5 helps regulate how sensitive the body is to cortisol. It acts as a negative regulator, meaning it can decrease the receptor's affinity for cortisol and influence how effectively the body 'turns off' the stress response once a threat has passed. This process is known as negative feedback regulation of the hypothalamic-pituitary-adrenal (HPA) axis. When FKBP5 levels or function are altered, it may theoretically impact how an individual's body manages and recovers from stressful situations.
Research and Evidence Strength
Scientific evidence regarding the impact of rs3800374 is currently considered limited. While the FKBP5 gene is well-studied in the context of stress and psychiatric research, the specific functional consequences of the rs3800374 variant are not fully established. Some studies have investigated this SNP as a 'tag' variant, used to help researchers identify broader patterns of genetic variation in the region. Research has explored whether this variant, sometimes in combination with others, correlates with differences in cortisol response to acute psychosocial stress. However, results have been mixed, with some studies finding sex-specific effects or subtle associations, while others have not found significant correlations with peak cortisol levels. Because the HPA axis is influenced by a vast array of genetic, environmental, and epigenetic factors, it is difficult to isolate the effect of a single SNP. Consequently, current findings should be viewed as exploratory rather than definitive clinical markers.
What You Can Do With This Information
Genetic information like your status for rs3800374 is primarily for educational and research purposes. It is important to understand that this variant is not a diagnostic tool and cannot predict your personal stress response or health outcomes. Many factors, including your environment, lifestyle, and the interaction of thousands of other genes, play a much larger role in your biology than any single SNP. If you are interested in how your genetics might relate to your health, the best approach is to discuss your questions with a qualified healthcare provider or a genetic counselor. They can help you interpret information in the context of your overall health history. If you are taking medications that interact with the HPA axis or glucocorticoid pathways, always consult your clinician or pharmacist before making any changes to your treatment plan, as they are the only ones qualified to provide medical advice.
How common is this variant?
The minor allele (T) has a frequency of approximately 0.30 in European populations and 0.40 in African populations.
Frequently asked questions
Does having the rs3800374 variant mean I have a stress disorder?
No. This variant is a common genetic difference found in healthy individuals and is not a diagnostic marker for any medical condition or psychiatric disorder.
Can I use this information to choose a medication?
No. You should never use genetic information to make decisions about medication. Always consult your doctor or pharmacist regarding any treatment or dosing questions.
Is this variant the same as the ones studied in depression?
While rs3800374 is in the same gene as other variants studied in depression, it is a distinct SNP. Research on FKBP5 variants is ongoing and often focuses on different SNPs depending on the study.
Where can I find more information about my specific results?
If you have received genetic testing results, you should consult the documentation provided by your testing service or speak with a genetic counselor who can explain the findings in the context of your health.
Sources & further reading
Educational information only, last refreshed 10/10/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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This intronic variant in the FKBP5 gene modulates glucocorticoid receptor sensitivity and is linked to altered stress reactivity and susceptibility to psychiatric conditions like PTSD and depression.
Intronic variant in FKBP5; while FKBP5 is a well-established stress-response gene, specific associations for rs4713919 with HPA axis dynamics are less robustly replicated than other variants like rs1360780.
Regulatory variant in FKBP5 affecting glucocorticoid receptor chaperone activity and susceptibility to stress-related neuropsychiatric outcomes.
Intronic regulatory variant within FKBP5 linked to altered glucocorticoid receptor sensitivity and acute cortisol response following psychosocial stress.
Functional polymorphism in FKBP5 that modulates ultradian and stress-induced cortisol secretion and alters recovery trajectories following acute psychological stress.
A well-characterized non-coding FKBP5 tag variant linked with altered cortisol awakening response and susceptibility to stress-induced anxiety disorders.