What you carry at this position in your DNA and what research says about it.
Depression Risk: 6/10 evidence, 53 publications.
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Sample genotype (not yours): T/T
Higher Depression Risk and Better Antidepressant Response
Stress sensitivity and depression risk are elevated in those with two T alleles, though antidepressant response is often enhanced.
What this genotype means: Increased risk of depression; Enhanced response to certain antidepressants; Higher vulnerability to stress-induced PTSD.
Sample genotype (not yours): C/C
Typical Depression and Stress Risk
A typical stress response and baseline risk for depression are associated with the C/C genotype.
What this genotype means: Standard baseline risk for depression; Typical stress recovery patterns; Lower risk of medication-induced suicidal thoughts.
Sample genotype (not yours): T/C
Higher Depression and Stress Risk
Stress sensitivity and depression risk are moderately elevated in those with one T allele.
What this genotype means: Moderately increased depression risk; Slower recovery from acute stress; Slightly better response to some antidepressants.
Gene function and biological role
Gene Function: The FKBP5 gene encodes a co-chaperone protein that plays a critical role in regulating the body's stress response system [1]. It acts as a regulator of the glucocorticoid receptor, which binds to the stress hormone cortisol [1]. When stress levels rise, this protein helps modulate how sensitive brain cells are to cortisol, helping to shut down the stress response once the threat has passed [2]. Dysregulation of this feedback loop can lead to prolonged cortisol exposure, which is linked to mood disorders [2]. Research shows that variations in this gene can alter its expression levels, affecting emotional resilience and vulnerability to psychiatric conditions [3].
Variant Impact: The rs1360780 variant is located in an intron of the FKBP5 gene and acts as a functional regulator of gene expression [1]. The T allele is a high-induction variant that increases the production of the FKBP5 protein in response to stress [1]. This overproduction reduces the sensitivity of glucocorticoid receptors, leading to cortisol resistance and a prolonged fight-or-flight response [2]. Conversely, the C allele is associated with lower gene expression and a more typical stress recovery pattern [2]. This genetic difference interacts strongly with environmental factors, particularly early-life stress, to shape adult emotional health [4].
Key Insight: The same genetic variant that increases vulnerability to stress and depression also makes people respond significantly better to antidepressant medications.
Location: FKBP5. Chromosome 6 · 6p21.31 · 35.6 Mb
Estimated prevalence by population
Global 11.1%; European 9.2%; African 17.1%; East Asian 6.9%; South Asian 11.7%; Americas 10.6%; Ashkenazi 7.3%; Finnish 3.9%; Middle Eastern 12.8%; Amish 6.8%.
Estimated TT genotype frequency.
Global 43.3%; European 42.3%; African 48.5%; East Asian 38.7%; South Asian 45.0%; Americas 43.9%; Ashkenazi 39.5%; Finnish 31.6%; Middle Eastern 45.9%; Amish 38.5%.
Estimated TC genotype frequency.
Global 45.6%; European 48.5%; African 34.5%; East Asian 54.4%; South Asian 43.3%; Americas 45.5%; Ashkenazi 53.1%; Finnish 64.5%; Middle Eastern 41.3%; Amish 54.8%.
Estimated CC genotype frequency.
Showing effects for T/T genotype
Neurology & Mental Health
Mood Disorders
Depression. Evidence: 6/10. Source: PMID 15565110. ~1.3x Increased Risk.
Suicidal Thoughts. Evidence: 5/10. Source: PMID 21449676. Increased Risk.
Lifestyle, Fitness & Aging
Stress Response & Resilience
Stress Sensitivity. Evidence: 4/10. Source: PMID 18349090. Increased Risk.
Pharmacogenomics
Antidepressant & Psychiatric Drug Response
Antidepressant Response. Evidence: 6/10. Source: PMID 15565110. Stronger Response.
Showing effects for C/C genotype
Depression. Evidence: 6/10. Source: PMID 15565110. Typical Risk.
Suicidal Thoughts. Evidence: 5/10. Source: PMID 21449676. Typical Risk.
Stress Sensitivity. Evidence: 4/10. Source: PMID 18349090. Typical Risk.
Antidepressant Response. Evidence: 6/10. Source: PMID 15565110. Poorer Response.
Showing effects for T/C genotype
What this genotype means for the people who carry it
Sample genotype: TT (Homozygous)
Major depression risk is increased by roughly 1.3-fold in the presence of two T alleles [1]. This genetic profile leads to higher production of the FKBP5 protein, which can cause the body's stress response system to remain active longer than usual [2]. When combined with childhood trauma or severe life stress, this variant significantly increases the likelihood of developing post-traumatic stress disorder (PTSD) in adulthood [3]. Despite these challenges, there is a notable clinical silver lining: individuals with this genotype often show a faster and more complete response to antidepressant treatments [4]. However, some studies also note an increased risk of experiencing suicidal thoughts when starting specific medications like paroxetine or lithium [5]. Understanding these patterns helps researchers map how genetic stress sensitivity influences treatment outcomes [6].
Increased risk of depression; Enhanced response to certain antidepressants; Higher vulnerability to stress-induced PTSD.
Sample genotype: CC (Homozygous)
Typical levels of stress sensitivity and baseline depression risk are characteristic of the C/C genotype [1]. This genotype does not cause the overproduction of the FKBP5 protein seen with the T allele, allowing for a more typical recovery from stress [2]. Studies show that individuals with this profile do not have the elevated risk of PTSD or depression associated with the T allele, even when exposed to early-life trauma [3]. While this represents a protective advantage against stress-induced mood disorders, it also means these individuals may not experience the rapid antidepressant response seen in T allele carriers [4]. In clinical trials, those with the C/C genotype sometimes show a slower or poorer response to initial antidepressant therapies [5]. However, they also have a lower risk of developing treatment-induced suicidal thoughts on medications like paroxetine [6]. Overall, this genotype represents a stable, typical stress-response profile [1].
Standard baseline risk for depression; Typical stress recovery patterns; Lower risk of medication-induced suicidal thoughts.
Sample genotype: TC (Heterozygous)
Depression and anxiety risk are moderately increased in individuals carrying one T allele [1]. The T allele acts as a high-induction variant, meaning it increases the expression of the FKBP5 protein when stress hormones are released [2]. This overproduction can desensitize glucocorticoid receptors, making it harder for the brain to turn off the stress response [2]. Research indicates that this genotype interacts with early-life adversity, elevating the risk of adult PTSD and emotional difficulties [3]. On the therapeutic side, carriers of this genotype may experience a better response to some antidepressant medications compared to those with the typical genotype [4]. However, there is also a documented association with an increased risk of suicidal ideation when taking certain antidepressants or mood stabilizers [5]. These findings highlight the complex role of stress-response genes in mental health and treatment [6].
Moderately increased depression risk; Slower recovery from acute stress; Slightly better response to some antidepressants.
Variants with shared genetic architecture
rs3800373 · FKBP5 Gene · Chr 6 · Stress and PTSD Risk
rs4713916 · FKBP5 Gene · Chr 6 · Depression and Stress Response
rs9296158 · FKBP5 Gene · Chr 6 · Trauma Sensitivity
Genetic variants in FKBP5 affecting response to antidepressant drug treatment.
Pharmacogenetics in major depression: a comprehensive meta-analysis.
Content updated August 2026.
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