What you carry at this position in your DNA and what research says about it.
Stress and PTSD Risk: 6/10 evidence, 32 publications.
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Sample genotype (not yours): C/C
Higher Stress Sensitivity and PTSD Risk
Carrying two copies of the C allele is associated with increased sensitivity to stress and a higher risk of developing PTSD after trauma. However, this genotype may also correlate with a more rapid and favorable response to certain antidepressant treatments.
What this genotype means: Higher risk of PTSD after trauma; Increased sensitivity to stress; Better response to antidepressants.
Sample genotype (not yours): A/A
Typical Stress Resilience and Lower PTSD Risk
Carrying two copies of the A allele is associated with typical stress resilience and a lower risk of developing PTSD or chronic pain after trauma. Antidepressant response is expected to be typical.
What this genotype means: Typical stress resilience; Lower risk of PTSD after trauma; Typical response to antidepressants.
Sample genotype (not yours): C/A
Increased Stress Sensitivity and PTSD Risk
Carrying one copy of the C allele is linked to heightened stress sensitivity and an elevated risk of PTSD following traumatic events. It is also associated with a better response to antidepressant medications.
What this genotype means: Increased risk of PTSD after trauma; Elevated stress sensitivity; Better response to antidepressants.
Gene function and biological role
Gene Function: The FKBP5 gene encodes the FK506-binding protein 5, which plays a critical role in regulating the body's stress response system [1]. It acts as a regulator of the glucocorticoid receptor, which binds the stress hormone cortisol [1]. When stress levels rise, FKBP5 helps control the sensitivity of these receptors to prevent overactivation of the stress response [2]. However, altered FKBP5 activity can disrupt this feedback loop, leading to prolonged cortisol exposure and glucocorticoid resistance [2]. This disruption is a key biological mechanism underlying stress-related psychiatric disorders [1] [2].
Variant Impact: The rs3800373 variant is located in the 3 prime untranslated region of the FKBP5 gene [2]. This genetic change alters the secondary structure of the messenger RNA, which affects how microRNAs bind and regulate the gene's expression [2]. Specifically, the C allele prevents microRNA-320a from downregulating FKBP5 during stressful events, leading to excess FKBP5 protein levels [2]. This excess protein causes glucocorticoid receptor resistance, impairing the body's ability to recover from stress [2] [3]. Consequently, this variant is a major genetic modulator of stress sensitivity and trauma vulnerability [3].
Key Insight: The genetic variant that increases vulnerability to PTSD and chronic pain actually makes individuals respond faster and more effectively to antidepressant medications.
Location: FKBP5. Chromosome 6 · 6p21.31 · 35.6 Mb
Estimated prevalence by population
Global 10.8%; European 8.0%; African 18.3%; East Asian 6.6%; South Asian 11.3%; Americas 10.6%; Ashkenazi 8.2%; Finnish 3.5%; Middle Eastern 12.7%; Amish 2.4%.
Estimated CC genotype frequency.
Global 42.5%; European 40.5%; African 49.0%; East Asian 38.3%; South Asian 44.6%; Americas 43.9%; Ashkenazi 40.9%; Finnish 30.4%; Middle Eastern 45.9%; Amish 26.3%.
Estimated CA genotype frequency.
Global 46.7%; European 51.5%; African 32.8%; East Asian 55.1%; South Asian 44.1%; Americas 45.5%; Ashkenazi 50.9%; Finnish 66.2%; Middle Eastern 41.4%; Amish 71.3%.
Estimated AA genotype frequency.
Showing effects for C/C genotype
Neurology & Mental Health
Anxiety & Stress Disorders
PTSD Risk. Evidence: 4/10. Source: PMID 20393453. Increased Risk.
Mood Disorders
Depression and Anxiety. Evidence: 4/10. Source: PMID 24856550. Increased Risk.
Pharmacogenomics
Antidepressant & Psychiatric Drug Response
Antidepressant Response. Evidence: 6/10. Source: PMID 15565110. Stronger Response.
Organ Systems
Chronic Pain
Chronic Pain. Evidence: 3/10. Source: PMID 27648526. Increased Risk.
Showing effects for A/A genotype
PTSD Risk. Evidence: 4/10. Source: PMID 20393453. Typical Risk.
Depression and Anxiety. Evidence: 4/10. Source: PMID 24856550. Typical Risk.
Antidepressant Response. Evidence: 6/10. Source: PMID 15565110. Typical Response.
Chronic Pain. Evidence: 3/10. Source: PMID 27648526. Typical Risk.
Showing effects for C/A genotype
What this genotype means for the people who carry it
Sample genotype: CC (Homozygous)
This genotype is characterized by two copies of the C risk allele, which alters the regulation of the FKBP5 gene [1]. Under stressful conditions, this genetic change prevents the normal downregulation of FKBP5, leading to glucocorticoid receptor resistance and prolonged stress hormone activity [1]. Research shows that individuals with this genotype who experience childhood trauma or severe life stress have a significantly higher risk of developing PTSD and severe depressive symptoms [2] [3]. Additionally, this variant is associated with an increased susceptibility to chronic physical pain following traumatic events like motor vehicle accidents [1]. Interestingly, clinical studies have found that individuals with this genotype often show a faster and more complete response to antidepressant medications, particularly SSRIs [4] [5]. This suggests that while the stress response system is more sensitive, it may also be more adaptable to therapeutic interventions [4].
Higher risk of PTSD after trauma; Increased sensitivity to stress; Better response to antidepressants; Higher risk of chronic post-traumatic pain.
Sample genotype: AA (Homozygous)
This genotype consists of two copies of the A allele, which is the major and protective variant at this locus. Without the C risk allele, the FKBP5 gene is regulated normally by microRNAs during stressful events, allowing the body to efficiently reset its cortisol levels [1]. Consequently, individuals with this genotype show greater natural resilience to the psychological impacts of trauma and childhood adversity, with a lower risk of developing PTSD or depression [2] [3]. They also have a lower susceptibility to developing chronic pain in the aftermath of physical trauma [1]. While this genotype is highly protective against stress-related disorders, some studies suggest that individuals with this profile may have a more typical, standard rate of response to antidepressant medications rather than the rapid response seen in C allele carriers [4] [5]. Overall, this genetic profile supports a robust and stable stress response system [2].
Typical stress resilience; Lower risk of PTSD after trauma; Typical response to antidepressants; Lower risk of chronic post-traumatic pain.
Sample genotype: CA (Heterozygous)
This genotype represents a heterozygous state, carrying one copy of the C risk allele and one copy of the protective A allele. The presence of the C allele is sufficient to alter FKBP5 expression and impair the body's natural stress recovery mechanisms [1]. Individuals with this genotype who are exposed to childhood adversity or severe trauma show an increased risk of developing PTSD, depression, and anxiety [2] [3]. Furthermore, this genetic profile is linked to a higher likelihood of experiencing chronic post-traumatic pain [1]. On the positive side, clinical trials indicate that carriers of the C allele tend to experience a more rapid and effective response to antidepressant treatments compared to non-carriers [4] [5]. This suggests that the biological pathways influenced by this variant are highly responsive to medical treatment [4].
Increased risk of PTSD after trauma; Elevated stress sensitivity; Better response to antidepressants; Increased risk of chronic post-traumatic pain.
Variants with shared genetic architecture
rs1360780 · FKBP5 Gene · Chr 6 · Depression Risk
rs4713916 · FKBP5 Gene · Chr 6 · Depression and Stress Response
rs9296158 · FKBP5 Gene · Chr 6 · Trauma Sensitivity
Risk and resilience: genetic and environmental influences on development of the stress response.
Interaction of FKBP5 with childhood adversity on risk for post-traumatic stress disorder.
FKBP5 Genotype Linked to Combined PTSD-Depression Symptom in Chinese Earthquake Survivors.
Genetic variants in FKBP5 affecting response to antidepressant drug treatment.
Content updated August 2026.
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