NR3C1 rs10482614: Understanding Glucocorticoid Receptor Variants
The rs10482614 variant is a single nucleotide polymorphism located in the promoter region of the NR3C1 gene, which encodes the glucocorticoid receptor. Research suggests this variant may play a role in modulating how the body's stress response system, specifically the HPA axis, regulates cortisol feedback sensitivity.
What each genotype means
Typical cortisol feedback sensitivity
You carry two copies of the common G allele (historically referred to in promoter studies as -2722G). Research suggests individuals with this genotype exhibit typical glucocorticoid receptor promoter activity and baseline hypothalamic-pituitary-adrenal (HPA) axis stress responsiveness. In physical training and metabolic studies, this baseline genotype reflects the standard population reference response.
Carried by approximately 70% to 75% of individuals of European ancestry and is the predominant genotype across global populations.
Altered stress response potential
You carry one copy of the less common A allele, which disrupts a CpG island site within the NR3C1 promoter and has been evaluated as an expression quantitative trait locus (eQTL). Evidence linking this heterozygous profile to altered cortisol feedback regulation or metabolic differences is limited and primarily observed in multi-variant haplotype analyses. This genotype does not cause disease and reflects normal physiological variability in stress reactivity.
Carried by roughly 20% to 25% of individuals of European ancestry and is less frequent in African and East Asian ancestries.
Modulated glucocorticoid receptor activity
You carry two copies of the minor A allele at this regulatory promoter position. In exploratory human studies, homozygous carriers have shown differences in tissue-specific NR3C1 expression, cortisol negative-feedback dynamics during acute challenges, and distinct physiological adaptations to exercise. However, the scientific evidence base remains limited, and clinical guidelines do not currently recommend modifying any medical care or medication management based on this variant alone.
Carried by approximately 2% to 3% of individuals of European descent and is rare in most non-European populations.
What is rs10482614?
The rs10482614 variant is a specific genetic change, often identified as a C to T mutation, situated in the promoter region of the NR3C1 gene. Located on chromosome 5, this gene provides instructions for creating the glucocorticoid receptor, a protein that plays a critical role in how cells respond to cortisol, the body's primary stress hormone. Because this variant sits in the promoter region—the "on-off switch" area of a gene—researchers have investigated whether it influences how much receptor protein is produced. While some studies have examined its potential to alter gene expression, it is important to note that genetic variants in this region do not act in isolation. They are often part of larger genetic patterns, or haplotypes, that collectively influence how an individual's endocrine system manages stress.
The Role of the NR3C1 Gene
The NR3C1 gene is essential for the function of the glucocorticoid receptor, which is found in almost every cell in the human body. When cortisol binds to this receptor, the complex moves into the cell nucleus to turn specific genes on or off. This process is vital for regulating metabolism, immune response, and the body's reaction to stress. The receptor acts as a feedback mechanism; once the body has responded to a stressor, the receptor helps signal the hypothalamus and pituitary gland to slow down the production of cortisol. If the receptor's function is altered by genetic variation, it may theoretically change the efficiency of this feedback loop, potentially leading to differences in how individuals perceive or physiologically react to acute stress challenges.
Research and Evidence Strength
The scientific evidence linking rs10482614 to specific clinical outcomes is currently considered limited. While some studies have explored its association with cortisol suppression tests and metabolic markers, results have been mixed. For instance, some research has indicated that the variant may not be functional on its own but might show effects when inherited alongside other specific NR3C1 variants. Because the HPA axis is a complex system influenced by many genes and environmental factors, isolating the effect of a single SNP like rs10482614 is challenging. Current literature does not support using this variant to predict health outcomes or diagnose stress-related conditions. Further large-scale, peer-reviewed studies are required to clarify whether this variant has a meaningful impact on human physiology or disease risk.
What You Can Do With This Information
It is important to understand that genetic information regarding rs10482614 is for educational purposes only and should not be used to make medical decisions. Because the evidence for this variant is limited and inconsistent, it cannot be used to predict your personal stress response or risk for any medical condition. If you have concerns about your stress levels, cortisol regulation, or metabolic health, please consult with a qualified healthcare provider. They can evaluate your symptoms, medical history, and lifestyle factors to provide appropriate guidance. Never use genetic data to self-diagnose or alter any prescribed medications. If you are currently taking medications that interact with your endocrine system, always discuss any questions about your treatment or dosing with your clinician or pharmacist.
How common is this variant?
The minor allele frequency for rs10482614 is approximately 0.15 in European populations according to gnomAD data. Frequencies can vary significantly across different global ancestries.
Frequently asked questions
Can this variant predict my stress levels?
No. Current scientific evidence is too limited to use this variant to predict individual stress levels or psychological responses to stress.
Is rs10482614 linked to depression?
While some research has explored the role of NR3C1 variants in mood disorders, there is no definitive evidence that rs10482614 is a direct cause of depression.
Should I change my medication based on this result?
Absolutely not. You should never change your medication or dosage based on genetic test results without consulting your doctor or pharmacist.
Is this a 'stress gene'?
The NR3C1 gene is involved in the stress response, but it is not a 'stress gene' in the sense that it determines your personality or ability to handle stress. Many genes and environmental factors contribute to how we experience stress.
Sources & further reading
Educational information only, last refreshed 10/18/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Known as the BclI intronic variant of the glucocorticoid receptor gene, associated with hypersensitivity to cortisol and altered HPA-axis negative feedback.
Variant in the 3-prime untranslated region of the glucocorticoid receptor gene associated with altered cortisol sensitivity, blood pressure responses, and nutrient-driven metabolic stress.
Variant in the glucocorticoid receptor gene (GR-9beta) that increases glucocorticoid receptor beta expression and promotes glucocorticoid resistance during physiological and psychological stress.
Intronic variant within the glucocorticoid receptor gene NR3C1 modulating feedback inhibition of the HPA axis and baseline stress resilience.
Known as R23K, this variant is associated with glucocorticoid sensitivity and altered cortisol awakening response.
Rare variant in the glucocorticoid receptor gene (NR3C1).