NR3C1 rs41423247: Understanding the BclI Glucocorticoid Variant
The rs41423247 variant, commonly referred to as the BclI polymorphism, is a genetic change located within the NR3C1 gene. It is frequently studied for its potential association with altered sensitivity to cortisol and variations in how the body manages stress responses.
What each genotype means
Typical Glucocorticoid Sensitivity
You carry two copies of the C allele, representing the baseline reference genotype for the BclI polymorphism in the NR3C1 gene. Research generally links this genotype to typical glucocorticoid receptor sensitivity and standard feedback signaling along the hypothalamic-pituitary-adrenal (HPA) axis. Some studies note a lower relative frequency of mood and stress-related vulnerabilities compared to G allele carriers, though evidence across diverse populations remains limited and complex.
Carried by approximately 35% to 50% of individuals of European ancestry and is commonly observed across other global populations.
Altered Glucocorticoid Sensitivity
You carry one copy of the BclI G variant allele alongside one C allele. Published studies suggest this heterozygous genotype may be linked to modestly altered glucocorticoid receptor sensitivity and variations in cortisol reactivity during stress. Because research findings are mixed and influenced by environmental context, carrying this genotype indicates only a statistical association rather than a certain physiological outcome.
Carried by roughly 40% to 50% of individuals of European descent, representing the most common genotype in several cohorts.
Increased Glucocorticoid Sensitivity
You carry two copies of the BclI G variant allele in the NR3C1 gene. Literature associates this homozygous genotype with increased sensitivity to glucocorticoids, altered negative feedback in the HPA axis, and modest statistical correlations with mood alterations or metabolic parameters in some cohorts. These associations are based on limited and preliminary research, and if you have questions regarding cortisol-affecting medications, discuss them with your physician or pharmacist.
Carried by approximately 10% to 15% of people of European ancestry, with varying frequencies across other global groups.
What is the rs41423247 Variant?
The rs41423247 variant is a single nucleotide polymorphism (SNP) situated in the second intron of the NR3C1 gene on chromosome 5. In genetic research, this specific site is widely known as the BclI polymorphism. Because it is located in an intronic region—a part of the gene that does not directly code for the final protein sequence—researchers investigate whether it influences how the gene is regulated or processed. Geneticists track this variant by observing the presence of either a cytosine (C) or a guanine (G) nucleotide at this specific position. Understanding its location helps scientists determine if the variant might affect the expression levels of the glucocorticoid receptor, which is essential for the body's hormonal signaling pathways.
The Role of the NR3C1 Gene
The NR3C1 gene provides the instructions for creating the glucocorticoid receptor (GR). This receptor acts as a critical transcription factor that binds to glucocorticoids, such as cortisol, which are hormones released by the body in response to stress. Once activated, the glucocorticoid receptor travels into the cell nucleus to regulate the expression of various genes involved in metabolism, immune function, and the stress response. By modulating these pathways, the GR helps the body maintain homeostasis after a stressful event. Because this receptor is so central to physiological regulation, variations in the NR3C1 gene are of significant interest to researchers studying how individuals differ in their biological responses to environmental pressures and metabolic challenges.
Research Associations and Evidence Strength
Research into rs41423247 has explored its potential links to various health outcomes, though the evidence remains limited and sometimes mixed. Some studies have associated the G allele with increased sensitivity to glucocorticoids and a higher risk for metabolic syndrome, including factors like increased body mass index and abdominal obesity. Other research has examined its role in psychological traits, such as anxiety scores or depression risk, with some findings suggesting that carriers of the G allele may show different cortisol reactivity patterns under stress. Additionally, some studies in pediatric populations have looked at whether this variant influences the therapeutic response to certain medications. It is important to note that these associations are statistical in nature and often vary by population or study design, meaning the clinical significance of this variant is not yet fully established.
Population Frequency
The frequency of the rs41423247 variant varies across different global populations. In many European ancestries, the minor allele (G) is relatively common, with a frequency typically reported between 0.30 and 0.40. Because allele frequencies can differ significantly based on geographic and ancestral background, researchers must account for these differences when conducting genetic studies to ensure that findings are not skewed by population structure. Data from large-scale projects like gnomAD provide ongoing updates on these frequencies, helping scientists refine their understanding of how common this variant is across diverse human groups.
Interpreting Genetic Information
Genetic variants like rs41423247 provide a window into the complexity of human biology, but they do not act in isolation. Most traits and health outcomes are influenced by a combination of many genetic factors, environmental exposures, and lifestyle choices. Consequently, having a specific genotype for this variant does not determine a person's health status or predict a specific medical outcome. If you are interested in how genetic information might relate to your health or medication response, it is essential to consult with a qualified healthcare provider or a pharmacist. They can help interpret your results in the context of your overall health history and provide guidance that is appropriate for your individual needs. Never use genetic data to make independent medical decisions or changes to prescribed treatments.
How common is this variant?
The minor allele (G) has a frequency of approximately 0.30–0.40 in European populations, though frequencies can differ across other ancestral groups.
Frequently asked questions
Is rs41423247 a diagnostic test for stress?
No, rs41423247 is not a diagnostic test. It is a common genetic variant that researchers study to understand biological differences in stress responses, but it cannot predict or diagnose any medical condition.
Does the G allele mean I am more sensitive to stress?
Some studies suggest an association between the G allele and altered cortisol sensitivity, but this does not mean you are inherently 'more sensitive' to stress. Genetic associations are complex and influenced by many other factors.
Should I change my medication based on this SNP?
You should never change your medication based on genetic information without consulting your doctor. Always discuss any concerns about medication response with your clinician or pharmacist.
Where can I find more information on NR3C1?
You can find reliable information about the NR3C1 gene and its functions through resources like MedlinePlus Genetics or the National Center for Biotechnology Information (NCBI) Gene database.
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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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.
Variant in the glucocorticoid receptor gene (NR3C1).
Rare variant in the glucocorticoid receptor gene (NR3C1).