NR3C1 rs6190: Understanding the R23K Glucocorticoid Receptor Variant
The rs6190 variant, located in the NR3C1 gene, results in an amino acid change known as R23K. This genetic variation is associated with altered glucocorticoid receptor function, potentially influencing how the body responds to stress and regulates certain metabolic processes.
What each genotype means
Typical glucocorticoid receptor function
This is the most common genotype for the rs6190 variant, often referred to as the wild-type or reference sequence. Individuals with this genotype typically exhibit standard glucocorticoid receptor sensitivity and metabolic regulation. No specific action is required based on this result.
This is the most common genotype found in the vast majority of the global population.
Altered glucocorticoid receptor sensitivity
This genotype, which includes the R23K variant (also known as ER22/23EK due to linkage with rs6189), is associated with a slight reduction in glucocorticoid receptor sensitivity. Research suggests this may influence cortisol awakening responses and metabolic markers, such as cholesterol levels, though findings can be mixed across different studies. If you are prescribed glucocorticoid medications, please discuss your treatment and dosing with your clinician or pharmacist.
This genotype is carried by approximately 3% to 5% of individuals of European ancestry.
Reduced glucocorticoid receptor sensitivity
Carrying two copies of the A allele is associated with diminished glucocorticoid receptor function, which may lead to relative glucocorticoid resistance. Some studies have linked this variant to altered metabolic profiles, including potential impacts on cholesterol regulation and insulin sensitivity. As this variant may affect how your body responds to stress or specific medications, please consult with your healthcare provider regarding any clinical concerns.
This genotype is rare, occurring in less than 1% of the general population.
What is the rs6190 Variant?
The rs6190 variant is a single nucleotide polymorphism (SNP) found within the NR3C1 gene, which provides instructions for making the glucocorticoid receptor. In scientific literature, this variant is often referred to as p.R23K, indicating that the amino acid arginine is replaced by lysine at position 23 of the protein. It is frequently studied alongside a nearby silent mutation, and the two are sometimes collectively referred to as the ER22/23EK haplotype. Located on chromosome 5, this variant is categorized as a low-frequency genetic change. Because it sits in a region of the gene that influences the receptor's transcriptional activity, researchers have long investigated whether this change alters how cells interpret signals from glucocorticoid hormones, which are essential for managing stress, inflammation, and metabolism throughout the body.
The Role of the NR3C1 Gene
The NR3C1 gene encodes the glucocorticoid receptor, a protein that acts as a transcription factor. When glucocorticoid hormones—such as cortisol—bind to this receptor, the complex moves into the cell nucleus to turn specific genes on or off. This system is a cornerstone of the body's stress response, helping to regulate blood sugar, immune function, and cardiovascular health. Because the receptor is expressed in almost every cell type, its proper function is vital for maintaining homeostasis. Variations in this gene, like rs6190, can potentially change the sensitivity of these receptors to hormones. If the receptor's ability to bind or activate target genes is diminished, it may lead to a state of relative glucocorticoid resistance, where the body requires higher levels of hormones to achieve the same physiological effect.
Research and Associations
Research into rs6190 has yielded mixed and evolving results. Some studies have explored its association with the cortisol awakening response and individual differences in stress reactivity. More recent investigations have looked beyond the stress response, identifying potential links between this variant and metabolic markers, such as blood cholesterol levels and atherosclerosis risk. However, the evidence strength for many of these associations remains limited. Some early findings regarding its impact on psychiatric or inflammatory conditions have not been consistently replicated across different cohorts, highlighting the complexity of genetic influence. Because the glucocorticoid receptor interacts with many other biological pathways, it is difficult to isolate the effect of a single variant. Current research continues to use large-scale datasets, such as the UK Biobank, to better understand how this variant influences health outcomes in diverse populations.
Population Frequency
The rs6190 variant is considered a low-frequency variant. In individuals of European ancestry, the minor allele frequency is typically reported in the range of approximately 2.75% to 5%. Because it is relatively uncommon, most individuals carry the common (reference) genotype, while heterozygous carriers are less frequent, and homozygous individuals for the variant allele are rare.
Interpreting Genetic Information
Understanding your genotype for rs6190 provides a glimpse into one small piece of your biological makeup, but it is not a diagnostic tool. Genetic associations are statistical in nature and do not predict individual health outcomes or disease development. Many factors, including environment, lifestyle, and other genetic variants, play a much larger role in your overall health. If you are concerned about how your body responds to stress, inflammation, or specific medications, it is essential to consult with a qualified healthcare provider. Never use genetic information to make decisions about your medical care or to adjust prescribed treatments. A clinician or pharmacist can help you interpret your health history in the context of your genetics and provide guidance tailored to your specific needs.
How common is this variant?
The rs6190 variant is a low-frequency variant with a minor allele frequency of approximately 2.75% to 5% in European ancestry populations.
Frequently asked questions
Is rs6190 a cause of disease?
No, rs6190 is a genetic variant associated with variations in receptor function, not a direct cause of disease. Most people with this variant live healthy lives, and its clinical significance is still being researched.
Does this variant affect my stress levels?
Some research suggests it may influence the cortisol awakening response, which is part of how the body manages stress. However, these findings are not definitive and vary between studies.
Should I change my medication based on this result?
Absolutely not. You should never change or stop any medication based on genetic test results without speaking to your doctor or pharmacist first.
Where can I find more information on NR3C1?
You can visit resources like MedlinePlus Genetics or the NCBI Gene database for comprehensive, peer-reviewed information on the NR3C1 gene and its functions.
Sources & further reading
Educational information only, last refreshed 9/24/2026. 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.
Rare variant in the glucocorticoid receptor gene (NR3C1).
Variant in the glucocorticoid receptor gene (NR3C1).