NR3C1 rs377135940: Understanding This Rare Genetic Variant
The rs377135940 variant is a rare genetic change located within the NR3C1 gene, which provides instructions for making the glucocorticoid receptor. This receptor is essential for regulating the body's physiological stress response and managing cortisol levels.
What each genotype means
Typical glucocorticoid receptor profile
This is the most common genotype for this location in the NR3C1 gene. It represents the standard genetic sequence associated with typical glucocorticoid receptor function in the hypothalamic-pituitary-adrenal axis.
This is the predominant genotype found in the vast majority of individuals across all global populations.
Rare variant carrier
You carry one copy of this rare variant in the NR3C1 gene. Because this variant is extremely rare and evidence regarding its specific functional impact is limited, its clinical significance remains uncertain. If you are undergoing treatment with glucocorticoid medications, please discuss your health history and any concerns about medication response with your clinician or pharmacist.
This genotype is extremely rare, with the variant allele occurring at a frequency of approximately 0.00002 in the general population.
Rare homozygous variant
You carry two copies of this rare variant in the NR3C1 gene. Given the extreme rarity of this genotype, there is currently insufficient published research to define its specific physiological effects or clinical implications. Please consult with a medical professional or genetic counselor to discuss how this finding relates to your personal health context, especially if you have questions regarding glucocorticoid sensitivity.
This genotype is exceptionally rare and is not expected to be observed in most population cohorts.
What is the rs377135940 Variant?
The rs377135940 variant is a specific alteration in the DNA sequence of the NR3C1 gene. In genomics, a single nucleotide polymorphism (SNP) like this represents a variation at a single position in the genome. Because this variant is classified as rare, it is not commonly found in the general population. It sits within the coding region of the NR3C1 gene, which is located on chromosome 5. Scientists study such variants to understand how minor changes in our genetic code might influence the structure or function of the proteins they encode. While many variants have no observable effect, others can alter how a gene functions, potentially impacting biological pathways. Research into this specific variant is ongoing, and its presence does not automatically imply a specific health outcome or clinical condition.
The Role of the NR3C1 Gene
The NR3C1 gene encodes the glucocorticoid receptor (GR), a protein that plays a critical role in the hypothalamic-pituitary-adrenal (HPA) axis. This axis is the body's primary system for managing stress. When the body perceives stress, the HPA axis triggers the release of cortisol, a hormone that helps regulate metabolism, immune response, and inflammation. The glucocorticoid receptor acts as a sensor for these hormones; once it binds to cortisol, it moves into the cell nucleus to turn specific genes on or off. By controlling this process, the NR3C1 gene helps the body return to a state of balance after a stressful event. Because of its central role in these processes, variations in NR3C1 are frequently studied in the context of metabolic health, inflammatory conditions, and how individuals respond to stress.
Research and Evidence Strength
Current scientific evidence regarding the rs377135940 variant is considered limited. While the NR3C1 gene itself is well-characterized in medical literature—particularly in relation to glucocorticoid resistance syndromes and inflammatory conditions like asthma—specific data linking rs377135940 to clinical outcomes is sparse. In genomics, 'limited' evidence means that while the variant has been identified, there is not yet enough peer-reviewed research to establish a clear, consistent link between this specific change and a particular disease or trait. It is important to distinguish between the well-known functions of the NR3C1 gene and the unknown or unproven effects of this specific rare variant. Researchers continue to use large-scale databases to track such variants, but until more studies are published, the functional impact of rs377135940 remains a subject of scientific investigation rather than established clinical fact.
Population Frequency
The rs377135940 variant is classified as very rare, with an estimated allele frequency of approximately 0.00002. This means that the variant is found in only a tiny fraction of the individuals sequenced in global population databases like gnomAD. Because it is so uncommon, it is difficult for researchers to gather enough data to determine if the variant is more prevalent in specific ancestral groups or if it has a uniform distribution. In many cases, rare variants like this are identified through exome sequencing projects that look at thousands of individuals to catalog human genetic diversity. The low frequency suggests that this variant is not a common driver of health traits in the general population, and its presence is likely an isolated finding for the vast majority of people who might carry it.
What This Information Means for You
If you have encountered this variant in a genetic report, it is important to understand that genetic information is complex and often requires professional interpretation. Because the evidence for rs377135940 is limited, it is not currently used to make medical diagnoses or predict health outcomes. Genetic variants are only one piece of a much larger puzzle that includes your environment, lifestyle, and other genetic factors. You should never use this information to make changes to your health regimen or medication usage. If you have concerns about your stress response, metabolic health, or any other condition, the best course of action is to consult with a qualified healthcare provider or a genetic counselor. They can help you put your genetic results into the proper context of your overall health history and provide guidance based on established clinical standards.
How common is this variant?
The rs377135940 variant is very rare, with an allele frequency of approximately 0.00002 across global populations.
Frequently asked questions
What is the NR3C1 gene?
The NR3C1 gene provides instructions for making the glucocorticoid receptor, a protein that helps regulate the body's response to stress and inflammation.
Is rs377135940 associated with a specific disease?
Currently, there is limited evidence linking this specific rare variant to any clinical disease. While the NR3C1 gene is involved in various health conditions, the impact of this specific SNP is not well-established.
Should I be worried if I have this variant?
Finding a rare variant does not necessarily mean you have a health problem. Because the evidence for this variant is limited, it is best to discuss your results with a healthcare professional who can provide context based on your personal health.
Where can I learn more about my genetic variants?
You can search for your specific rsID on databases like ClinVar or the NCBI SNP database. Always consult with a genetic counselor or doctor to interpret what these findings mean for your health.
Sources & further reading
Educational information only, last refreshed 9/15/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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A variant in the glucocorticoid receptor gene associated with individual differences in transcriptional responses to stress.
Located in the glucocorticoid receptor gene (BclI polymorphism), this variant alters sensitivity of the hypothalamic-pituitary-adrenal axis and is associated with heightened cortisol suppression and altered physiological stress responses.
A promoter variant of the glucocorticoid receptor gene that modulates cortisol feedback sensitivity during acute stress challenge tests.
A synonymous variant (c.1088A>G) in exon 2 of the glucocorticoid receptor gene that belongs to haplotypes modifying dexamethasone suppression sensitivity.
Known as the BclI intronic variant of the glucocorticoid receptor gene, associated with hypersensitivity to cortisol and altered HPA-axis negative feedback.
Known as R23K, this variant diminishes glucocorticoid receptor function, leading to relative glucocorticoid resistance and altered cortisol awakening response.