NOD2 rs2066845: What Your Genotype Means
The rs2066845 variant is a specific change in the NOD2 gene, often referred to as the G908R mutation. It is statistically associated with an increased risk of developing Crohn's disease, a type of inflammatory bowel disease.
What each genotype means
Typical risk profile
This genotype represents the most common version of the NOD2 gene at this position, often referred to as the wild-type or reference allele. It is not associated with the increased risk of Crohn's disease linked to the G908R variant. Having this genotype does not guarantee protection from inflammatory bowel disease, as many other genetic and environmental factors contribute to the condition.
This is the most common genotype across all global populations.
Increased Crohn's disease risk
This genotype indicates you carry one copy of the G908R variant (also known as c.2722G>C). Research indicates that individuals with this variant may have an increased statistical risk for developing Crohn's disease compared to those without it. This variant is located in the leucine-rich repeat region of the NOD2 protein, which may affect how the immune system recognizes certain bacteria.
The C allele is carried by approximately 1-2% of people of European ancestry and is very rare in other ancestral groups.
Elevated Crohn's disease risk
This genotype indicates you carry two copies of the G908R variant. Studies have associated this genotype with a higher relative risk for Crohn's disease compared to individuals with one or no copies of the variant. Because this is a complex genetic association, it is important to remember that this result is not a diagnosis and many people with this genotype do not develop the disease.
This homozygous genotype is very rare, occurring in a small fraction of the 1-2% of individuals of European ancestry who carry the minor allele.
Understanding the rs2066845 Variant
The rs2066845 variant is a single nucleotide polymorphism (SNP) located within the NOD2 gene on chromosome 16. In genetic terms, this variant represents a substitution where the nucleotide guanine (G) is replaced by cytosine (C). This specific change results in an amino acid alteration in the protein product of the gene, where glycine is replaced by arginine at position 908, commonly abbreviated as p.Gly908Arg or G908R. This variant is situated in the leucine-rich repeat (LRR) region of the NOD2 protein, a domain critical for the protein's ability to recognize and respond to bacterial components. Because this change occurs in a functional part of the protein, researchers have long investigated how it might alter the body's immune response and contribute to chronic inflammatory conditions.
The Role of the NOD2 Gene
The NOD2 gene provides instructions for making a protein that acts as an intracellular sensor for bacterial pathogens. When the NOD2 protein detects fragments of bacterial cell walls, it triggers a signaling cascade that activates the transcription factor NF-κB. This process is essential for the innate immune system, as it leads to the production of inflammatory cytokines and antimicrobial peptides that help the body fight off infections. When the NOD2 protein is functioning correctly, it helps maintain a healthy balance in the gut microbiome and protects the intestinal lining. However, variants like rs2066845 can impair the protein's ability to bind to bacterial components or initiate the necessary immune signaling. This dysfunction is thought to lead to an inadequate immune response to gut bacteria, which may contribute to the chronic inflammation observed in conditions like Crohn's disease.
Research and Clinical Associations
Scientific research has established a statistical association between the rs2066845 variant and an increased risk of Crohn's disease. Multiple studies have observed that individuals carrying the C allele are more likely to develop this form of inflammatory bowel disease compared to those who do not. The evidence for this association is considered moderate-to-high in terms of relative risk, particularly in European populations. However, it is important to note that carrying this variant does not mean an individual will definitely develop the disease. Crohn's disease is a complex, multifactorial condition influenced by a combination of genetic, environmental, and immunological factors. While rs2066845 is a known risk factor, it is only one piece of a much larger puzzle, and many people with the variant never develop the condition.
What You Can and Cannot Do With This Information
Genetic information regarding the rs2066845 variant is intended for educational purposes and should not be used for self-diagnosis or medical decision-making. If you are concerned about your risk for inflammatory bowel disease or are experiencing symptoms such as persistent abdominal pain, diarrhea, or weight loss, it is essential to consult with a healthcare professional or a gastroenterologist. They can provide appropriate clinical evaluations, which may include blood tests, imaging, or endoscopic procedures that are far more diagnostic than genetic testing alone. Do not make changes to your diet, lifestyle, or medical regimen based on this genetic result without professional guidance. Understanding your genetic predispositions can be a tool for personal knowledge, but it should always be contextualized by a qualified clinician who understands your full medical history.
How common is this variant?
The minor allele frequency for rs2066845 is approximately 0.01 to 0.02 in European populations. It is found at very low frequencies in other ancestral groups.
Frequently asked questions
Does having the rs2066845 variant mean I have Crohn's disease?
No, having this variant does not mean you have or will develop Crohn's disease. It is a genetic risk factor, meaning it is statistically associated with an increased likelihood of the condition, but it is not a diagnostic test.
Should I get tested for the NOD2 variant?
Genetic testing for this variant is generally not recommended for the general population. If you have symptoms of inflammatory bowel disease, you should see a doctor for clinical testing rather than relying on genetic markers.
Is there a cure for the NOD2-related risk?
There is no 'cure' for a genetic variant, as it is a permanent part of your DNA. However, Crohn's disease is managed through various medical treatments and lifestyle adjustments overseen by gastroenterologists.
Are there other genes involved in Crohn's disease?
Yes, Crohn's disease is a complex condition involving many different genes, as well as environmental and lifestyle factors. NOD2 is just one of many genes that have been linked to the disease in scientific studies.
Sources & further reading
Educational information only, last refreshed 9/20/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Also known as Leu1007fsinsC (3020insC), this frameshift insertion/variant in NOD2 is one of the strongest genetic risk factors for Crohn's disease susceptibility.
Missense variant p.Arg702Trp in NOD2 associated with increased susceptibility to Crohn disease.