NOD2
NOD2 (nucleotide-binding oligomerization domain containing 2)
Gene Number: 64127
Location: 16q12.1
Key Functions: Bacterial recognition, innate immune signaling, intestinal defense, inflammation regulation
NOD2 helps cells recognize fragments of bacterial cell walls and activate immune defenses. This bacterial-sensing system is particularly important in the intestine, where the body must manage constant contact with gut microbes [R].
This report examines two protein-changing NOD2 variants: rs2066844 (R702W) and rs2066845 (G908R). Both have been associated with increased susceptibility to Crohn’s disease, an inflammatory bowel disease. These results cover selected variants rather than the entire NOD2 gene [R].
Explore your genotype below. For other genetic influences on intestinal inflammation, visit our guides to IL23R and inflammatory signaling and IL10 and inflammation regulation.
SNP ID | Your Genotype | Alt Allele | Interpretation |
|---|---|---|---|
rs2066844 | Analyze your DNA to see your genotype | T | Analyze your DNA to see a personalized result. |
rs2066845 | Analyze your DNA to see your genotype | C | Analyze your DNA to see a personalized result. |
rs2066844 — Bacterial Sensing and Crohn’s Disease
CC – Reference genotype. No copies of the T allele associated with increased Crohn’s disease susceptibility at this position.
CT – Increased susceptibility. One T allele. A 2021 DiscovEHR study reported approximately 1.3× the odds of Crohn’s disease [R].
TT – Higher susceptibility. Two T alleles. The same study reported approximately 4× the odds of Crohn’s disease [R].
Functional effect: The T allele changes the amino acid arginine to tryptophan at position 702 of the NOD2 protein. Experimental research links Crohn’s-associated NOD2 variants to weaker responses to muramyl dipeptide, a fragment of bacterial cell walls. This helps explain how altered bacterial sensing can contribute to intestinal inflammation [R, R].
rs2066845 — G908R and Crohn’s Disease
GG – Reference genotype. G908R variant not detected.
GC – Increased susceptibility. One copy of the C allele, which encodes the G908R variant.
CC – Increased susceptibility. Two copies of the C allele, which encodes the G908R variant.
Research findings: A meta-analysis of 75 studies reported approximately 2.6× the odds of Crohn’s disease per G908R allele [R].
Functional effect: The C allele replaces glycine with arginine at position 908 of the NOD2 protein. Laboratory experiments found reduced signaling responses to bacterial components, helping explain how this variant can affect intestinal immune defenses [R].
One Part of the Genetic Picture
NOD2 contains other Crohn’s-associated variants, so this result covers only two important positions rather than the whole gene [R].
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