Overview
NOD2 (also called CARD15) is an important protein of the innate immune system. It acts as an intracellular detector for bacterial cell wall components. Especially in the small intestine, it is crucial for detecting harmful bacteria and maintaining the integrity of the mucosa.
16q12.1 (Chromosome 16)
Immune System
Complex / Multifactorial
Variants present in approx. 10-15% of the population
Function & Significance
NOD2 recognizes muramyl dipeptide (MDP), an element of the bacterial cell wall. Once NOD2 binds MDP, it activates signaling pathways (such as NF-kB) that initiate inflammatory processes and trigger the release of antibacterial substances. A defect in this system allows bacteria to cross the intestinal barrier more easily.
⚠️ Crohn’s Disease Risk
NOD2 was the first gene clearly associated with Crohn’s disease, a chronic inflammatory bowel disease (IBD). Paradoxically, mutations often lead to a *diminished* initial immune response to intestinal bacteria, which later results in excessive, chronic inflammation.
🧬 Relevant SNPs
Three main mutations in the NOD2 gene are responsible for the increased risk of Crohn’s disease:
16:50693581
/
Arg702Trp:
This variant impairs bacterial recognition. Carriers have an approx. 2- to 4-fold increased risk of Crohn’s disease.
16:50700141
/
1007fs (Leu1007fsTer2):
Leads to a shortened, non-functional NOD2 protein. This is the strongest known risk variant for Crohn’s disease (up to 15-fold risk if homozygous).
📚 Data Sources
- OMIM: #605956 – Nucleotide Binding Oligomerization Domain Containing 2; NOD2
- dbSNP: rs2066844, rs2812378, rs2066845
- ClinVar: Pathogenic variants in IBD
Biological Function
Associated Conditions
Analyzed Markers
Arg702Trp - One of the three main variants significantly increasing Crohn's Disease risk (approx. 2-4 fold in heterozygotes).
Leu1007fsTer2 - Leads to a truncated protein. The strongest risk variant for Crohn's Disease.