|http://ghr.nlm.nih.gov/ A service of the U.S. National Library of Medicine®|
The official name of this gene is “nucleotide-binding oligomerization domain containing 2.”
NOD2 is the gene's official symbol. The NOD2 gene is also known by other names, listed below.
The NOD2 gene provides instructions for making a protein that plays an important role in immune system function. The NOD2 protein is active in some types of immune system cells (including monocytes, macrophages, and dendritic cells), which help protect the body against foreign invaders such as viruses and bacteria. The protein is also active in several types of epithelial cells, including Paneth cells, which are found in the lining of the intestine. These cells help defend the intestinal wall against bacterial infection.
The NOD2 protein has several critical functions in defending the body against foreign invaders. The protein is involved in recognizing certain bacteria and stimulating the immune system to respond properly. When triggered by specific substances produced by bacteria, the NOD2 protein turns on (activates) a protein complex called nuclear factor-kappa-B. This protein complex regulates the activity of multiple genes, including genes that control immune responses and inflammatory reactions. An inflammatory reaction occurs when the immune system sends signaling molecules and white blood cells to a site of injury or disease to fight microbial invaders and facilitate tissue repair.
The NOD2 protein also appears to play a role in a process called autophagy, which cells use to surround and destroy bacteria and viruses. In addition to protecting cells from infection, autophagy is used to recycle worn-out cell parts and break down certain proteins when they are no longer needed. This process is also involved in the self-destruction of cells (apoptosis).
The NOD2 gene belongs to a family of genes called NLR (nucleotide-binding domain and leucine rich repeat containing family).
A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.
At least 17 mutations in the NOD2 gene have been found to cause Blau syndrome, an inflammatory disorder that primarily affects the skin, joints, and eyes. These mutations change single protein building blocks (amino acids) in the NOD2 protein. All of these mutations result in a version of the NOD2 protein that is overactive, which can trigger an abnormal inflammatory reaction and cause swelling and irritation. However, it is unclear how the abnormally active protein causes the specific pattern of inflammation affecting the skin, joints, and eyes that is characteristic of Blau syndrome.
NOD2 gene mutations can also cause early-onset sarcoidosis, a similar condition that some researchers consider to be a non-inherited version of Blau syndrome.
Approximately 40 variations in the NOD2 gene have been associated with an increased risk of Crohn disease, a complex disorder of the digestive system. In particular, NOD2 gene changes are associated with a form of Crohn disease that affects the lower part of the small intestine (the ileum) in populations of northern European descent. The most common variation, written as 3020insC or 1007fs, leads to the production of a NOD2 protein that is slightly shorter than normal. Other common variations change single amino acids in the NOD2 protein. It is unclear how these genetic changes increase the risk of developing Crohn disease. Studies suggest that changes in the NOD2 gene prevent the protein from recognizing bacteria, allowing these microbes to grow unchecked and invade cells that line the intestine. An abnormal immune response to these bacteria may contribute to chronic inflammation and the digestive problems characteristic of Crohn disease.
A few studies have suggested a possible association between changes in the NOD2 gene, particularly the common variation 3020insC, and the development of several types of cancer. Although some of these studies found an increased risk of cancer in people with a NOD2 gene variation, other research found no such association. It is unclear how changes in this gene might contribute to cancer risk.
Several studies have considered variations in the NOD2 gene as a possible risk factor for a condition called graft-versus-host disease (GVHD). Graft-versus-host disease can occur following certain cancer treatments, such as allogeneic stem cell transplantation. This procedure, which is typically used to treat cancers of the blood and immune system, replaces a patient's diseased blood-forming cells (a type of stem cell) with stem cells from a healthy donor. If the donor's stem cells (the graft) recognize the patient's body (the host) as foreign, they may attack organs and tissues such as the liver, digestive system, and skin. Graft-versus-host disease is the term used to describe this potentially severe reaction.
A few studies have suggested that variations in the NOD2 gene influence the risk of developing severe complications of graft-versus-host disease following an allogeneic stem cell transplant. The presence of NOD2 gene variations in both the stem cell donor and the recipient is associated with the greatest risk of a severe reaction. However, other research has found no relationship between NOD2 gene changes and the risk of developing graft-versus-host disease.
Cytogenetic Location: 16q21
Molecular Location on chromosome 16: base pairs 50,731,049 to 50,766,986
The NOD2 gene is located on the long (q) arm of chromosome 16 at position 21.
More precisely, the NOD2 gene is located from base pair 50,731,049 to base pair 50,766,986 on chromosome 16.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
You and your healthcare professional may find the following resources about NOD2 helpful.
You may also be interested in these resources, which are designed for genetics professionals and researchers.
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
acids ; allogeneic ; allogeneic stem cell transplantation ; apoptosis ; autophagy ; bacteria ; cancer ; caspase ; cell ; chronic ; digestive ; digestive system ; domain ; epithelial ; gene ; graft-versus-host disease ; GVHD ; ileum ; immune response ; immune system ; infection ; inflammation ; injury ; innate immunity ; intestine ; juvenile ; nucleotide ; protein ; sarcoidosis ; stem cells ; syndrome ; tissue ; white blood cells
You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).
The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.