NOD1 Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the NOD1 gene, its protein product, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | NOD1 |
|---|---|
| Full Name | Nucleotide binding oligomerization domain containing 1 |
| Gene Type | protein coding |
| Chromosomal Location | 7p14.3 |
| NCBI Gene ID | 10392 ncbi.nlm.nih.gov/gene/10392 |
| Ensembl ID | ENSG00000106100 |
| UniProt ID | Q9Y239 |
| OMIM ID | 605980 |
| HGNC ID | HGNC:7868 |
| Aliases | CARD4, NLRC1, NOD1 |
Description
NOD1 (nucleotide binding oligomerization domain containing 1) encodes a cytosolic pattern recognition receptor that detects bacterial peptidoglycan fragments, particularly meso-diaminopimelic acid (meso-DAP) found in Gram-negative bacteria. Upon ligand binding, NOD1 undergoes oligomerization and activates NF-κB and MAPK signaling pathways via RIPK2, leading to pro-inflammatory cytokine production. NOD1 plays a critical role in innate immunity, host defense, and inflammatory responses. Genetic variants in NOD1 have been associated with susceptibility to inflammatory diseases, asthma, and certain cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Inflammatory bowel disease (IBD) | NOD1 variants may alter bacterial sensing, leading to dysregulated immune responses and chronic intestinal inflammation. | Case-control studies; PMID: 17952075 |
| Asthma | NOD1 polymorphisms (e.g., rs5743336) are associated with increased risk of asthma and altered innate immune responses to bacterial components. | Genetic association studies; PMID: 16236737 |
| Gastric cancer | NOD1 expression is upregulated in gastric mucosa infected with Helicobacter pylori, contributing to chronic inflammation and carcinogenesis. | Expression analysis; PMID: 16951321 |
| Sepsis | NOD1 activation by bacterial ligands contributes to systemic inflammatory response syndrome; genetic variants may influence susceptibility. | Functional studies; PMID: 22095570 |
| Atopic dermatitis | NOD1 variants have been linked to altered skin barrier immunity and increased susceptibility to eczema. | Genetic association; PMID: 19222412 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 12.5 | Medium |
| Small intestine | 10.2 | Medium |
| Colon | 9.8 | Medium |
| Spleen | 8.5 | Low |
| Liver | 6.3 | Low |
| Kidney | 5.1 | Low |
| Brain | 2.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocyte) | 15.3 | High expression; responds to bacterial ligands |
| A549 (lung epithelial) | 8.7 | Moderate expression; involved in airway immunity |
| HeLa (cervical) | 6.2 | Low expression; used in NOD1 signaling studies |
| HCT116 (colon) | 9.1 | Moderate expression; relevant to intestinal inflammation |
| Jurkat (T cell) | 3.4 | Low expression; less studied |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs5743336 (G796A) | SNP (missense) | Minor allele frequency ~0.15 | Associated with asthma and inflammatory diseases; may alter ligand binding |
| rs2075820 (E266K) | SNP (missense) | MAF ~0.05 | Potential effect on protein function; linked to IBD susceptibility |
| rs2907749 (intronic) | SNP (intronic) | MAF ~0.20 | May affect splicing or regulatory elements; associated with sepsis outcomes |
| c.1100C>T (p.S367F) | SNP (missense) | Rare | Reported in ClinVar; uncertain significance |
| c.1966G>A (p.V656M) | SNP (missense) | Rare | Reported in ClinVar; likely benign |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in NOD1 (e.g., frameshift or nonsense) impair bacterial sensing, leading to reduced NF-κB activation and increased susceptibility to bacterial infections. Such variants are rare and often associated with immunodeficiency.
Gain of Function (GOF)
Gain-of-function mutations are not well documented for NOD1. However, certain SNPs may enhance ligand binding or oligomerization, leading to hyperinflammatory responses, as suggested in some asthma studies.
Dominant Negative (DN)
Dominant-negative mutations have been proposed in NOD1, where a mutant allele interferes with wild-type protein function, potentially disrupting signaling. Experimental evidence is limited, but some variants in the NACHT domain may exert such effects.
View complete mutation data：
Gene Ontology (GO)
| • protein homodimerization activity | • ATP binding |
| • pattern recognition receptor activity | • peptidoglycan binding |
| • protein kinase binding | • signal transducer activity |
| • identical protein binding | • zinc ion binding |
| • cytosol | • cytoplasm |
| • nucleus | • signal transduction |
| • innate immune response | • positive regulation of NF-κB transcription factor activity |
| • positive regulation of MAPK cascade | • inflammatory response |
| • apoptotic process | • response to peptidoglycan |
| • regulation of cytokine production |
Pathways
• NOD-like receptor signaling pathway (KEGG: hsa04621)
• Cytosolic DNA-sensing pathway (KEGG: hsa04623)
• Toll-like receptor signaling pathway (KEGG: hsa04620) - crosstalk
• NF-kappa B signaling pathway (KEGG: hsa04064)
• MAPK signaling pathway (KEGG: hsa04010)
• Innate Immune System (Reactome: R-HSA-168249)
• NOD1/2 Signaling Pathway (Reactome: R-HSA-168638)
Protein Summary
The NOD1 protein (UniProt Q9Y239) is a 953-amino acid cytosolic receptor composed of an N-terminal caspase recruitment domain (CARD), a central nucleotide-binding oligomerization domain (NOD/NACHT), and C-terminal leucine-rich repeats (LRRs). The CARD domain mediates interaction with RIPK2, while the NACHT domain binds ATP and facilitates oligomerization. LRRs are responsible for ligand recognition. Upon binding meso-DAP, NOD1 undergoes conformational changes, oligomerizes, and recruits RIPK2 via CARD-CARD interactions, leading to activation of NF-κB and MAPK pathways. Post-translational modifications include ubiquitination and phosphorylation, which regulate its activity. NOD1 is widely expressed in epithelial cells and immune cells, playing a key role in mucosal immunity and inflammation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NOD1 Knockout HEK293 Cell Line | EDJ-KQ1045 | Human | 10392 | Details Get a Quote |
| NOD1 Knockout A-549 Cell Line | EDJ-KQ20152 | Human | 10392 | Details Get a Quote |
| NOD1 Knockout HCT 116 Cell Line | EDJ-KQ20153 | Human | 10392 | Details Get a Quote |
| NOD1 Knockout HeLa Cell Line | EDJ-KQ20154 | Human | 10392 | Details Get a Quote |
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