IRGM: Immunity-Related GTPase M
A key regulator of autophagy and inflammatory responses, associated with Crohn's disease and infectious diseases.
Gene Information Card
| Symbol | IRGM |
|---|---|
| Full Name | Immunity-Related GTPase M |
| Gene Type | Protein coding |
| Chromosomal Location | 5q33.1 |
| NCBI Gene ID | 345611 ncbi.nlm.nih.gov/gene/345611 |
| Ensembl ID | ENSG00000187608 |
| UniProt ID | A1A4Y4 |
| OMIM ID | 608212 |
| HGNC ID | 29596 |
| Aliases | IRGM1, LRG-47, IFI1 |
Description
IRGM (Immunity-Related GTPase M) is a protein-coding gene that encodes a member of the p47 immunity-related GTPase (IRG) family. The protein is involved in autophagy, a cellular process that degrades damaged organelles and intracellular pathogens. IRGM is essential for interferon-gamma-induced autophagy and plays a critical role in host defense against intracellular bacteria such as Mycobacterium tuberculosis and Salmonella. Polymorphisms in IRGM are strongly associated with susceptibility to Crohn's disease, an inflammatory bowel disorder. The gene is located on chromosome 5q33.1 and is expressed in various tissues, particularly in immune cells.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Crohn's Disease | IRGM polymorphisms (e.g., rs13361189, rs10065172) alter autophagy function, impairing clearance of intracellular bacteria and leading to chronic intestinal inflammation. | NCBI Gene, OMIM |
| Tuberculosis | Reduced IRGM expression or function compromises IFN-γ-induced autophagy, allowing survival of Mycobacterium tuberculosis in macrophages. | NCBI Gene, PubMed |
| Systemic Lupus Erythematosus | IRGM variants may contribute to defective autophagy and increased inflammatory responses. | OMIM |
| Inflammatory Bowel Disease | IRGM risk alleles are associated with impaired autophagy and altered immune response to gut microbiota. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | 12.5 | Medium |
| Lymph Node | 10.2 | Medium |
| Spleen | 9.8 | Medium |
| Lung | 6.1 | Low |
| Small Intestine | 5.4 | Low |
| Colon | 4.7 | Low |
| Whole Blood | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocyte) | 15.3 | High expression in monocytes |
| U937 (macrophage) | 12.1 | High expression in macrophages |
| HeLa (cervical) | 2.5 | Low expression |
| HEK293 (embryonic kidney) | 1.8 | Very low expression |
| A549 (lung) | 3.0 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs13361189 | SNP (C>T) | ~0.30 (European) | Associated with increased Crohn's disease risk; may alter IRGM expression. |
| rs10065172 | SNP (C>T) | ~0.25 (European) | Linked to reduced autophagy and increased susceptibility to Crohn's disease. |
| rs4958847 | SNP (A>G) | ~0.20 (European) | Associated with altered IRGM expression and inflammatory bowel disease. |
Mutation functional classification
Loss of Function (LOF)
IRGM polymorphisms (e.g., rs13361189) reduce IRGM expression or impair its GTPase activity, leading to defective autophagy and increased susceptibility to intracellular pathogens and Crohn's disease.
Gain of Function (GOF)
Not well characterized; no common gain-of-function mutations reported in IRGM.
Dominant Negative (DN)
Not reported for IRGM; the gene is not known to exhibit dominant-negative effects.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activity | • GTP binding |
| • autophagy | • innate immune response |
| • response to interferon-gamma | • defense response to bacterium |
| • autophagosome maturation | • cytoplasm |
Pathways
• Autophagy (KEGG hsa04140)
• Tuberculosis (KEGG hsa05152)
• Salmonella infection (KEGG hsa05132)
• NOD-like receptor signaling pathway (KEGG hsa04621)
Protein Summary
The IRGM protein (Immunity-Related GTPase M) is a 47 kDa GTPase belonging to the p47 IRG family. It localizes to the cytoplasm and is recruited to autophagosomal membranes upon interferon-gamma stimulation. IRGM promotes autophagosome formation and maturation, facilitating the degradation of intracellular bacteria such as Mycobacterium tuberculosis and Salmonella. The protein contains a GTP-binding domain and exhibits intrinsic GTPase activity. IRGM is essential for IFN-γ-induced autophagy and plays a key role in regulating inflammatory responses. Polymorphisms in IRGM that reduce its expression or function are linked to Crohn's disease and other inflammatory conditions.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IRGM Knockout HEK293 Cell Line | EDJ-KQ3168 | Human | 345611 | Details Get a Quote |
| IRGM Knockout U-251MG Cell Line | EDJ-KZ30 | Human | 345611 | Details Get a Quote |
| IRGM Knockout HeLa Cell Line | EDJ-KQ59790 | Human | 345611 | Details Get a Quote |
| IRGM Knockout A-549 Cell Line | EDJ-KQ68258 | Human | 345611 | Details Get a Quote |
| IRGM Knockout HCT 116 Cell Line | EDJ-KQ76635 | Human | 345611 | Details Get a Quote |
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