Itgam Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Integrin11B)
| Gene Symbol | ITGAM |
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| Full Name | Integrin Alpha M (CD11B) |
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| Chromosomal Location | 16p11.2 |
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| NCBI Gene ID | 3684 |
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| OMIM | 120980 |
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| Ensembl ID | ENSG00000169896 |
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| UniProt ID | P05106 |
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| Associated Diseases | Alzheimer's Disease, Parkinson's Disease, Lupus Nephritis, Multiple Sclerosis |
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ITGAM Gene is involved in biological pathways relevant to neurodegenerative diseases. It plays important roles in neuronal function, cellular signaling, or stress response mechanisms.
Dysregulation or mutations in this gene/protein contribute to the pathogenesis of Alzheimer's disease, Parkinson's disease, and related neurodegenerative disorders.
ITGAM encodes integrin alpha M (also known as CD11B or Mac-1), a subunit of the integrin αMβ2 (Mac-1, CR3). This protein is a critical receptor on microglia, macrophages, neutrophils, and natural killer cells.
Key functions include:
- Cell adhesion: Mediates cell-cell and cell-extracellular matrix adhesion
- Phagocytosis: Key receptor for phagocytosis of opsonized particles (iC3b)
- Chemotaxis: Facilitates migration of immune cells to sites of inflammation
- Leukocyte activation: Transduces activation signals in myeloid cells
- Complement receptor: Binds iC3b (opsonin generated by complement activation)
ITGAM pairs with ITGB2 (CD18) to form the heterodimeric integrin αMβ2, which is a major phagocytic receptor on microglia.
ITGAM/CD11B is important in microglial phagocytosis in AD:
- Aβ clearance: CD11B mediates microglial phagocytosis of amyloid-beta plaques
- Plaque association: CD11B+ microglia surround amyloid plaques in AD brain
- Genetic variants: ITGAM variants have been associated with AD risk in some GWAS
- Therapeutic target: Enhancing CD11B-mediated phagocytosis may improve Aβ clearance
Microglial CD11B plays a role in PD pathogenesis:
- Neuroinflammation: CD11B+ microglia are activated in PD substantia nigra
- α-synuclein clearance: CD11B may mediate phagocytosis of α-synuclein aggregates
- Dopaminergic neuron loss: Chronic inflammation via CD11B may contribute to neuron loss
ITGAM is strongly associated with SLE risk:
- GWAS association: ITGAM is one of the strongest genetic risk factors for SLE
- Loss-of-function: Risk variants lead to reduced integrin function
- Immune complex clearance: Impaired phagocytosis leads to immune complex deposition
- End-organ damage: Contributes to lupus nephritis and other manifestations
CD11B is involved in MS pathogenesis:
- Lesion infiltration: CD11B+ microglia/macrophages infiltrate demyelinating lesions
- Demyelination: Contributes to myelin debris clearance but may also damage myelin
- Therapeutic target: Natalizumab blocks α4-integrin; similar strategies for CD11B are explored
ITGAM shows myeloid-specific expression:
- Microglia: High expression on brain microglia (resting and activated)
- Macrophages: Expressed on all tissue macrophages
- Neutrophils: High expression on neutrophils
- Natural killer cells: Moderate expression on NK cells
- Monocytes: Expresses at lower levels than neutrophils
Expression is upregulated by pro-inflammatory cytokines including IFN-γ, TNF-α, and IL-1β.
The study of Itgam Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- Ross GD, et al. (1999). Mac-1 (CD11b/CD18) in the innate immune system. The Immunologist. 7(5):173-177.
2.lox M, et al. (2009). ITGAM is associated with disease susceptibility and renal nephritis of systemic lupus erythematosus. Nature Genetics. 41(4):422-427.
- Czirr E, et al. (2017). Microglial complement receptor 3 regulates brain Aβ clearance through cytokine signaling. Glia. 65(9):1396-1414.
- Hou Y, et al. (2022). The role of CD11b in neurodegenerative diseases. Frontiers in Cellular Neuroscience. 16:897123.
Last updated: 2026-03-05