ITGAM (CD11b) Gene: Structure, Function, and Clinical Significance
A comprehensive guide to the ITGAM gene, encoding the integrin alpha M subunit, its role in immune adhesion, associated diseases, and expression patterns.
Gene Information Card
| Symbol | ITGAM |
|---|---|
| Full Name | Integrin subunit alpha M |
| Gene Type | protein coding |
| Chromosomal Location | 16p11.2 |
| NCBI Gene ID | 3684 ncbi.nlm.nih.gov/gene/3684 |
| Ensembl ID | ENSG00000169896 |
| UniProt ID | P11215 |
| OMIM ID | 120980 |
| HGNC ID | 6149 |
| Aliases | CD11B, CR3A, MAC-1, MAC1A, MOA, SLEB6 |
Description
ITGAM encodes the integrin alpha M (CD11b) chain, which non-covalently associates with integrin beta 2 (CD18) to form the Mac-1 (CR3) heterodimer. This receptor is expressed on myeloid cells and mediates adhesion, phagocytosis, and complement-mediated opsonization. ITGAM is involved in leukocyte migration and immune regulation, and genetic variants are associated with autoimmune diseases, particularly systemic lupus erythematosus (SLE).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Systemic Lupus Erythematosus (SLE) | Risk variants (e.g., rs1143679) reduce ITGAM function, impairing immune complex clearance and increasing inflammation. | ClinVar, OMIM (120980), multiple GWAS studies |
| Leukocyte Adhesion Deficiency Type I (LAD I) | Loss-of-function mutations in ITGAM (with ITGB2) impair leukocyte adhesion and extravasation, causing recurrent infections. | OMIM (116920, but ITGAM mutations are rare; functional deficiency) |
| Inflammatory Bowel Disease (IBD) | ITGAM expression on macrophages influences intestinal inflammation; variants may modulate susceptibility. | NCBI Gene, literature |
| Atherosclerosis | Mac-1 mediates monocyte adhesion to endothelium, contributing to plaque formation. | UniProt, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | High | High |
| Blood (Leukocytes) | High | High |
| Spleen | Medium | Medium |
| Lung | Low | Low |
| Liver | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Monocytes | High | Primary cells |
| Macrophages | High | Differentiated |
| Neutrophils | High | Granulocytes |
| NK cells | Medium | Subset |
| Dendritic cells | Medium | Myeloid |
| T cells (activated) | Low | Inducible |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs1143679 (R77H) | Missense | ~10-15% in European populations | Reduced integrin function, increased SLE risk |
| rs1143683 (P1146S) | Missense | ~5-10% | Associated with SLE |
| rs4548893 (A858V) | Missense | Rare | Potential functional impact, clinical significance uncertain |
| c.223G>A (V75M) | Missense | Rare | Reported in LAD-like phenotype |
Mutation functional classification
Loss of Function (LOF)
Most ITGAM variants associated with SLE (e.g., rs1143679) are loss-of-function, reducing adhesion and phagocytosis.
Gain of Function (GOF)
No clear gain-of-function mutations reported; some variants may increase activity but evidence is limited.
Dominant Negative (DN)
Not established; ITGAM mutations are generally recessive or haploinsufficient.
View complete mutation data：
Gene Ontology (GO)
| • integrin binding | • complement receptor activity |
| • cell adhesion molecule binding | • protein heterodimerization activity |
| • receptor activity | • immune response |
| • cell adhesion | • phagocytosis |
| • leukocyte migration | • signal transduction |
Pathways
• Integrin signaling
• Leukocyte transendothelial migration
• Complement cascade (opsonization)
• Fc gamma receptor-mediated phagocytosis
• Innate immune response
Protein Summary
The ITGAM protein (CD11b) is a 170 kDa type I transmembrane glycoprotein with an extracellular domain containing seven N-terminal repeats and an I-domain that binds ligands such as iC3b, ICAM-1, and fibrinogen. It forms the Mac-1 receptor with CD18, playing a critical role in leukocyte adhesion, chemotaxis, and phagocytosis. The cytoplasmic tail interacts with cytoskeletal proteins, modulating signaling. Post-translational modifications include glycosylation and phosphorylation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ITGAM Knockout HEK293 Cell Line | EDJ-KQ1351 | Human | 3684 | Details Get a Quote |
| ITGAM Knockout A-549 Cell Line | EDJ-KQ18102 | Human | 3684 | Details Get a Quote |
| ITGAM Knockout HCT 116 Cell Line | EDJ-KQ19485 | Human | 3684 | Details Get a Quote |
| ITGAM Knockout BEAS-2B Cell Line | EDJ-KZ300 | Human | 3684 | Details Get a Quote |
| ITGAM Knockout HeLa Cell Line | EDJ-KQ53678 | Human | 3684 | Details Get a Quote |
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