ITGB2 (CD18): The Beta-2 Integrin Subunit in Leukocyte Adhesion and Immune Function
A comprehensive biomedical reference for ITGB2, covering genomic architecture, protein function, associated diseases, tissue expression, and mutation landscape.
Gene Information Card
| Symbol | ITGB2 |
|---|---|
| Full Name | Integrin Subunit Beta 2 |
| Gene Type | protein coding |
| Chromosomal Location | 21q22.3 |
| NCBI Gene ID | 3689 ncbi.nlm.nih.gov/gene/3689 |
| Ensembl ID | ENSG00000160255 |
| UniProt ID | P05107 |
| OMIM ID | 600065 |
| HGNC ID | 6155 |
| Aliases | CD18, LAD, LCAMB, MFI7 |
Description
The ITGB2 gene encodes the integrin beta-2 (CD18) protein, a crucial component of the beta-2 integrin family. These are transmembrane receptors expressed on the surface of leukocytes (white blood cells). CD18 pairs with one of four different alpha subunits (CD11a, CD11b, CD11c, or CD11d) to form functional heterodimers, such as LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18). These integrins are essential for leukocyte adhesion, migration, and cell-cell interactions during immune responses, including the process of leukocyte extravasation from blood vessels to sites of inflammation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Disease | Mechanism | Evidence |
| Leukocyte Adhesion Deficiency Type 1 (LAD-1) | Loss-of-function mutations in ITGB2 prevent the expression of functional beta-2 integrins on the leukocyte surface. This impairs leukocyte adhesion to endothelial cells and their migration to sites of infection, leading to recurrent severe bacterial infections and impaired wound healing. | ClinVar, OMIM |
| Recurrent Bacterial Infections | The absence of functional CD18 leads to defective neutrophil and monocyte extravasation, resulting in an inability to clear bacterial pathogens, particularly at skin and mucosal surfaces. | OMIM, NCBI Gene |
| Periodontitis (Severe) | Patients with LAD-1 often exhibit severe early-onset periodontitis due to defective neutrophil function and impaired immune surveillance in the oral cavity. | OMIM, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Tissue | nTPM | Level |
| Bone Marrow | High | High |
| Spleen | High | High |
| Lymph Node | High | High |
| Blood (Leukocytes) | High | High |
| Lung | Medium | Medium |
| Liver | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cell Line | nTPM | Notes |
| THP-1 (Monocytic leukemia) | High | Constitutive expression of CD18 on monocyte/macrophage lineage cells. |
| HL-60 (Promyeloblast) | High | Expression increases upon differentiation into granulocytes or monocytes. |
| Jurkat (T-cell leukemia) | Medium | Expressed on T lymphocytes, particularly after activation. |
| Raji (Burkitt's lymphoma) | Low | B cells express lower levels of beta-2 integrins compared to myeloid cells. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Variant | Type | Frequency | Effect |
| c.817G>A (p.Gly273Arg) | Missense | Rare (found in LAD-1 patients) | Disrupts protein folding and prevents heterodimer formation with alpha subunits, leading to loss of surface expression. |
| c.562C>T (p.Arg188Ter) | Nonsense | Rare (found in LAD-1 patients) | Introduces a premature stop codon, leading to a truncated, non-functional protein that is likely degraded. |
| c.1777C>T (p.Arg593Ter) | Nonsense | Rare (found in LAD-1 patients) | Results in a truncated protein lacking the cytoplasmic domain, impairing integrin signaling and function. |
| c.382G>A (p.Gly128Ser) | Missense | Rare (found in LAD-1 patients) | Affects the beta-propeller domain, crucial for alpha subunit interaction, leading to reduced surface expression. |
Mutation functional classification
Loss of Function (LOF)
The vast majority of disease-causing ITGB2 mutations are loss-of-function. They result in either the complete absence of the CD18 protein on the cell surface or the production of a non-functional protein that cannot pair with alpha subunits or bind ligands. This leads to the clinical phenotype of LAD-1.
Gain of Function (GOF)
No gain-of-function mutations have been clinically characterized for ITGB2. Such mutations would be predicted to cause hyper-adhesive leukocytes, but this has not been reported in the literature.
Dominant Negative (DN)
While LAD-1 is typically inherited in an autosomal recessive manner, some missense mutations in the extracellular domain can exert a dominant-negative effect. The mutant protein can dimerize with the wild-type alpha subunit but form a non-functional complex, thereby reducing the overall number of functional integrins on the cell surface.
View complete mutation data：
Gene Ontology (GO)
| • integrin-mediated signaling pathway | • cell adhesion |
| • leukocyte migration | • cell-matrix adhesion |
| • receptor binding | • protein heterodimerization activity |
| • extracellular matrix binding | • immune response |
| • integrin complex | • plasma membrane |
Pathways
• Integrin Signaling Pathway
• Leukocyte Transendothelial Migration
• Cell adhesion molecules (CAMs)
• Fc gamma R-mediated phagocytosis
• Regulation of actin cytoskeleton
Protein Summary
The ITGB2 protein (CD18) is a type I transmembrane glycoprotein that serves as the common beta subunit for the beta-2 integrin family. It is synthesized in the endoplasmic reticulum where it must associate with one of four alpha subunits (CD11a-d) to form a stable, functional heterodimer. The mature integrin is expressed on the cell surface and mediates divalent cation-dependent adhesion to ligands such as ICAM-1, iC3b, and fibrinogen. CD18 is critical for the firm adhesion of leukocytes to the endothelium, a prerequisite for their migration into tissues. It also plays a role in phagocytosis, cell signaling, and apoptosis. Mutations in this gene lead to Leukocyte Adhesion Deficiency type 1 (LAD-1), a severe immunodeficiency.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ITGB2 Knockout HEK293 Cell Line | EDJ-KQ1352 | Human | 3689 | Details Get a Quote |
| ITGB2 Knockout HeLa Cell Line | EDJ-KQ53680 | Human | 3689 | Details Get a Quote |
| ITGB2 Knockout A-549 Cell Line | EDJ-KQ62155 | Human | 3689 | Details Get a Quote |
| ITGB2 Knockout HCT 116 Cell Line | EDJ-KQ70644 | Human | 3689 | Details Get a Quote |
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