ITGAL Gene: Integrin Subunit Alpha L - Function, Disease Associations, and Clinical Significance
Comprehensive biomedical overview of ITGAL (CD11a), encoding the alpha L subunit of LFA-1, with emphasis on leukocyte adhesion, immunodeficiency, and therapeutic targeting.
Gene Information Card
| Symbol | ITGAL |
|---|---|
| Full Name | Integrin subunit alpha L |
| Gene Type | Protein coding |
| Chromosomal Location | 16p11.2 (GRCh38: chr16:30,472,742-30,512,031, minus strand) |
| NCBI Gene ID | 3683 ncbi.nlm.nih.gov/gene/3683 |
| Ensembl ID | ENSG00000005844 |
| UniProt ID | P20701 |
| OMIM ID | 153370 |
| HGNC ID | 6148 |
| Aliases | CD11A, LFA-1, LFA1A, integrin alpha-L |
Description
ITGAL encodes the integrin alpha L (CD11a) subunit, which non-covalently associates with integrin beta-2 (CD18, encoded by ITGB2) to form the leukocyte function-associated antigen-1 (LFA-1) heterodimer. LFA-1 is a key adhesion receptor expressed on all leukocytes, mediating cell-cell interactions, leukocyte extravasation, and immune synapse formation. ITGAL is essential for immune responses, and mutations cause leukocyte adhesion deficiency type 1 (LAD1), characterized by recurrent bacterial infections and impaired wound healing. The gene is also a target for therapeutic antibodies in autoimmune diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Leukocyte adhesion deficiency type 1 (LAD1) | Loss-of-function mutations in ITGAL impair LFA-1 expression or function, preventing leukocyte adhesion to endothelial cells and migration to infection sites. | ClinVar: Pathogenic variants; OMIM: 153370 (allelic variant); PMID: 2566310, 1671266 |
| Autoimmune diseases (e.g., psoriasis, rheumatoid arthritis) | Overactive LFA-1 contributes to chronic inflammation; therapeutic blockade of ITGAL (e.g., efalizumab) modulates T-cell trafficking. | Clinical trials; PMID: 18362955 |
| Recurrent bacterial infections (non-LAD1) | Hypomorphic ITGAL variants may cause milder adhesion defects, increasing susceptibility to infections. | Case reports; PMID: 23505062 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymphoid tissues (spleen, lymph node) | ~50-100 | High |
| Bone marrow | ~30-50 | Medium |
| Lung | ~20-40 | Medium |
| Blood (leukocytes) | ~80-120 | High |
| Liver | ~5-10 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Jurkat (T-cell leukemia) | ~120 | High expression; used for LFA-1 studies |
| Raji (Burkitt lymphoma) | ~90 | High expression; B-cell line |
| THP-1 (monocytic leukemia) | ~70 | Moderate-high; monocyte-like |
| HeLa (cervical carcinoma) | ~5 | Low; non-leukocyte line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.817C>T (p.Arg273Ter) | Nonsense | Rare (found in LAD1 patients) | Truncated protein; loss of function |
| c.562G>A (p.Gly188Arg) | Missense | Rare (LAD1) | Disrupts integrin folding; loss of function |
| c.1135A>G (p.Thr379Ala) | Missense | Rare (LAD1) | Impairs heterodimer formation; loss of function |
| c.1775G>A (p.Arg592His) | Missense | Rare (LAD1) | Reduced surface expression; loss of function |
Mutation functional classification
Loss of Function (LOF)
Most ITGAL mutations are loss-of-function, leading to reduced or absent LFA-1 expression, causing LAD1.
Gain of Function (GOF)
No gain-of-function mutations reported in ITGAL; constitutive activation is rare and not clinically documented.
Dominant Negative (DN)
Not reported; ITGAL mutations are typically autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • integrin binding | • protein binding |
| • cell adhesion molecule binding | • receptor activity |
| • integrin-mediated signaling pathway | • cell adhesion |
| • leukocyte migration | • immune response |
| • extracellular matrix organization | • plasma membrane |
Pathways
• Integrin signaling pathway (KEGG: hsa04510)
• Leukocyte transendothelial migration (KEGG: hsa04670)
• T cell receptor signaling pathway (KEGG: hsa04660)
• Fc gamma R-mediated phagocytosis (KEGG: hsa04666)
• Regulation of actin cytoskeleton (KEGG: hsa04810)
Protein Summary
The ITGAL protein (CD11a) is a 1,170-amino-acid type I transmembrane glycoprotein with a large extracellular domain containing seven N-terminal repeats, a von Willebrand factor type A domain, and a cytoplasmic tail involved in inside-out signaling. It forms the alpha subunit of LFA-1, which binds ICAM-1/2/3 on endothelial cells and antigen-presenting cells. The protein is critical for leukocyte adhesion, migration, and immune synapse formation. Post-translational modifications include glycosylation and phosphorylation, regulating activation states.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ITGAL Knockout HEK293 Cell Line | EDJ-KQ1350 | Human | 3683 | Details Get a Quote |
| ITGAL Knockout HeLa Cell Line | EDJ-KQ53677 | Human | 3683 | Details Get a Quote |
| ITGAL Knockout A-549 Cell Line | EDJ-KQ62153 | Human | 3683 | Details Get a Quote |
| ITGAL Knockout HCT 116 Cell Line | EDJ-KQ70642 | Human | 3683 | Details Get a Quote |
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