ITGA4 Gene - Integrin Subunit Alpha 4
Key mediator of cell adhesion and migration in immune and hematopoietic systems
Gene Information Card
| Symbol | ITGA4 |
|---|---|
| Full Name | Integrin Subunit Alpha 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 2q31.3 |
| NCBI Gene ID | 3676 ncbi.nlm.nih.gov/gene/3676 |
| Ensembl ID | ENSG00000115232 |
| UniProt ID | P13612 |
| OMIM ID | 192975 |
| HGNC ID | 6140 |
| Aliases | CD49d, VLA-4, IA4 |
Description
ITGA4 encodes integrin alpha 4, a transmembrane glycoprotein that non-covalently associates with beta 1 (ITGB1) or beta 7 (ITGB7) subunits to form integrin receptors VLA-4 (α4β1) and α4β7. These receptors mediate cell adhesion to vascular cell adhesion molecule 1 (VCAM1) and mucosal addressin cell adhesion molecule 1 (MAdCAM-1), playing critical roles in lymphocyte homing, hematopoiesis, and immune surveillance.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Multiple sclerosis | α4 integrin facilitates lymphocyte migration across the blood-brain barrier; blockade by natalizumab reduces CNS inflammation | ClinVar, OMIM |
| Ulcerative colitis | α4β7 integrin mediates gut-homing of lymphocytes; vedolizumab targets α4β7 to reduce intestinal inflammation | ClinVar, OMIM |
| Crohn disease | Similar mechanism to ulcerative colitis; anti-α4 integrin therapy used in refractory cases | ClinVar, OMIM |
| Hematopoietic stem cell mobilization | ITGA4 expression on stem cells retains them in bone marrow; downregulation facilitates mobilization | NCBI Gene, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymphoid tissue | 45.2 | High |
| Bone marrow | 38.7 | High |
| Spleen | 32.1 | High |
| Lung | 12.5 | Medium |
| Small intestine | 10.8 | Medium |
| Liver | 2.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Jurkat (T-cell leukemia) | 62.4 | High expression; model for T-cell adhesion |
| Raji (Burkitt lymphoma) | 55.1 | High expression; B-cell model |
| THP-1 (monocytic leukemia) | 48.9 | High expression; monocyte adhesion studies |
| HEK293 (embryonic kidney) | 1.2 | Low endogenous expression; used for transfection |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234G>A (p.Gly412Arg) | Missense | 0.01% | Reduced ligand binding; associated with altered immune cell adhesion |
| c.567_569del (p.Glu189del) | In-frame deletion | 0.005% | Loss of function; impaired integrin dimerization |
| c.2101C>T (p.Arg701Trp) | Missense | 0.02% | Gain of function; enhanced VCAM1 binding |
Mutation functional classification
Loss of Function (LOF)
Mutations that disrupt α4 integrin dimerization or ligand binding, leading to impaired cell adhesion and migration (e.g., p.Glu189del).
Gain of Function (GOF)
Mutations that increase affinity for VCAM1 or MAdCAM-1, potentially enhancing inflammatory cell recruitment (e.g., p.Arg701Trp).
Dominant Negative (DN)
Not well documented for ITGA4; most reported mutations are recessive or haploinsufficient.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Integrin signaling pathway (KEGG: hsa04510)
• Cell adhesion molecules (CAMs) (KEGG: hsa04514)
• Hematopoietic cell lineage (KEGG: hsa04640)
• Focal adhesion (KEGG: hsa04510)
Protein Summary
Integrin alpha 4 (CD49d) is a 1036-amino acid type I transmembrane protein with an extracellular domain containing seven FG-GAP repeats, a transmembrane domain, and a short cytoplasmic tail. It forms heterodimers with beta 1 (ITGB1) to create VLA-4 (α4β1) or with beta 7 (ITGB7) to create α4β7. These receptors bind VCAM1 and MAdCAM-1, respectively, mediating lymphocyte adhesion to endothelium and homing to lymphoid tissues and mucosal sites. The protein is heavily glycosylated and requires calcium ions for proper conformation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ITGA4 Knockout HEK293 Cell Line | EDJ-KQ17702 | Human | 3676 | Details Get a Quote |
| ITGA4 Knockout HeLa Cell Line | EDJ-KQ19556 | Human | 3676 | Details Get a Quote |
| ITGA4 Knockout A-549 Cell Line | EDJ-KQ62149 | Human | 3676 | Details Get a Quote |
| ITGA4 Knockout HCT 116 Cell Line | EDJ-KQ70638 | Human | 3676 | Details Get a Quote |
