ITGB4 Gene: Integrin Subunit Beta 4
Key mediator of hemidesmosome assembly, epithelial integrity, and signaling in development and cancer.
Gene Information Card
| Symbol | ITGB4 |
|---|---|
| Full Name | Integrin Subunit Beta 4 |
| Gene Type | protein coding |
| Chromosomal Location | 17q25.1 |
| NCBI Gene ID | 3691 ncbi.nlm.nih.gov/gene/3691 |
| Ensembl ID | ENSG00000132470 |
| UniProt ID | P16144 |
| OMIM ID | 147557 |
| HGNC ID | 6158 |
| Aliases | CD104, GP150 |
Description
ITGB4 encodes the integrin beta-4 subunit, which pairs with integrin alpha-6 to form the α6β4 integrin, a major receptor for laminins. This integrin is a critical component of hemidesmosomes, anchoring epithelial cells to the basement membrane. Beyond adhesion, ITGB4 participates in signaling pathways that regulate cell survival, proliferation, and migration, with implications in development and cancer progression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Epidermolysis Bullosa (Junctional, with Pyloric Atresia) | Loss-of-function mutations in ITGB4 disrupt hemidesmosome formation, leading to skin fragility and blistering. | ClinVar; OMIM |
| Epidermolysis Bullosa (Non-Herlitz Junctional) | Mutations affecting ITGB4 impair basement membrane adhesion, causing chronic skin blistering. | ClinVar; OMIM |
| Cancer (various types, e.g., breast, pancreatic) | Overexpression or altered signaling of ITGB4 promotes tumor invasion and metastasis via PI3K/Akt and other pathways. | COSMIC; PubMed (via NCBI) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | High | High |
| Esophagus | High | High |
| Breast | Medium | Medium |
| Lung | Medium | Medium |
| Liver | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (Lung) | Medium | Epithelial-like expression |
| MCF7 (Breast) | High | Strong expression in adherent cells |
| HeLa (Cervical) | Medium | Detected in epithelial lines |
| HepG2 (Liver) | Low | Low expression in hepatocyte lines |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.3979C>T (p.Arg1327Ter) | Nonsense | Rare | Loss of function; causes junctional epidermolysis bullosa with pyloric atresia |
| c.433G>A (p.Gly145Arg) | Missense | Rare | Impairs integrin function; associated with skin fragility |
| c.3793G>A (p.Glu1265Lys) | Missense | Rare | Alters ligand binding; linked to non-Herlitz junctional epidermolysis bullosa |
Mutation functional classification
Loss of Function (LOF)
Most ITGB4 mutations are loss-of-function, leading to defective hemidesmosome assembly and skin blistering.
Gain of Function (GOF)
Gain-of-function mutations are rare; some cancer-associated variants may enhance signaling but are not well characterized.
Dominant Negative (DN)
Dominant-negative effects have been suggested in some missense mutations that disrupt heterodimer formation, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • integrin-mediated signaling pathway | • cell adhesion |
| • hemidesmosome assembly | • extracellular matrix organization |
| • cell-matrix adhesion | • laminin binding |
| • protein heterodimerization activity |
Pathways
• PI3K-Akt signaling pathway
• Focal adhesion
• ECM-receptor interaction
• Hemidesmosome assembly
Protein Summary
The integrin beta-4 subunit is a type I transmembrane protein with a large cytoplasmic domain (~1000 amino acids) that links to intermediate filaments via plectin and BP230. It forms the α6β4 integrin, which binds laminin-332 in the basement membrane. This interaction is essential for hemidesmosome stability. In addition to structural roles, ITGB4 activates signaling cascades (e.g., PI3K/Akt, MAPK) that promote cell survival and motility, contributing to cancer invasion when dysregulated.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ITGB4 Knockout HEK293 Cell Line | EDJ-KQ819 | Human | 3691 | Details Get a Quote |
| ITGB4 Knockout A-549 Cell Line | EDJ-KQ19571 | Human | 3691 | Details Get a Quote |
| ITGB4 Knockout HCT 116 Cell Line | EDJ-KQ19572 | Human | 3691 | Details Get a Quote |
| ITGB4 Knockout HeLa Cell Line | EDJ-KQ19573 | Human | 3691 | Details Get a Quote |
| ITGB4 Overexpression A-549 Stable Cell Line | EDC90139 | Human | 3691 | Details Get a Quote |
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