COL4A2
Collagen Type IV Alpha 2 Chain
Gene Information Card
| Symbol | COL4A2 |
|---|---|
| Full Name | Collagen Type IV Alpha 2 Chain |
| Gene Type | Protein coding |
| Chromosomal Location | 13q34 |
| NCBI Gene ID | 1284 ncbi.nlm.nih.gov/gene/1284 |
| Ensembl ID | ENSG00000134871 |
| UniProt ID | P08572 |
| OMIM ID | 120090 |
| HGNC ID | 2202 |
| Aliases | ICH, ICH2, POREN2, BSVD, COL4A2 |
Description
The COL4A2 gene encodes the alpha-2 chain of type IV collagen, a major structural component of basement membranes. Type IV collagen forms a network that provides structural support and filtration function in various tissues, including the kidney glomerulus, inner ear, and eye. Mutations in COL4A2 are associated with several vascular and renal disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Brain Small Vessel Disease 2 (BSVD2) | Missense mutations in the collagen triple helix domain disrupt basement membrane integrity in cerebral vessels, leading to hemorrhage and porencephaly. | ClinVar, OMIM |
| Porencephaly 2 (POREN2) | Dominant negative mutations cause defective collagen IV network in brain capillaries, resulting in cystic cavities. | ClinVar, OMIM |
| Hemorrhagic Stroke, Susceptibility to | Variants affecting collagen IV assembly increase fragility of cerebral arteries. | ClinVar, OMIM |
| Alport Syndrome (rare) | Biallelic loss-of-function mutations impair glomerular basement membrane structure, causing progressive nephropathy. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 48.2 | High |
| Lung | 35.1 | High |
| Heart | 28.7 | Medium |
| Brain | 22.4 | Medium |
| Liver | 15.3 | Medium |
| Skeletal Muscle | 10.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 62.5 | High expression in embryonic kidney cells |
| A549 | 45.3 | Lung carcinoma cell line |
| HUVEC | 38.9 | Endothelial cells |
| SH-SY5Y | 18.2 | Neuroblastoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1537G>A (p.Gly513Arg) | Missense | Rare | Dominant negative; disrupts triple helix formation in collagen IV, associated with BSVD2 |
| c.4420G>A (p.Gly1474Arg) | Missense | Rare | Dominant negative; linked to porencephaly and intracerebral hemorrhage |
| c.1978G>A (p.Gly660Arg) | Missense | Rare | Dominant negative; causes vascular fragility in brain small vessel disease |
| c.3505G>A (p.Gly1169Ser) | Missense | Rare | Dominant negative; associated with hemorrhagic stroke |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations (e.g., nonsense, frameshift) lead to reduced collagen IV alpha-2 chain, causing Alport syndrome-like nephropathy.
Gain of Function (GOF)
Not reported for COL4A2.
Dominant Negative (DN)
Most pathogenic missense mutations (glycine substitutions in Gly-X-Y repeats) act via dominant negative mechanism, disrupting collagen IV network assembly and causing vascular fragility.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005587 - collagen type IV trimer | • GO:0005201 - extracellular matrix structural constituent |
| • GO:0031012 - extracellular matrix | • GO:0005604 - basement membrane |
| • GO:0007155 - cell adhesion | • GO:0005515 - protein binding |
Pathways
• Collagen IV network assembly (Reactome: R-HSA-2168880)
• Extracellular matrix organization (Reactome: R-HSA-1474244)
• Basement membrane formation (KEGG: hsa04512)
Protein Summary
The COL4A2 protein (UniProt P08572) is a 1712-amino acid alpha-2 chain of type IV collagen. It contains a central collagen triple helix domain with Gly-X-Y repeats, an N-terminal 7S domain, and a C-terminal NC1 domain. The protein assembles into heterotrimers (alpha-1/alpha-2/alpha-1) that form a network in basement membranes. Post-translational modifications include hydroxylation of proline and lysine residues. Mutations in the triple helix domain are a common cause of dominant-negative vascular disease.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| COL4A2 Knockout HEK293 Cell Line | EDJ-KQ254 | Human | 1284 | Details Get a Quote |
| COL4A2 Knockout A-549 Cell Line | EDJ-KQ19469 | Human | 1284 | Details Get a Quote |
| COL4A2 Knockout HeLa Cell Line | EDJ-KQ19471 | Human | 1284 | Details Get a Quote |
| COL4A2 Knockout HCT 116 Cell Line | EDJ-KQ69913 | Human | 1284 | Details Get a Quote |
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