COL4A4
Collagen Type IV Alpha 4 Chain
Gene Information Card
| Symbol | COL4A4 |
|---|---|
| Full Name | Collagen Type IV Alpha 4 Chain |
| Gene Type | Protein coding |
| Chromosomal Location | 2q36.3 |
| NCBI Gene ID | 1286 ncbi.nlm.nih.gov/gene/1286 |
| Ensembl ID | ENSG00000134871 |
| UniProt ID | P53420 |
| OMIM ID | 120131 |
| HGNC ID | 2204 |
| Aliases | CA44, collagen alpha-4(IV) chain |
Description
The COL4A4 gene encodes the alpha-4 chain of type IV collagen, a major structural component of basement membranes. This chain assembles into heterotrimers (e.g., alpha-3-alpha-4-alpha-5) that form the collagen IV network in the glomerular basement membrane, inner ear, and eye. Mutations in COL4A4 cause autosomal recessive Alport syndrome and autosomal dominant hematuria with or without progressive kidney disease.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alport syndrome (autosomal recessive) | Loss-of-function mutations disrupt collagen IV network in glomerular basement membrane, leading to progressive nephritis, sensorineural hearing loss, and ocular abnormalities. | ClinVar, OMIM #203780 |
| Thin basement membrane nephropathy (benign familial hematuria) | Heterozygous COL4A4 mutations cause thinning of glomerular basement membrane, resulting in persistent hematuria with usually preserved kidney function. | ClinVar, OMIM #141200 |
| Hematuria with focal segmental glomerulosclerosis | Some COL4A4 variants predispose to progressive kidney scarring and proteinuria. | ClinVar, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.5 | Medium |
| Lung | 8.3 | Medium |
| Testis | 6.1 | Low |
| Eye (retina) | 5.4 | Low |
| Cochlea | 4.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Podocytes (differentiated) | 15.2 | High expression in glomerular epithelial cells |
| Renal proximal tubule epithelial cells | 7.8 | Moderate expression |
| Lung fibroblasts | 5.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.3979G>A (p.Gly1327Arg) | Missense | Rare | Disrupts collagen triple helix formation; associated with Alport syndrome |
| c.2881+1G>A | Splice donor | Rare | Exon skipping leads to frameshift and loss of function |
| c.4421_4422del (p.Gly1474Valfs*3) | Frameshift deletion | Rare | Premature stop; loss of protein function |
| c.497G>A (p.Gly166Glu) | Missense | Rare | Glycine substitution in collagenous domain; pathogenic |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and splice-site mutations that lead to truncated or absent alpha-4(IV) chain, impairing basement membrane integrity.
Gain of Function (GOF)
Not described for COL4A4.
Dominant Negative (DN)
Missense glycine substitutions in the collagenous domain can interfere with heterotrimer assembly, exerting a dominant-negative effect in heterozygous carriers.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Collagen IV network formation (Reactome: R-HSA-2168880)
• Extracellular matrix organization (Reactome: R-HSA-1474244)
• Integrin cell surface interactions (Reactome: R-HSA-216083)
Protein Summary
The COL4A4 protein (alpha-4 chain of type IV collagen) is 1,690 amino acids long and contains a central collagenous domain with Gly-X-Y repeats flanked by N-terminal 7S domain and C-terminal NC1 domain. It forms heterotrimers with alpha-3 and alpha-5 chains to create the collagen IV scaffold in basement membranes. The NC1 domain mediates chain selection and network assembly. Mutations in the collagenous domain disrupt triple helix stability, while NC1 mutations impair trimerization.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| COL4A4 Knockout HEK293 Cell Line | EDJ-KQ772 | Human | 1286 | Details Get a Quote |
| COL4A4 Knockout A-549 Cell Line | EDJ-KQ19475 | Human | 1286 | Details Get a Quote |
| COL4A4 Knockout HCT 116 Cell Line | EDJ-KQ19476 | Human | 1286 | Details Get a Quote |
| COL4A4 Knockout HeLa Cell Line | EDJ-KQ19477 | Human | 1286 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
