COL4A6
Collagen Type IV Alpha 6 Chain
Gene Information Card
| Symbol | COL4A6 |
|---|---|
| Full Name | Collagen Type IV Alpha 6 Chain |
| Gene Type | Protein coding |
| Chromosomal Location | Xq22.3 |
| NCBI Gene ID | 1288 ncbi.nlm.nih.gov/gene/1288 |
| Ensembl ID | ENSG00000197565 |
| UniProt ID | Q14031 |
| OMIM ID | 303631 |
| HGNC ID | 2208 |
| Aliases | COL4A6, collagen alpha-6(IV) chain, DKFZp686K03198 |
Description
COL4A6 encodes the alpha-6 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 or alpha-5/alpha-5/alpha-6) that form network-like scaffolds in the glomerular basement membrane, inner ear, and other tissues. Mutations in COL4A6 are associated with X-linked Alport syndrome and diffuse leiomyomatosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alport syndrome, X-linked | Loss-of-function mutations disrupt collagen IV network in glomerular basement membrane, leading to progressive nephritis, sensorineural hearing loss, and ocular abnormalities. | ClinVar, OMIM |
| Diffuse leiomyomatosis with Alport syndrome | Deletions involving COL4A5 and COL4A6 cause smooth muscle tumors (esophageal, genital) and Alport features. | OMIM, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 5.2 | Medium |
| Lung | 3.8 | Low |
| Testis | 2.1 | Low |
| Heart | 1.5 | Low |
| Brain | 0.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 4.5 | Embryonic kidney cells |
| A549 | 3.2 | Lung carcinoma |
| HepG2 | 1.0 | Hepatocellular carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.442G>A (p.Gly148Arg) | Missense | <0.01% | Disrupts Gly-X-Y repeat, destabilizes triple helix |
| c.497_498del (p.Gly166Valfs*2) | Frameshift | <0.01% | Premature stop, loss of function |
| Deletion exons 1-5 | Structural variant | Rare | Complete loss of COL4A6, often contiguous with COL4A5 deletion |
Mutation functional classification
Loss of Function (LOF)
Most COL4A6 mutations (nonsense, frameshift, splice-site) lead to loss of functional alpha-6 chain, impairing basement membrane integrity.
Gain of Function (GOF)
No evidence for gain-of-function mutations in COL4A6.
Dominant Negative (DN)
Missense mutations (e.g., glycine substitutions) can exert dominant-negative effects by incorporating mutant chains into heterotrimers, disrupting network assembly.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Collagen IV network formation (Reactome: R-HSA-2168880)
• ECM-receptor interaction (KEGG: hsa04512)
• Focal adhesion (KEGG: hsa04510)
Protein Summary
The COL4A6 protein (alpha-6(IV) chain) is 1,691 amino acids long with a central collagenous domain containing Gly-X-Y repeats, flanked by N-terminal 7S domain and C-terminal NC1 domain. It forms heterotrimers with other type IV collagen chains, particularly alpha-5, to assemble into basement membrane networks. The protein is essential for structural integrity of kidney glomeruli, cochlea, and smooth muscle layers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| COL4A6 Knockout HEK293 Cell Line | EDJ-KQ774 | Human | 1288 | Details Get a Quote |
| COL4A6 Knockout A-549 Cell Line | EDJ-KQ19481 | Human | 1288 | Details Get a Quote |
| COL4A6 Knockout HCT 116 Cell Line | EDJ-KQ19482 | Human | 1288 | Details Get a Quote |
| COL4A6 Knockout HeLa Cell Line | EDJ-KQ19483 | Human | 1288 | Details Get a Quote |
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