COL4A1 Gene: Structure, Function, and Associated Diseases

COL4A1 encodes the alpha-1 chain of type IV collagen, a major structural component of basement membranes. This protein forms heterotrimers with alpha-2 chains to create a network that provides mechanical stability and filtration properties to basement membranes in blood vessels, kidneys, eyes, and other tissues. Mutations in COL4A1 cause a spectrum of autosomal dominant disorders affecting small vessels, leading to cerebral hemorrhage, porencephaly, and renal involvement.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Collagen IV network formation (Reactome R-HSA-2168880)

• ECM-receptor interaction (KEGG hsa04512)

• Focal adhesion (KEGG hsa04510)

• PI3K-Akt signaling pathway (KEGG hsa04151)

The COL4A1 protein (alpha-1 type IV collagen) is a 1669-amino acid chain that contains a central triple-helical domain with repeating Gly-X-Y motifs, flanked by N-terminal 7S domain and C-terminal NC1 domain. It assembles into heterotrimers with COL4A2 chains, forming a chicken-wire meshwork essential for basement membrane integrity. Post-translational modifications include hydroxylation of proline and lysine residues. The protein is secreted and incorporated into extracellular matrices of blood vessels, renal glomeruli, ocular lens, and other tissues.