HGNC Approved Gene Symbol: COL8A1
Cytogenetic location: 3q12.1 Genomic coordinates (GRCh38): 3:99,638,594-99,799,217 (from NCBI)
Type VIII collagen molecules, expressed by corneal and vascular endothelial cells, are heterotrimers composed of 2 genetically distinct polypeptides, alpha-1(VIII) and alpha-2(VIII) (COL8A2; 120252), in the ratio of 2:1. Collagen VIII is a member of the 'short chain collagen' gene family. It is a major component of the hexagonal lattice in the Descemet membrane (Muragaki et al., 1991).
By sequence analysis of a cDNA isolated from a library made with mRNA from rabbit corneal endothelial cells, Yamaguchi et al. (1989) identified the alpha-1 type VIII collagen polypeptide consisting of a triple-helical domain of 454 amino acids flanked by nontriple-helical domains of 117 and 173 amino acids at the N- and C-terminal ends, respectively. Because of similarities of the alpha-1(VIII) collagen to parts of chicken alpha-1(X) collagen, Yamaguchi et al. (1989) suggested that the triple-helix coding portions and carboxyl three-quarters of the NC1 domains of the COL8A1 and COL10A1 (120110) genes have a common evolutionary origin.
Muragaki et al. (1991) isolated human genomic DNA encoding the alpha-1(VIII) collagen chain. The deduced protein contains a triple-helical domain (COL1) of 454 amino acid residues that lies between a short N-terminal nontriple-helical domain (NC2, 117 residues including a signal peptide) and a longer C-terminal nontriple-helical domain (NC1, 173 residues). The human and rabbit sequences share 94.1% similarity. Because of the relatively small size of the triple-helical domain, types VIII and X collagen have been called 'short chain collagens.'
Using a gene fragment as a probe, Muragaki et al. (1992) performed Northern blot hybridization analysis of RNA prepared from newborn mice and demonstrated that Col8a1 mRNA is expressed in the calvarium, eye, and skin. In situ hybridization demonstrated Col8a1 RNA in skin keratinocytes, corneal epithelial and endothelial cells, lens epithelial cells, as well as in mesenchymal cells surrounding cartilage and calvarial bone and in the meninges surrounding the brain.
In the rabbit, the COL8A1 gene consists of only 4 exons, one of which is large and encodes the entire triple-helical and carboxyl nontriple-helical domains. Muragaki et al. (1991) demonstrated that the structure of the human COL8A1 gene is identical to that of the rabbit.
By in situ hybridization, Muragaki et al. (1991) mapped the COL8A1 gene to 3q12-q13.1.
Associations Pending Confirmation
For discussion of a possible association between variation near the COL8A1 gene and age-related macular degeneration, see ARMD1 (603075).
Yamaguchi et al. (1989) noted that type VIII collagen was first detected and designated EC (endothelial cell) collagen in biosynthetic studies of bovine aortic endothelial cells and rabbit corneal endothelial cells.
Muragaki, Y., Mattei, M.-G., Yamaguchi, N., Olsen, B. R., Ninomiya, Y. The complete primary structure of the human alpha-1(VIII) chain and assignment of its gene (COL8A1) to chromosome 3. Europ. J. Biochem. 197: 615-622, 1991. [PubMed: 2029894] [Full Text: https://doi.org/10.1111/j.1432-1033.1991.tb15951.x]
Muragaki, Y., Shiota, C., Inoue, M., Ooshima, A., Olsen, B. R., Ninomiya, Y. Alpha-1(VIII)-collagen gene transcripts encode a short-chain collagen polypeptide and are expressed by various epithelial, endothelial and mesenchymal cells in newborn mouse tissues. Europ. J. Biochem. 207: 895-902, 1992. [PubMed: 1499564] [Full Text: https://doi.org/10.1111/j.1432-1033.1992.tb17122.x]
Yamaguchi, N., Benya, P. D., van der Rest, M., Ninomiya, Y. The cloning and sequencing of alpha-1(VIII) collagen cDNAs demonstrate that type VIII collagen is a short chain collagen and contains triple-helical and carboxyl-terminal non-triple-helical domains similar to those of type X collagen. J. Biol. Chem. 264: 16022-16029, 1989. [PubMed: 2476437]