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Gene Review

COL4A2  -  collagen, type IV, alpha 2

Homo sapiens

Synonyms: Collagen alpha-2(IV) chain, DKFZp686I14213, FLJ22259, ICH, POREN2
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Disease relevance of COL4A2

  • An additional negative regulatory element has now been identified within the third intron of the COL4A2 gene which is able to inhibit transcription of both COL4 genes from their shared promoter, as well as the nonrelated herpes simplex virus thymidine kinase promoter [1].

High impact information on COL4A2

  • Thus, both genes are expressed in a tissue-specific manner, perhaps due to the unique function of the bidirectional promoter for both genes, which is presumably different from that for COL4A1 and COL4A2 [2].
  • The genes for the alpha-1 and alpha-2 chains of type IV collagen (COL4A1 and COL4A2) map to the same chromosomal band (13q34) and have a high degree of nucleotide homology [3].
  • COL4A2, the precursor for an angiogenesis inhibitor, canstatin, was increased relative to myometrium [4].
  • The gene organization of the region coding for the NCl domain is similar to that of the human genes COL4A2, COL4A4 and COL4A6 [5].
  • CONCLUSION: This high-resolution analysis allowed us to propose novel candidate target genes such as STIM2 at 4p15, and TNFSF13B or COL4A2 at 13q32-34 that could potentially contribute to the pathogenesis of these tumors and which would require futher investigations [6].

Biological context of COL4A2

  • The two genes COL4A1 and COL4A2 that code for the subunits are found closely linked on chromosome 13 in a head-to-head arrangement and are transcribed in divergent directions [7].
  • Genes encoding the alpha 1(IV) and alpha 2(IV) chains (COL4A1 and COL4A2) both map to human chromosome 13q34 and have been shown to be transcribed from opposite DNA strands using a common bidirectional promoter that allows coordinate regulation of the two chains [8].
  • The common promoter region of the human collagen type IV genes COL4A1 and COL4A2 comprises a C5TC7 sequence ('CTC box') which is specifically recognized by the recently identified transcription factor CTC box binding factor (CTCBF) involved in the control of divergent transcription of the two genes [9].
  • The lack of linkage disequilibrium between COL4A1 and COL4A2 is in agreement with the relatively high recombination that is observed [10].
  • The two subunit genes COL4A1 and COL4A2 are found closely linked in the human and murine genomes and are transcribed divergently from a common promoter [1].

Analytical, diagnostic and therapeutic context of COL4A2


  1. Identification and characterization of a novel transcriptional silencer in the human collagen type IV gene COL4A2. Haniel, A., Welge-Lüssen, U., Kühn, K., Pöschl, E. J. Biol. Chem. (1995) [Pubmed]
  2. Differential expression of two basement membrane collagen genes, COL4A6 and COL4A5, demonstrated by immunofluorescence staining using peptide-specific monoclonal antibodies. Ninomiya, Y., Kagawa, M., Iyama, K., Naito, I., Kishiro, Y., Seyer, J.M., Sugimoto, M., Oohashi, T., Sado, Y. J. Cell Biol. (1995) [Pubmed]
  3. Macrorestriction mapping of COL4A1 and COL4A2 collagen genes on human chromosome 13q34. Cutting, G.R., Kazazian, H.H., Antonarakis, S.E., Killen, P.D., Yamada, Y., Francomano, C.A. Genomics (1988) [Pubmed]
  4. Fibroids display an anti-angiogenic gene expression profile when compared with adjacent myometrium. Weston, G., Trajstman, A.C., Gargett, C.E., Manuelpillai, U., Vollenhoven, B.J., Rogers, P.A. Mol. Hum. Reprod. (2003) [Pubmed]
  5. Type IV collagen in sponges, the missing link in basement membrane ubiquity. Boute, N., Exposito, J.Y., Boury-Esnault, N., Vacelet, J., Noro, N., Miyazaki, K., Yoshizato, K., Garrone, R. Biol. Cell (1996) [Pubmed]
  6. Identification of novel candidate target genes in amplicons of Glioblastoma multiforme tumors detected by expression and CGH microarray profiling. Ruano, Y., Mollejo, M., Ribalta, T., Fia??o, C., Camacho, F.I., G??mez, E., de Lope, A.R., Hern??ndez-Moneo, J.L., Mart??nez, P., Mel??ndez, B. Mol. Cancer (2006) [Pubmed]
  7. Identification of a novel sequence element in the common promoter region of human collagen type IV genes, involved in the regulation of divergent transcription. Fischer, G., Schmidt, C., Opitz, J., Cully, Z., Kühn, K., Pöschl, E. Biochem. J. (1993) [Pubmed]
  8. Colocalization of the genes for the alpha 3(IV) and alpha 4(IV) chains of type IV collagen to chromosome 2 bands q35-q37. Mariyama, M., Zheng, K., Yang-Feng, T.L., Reeders, S.T. Genomics (1992) [Pubmed]
  9. Purification of the sequence-specific transcription factor CTCBF, involved in the control of human collagen IV genes: subunits with homology to Ku antigen. Genersch, E., Eckerskorn, C., Lottspeich, F., Herzog, C., Kühn, K., Pöschl, E. EMBO J. (1995) [Pubmed]
  10. High recombination between two physically close human basement membrane collagen genes at the distal end of chromosome 13q. Bowcock, A.M., Hebert, J.M., Wijsman, E., Gadi, I., Cavalli-Sforza, L.L., Boyd, C.D. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
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