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Gene Review

COL4A5  -  collagen, type IV, alpha 5

Homo sapiens

Synonyms: ASLN, ATS, CA54, Collagen alpha-5(IV) chain
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Disease relevance of COL4A5


Psychiatry related information on COL4A5

  • We observed a family in which two boys were diagnosed with Alport syndrome, elliptocytosis, and mental retardation and carried a large deletion of the Xq22.3-q23 region, encompassing the COL4A5 gene [6].
  • A score (ATS) was calculated by summing the percent lumen narrowing of all main vessels; alcohol consumption was quantitated by questionnaire [7].

High impact information on COL4A5


Chemical compound and disease context of COL4A5


Biological context of COL4A5

  • However, the COL4A5 gene contains 51 exons, or one less than COL4A1 [15].
  • The alpha5(IV) gene (COL4A5) and the alpha6(IV) gene (COL4A6) are on chromosome Xq22 and are regulated by a bidirectional promoter [2].
  • In conclusion, the hypermethylation of the bidirectional promoter region of COL4A5/COL4A6 is one of the events that is responsible for the loss of expression of the alpha5(IV)/alpha6(IV) chains and the remodeling of the epithelial BM during cancer cell invasion [2].
  • Recently, the target for alloantibodies from an X-linked Alport patient with complete COL4A5 gene deletion was determined to be the alpha 3 chain of type IV collagen [16].
  • RESULTS: In four cases with the COL4A5 frameshift or missense mutations, the COL4A5 chain was either lacking from the EBM (male) or showed a focally negative pattern (female) [17].

Anatomical context of COL4A5


Associations of COL4A5 with chemical compounds

  • After systematic analysis of all 51 exons of COL4A5, we have now identified 30 different mutations: 10 glycine substitutions in the triple helical domain of the protein, 9 frameshift mutations, 4 in-frame deletions, 1 start codon, 1 nonsense, and 5 splice-site mutations [22].
  • The second mutation, located in exon 46, substituted a cysteine proximal to the NC1 domain of COL4A5 for an arginine [9].
  • One mutation (G289V) occurred in exon 15 and converted a glycine in a collagenous domain of COL4A5 to a valine [9].
  • In contrast, the xenograft from recipients treated with 5 doses of ATS still contained well-preserved islet tissue with many insulin and glucagon containing cells on the day of graft removal when blood glucose had returned to the hyperglycemic level [23].
  • When transplanted into ATS-treated hamsters, the cells transformed by MNNG (0.01 mug/ml) and Ki-MSV produced tumors but MNNG (0.1 mug/ml) transformed cells did not produce tumors [24].

Other interactions of COL4A5

  • Recently, several mutations in three other collagen genes (COL2A1, COL3A1, and COL4A5) have been found in probands with genetic diseases involving tissues rich in these collagens [25].
  • Approximately 85% of patients with Alport syndrome (hereditary nephritis) have been estimated to have mutations in the X chromosomal COL4A5 collagen gene; the remaining cases are autosomal with mutations in the COL4A3 or COL4A4 genes located on chromosome 2 [26].
  • The results establish the target for the alloantibodies from an autosomal recessive Alport patient with COL4A3 deletion as principally the alpha 3(IV) collagen chain, similar to the post-transplant alloantibodies from X-linked Alport patients with COL4A5 gene deletions [16].
  • Other candidate collagen genes encoding basement membrane collagen (COL4A1/A2 and COL4A5/A6) were excluded by linkage analysis (13q33-q34 and Xq22), or by sequence (COL4A3) [27].
  • X-linked Alport syndrome is much less common than TBMN and can often be identified in family members by its typical clinical features (including retinopathy), a lamellated GBM without the collagen alpha3(IV), alpha4(IV), and alpha5(IV) chains, and by gene linkage studies or the demonstration of a COL4A5 mutation [28].

Analytical, diagnostic and therapeutic context of COL4A5


  1. Deletion of the paired alpha 5(IV) and alpha 6(IV) collagen genes in inherited smooth muscle tumors. Zhou, J., Mochizuki, T., Smeets, H., Antignac, C., Laurila, P., de Paepe, A., Tryggvason, K., Reeders, S.T. Science (1993) [Pubmed]
  2. Loss of expression of type IV collagen alpha5 and alpha6 chains in colorectal cancer associated with the hypermethylation of their promoter region. Ikeda, K., Iyama, K., Ishikawa, N., Egami, H., Nakao, M., Sado, Y., Ninomiya, Y., Baba, H. Am. J. Pathol. (2006) [Pubmed]
  3. Alport syndrome. An inherited disorder of renal, ocular, and cochlear basement membranes. Kashtan, C.E. Medicine (Baltimore) (1999) [Pubmed]
  4. COL4A4 mutation in thin basement membrane disease previously described in Alport syndrome. Buzza, M., Wang, Y.Y., Dagher, H., Babon, J.J., Cotton, R.G., Powell, H., Dowling, J., Savige, J. Kidney Int. (2001) [Pubmed]
  5. Identification of mutations in the COL4A5 collagen gene in Alport syndrome. Barker, D.F., Hostikka, S.L., Zhou, J., Chow, L.T., Oliphant, A.R., Gerken, S.C., Gregory, M.C., Skolnick, M.H., Atkin, C.L., Tryggvason, K. Science (1990) [Pubmed]
  6. FACL4, a new gene encoding long-chain acyl-CoA synthetase 4, is deleted in a family with Alport syndrome, elliptocytosis, and mental retardation. Piccini, M., Vitelli, F., Bruttini, M., Pober, B.R., Jonsson, J.J., Villanova, M., Zollo, M., Borsani, G., Ballabio, A., Renieri, A. Genomics (1998) [Pubmed]
  7. Coronary atherosclerosis and alcohol consumption: angiographic and mortality data. Femia, R., Natali, A., L'Abbate, A., Ferrannini, E. Arterioscler. Thromb. Vasc. Biol. (2006) [Pubmed]
  8. FACL4, encoding fatty acid-CoA ligase 4, is mutated in nonspecific X-linked mental retardation. Meloni, I., Muscettola, M., Raynaud, M., Longo, I., Bruttini, M., Moizard, M.P., Gomot, M., Chelly, J., des Portes, V., Fryns, J.P., Ropers, H.H., Magi, B., Bellan, C., Volpi, N., Yntema, H.G., Lewis, S.E., Schaffer, J.E., Renieri, A. Nat. Genet. (2002) [Pubmed]
  9. Severe alport phenotype in a woman with two missense mutations in the same COL4A5 gene and preponderant inactivation of the X chromosome carrying the normal allele. Guo, C., Van Damme, B., Vanrenterghem, Y., Devriendt, K., Cassiman, J.J., Marynen, P. J. Clin. Invest. (1995) [Pubmed]
  10. De novo mutation in the COL4A5 gene converting glycine 325 to glutamic acid in Alport syndrome. Renieri, A., Seri, M., Myers, J.C., Pihlajaniemi, T., Massella, L., Rizzoni, G., De Marchi, M. Hum. Mol. Genet. (1992) [Pubmed]
  11. A novel frameshift deletion in type IV collagen alpha 5 gene in a juvenile-type Alport syndrome patient: an adenine deletion (2940/2943 del A) in exon 34 of COL4A5. Peissel, B., Rossetti, S., Renieri, A., Galli, L., De Marchi, M., Battini, G., Meroni, M., Sessa, A., Schiavano, S., Pignatti, P.F. Hum. Mutat. (1994) [Pubmed]
  12. Tumor-associated mucin-type glycoprotein (CA54/61) defined by two monoclonal antibodies (MA54 and MA61) in ovarian cancers. Nozawa, S., Yajima, M., Kojima, K., Iizuka, R., Mochizuki, H., Sugawara, T., Iwamori, M., Nagai, Y. Cancer Res. (1989) [Pubmed]
  13. Microbial conversion products of leptomycin B. Kuhnt, M., Bitsch, F., Ponelle, M., Sanglier, J.J., Wang, Y., Wolff, B. Appl. Environ. Microbiol. (1998) [Pubmed]
  14. Sensitivity of FEV1 and indices of flow volume curve in the methacholine test. Mannino, F., Mariotta, S., Anticoli, S., Lambert-Gardini, S., Terzano, C. Allergologia et immunopathologia. (1996) [Pubmed]
  15. Structure of the human type IV collagen COL4A5 gene. Zhou, J., Leinonen, A., Tryggvason, K. J. Biol. Chem. (1994) [Pubmed]
  16. A COL4A3 gene mutation and post-transplant anti-alpha 3(IV) collagen alloantibodies in Alport syndrome. Kalluri, R., van den Heuvel, L.P., Smeets, H.J., Schroder, C.H., Lemmink, H.H., Boutaud, A., Neilson, E.G., Hudson, B.G. Kidney Int. (1995) [Pubmed]
  17. Identification of COL4A5 defects in Alport's syndrome by immunohistochemistry of skin. van der Loop, F.T., Monnens, L.A., Schröder, C.H., Lemmink, H.H., Breuning, M.H., Timmer, E.D., Smeets, H.J. Kidney Int. (1999) [Pubmed]
  18. Tissue- and developmental stage-specific activation of alpha 5 and alpha 6(IV) collagen expression in the upper gastrointestinal tract of transgenic mice. Herzog, C., Zhuang, L., Gorgan, L., Segal, Y., Zhou, J. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  19. Ultrastructural, physiological, and molecular defects in the inner ear of a gene-knockout mouse model for autosomal Alport syndrome. Cosgrove, D., Samuelson, G., Meehan, D.T., Miller, C., McGee, J., Walsh, E.J., Siegel, M. Hear. Res. (1998) [Pubmed]
  20. Differential splicing of COL4A5 mRNA in kidney and white blood cells: a complex mutation in the COL4A5 gene of an Alport patient deletes the NC1 domain. Guo, C., Van Damme, B., Van Damme-Lombaerts, R., Van den Berghe, H., Cassiman, J.J., Marynen, P. Kidney Int. (1993) [Pubmed]
  21. Detection of mutations in the COL4A5 gene by analyzing cDNA of skin fibroblasts. Wang, F., Wang, Y., Ding, J., Yang, J. Kidney Int. (2005) [Pubmed]
  22. X-linked Alport syndrome: an SSCP-based mutation survey over all 51 exons of the COL4A5 gene. Renieri, A., Bruttini, M., Galli, L., Zanelli, P., Neri, T., Rossetti, S., Turco, A., Heiskari, N., Zhou, J., Gusmano, R., Massella, L., Banfi, G., Scolari, F., Sessa, A., Rizzoni, G., Tryggvason, K., Pignatti, P.F., Savi, M., Ballabio, A., De Marchi, M. Am. J. Hum. Genet. (1996) [Pubmed]
  23. Human islet xenograft survival in diabetic rats. A functional and immunohistochemical study. Tze, W.J., Tai, J., Cheung, S. Transplantation (1990) [Pubmed]
  24. Characterization of human cells transformed in vitro by N-methyl-N'-nitro-N-nitrosoguanidine. Rhim, J.S., Putman, D.L., Arnstein, P., Huebner, R.J., McAllister, R.M. Int. J. Cancer (1977) [Pubmed]
  25. Mutations in collagen genes: causes of rare and some common diseases in humans. Kuivaniemi, H., Tromp, G., Prockop, D.J. FASEB J. (1991) [Pubmed]
  26. High mutation detection rate in the COL4A5 collagen gene in suspected Alport syndrome using PCR and direct DNA sequencing. Martin, P., Heiskari, N., Zhou, J., Leinonen, A., Tumelius, T., Hertz, J.M., Barker, D., Gregory, M., Atkin, C., Styrkarsdottir, U., Neumann, H., Springate, J., Shows, T., Pettersson, E., Tryggvason, K. J. Am. Soc. Nephrol. (1998) [Pubmed]
  27. Identification of a new mutation in the alpha4(IV) collagen gene in a family with autosomal dominant Alport syndrome and hypercholesterolaemia. Ciccarese, M., Casu, D., Ki Wong, F., Faedda, R., Arvidsson, S., Tonolo, G., Luthman, H., Satta, A. Nephrol. Dial. Transplant. (2001) [Pubmed]
  28. Thin basement membrane nephropathy. Savige, J., Rana, K., Tonna, S., Buzza, M., Dagher, H., Wang, Y.Y. Kidney Int. (2003) [Pubmed]
  29. 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]
  30. Substitution of arginine for glycine 325 in the collagen alpha 5 (IV) chain associated with X-linked Alport syndrome: characterization of the mutation by direct sequencing of PCR-amplified lymphoblast cDNA fragments. Knebelmann, B., Deschenes, G., Gros, F., Hors, M.C., Grünfeld, J.P., Zhou, J., Tryggvason, K., Gubler, M.C., Antignac, C. Am. J. Hum. Genet. (1992) [Pubmed]
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