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Gene Review

COL7A1  -  collagen, type VII, alpha 1

Homo sapiens

Synonyms: Collagen alpha-1(VII) chain, EBD1, EBDCT, EBR1, LC collagen, ...
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Disease relevance of COL7A1


High impact information on COL7A1

  • Dystrophic epidermolysis bullosa (DEB) is a family of inherited mechano-bullous disorders caused by mutations in the human type VII collagen gene (COL7A1) [6].
  • Transduction of lentiviral vectors containing the COL7A1 transgene into recessive DEB (RDEB) keratinocytes and fibroblasts (in which type VII collagen was absent) resulted in persistent synthesis and secretion of type VII collagen [6].
  • Ultrastructural observations of altered anchoring fibrils and genetic linkage to the type VII collagen locus (COL7A1) have implicated COL7A1 as the candidate gene in the dystrophic forms of EB [7].
  • The patients are compound heterozygotes for two different mutations, both of which result in a premature termination codon in COL7A1, and the parents were shown to be clinically heterozygous carries of the respective mutations [7].
  • Since there were no recombinants between the COL7A1 and EBDD loci, our findings suggest that type VII collagen is the candidate gene that may harbor the mutations responsible for the EB phenotype in these three families [8].

Biological context of COL7A1

  • The recessive dystrophic epidermolysis bullosa patients had a homozygous single base-pair frameshift mutation in exon 19 of COL7A1 (2470insG) [9].
  • Finally, the major, if not the exclusive, component of anchoring fibrils is type VII collagen, encoded by the gene (COL7A1) which consists of 118 distinct exons, the largest number of exons in any gene published thus far [10].
  • Inspection of the locations of the glycine substitutions along the COL7A1 polypeptide suggests that the consequences of these mutations, in terms of phenotype and pattern of inheritance, are position independent [11].
  • We have recently demonstrated tight genetic linkage between the type VII collagen gene (COL7A1) and both the dominant and recessive forms of dystrophic EB [12].
  • Patients who were homozygous or compound heterozygotes for mutations leading to PTCs displayed both absence or drastic reduction of COL7A1 transcripts and undetectable type VII collagen protein in skin [13].

Anatomical context of COL7A1

  • Consistent with the normal levels of COL7A1 mRNA transcripts detected by northern analysis, immunoblotting and immunofluorescence studies evidenced that the patient keratinocytes synthesize and secrete normal amounts of stable type VII collagen, which is correctly deposited at the dermal-epidermal junction [14].
  • Mutations in the gene COL7A1 encoding type VII collagen cause dystrophic epidermolysis bullosa, a clinically heterogeneous autosomal dominant or recessive blistering disorder of the skin and mucous membranes [14].
  • Previous studies have shown that pro-inflammatory cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta up-regulate type VII collagen gene (COL7A1) expression in cultured dermal fibroblasts [15].
  • Toenail dystrophy with COL7A1 glycine substitution mutations segregates as an autosomal dominant trait in 2 families with dystrophic epidermolysis bullosa [16].
  • Polymerase chain reaction and sequencing of the cDNA, reverse transcribed from the proband's peripheral lymphocyte RNA, suggest that this mutation causes aberrant COL7A1 mRNA splicing of exon 87 skipping [17].

Associations of COL7A1 with chemical compounds

  • Mutation detection of the COL7A1 gene revealed a G-->A transition at nucleotide position 6110 in the mutant allele converting a glycine to glutamic acid (G2037E) [18].
  • All exons in the COL7A1 triple helix coding region that do not begin with sequences corresponding to imperfections of the triple helix begin with intact codons for Gly residues of Gly-X-Y repeats [19].
  • In this study, we have examined the pharmacological control of COL7A1 gene expression by the glucocorticorticoid dexamethasone [20].
  • To gain insight into the molecular mechanisms underlying the up-regulation of COL7A1 by this growth factor, we performed transient cell transfections with a series of 5'-deletion promoter/chloramphenicol acetyltransferase reporter gene constructs [21].
  • The study revealed a G-to-A transition at nucleotide 6724 within exon 85 of COL7A1, converting a glycine to an arginine (G2242R) within the triple-helical domain of the type VII collagen in affected individuals [22].

Physical interactions of COL7A1

  • Deletion analysis of the TGF-betaresponsive region of the COL7A1 promoter by EMSA identified segment -496/-444 as the minimal fragment capable of binding the TGF-beta-induced complex [21].

Other interactions of COL7A1


Analytical, diagnostic and therapeutic context of COL7A1


  1. Proteinases of the bone morphogenetic protein-1 family convert procollagen VII to mature anchoring fibril collagen. Rattenholl, A., Pappano, W.N., Koch, M., Keene, D.R., Kadler, K.E., Sasaki, T., Timpl, R., Burgeson, R.E., Greenspan, D.S., Bruckner-Tuderman, L. J. Biol. Chem. (2002) [Pubmed]
  2. Pretibial epidermolysis bullosa: genetic linkage to COL7A1 and identification of a glycine-to-cysteine substitution in the triple-helical domain of type VII collagen. Christiano, A.M., Lee, J.Y., Chen, W.J., LaForgia, S., Uitto, J. Hum. Mol. Genet. (1995) [Pubmed]
  3. Comparative mutation detection screening of the type VII collagen gene (COL7A1) using the protein truncation test, fluorescent chemical cleavage of mismatch, and conformation sensitive gel electrophoresis. Whittock, N.V., Ashton, G.H., Mohammedi, R., Mellerio, J.E., Mathew, C.G., Abbs, S.J., Eady, R.A., McGrath, J.A. J. Invest. Dermatol. (1999) [Pubmed]
  4. Fibroblasts show more potential as target cells than keratinocytes in COL7A1 gene therapy of dystrophic epidermolysis bullosa. Goto, M., Sawamura, D., Ito, K., Abe, M., Nishie, W., Sakai, K., Shibaki, A., Akiyama, M., Shimizu, H. J. Invest. Dermatol. (2006) [Pubmed]
  5. Different phenotypes in recessive dystrophic epidermolysis bullosa patients sharing the same mutation in compound heterozygosity with two novel mutations in the type VII collagen gene. Gardella, R., Zoppi, N., Zambruno, G., Barlati, S., Colombi, M. Br. J. Dermatol. (2002) [Pubmed]
  6. Restoration of type VII collagen expression and function in dystrophic epidermolysis bullosa. Chen, M., Kasahara, N., Keene, D.R., Chan, L., Hoeffler, W.K., Finlay, D., Barcova, M., Cannon, P.M., Mazurek, C., Woodley, D.T. Nat. Genet. (2002) [Pubmed]
  7. Premature termination codons on both alleles of the type VII collagen gene (COL7A1) in three brothers with recessive dystrophic epidermolysis bullosa. Christiano, A.M., Suga, Y., Greenspan, D.S., Ogawa, H., Uitto, J. J. Clin. Invest. (1995) [Pubmed]
  8. Genetic linkage of type VII collagen (COL7A1) to dominant dystrophic epidermolysis bullosa in families with abnormal anchoring fibrils. Ryynänen, M., Ryynänen, J., Sollberg, S., Iozzo, R.V., Knowlton, R.G., Uitto, J. J. Clin. Invest. (1992) [Pubmed]
  9. Moderation of phenotypic severity in dystrophic and junctional forms of epidermolysis bullosa through in-frame skipping of exons containing non-sense or frameshift mutations. McGrath, J.A., Ashton, G.H., Mellerio, J.E., Salas-Alanis, J.C., Swensson, O., McMillan, J.R., Eady, R.A. J. Invest. Dermatol. (1999) [Pubmed]
  10. Molecular complexity of the cutaneous basement membrane zone. Uitto, J., Pulkkinen, L. Mol. Biol. Rep. (1996) [Pubmed]
  11. Glycine substitutions in the triple-helical region of type VII collagen result in a spectrum of dystrophic epidermolysis bullosa phenotypes and patterns of inheritance. Christiano, A.M., McGrath, J.A., Tan, K.C., Uitto, J. Am. J. Hum. Genet. (1996) [Pubmed]
  12. Dominant dystrophic epidermolysis bullosa: identification of a Gly-->Ser substitution in the triple-helical domain of type VII collagen. Christiano, A.M., Ryynänen, M., Uitto, J. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  13. Characterization of 18 new mutations in COL7A1 in recessive dystrophic epidermolysis bullosa provides evidence for distinct molecular mechanisms underlying defective anchoring fibril formation. Hovnanian, A., Rochat, A., Bodemer, C., Petit, E., Rivers, C.A., Prost, C., Fraitag, S., Christiano, A.M., Uitto, J., Lathrop, M., Barrandon, Y., de Prost, Y. Am. J. Hum. Genet. (1997) [Pubmed]
  14. Compound heterozygosity for a recessive glycine substitution and a splice site mutation in the COL7A1 gene causes an unusually mild form of localized recessive dystrophic epidermolysis bullosa. Terracina, M., Posteraro, P., Schubert, M., Sonego, G., Atzori, F., Zambruno, G., Bruckner-Tuderman, L., Castiglia, D. J. Invest. Dermatol. (1998) [Pubmed]
  15. Keratinocyte-specific modulation of type VII collagen gene expression by pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-1beta). Takeda, H., Kon, A., Ito, N., Sawamura, D., Takagaki, K., Hashimoto, I., Hanada, K. Exp. Dermatol. (2005) [Pubmed]
  16. Toenail dystrophy with COL7A1 glycine substitution mutations segregates as an autosomal dominant trait in 2 families with dystrophic epidermolysis bullosa. Sato-Matsumura, K.C., Yasukawa, K., Tomita, Y., Shimizu, H. Archives of dermatology. (2002) [Pubmed]
  17. A novel splice site mutation in collagen type VII gene in a Chinese family with dominant dystrophic epidermolysis bullosa pruriginosa. Jiang, W., Bu, D., Yang, Y., Zhu, X. Acta Derm. Venereol. (2002) [Pubmed]
  18. Dominant dystrophic epidermolysis bullosa (Pasini) caused by a novel glycine substitution mutation in the type VII collagen gene (COL7A1). Jonkman, M.F., Moreno, G., Rouan, F., Oranje, A.P., Pulkkinen, L., Uitto, J. J. Invest. Dermatol. (1999) [Pubmed]
  19. Structural organization of the human type VII collagen gene (COL7A1), composed of more exons than any previously characterized gene. Christiano, A.M., Hoffman, G.G., Chung-Honet, L.C., Lee, S., Cheng, W., Uitto, J., Greenspan, D.S. Genomics (1994) [Pubmed]
  20. Downregulation of human type VII collagen (COL7A1) promoter activity by dexamethasone. Identification of a glucocorticoid receptor binding region. Gras, M.P., Verrecchia, F., Uitto, J., Mauviel, A. Exp. Dermatol. (2001) [Pubmed]
  21. Smad-dependent transcriptional activation of human type VII collagen gene (COL7A1) promoter by transforming growth factor-beta. Vindevoghel, L., Kon, A., Lechleider, R.J., Uitto, J., Roberts, A.B., Mauviel, A. J. Biol. Chem. (1998) [Pubmed]
  22. A glycine-to-arginine substitution in the triple-helical domain of type VII collagen in a family with dominant dystrophic epidermolysis bullosa pruriginosa. Lee, J.Y., Pulkkinen, L., Liu, H.S., Chen, Y.F., Uitto, J. J. Invest. Dermatol. (1997) [Pubmed]
  23. SMAD3/4-dependent transcriptional activation of the human type VII collagen gene (COL7A1) promoter by transforming growth factor beta. Vindevoghel, L., Lechleider, R.J., Kon, A., de Caestecker, M.P., Uitto, J., Roberts, A.B., Mauviel, A. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  24. Identification of COL7A1 alternative splicing inserting 9 amino acid residues into the fibronectin type III linker domain. Sawamura, D., Goto, M., Yasukawa, K., Kon, A., Akiyama, M., Shimizu, H. J. Invest. Dermatol. (2003) [Pubmed]
  25. Human type VII collagen: cDNA cloning and chromosomal mapping of the gene. Parente, M.G., Chung, L.C., Ryynänen, J., Woodley, D.T., Wynn, K.C., Bauer, E.A., Mattei, M.G., Chu, M.L., Uitto, J. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  26. Cloning of human type VII collagen. Complete primary sequence of the alpha 1(VII) chain and identification of intragenic polymorphisms. Christiano, A.M., Greenspan, D.S., Lee, S., Uitto, J. J. Biol. Chem. (1994) [Pubmed]
  27. Allelic heterogeneity of dominant and recessive COL7A1 mutations underlying epidermolysis bullosa pruriginosa. Mellerio, J.E., Ashton, G.H., Mohammedi, R., Lyon, C.C., Kirby, B., Harman, K.E., Salas-Alanis, J.C., Atherton, D.J., Harrison, P.V., Griffiths, W.A., Black, M.M., Eady, R.A., McGrath, J.A. J. Invest. Dermatol. (1999) [Pubmed]
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