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Gene Review

COL4A4  -  collagen, type IV, alpha 4

Homo sapiens

Synonyms: CA44, Collagen alpha-4(IV) chain
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Disease relevance of COL4A4


High impact information on COL4A4


Biological context of COL4A4

  • To investigate, in vivo, the regulation of the expression, assembly, and function of the alpha3alpha4alpha5(IV) protomer, we have generated a yeast artificial chromosome transgenic line of mice carrying the human COL4A3-COL4A4 locus [8].
  • Autosomal dominant AS has been mapped to chromosome 2 in the region of COL4A3 and COL4A4 [9].
  • CONCLUSIONS: This study extends the mutation spectrum of COL4A3 and COL4A4 genes, and suggests a possible relationship between production of abnormal COL IV chains and dominant expression of a continuous spectrum of phenotypes, from ATS to BFH [10].
  • RESULTS: We identified seven previously undescribed COL4A3 mutations: in two genetic compounds and three heterozygotes, and one in COL4A4 [10].
  • DNA sequence analysis of the COL4A4 gene revealed that the Lys325Asn mutation was present in all affected family members, but was absent in all unaffected members and in a random sample of the Sardinian population [11].

Anatomical context of COL4A4


Associations of COL4A4 with chemical compounds

  • A mutation in COL4A4 that changed C to T resulting in an arginine residue being replaced by a stop codon (R1377X) was demonstrated in exon 44, which encodes part of the alpha 4(IV) collagen sequence close to the junction with the noncollagenous domain [3].

Other interactions of COL4A4

  • In view of this relationship and the structural similarities between alpha 1(IV) and alpha 3(IV) and between alpha 2(IV) and alpha 4(IV), we hypothesized that COL4A3 and COL4A4, the genes encoding alpha 3(IV) and alpha 4(IV), respectively, have a genomic organization similar to that of COL4A1 and COL4A2.(ABSTRACT TRUNCATED AT 250 WORDS)[13]
  • METHODS: We analyzed 36 ATS patients for COL4A3 and COL4A4 mutations by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and direct sequencing [10].
  • The autosomal recessive form is caused by mutation in the COL4A3 gene, which encodes the alpha 3 chain of type IV collagen, or in the COL4A4 gene, which encodes the alpha 4 chain of type IV collagen [14].
  • To determine transcription start site for COL4A4 gene, we performed RACE and RNase protection assays, indicating that there are two alternative transcripts presumably derived from two different promoters [15].
  • A DNA analysis of autosomal type IV collagen alpha3 and alpha4 chain genes (COL4A3 and COL4A4) and an immunohistochemical study of type IV collagen alpha1 to alpha6 chains were performed in an inbred family with autosomal recessive Alport's syndrome (AS) [16].

Analytical, diagnostic and therapeutic context of COL4A4


  1. The clinical spectrum of type IV collagen mutations. Lemmink, H.H., Schröder, C.H., Monnens, L.A., Smeets, H.J. Hum. Mutat. (1997) [Pubmed]
  2. Determination of the genomic structure of the COL4A4 gene and of novel mutations causing autosomal recessive Alport syndrome. Boye, E., Mollet, G., Forestier, L., Cohen-Solal, L., Heidet, L., Cochat, P., Grünfeld, J.P., Palcoux, J.B., Gubler, M.C., Antignac, C. Am. J. Hum. Genet. (1998) [Pubmed]
  3. 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]
  4. Thin glomerular basement membrane disease. Frascá, G.M., Onetti-Muda, A., Renieri, A. J. Nephrol. (2000) [Pubmed]
  5. Benign familial hematuria due to mutation of the type IV collagen alpha4 gene. Lemmink, H.H., Nillesen, W.N., Mochizuki, T., Schröder, C.H., Brunner, H.G., van Oost, B.A., Monnens, L.A., Smeets, H.J. J. Clin. Invest. (1996) [Pubmed]
  6. Isolation and sequencing of cDNAs and genomic DNAs encoding the alpha 4 chain of basement membrane collagen type IV and assignment of the gene to the distal long arm of human chromosome 2. Kamagata, Y., Mattei, M.G., Ninomiya, Y. J. Biol. Chem. (1992) [Pubmed]
  7. 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]
  8. A human-mouse chimera of the alpha3alpha4alpha5(IV) collagen protomer rescues the renal phenotype in Col4a3-/- Alport mice. Heidet, L., Borza, D.B., Jouin, M., Sich, M., Mattei, M.G., Sado, Y., Hudson, B.G., Hastie, N., Antignac, C., Gubler, M.C. Am. J. Pathol. (2003) [Pubmed]
  9. Alport syndrome. An inherited disorder of renal, ocular, and cochlear basement membranes. Kashtan, C.E. Medicine (Baltimore) (1999) [Pubmed]
  10. COL4A3/COL4A4 mutations: from familial hematuria to autosomal-dominant or recessive Alport syndrome. Longo, I., Porcedda, P., Mari, F., Giachino, D., Meloni, I., Deplano, C., Brusco, A., Bosio, M., Massella, L., Lavoratti, G., Roccatello, D., Frascá, G., Mazzucco, G., Muda, A.O., Conti, M., Fasciolo, F., Arrondel, C., Heidet, L., Renieri, A., De Marchi, M. Kidney Int. (2002) [Pubmed]
  11. 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]
  12. 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]
  13. 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]
  14. Clinical and molecular diagnosis of Alport syndrome. Kashtan, C.E. Proc. Assoc. Am. Physicians (1995) [Pubmed]
  15. Two genes, COL4A3 and COL4A4 coding for the human alpha3(IV) and alpha4(IV) collagen chains are arranged head-to-head on chromosome 2q36. Momota, R., Sugimoto, M., Oohashi, T., Kigasawa, K., Yoshioka, H., Ninomiya, Y. FEBS Lett. (1998) [Pubmed]
  16. Molecular genetic and immunohistochemical study of autosomal recessive Alport's syndrome. Nomura, S., Naito, I., Fukushima, T., Tokura, T., Kataoka, N., Tanaka, I., Tanaka, H., Osawa, G. Am. J. Kidney Dis. (1998) [Pubmed]
  17. Autosomal-dominant Alport syndrome: natural history of a disease due to COL4A3 or COL4A4 gene. Pescucci, C., Mari, F., Longo, I., Vogiatzi, P., Caselli, R., Scala, E., Abaterusso, C., Gusmano, R., Seri, M., Miglietti, N., Bresin, E., Renieri, A. Kidney Int. (2004) [Pubmed]
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