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COL4A4 gene

collagen type IV alpha 4 chain
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Normal Function

The COL4A4 gene provides instructions for making one component of type IV collagen, which is a flexible protein. Specifically, this gene makes the alpha4(IV) chain of type IV collagen. This chain combines with two other types of alpha (IV) chains (the alpha3 and alpha5 chains) to make a complete type IV collagen molecule. Type IV collagen molecules attach to each other to form complex protein networks. These networks make up a large portion of basement membranes, which are thin sheet-like structures that separate and support cells in many tissues. Type IV collagen alpha3-4-5 networks play an especially important role in the basement membranes of the kidney, inner ear, and eye.

Health Conditions Related to Genetic Changes

Alport syndrome

More than 20 mutations in the COL4A4 gene have been found to cause Alport syndrome. Most of these mutations change single protein building blocks (amino acids) in a region where the alpha4(IV) collagen chain combines with other type IV collagen chains. Other mutations in the COL4A4 gene severely decrease or prevent the production of alpha4(IV) chains. As a result, there is a serious deficiency of the type IV collagen alpha3-4-5 network in the basement membranes of the kidney, inner ear, and eye. In the kidney, other types of collagen accumulate in the basement membranes, eventually leading to scarring of the kidneys and kidney failure. Mutations in this gene can also lead to abnormal function in the inner ear, resulting in hearing loss.

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Keratoconus

MedlinePlus Genetics provides information about Keratoconus

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Other disorders

Mutations in the COL4A4 gene have been found to cause thin basement membrane nephropathy. This condition typically causes people to have blood in their urine (hematuria) but no other signs or symptoms of kidney disease. In the past, this condition was often called benign familial hematuria. Thin basement membrane nephropathy rarely progresses to kidney failure.

Other Names for This Gene

  • alpha 4 type IV collagen
  • CA44
  • CO4A4_HUMAN
  • Collagen IV, alpha-4 polypeptide
  • collagen of basement membrane, alpha-4 chain
  • collagen type IV alpha 4
  • collagen, type IV, alpha 4

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Research Resources

References

  • Buzza M, Dagher H, Wang YY, Wilson D, Babon JJ, Cotton RG, Savige J. Mutations in the COL4A4 gene in thin basement membrane disease. Kidney Int. 2003 Feb;63(2):447-53. Citation on PubMed
  • Gregory MC. The clinical features of thin basement membrane nephropathy. Semin Nephrol. 2005 May;25(3):140-5. Review. Citation on PubMed
  • Gross O, Netzer KO, Lambrecht R, Seibold S, Weber M. Novel COL4A4 splice defect and in-frame deletion in a large consanguine family as a genetic link between benign familial haematuria and autosomal Alport syndrome. Nephrol Dial Transplant. 2003 Jun;18(6):1122-7. Citation on PubMed
  • Kashtan CE. Alport Syndrome. 2001 Aug 28 [updated 2019 Feb 21]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from http://www.ncbi.nlm.nih.gov/books/NBK1207/ Citation on PubMed
  • Kashtan CE. Alport syndrome. An inherited disorder of renal, ocular, and cochlear basement membranes. Medicine (Baltimore). 1999 Sep;78(5):338-60. Review. Citation on PubMed
  • 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 AO, Conti M, Fasciolo F, Arrondel C, Heidet L, Renieri A, De Marchi M. COL4A3/COL4A4 mutations: from familial hematuria to autosomal-dominant or recessive Alport syndrome. Kidney Int. 2002 Jun;61(6):1947-56. Citation on PubMed
  • Pescucci C, Mari F, Longo I, Vogiatzi P, Caselli R, Scala E, Abaterusso C, Gusmano R, Seri M, Miglietti N, Bresin E, Renieri A. Autosomal-dominant Alport syndrome: natural history of a disease due to COL4A3 or COL4A4 gene. Kidney Int. 2004 May;65(5):1598-603. Citation on PubMed
  • Rana K, Wang YY, Buzza M, Tonna S, Zhang KW, Lin T, Sin L, Padavarat S, Savige J. The genetics of thin basement membrane nephropathy. Semin Nephrol. 2005 May;25(3):163-70. Review. Citation on PubMed
  • Slajpah M, Gorinsek B, Berginc G, Vizjak A, Ferluga D, Hvala A, Meglic A, Jaksa I, Furlan P, Gregoric A, Kaplan-Pavlovcic S, Ravnik-Glavac M, Glavac D. Sixteen novel mutations identified in COL4A3, COL4A4, and COL4A5 genes in Slovenian families with Alport syndrome and benign familial hematuria. Kidney Int. 2007 Jun;71(12):1287-95. Epub 2007 Mar 28. Citation on PubMed
  • Tazón Vega B, Badenas C, Ars E, Lens X, Milà M, Darnell A, Torra R. Autosomal recessive Alport's syndrome and benign familial hematuria are collagen type IV diseases. Am J Kidney Dis. 2003 Nov;42(5):952-9. Citation on PubMed
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