COL4A1 and COL4A2 mutations and disease: insights into pathogenic mechanisms and potential therapeutic targets

Hum Mol Genet. 2012 Oct 15;21(R1):R97-110. doi: 10.1093/hmg/dds346. Epub 2012 Aug 21.


Heterotrimers composed of collagen type IV alpha 1 (COL4A1) and alpha 2 (COL4A2) constitute one of the most abundant components of nearly all basement membranes. Accordingly, mutations in COL4A1 or COL4A2 are pleiotropic and contribute to a broad spectrum of disorders, including myopathy, glaucoma and hemorrhagic stroke. Here, we summarize the contributions of COL4A1 and COL4A2 mutations in human disease, integrate knowledge gained from model organisms and evaluate the implications for pathogenic mechanisms and therapeutic approaches.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Basement Membrane / metabolism
  • Biological Transport
  • Collagen Type IV / chemistry
  • Collagen Type IV / genetics*
  • Collagen Type IV / metabolism
  • Genetic Predisposition to Disease
  • Glaucoma / genetics*
  • Humans
  • Mice
  • Molecular Targeted Therapy
  • Muscular Diseases / genetics*
  • Mutation
  • Phenotype
  • Protein Multimerization
  • Stroke / genetics*


  • COL4A1 protein, human
  • COL4A2 protein, human
  • Collagen Type IV