Genetic Basis of Type IV Collagen Disorders of the Kidney

Clin J Am Soc Nephrol. 2021 Jul;16(7):1101-1109. doi: 10.2215/CJN.19171220. Epub 2021 Apr 13.


The glomerular basement membrane is a vital component of the filtration barrier of the kidney and is primarily composed of a highly structured matrix of type IV collagen. Specific isoforms of type IV collagen, the α3(IV), α4(IV), and α5(IV) isoforms, assemble into trimers that are required for normal glomerular basement membrane function. Disruption or alteration in these isoforms leads to breakdown of the glomerular basement membrane structure and function and can lead to progressive CKD known as Alport syndrome. However, there is wide variability in phenotype among patients with mutations affecting type IV collagen that depends on a complex interplay of sex, genotype, and X-chromosome inactivation. This article reviews the genetic basis of collagen disorders of the kidney as well as potential treatments for these conditions, including direct alteration of the DNA, RNA therapies, and manipulation of collagen proteins.

Keywords: Alport syndrome; collagen diseases; gene therapy; kidney genomics series; type IV collagen.

Publication types

  • Review

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Animals
  • Collagen Type IV / genetics*
  • Gene Editing
  • Genetic Therapy
  • Humans
  • Molecular Chaperones / therapeutic use
  • Nephritis, Hereditary / complications
  • Nephritis, Hereditary / genetics*
  • Nephritis, Hereditary / therapy*
  • Protein Isoforms / genetics
  • RNA Interference
  • RNA, Small Interfering / therapeutic use
  • mRNA Vaccines / therapeutic use


  • Angiotensin-Converting Enzyme Inhibitors
  • Collagen Type IV
  • Molecular Chaperones
  • Protein Isoforms
  • RNA, Small Interfering
  • mRNA Vaccines