The spectrum of phenotypes caused by variants in the CFH gene

Mol Immunol. 2009 May;46(8-9):1573-94. doi: 10.1016/j.molimm.2009.02.013. Epub 2009 Mar 17.


Complement factor H (CFH) is a complement inhibitor, which is present as a soluble protein and attached to cell surfaces throughout the human body. As such, CFH is a key player in complement homeostasis, inhibiting excessive activation of the complement cascade, with an emphasis on the alternative pathway. The significance of CFH is demonstrated by the broad range of phenotypes associated with specific CFH gene variants. This phenotypic spectrum includes renal phenotypes, such as membranoproliferative glomerulonephritis and atypical hemolytic uremic syndrome, as well as ocular phenotypes, such as basal laminar drusen and age-related macular degeneration. In addition, several overlapping phenotypes have been described in association with CFH gene variants. The phenotypic outcome of these CFH variants depends on their differential impact on plasma- and surface-bound CFH function. Consequently, distinct genotype-phenotype correlations may be observed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Complement Factor H / chemistry
  • Complement Factor H / genetics*
  • Complement Factor H / metabolism
  • Complement Factor H / physiology
  • Genetic Predisposition to Disease*
  • Glomerulonephritis, Membranoproliferative / genetics
  • Hemolytic-Uremic Syndrome / genetics
  • Humans
  • Models, Biological
  • Phenotype
  • Polymorphism, Single Nucleotide / physiology*
  • Retinal Drusen / complications
  • Retinal Drusen / genetics
  • Signal Transduction / genetics
  • Structure-Activity Relationship


  • Complement Factor H