CFI Gene

The CFI gene (CFI stands for "complement factor I" ) is a protein-coding gene located on chromosome 4q25. The CFI gene encodes a serine proteinase that is essential for the regulation of the complement cascade. The encoded preprotein is cleaved. The cleavage products form both a heavy and a light chain linked by disulfide bonds to form a heterodimeric glycoprotein. This heterodimer acts as a protease and is capable of cleaving and inactivating complement components C4b and C3b (see complement system below). Defects in this gene cause complement factor I deficiency, a rare autosomal recessive disease associated with susceptibility to pyogenic infections.

Mutations in the CFI gene have been associated with a predisposition to atypical hemolytic uremic syndrome, a disease characterized by acute renal failure, microangiopathic hemolytic anemia, and thrombocytopenia. Other CFI-associated diseases include:

• Primary C3 glomerulonephritis.
• Age-related macular degeneration 13

Trypsin-like serine protease plays an essential role in regulating the immune response by controlling all complement pathways. It inhibits these pathways by cleaving three peptide bonds in the alpha chain of C3b and two bonds in the alpha chain of C4b, thereby inactivating these proteins.

1. Abramson N et al (1971) Deficiency of C3 inactivator in man. J Immun 107: 19-27.
2. Baracho GV et al (2003) Molecular characterization of homozygous hereditary factor I deficiency. Clin Exp Immun 131: 280-286.
3. Grumach AS et al (2006) Recurrent infections in partial complement factor I deficiency: evaluation of three generations of a Brazilian family. Clin Exp Immun 143: 297-304.
4. Sadallah S et al (1999) Glomerulonephritis in a patient with complement factor I deficiency. Am J Kidney Dis 33: 1153-1157.
5. Servais A et al (2007) Primary glomerulonephritis with isolated C3 deposits: a new entity which shares common genetic risk factors with haemolytic uremic syndrome. J Med Genet 44: 193-199.