CFH

CFH stands for complement factor H, a soluble regulatory protein of the immune system that controls the alternative pathway of complement activation. It circulates in plasma, largely produced by the liver, and helps protect host tissues from damage by limiting C3 convertase activity and promoting degradation of C3b on host surfaces.

The CFH protein is encoded by the CFH gene on chromosome 1q32, a member of a gene cluster that includes several CFH-related (CFHR) genes. The mature protein comprises about 20 short consensus repeat (SCR) domains. The N- and C-terminal SCRs mediate regulatory interactions with C3b and host surfaces, while central SCRs contribute to interactions with polyanions such as heparan sulfate, helping position CFH on host cells.

Functionally, CFH inhibits the alternative pathway by two main mechanisms: it acts as a cofactor for factor I-mediated cleavage of C3b and it accelerates the decay of the C3 convertase C3bBb, thereby limiting amplification of the complement cascade on host tissues.

Clinical significance includes associations between CFH variants and disease risk. The common Y402H polymorphism in SCR7 is strongly linked to an increased risk of age-related macular degeneration. Rare CFH mutations and copy-number variations in CFHR genes are associated with atypical hemolytic uremic syndrome and other forms of C3 glomerulopathy, reflecting the importance of precise regulation of complement.

Genetically, the CFH–CFHR region exhibits substantial copy-number variation and complex regulation, with CFHR proteins capable of modulating CFH function. Therapeutically, complement inhibitors and experimental CFH-based approaches are areas of active investigation for treating complement-mediated diseases.