Complement factor H-related protein 1 (CFHR1)

Complement factor H-related protein 1 (CFHR1) is a secreted glycoprotein of the factor H family, composed mainly of short consensus repeats (SCRs) and encoded within the regulators of complement activation gene cluster on chromosome 1. CFHR1 modulates the alternative pathway of the complement system, primarily by binding to the complement protein C3b and its fragment C3d, thereby competing with factor H—a key negative regulator. Through this competition, CFHR1 can act as an antagonist of factor H, potentially promoting or deregulating complement activation on surfaces. Genetic variations (deletion, duplication, SNPs) in CFHR1 influence susceptibility to inflammatory, renal, and ocular diseases. CFHR1 itself is not an enzymatic drug target, but its modulation and its genetic status are critical for disease mechanisms involving complement dysregulation; as such, it is relevant in the context of complement-targeted therapeutics and as a biomarker for certain pathologies.

Other names

CFHR1Factor H-like protein 1FHR-1Complement factor H-related protein 1H factor-like 1H-factor-like 1H36-1H36-2HFL1HFL2CFHL1CFHL1PCFHR1PFHR1

For drugs modulating the complement pathway, the mechanism often involves inhibition of the terminal complement complex (C5) or upstream complement factors to prevent uncontrolled complement activity. For potential CFHR1-targeting biologics, the mechanism would likely involve competitive inhibition or modulation of CFHR1's interaction with C3b/C3d to restore factor H function. Additionally, some genetic variants (deletion or duplication) impact complement regulation by altering CFHR1’s ability to compete with factor H.