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Complement factor H-related protein 3 (FHR-3)

Target: FHR-3
Molecular classification: Complement regulatory protein family, Plasma glycoprotein, Other (complement-related protein)

Overview

Complement factor H-related protein 3 (FHR-3) is a secreted glycoprotein and a member of the complement factor H (CFH) protein family. FHR-3 shares sequence similarities with CFH but lacks the domains required for classical complement regulatory activity. It binds to C3b and related fragments, potentially enhancing complement activation by competing with CFH for ligand binding. FHR-3 does not show significant cofactor or decay acceleration activity at physiological concentrations, unlike CFH itself. Genetic variations in CFHR3, such as deletions, have been implicated in susceptibility to and protection from several diseases linked to complement dysregulation, including age-related macular degeneration and autoimmune kidney diseases. Despite these associations, FHR-3 is not an established therapeutic target and its precise physiological role remains under investigation[2][3][5].

Other names: CFHR3FHR-3Complement factor H-related 3 protein

Biological functions

Modulation of complement activationCompeting with complement factor H for binding to C3b and related fragmentsPotential deregulation or promotion of alternative pathway (AP) complement activation

Disease associations

Age-related macular degenerationKidney diseases (e.g., IgA nephropathy, atypical hemolytic uremic syndrome)Autoimmune and inflammatory diseases (e.g., systemic lupus erythematosus)Other (evidence is mostly genetically or association-based, not direct causality)

Safety considerations

Dysregulation of FHR-3 (e.g., by copy number variation) may predispose to complement-mediated tissue injuryThe biological functions are still incompletely understood, creating uncertainty in therapeutic approaches

Biomarkers

Genetic deletion of CFHR3 is protective for age-related macular degeneration and associated with other complement-related pathologiesCFHR3-CFHR1 deletions used in genetic risk stratification

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