Table 3.

FHR fusion proteins in familial C3 glomerulopathy

Protein name	Protein structure	Phenotype	Comments	Refs.
Normal proteins
FHR1		NA	Homodimerizes and heterodimerizes with FHR2; competitive antagonist of factor H; C5 convertase inhibitor and terminal complement cascade blocker	42
FHR2		NA	Homodimerizes and heterodimerizes with FHR1; competitive antagonist of factor H; C3 convertase inhibitor	43
FHR3		NA	Exact function unknown	NA
FHR5		NA	Homodimerizes; competitive antagonist of factor H; binds to extracellular matrix; complement amplifier and surface anchor for properdin	44
Fusion proteins
FHR21,2–FHR51–9		DDD	Normal gene copies present in variant allele: CFHR3, CFHR1, CFHR4	45
FHR51,2–FHR51–9		C3GN	Normal gene copies present in variant allele: CFHR3, CFHR1, CFHR4, CFHR2, CFHR5	4,46
FHR31–2–FHR11–5		C3GN	Normal gene copies present in variant allele: CFHR3, CFHR1, CFHR4, CFHR2, CFHR5	47
FHR11,2–FHR51–9		C3GN and/or DDD	Normal gene copies present in variant allele: CFHR3, CFHR5	48
FHR11–4–FHR11–5		C3GN	Normal gene copies present in variant allele: CFHR3, CFHR4, CFHR2, CFHR5	35
FHR51,2–FHR21–4		C3GN	Normal gene copies present in variant allele: CFHR3, CFHR1, CFHR4, CFHR2, CFHR5	36

FHR proteins contain several complement control domains, also termed short consensus repeats (SCRs). FHR1, purple, contains five SCRs (1–5). FHR2, pale blue, contains four SCRs (1–4). FHR3, green, contains five SCRs (1–5). FHR5, orange, contains nine SCRs (1–9). The same SCR numbering is used in the fusion proteins. C, complement component; C3GN, C3 glomerulonephritis; DDD, dense deposit disease; NA not applicable.