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Gene Review:

CFHR5 - complement factor H-related 5

Homo sapiens

Synonyms: CFHL5, CFHR5D, Complement factor H-related protein 5, FHR-5, FHR5

McRae, J.L. et al., McRae, J.L. et al., Abrera-Abeleda, M.A. et al., McRae, J.L. et al., Murphy, B. et al., et al.

Murphy, Georgiou, Machet, Hill, McRae, McRae, Murphy, Eyre, Sutherland, Crawford, Cowan, McRae, Cowan, Power, Mitchelhill, Kemp, Morgan, Murphy, McRae, Duthy, Griggs, Ormsby, Cowan, Cromer, McKinstry, Parker, Murphy, Gordon,

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Disease relevance of CFHR5

Variations in the complement regulatory genes factor H (CFH) and factor H related 5 (CFHR5) are associated with membranoproliferative glomerulonephritis type II (dense deposit disease) [1].
This FHR protein is analogous to human FHR-5, both in structure and in potential involvement in glomerular immune complex diseases [2].
Given the prominent expression of FHR-5 in human membranous nephropathy, a disease in which complement activation occurs in the vicinity of GEC, the expression of FHR in a rat model of this disease was evaluated [2].

High impact information on CFHR5

FHR-5 inhibited alternative pathway C3 convertase activity in a fluid phase assay; however, dissociation of the convertase was not observed in a solid phase assay. rFHR-5 displayed factor I-dependent cofactor activity for C3b cleavage, although it was apparently less effective than fH [3].
These results demonstrate that FHR-5 shares properties of heparin and CRP binding and lipoprotein association with one or more of the other FHRs but is unique among this family of proteins in possessing independent complement-regulatory activity [3].
The short consensus repeats of FHR-5 show homology to Factor H and to other Factor H-related proteins, with some unique features demonstrated [4].
FHR-5 was purified by affinity chromatography from complement-lysed erythrocytes, and the peptide sequence was obtained [4].
In addition, we detected the recently discovered 65-kDa FH-related protein FHR-5 in the MEE [5].

Chemical compound and disease context of CFHR5

CONCLUSION: We have identified specific allele variants of CFH and CFHR5 associated with the MPGN II/DDD disease phenotype [1].

Biological context of CFHR5

RESULTS: Allele frequencies of four single nucleotide polymorphisms in CFH and three in CFHR5 were significantly different between MPGN II/DDD patients and controls [1].
This study shows FHR-5 to be strongly associated with glomerular complement deposition and suggests a role in complement activation or regulation [6].
Furthermore, the short consensus repeats (SCRs) of FHR-5 are encoded by individual exons and splicing is of type 1 [7].

Associations of CFHR5 with chemical compounds

The strong association of FHR-5 with tissue complement deposits in vivo suggests that this additional member of the Factor H family of proteins has a function in complement regulation [4].
Analysis of the genomic sequence indicates that the FHR-5 gene is situated between FHR-2 and the non-complement protein factor XIIIb (Fl3B) [7].

Other interactions of CFHR5

Statistical analysis showed that allelic variants in CFHR5 were prefentially associated with HUS [8].

Analytical, diagnostic and therapeutic context of CFHR5

Using fluorescence in situ hybridisation (FISH), radiation hybrid (RH) mapping and BLAST alignment analysis, we have established that the factor H-related 5 (FHR-5) gene is closely linked to the other factor H gene family members [7].
To determine the incidence and pattern of detection of FHR-5 in human renal biopsy specimens, a prospective study of 100 consecutive biopsies was performed using anti-FHR-5 monoclonal antibody and indirect immunofluorescence [6].

References

Variations in the complement regulatory genes factor H (CFH) and factor H related 5 (CFHR5) are associated with membranoproliferative glomerulonephritis type II (dense deposit disease). Abrera-Abeleda, M.A., Nishimura, C., Smith, J.L., Sethi, S., McRae, J.L., Murphy, B.F., Silvestri, G., Skerka, C., Józsi, M., Zipfel, P.F., Hageman, G.S., Smith, R.J. J. Med. Genet. (2006) [Pubmed]
Isolation and characterization of a novel rat factor H-related protein that is up-regulated in glomeruli under complement attack. Ren, G., Doshi, M., Hack, B.K., Alexander, J.J., Quigg, R.J. J. Biol. Chem. (2002) [Pubmed]
Human factor H-related protein 5 has cofactor activity, inhibits C3 convertase activity, binds heparin and C-reactive protein, and associates with lipoprotein. McRae, J.L., Duthy, T.G., Griggs, K.M., Ormsby, R.J., Cowan, P.J., Cromer, B.A., McKinstry, W.J., Parker, M.W., Murphy, B.F., Gordon, D.L. J. Immunol. (2005) [Pubmed]
Human factor H-related protein 5 (FHR-5). A new complement-associated protein. McRae, J.L., Cowan, P.J., Power, D.A., Mitchelhill, K.I., Kemp, B.E., Morgan, B.P., Murphy, B.F. J. Biol. Chem. (2001) [Pubmed]
Complement-regulator factor H and related proteins in otitis media with effusion. Närkiö-Mäkelä, M., Hellwage, J., Tahkokallio, O., Meri, S. Clin. Immunol. (2001) [Pubmed]
Factor H-related protein-5: a novel component of human glomerular immune deposits. Murphy, B., Georgiou, T., Machet, D., Hill, P., McRae, J. Am. J. Kidney Dis. (2002) [Pubmed]
Location and structure of the human FHR-5 gene. McRae, J.L., Murphy, B.E., Eyre, H.J., Sutherland, G.R., Crawford, J., Cowan, P.J. Genetica (2002) [Pubmed]
Genetic analysis of the complement factor H related 5 gene in haemolytic uraemic syndrome. Monteferrante, G., Brioschi, S., Caprioli, J., Pianetti, G., Bettinaglio, P., Bresin, E., Remuzzi, G., Noris, M. Mol. Immunol. (2007) [Pubmed]

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