Gene Symbol: FHR 4
Description: complement factor H related 4
Alias: CFHL4, FHR-4, FHR4, complement factor H-related protein 4
Species: human
Products:     FHR 4

Top Publications

  1. Valoti E, Alberti M, Carrara C, Breno M, Yilmaz Keskin E, Bresin E, et al. Hemolytic Uremic Syndrome in an Infant with Primary Hyperoxaluria Type II: An Unreported Clinical Association. Nephron. 2019;:1-7 pubmed publisher
  2. Yi C, Zhao F, Qiu H, Wang L, Huang J, Nie X, et al. [Analysis of variants in complement genes in Han Chinese children with atypical hemolytic uremic syndrome]. Zhonghua Er Ke Za Zhi. 2017;55:624-627 pubmed publisher
  3. Ermini L, Goodship T, Strain L, Weale M, Sacks S, Cordell H, et al. Common genetic variants in complement genes other than CFH, CD46 and the CFHRs are not associated with aHUS. Mol Immunol. 2012;49:640-8 pubmed publisher
    ..Haplotype analysis showed at-risk and protective haplotypes in both CD46 and CFH. The CD46 haplotype was only disease-associated in those patients with mutations. ..
  4. Cantsilieris S, Nelson B, HUDDLESTON J, Baker C, Harshman L, Penewit K, et al. Recurrent structural variation, clustered sites of selection, and disease risk for the complement factor H (CFH) gene family. Proc Natl Acad Sci U S A. 2018;115:E4433-E4442 pubmed publisher
    ..These data suggest a dynamic and recurrent pattern of mutation critical to the emergence of new CFHR genes but also in the predisposition to complex human genetic disease phenotypes. ..
  5. Li J, Ge X, Wang X, Liu X, Ma J. Complement System in the Pathogenesis of Benign Lymphoepithelial Lesions of the Lacrimal Gland. PLoS ONE. 2016;11:e0148290 pubmed publisher
    ..Local expression of complement components is prominently abnormal in BLEL, and may well play a role in its pathogenesis. ..
  6. Lorés Motta L, Paun C, Corominas J, Pauper M, Geerlings M, Altay L, et al. Genome-Wide Association Study Reveals Variants in CFH and CFHR4 Associated with Systemic Complement Activation: Implications in Age-Related Macular Degeneration. Ophthalmology. 2018;125:1064-1074 pubmed publisher
    ..The SNP rs6685931 in CFHR4 and its linked haplotype H1-2 also conferred a risk for AMD development, and therefore could be used to identify AMD patients who would benefit most from complement-inhibiting therapies. ..
  7. McCormack M, Gui H, Ingason A, Speed D, Wright G, Zhang E, et al. Genetic variation in CFH predicts phenytoin-induced maculopapular exanthema in European-descent patients. Neurology. 2018;90:e332-e341 pubmed publisher
  8. Osborne A, Breno M, Borsa N, Bu F, Fremeaux Bacchi V, Gale D, et al. Statistical Validation of Rare Complement Variants Provides Insights into the Molecular Basis of Atypical Hemolytic Uremic Syndrome and C3 Glomerulopathy. J Immunol. 2018;200:2464-2478 pubmed publisher
  9. Zhao J, Wu H, Khosravi M, Cui H, Qian X, Kelly J, et al. Association of genetic variants in complement factor H and factor H-related genes with systemic lupus erythematosus susceptibility. PLoS Genet. 2011;7:e1002079 pubmed publisher

More Information


  1. Veneman W, Spaink H, Brun N, Bosker T, Vijver M. Pathway analysis of systemic transcriptome responses to injected polystyrene particles in zebrafish larvae. Aquat Toxicol. 2017;190:112-120 pubmed publisher
    ..g. cfhl3, cfhl4, cfb and c9)...
  2. Józsi M, Tortajada A, Uzonyi B, Goicoechea de Jorge E, Rodríguez de Córdoba S. Factor H-related proteins determine complement-activating surfaces. Trends Immunol. 2015;36:374-84 pubmed publisher
  3. Sullivan M, Erlic Z, Hoffmann M, Arbeiter K, Patzer L, Budde K, et al. Epidemiological approach to identifying genetic predispositions for atypical hemolytic uremic syndrome. Ann Hum Genet. 2010;74:17-26 pubmed publisher
    ..Occurrence of homo- and heterozygous mutations in the same gene suggests that the number of necessary DNA variants remains unclear. Among clinical information only familial occurrence predicts a mutation. ..
  4. Jozsi M, Richter H, Löschmann I, Skerka C, Buck F, Beisiegel U, et al. FHR-4A: a new factor H-related protein is encoded by the human FHR-4 gene. Eur J Hum Genet. 2005;13:321-9 pubmed
    ..To our knowledge, FHR-4A provides the first evidence for alternative splicing among Factor H-related genes. ..
  5. Naj A, Scott W, Courtenay M, Cade W, Schwartz S, Kovach J, et al. Genetic factors in nonsmokers with age-related macular degeneration revealed through genome-wide gene-environment interaction analysis. Ann Hum Genet. 2013;77:215-31 pubmed publisher
    ..57, P = 2.73 × 10(-5) ), with an inverse association among smokers (OR = 1.42, P = 0.00228), suggesting that smoking modifies the effect of some genetic polymorphisms on AMD risk. ..
  6. Williams F, Carter A, Hysi P, Surdulescu G, Hodgkiss D, Soranzo N, et al. Ischemic stroke is associated with the ABO locus: the EuroCLOT study. Ann Neurol. 2013;73:16-31 pubmed publisher
    ..811). ABO gene variants are associated with large-vessel and cardioembolic stroke but not small-vessel disease. This work sheds light on the different pathogenic mechanisms underpinning stroke subtype. ..
  7. Gharavi A, Kiryluk K, Choi M, Li Y, Hou P, Xie J, et al. Genome-wide association study identifies susceptibility loci for IgA nephropathy. Nat Genet. 2011;43:321-7 pubmed publisher
  8. Lin W, Lee W. Incorporating prior knowledge to facilitate discoveries in a genome-wide association study on age-related macular degeneration. BMC Res Notes. 2010;3:26 pubmed publisher
    ..05. These include SNPs within three genes: CFH, CFHR4, and SGCD. Based on the success of this example, we advocate using the simple method of PSA to facilitate discoveries in future GWASs. ..
  9. Moore I, Strain L, Pappworth I, Kavanagh D, Barlow P, Herbert A, et al. Association of factor H autoantibodies with deletions of CFHR1, CFHR3, CFHR4, and with mutations in CFH, CFI, CD46, and C3 in patients with atypical hemolytic uremic syndrome. Blood. 2010;115:379-87 pubmed publisher
    ..In 5 patients mutations were identified: 1 in CFH, 1 in CFI, 1 in CD46, and 2 in C3. The latter observation emphasizes that multiple concurrent factors may be necessary in individual patients for disease manifestation. ..
  10. Mihlan M, Hebecker M, Dahse H, Hälbich S, Huber Lang M, Dahse R, et al. Human complement factor H-related protein 4 binds and recruits native pentameric C-reactive protein to necrotic cells. Mol Immunol. 2009;46:335-44 pubmed publisher
    ..In addition, CFHR4 facilitated binding of native CRP to the surface of necrotic cells. Altogether these data identify CFHR4 as a novel ligand for native CRP, and suggest a role for CFHR4 in opsonization of necrotic cells. ..
  11. Zhang H, Morrison M, Dewan A, Adams S, Andreoli M, Huynh N, et al. The NEI/NCBI dbGAP database: genotypes and haplotypes that may specifically predispose to risk of neovascular age-related macular degeneration. BMC Med Genet. 2008;9:51 pubmed publisher
    ..This is the first replication study on the NEI dbGAP SNPs, demonstrating that alleles on 1q, 2q and 10q may predispose an individual to AMD. ..
  12. Skerka C, Hellwage J, Weber W, Tilkorn A, Buck F, Marti T, et al. The human factor H-related protein 4 (FHR-4). A novel short consensus repeat-containing protein is associated with human triglyceride-rich lipoproteins. J Biol Chem. 1997;272:5627-34 pubmed
    ..This observation provides an intriguing new aspect on possible function(s) of this novel protein and the other factor H-related proteins. ..
  13. Hageman G, Hancox L, Taiber A, Gehrs K, Anderson D, Johnson L, et al. Extended haplotypes in the complement factor H (CFH) and CFH-related (CFHR) family of genes protect against age-related macular degeneration: characterization, ethnic distribution and evolutionary implications. Ann Med. 2006;38:592-604 pubmed
    ..The considerable diversity accumulated at this locus may be due to selection, which is consistent with an important role for the CFHR genes in innate immunity. ..
  14. Hellwage J, Skerka C, Zipfel P. Biochemical and functional characterization of the factor-H-related protein 4 (FHR-4). Immunopharmacology. 1997;38:149-57 pubmed
    ..Functional analyses show dose-dependent binding of recombinant FHR-4 to C3b, thus demonstrating a functional relatedness between FHR-4, factor H and FHL-1 and other complement regulators of the RCA gene cluster. ..
  15. Hughes A, Bridgett S, Meng W, Li M, Curcio C, Stambolian D, et al. Sequence and Expression of Complement Factor H Gene Cluster Variants and Their Roles in Age-Related Macular Degeneration Risk. Invest Ophthalmol Vis Sci. 2016;57:2763-9 pubmed publisher
    ..However, the striking difference between systemic and ocular expression of complement regulators shown in this study suggests important implications for the development of intraocular and systemic treatments. ..
  16. Hebecker M, Okemefuna A, Perkins S, Mihlan M, Huber Lang M, Jozsi M. Molecular basis of C-reactive protein binding and modulation of complement activation by factor H-related protein 4. Mol Immunol. 2010;47:1347-55 pubmed publisher
    ..In summary, these data reveal the molecular basis of the specific interaction of CFHR4 with native CRP and suggest a role for CFHR4 in enhancing opsonization via CRP binding. ..
  17. Hebecker M, Jozsi M. Factor H-related protein 4 activates complement by serving as a platform for the assembly of alternative pathway C3 convertase via its interaction with C3b protein. J Biol Chem. 2012;287:19528-36 pubmed publisher
    ..In conclusion, our results suggest that, in contrast to the complement inhibitor factor H, CFHR4 acts as an enhancer of opsonization by promoting complement activation. ..
  18. Diaz Guillen M, Rodriguez De Cordoba S, Heine Suñer D. A radiation hybrid map of complement factor H and factor H-related genes. Immunogenetics. 1999;49:549-52 pubmed
  19. Hellwage J, Jokiranta T, Koistinen V, Vaarala O, Meri S, Zipfel P. Functional properties of complement factor H-related proteins FHR-3 and FHR-4: binding to the C3d region of C3b and differential regulation by heparin. FEBS Lett. 1999;462:345-52 pubmed
    The human factor H-related proteins FHR-3 and FHR4 are members of a family of proteins related to the complement factor H. Here, we report that the two proteins bind to the C3d region of complement C3b...