Affinage

CFHR1

Complement factor H-related protein 1 · UniProt Q03591

Length
330 aa
Mass
37.7 kDa
Annotated
2026-06-09
74 papers in source corpus 20 papers cited in narrative 20 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CFHR1 (FHR-1) is a circulating complement regulatory protein that acts as a context-dependent modulator of the alternative complement pathway, distinct in mechanism from its relative complement factor H (CFH) (PMID:19528535). At the terminal complement level it inhibits the C5 convertase and blocks C5b surface deposition and membrane attack complex formation (PMID:19528535). In contrast, at the C3 convertase level it antagonizes CFH: FHR-1 binds C3b and C3d through a C-terminal interface essentially identical to the two C-terminal domains of CFH (SCR19-20), and this binding—which requires FHR-1 dimerization—sterically displaces CFH and CFHL-1, de-regulating CFH-mediated C3 convertase control and enhancing complement activation (PMID:27814381, PMID:33651882). FHR-1 circulates as homodimers and as FHR-1/FHR-2 heterodimers whose subunits exchange rapidly, oligomerization being mediated by its conserved N-terminal domains (PMID:29093712, PMID:23728178). Its lack of sialic-acid binding (unlike CFH) normally restricts competition with CFH on host surfaces; aHUS-associated FHR-1 mutants acquire sialic-acid binding and increased C3-fragment avidity, explaining their pathogenicity, as do gene-conversion allotypes and CFHR1/CFH hybrid proteins that potentiate FH antagonism and endothelial complement deposition (PMID:33651882, PMID:35126388, PMID:24904082). Beyond complement, FHR-1 binds necrotic cells via its N-terminus and triggers NLRP3 inflammasome activation and pro-inflammatory cytokine release in monocytes through the G-protein coupled receptor EMR2 and phospholipase C, independent of complement (PMID:31273197). It engages monomeric CRP, pentraxin 3, DNA, and extracellular matrix proteins (laminin, fibromodulin, osteoadherin, PRELP) through its C-terminal domains to further amplify complement activation on dead cells and ECM (PMID:28533443, PMID:32765490, PMID:35392081). FHR-1 is exploited by pathogens (Group A Streptococcus, Leptospira, Plasmodium falciparum) for complement evasion (PMID:20855886, PMID:22291192, PMID:30455399), and murine knockout studies establish its in vivo role in restraining alternative-pathway activation during bacterial infection and in promoting tissue inflammation in atherosclerosis and choroidal neovascularization (PMID:32636836, PMID:39128222, PMID:40611130, PMID:41583528). CFHR1 polymorphisms and copy-number variation are linked to atypical hemolytic uremic syndrome and C3 glomerulopathy (PMID:19745068, PMID:23728178).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 2009 High

    Established that FHR-1 is not redundant with CFH but acts at a distinct step—the C5 convertase—blocking terminal complement assembly, defining its first molecular function.

    Evidence In vitro C5 convertase activity and MAC deposition assays with cell-surface binding

    PMID:19528535

    Open questions at the time
    • Did not resolve the structural basis for C5 convertase inhibition
    • Did not address how FHR-1 and CFH share surface sites in vivo
  2. 2009 Medium

    Linked CFHR1 genetic variation and deficiency to aHUS, showing CFHR1 deficiency drives anti-factor-H autoantibody generation and that a gene-conversion allotype may antagonize FH.

    Evidence Proteomics, CFHR1 genomic sequencing and allotype characterization in patient cohorts

    PMID:19745068

    Open questions at the time
    • FH-competition model was inferred, not directly reconstituted
    • Mechanism connecting CFHR1 deficiency to autoantibody production unresolved
  3. 2010 High

    Showed pathogens exploit FHR-1: binding to streptococcal Scl1 via SCR3-5 interferes with FH-mediated C3 convertase regulation while preserving FHR-1 C5-level inhibition, demonstrating dual surface-protein-mediated complement evasion.

    Evidence Binding/ELISA, domain mutagenesis, hemolysis and complement regulation assays on bacterial surfaces

    PMID:20855886

    Open questions at the time
    • Did not establish in vivo relevance to streptococcal virulence
  4. 2012 Medium

    Extended pathogen complement-evasion role by showing FHR-1 is acquired on Leptospira surfaces via Lig proteins alongside other host regulators.

    Evidence Serum-based binding and competition assays on leptospiral proteins

    PMID:22291192

    Open questions at the time
    • Functional consequence for Leptospira survival not directly measured
    • Single lab, no in vivo confirmation
  5. 2013 High

    Defined FHR oligomerization architecture: native FHR-1/2/5 circulate as homo- and hetero-oligomers via conserved N-terminal domains, and a C3G mutation duplicating these domains creates large multimers with enhanced C3b avidity and FH competition—linking oligomerization state to disease.

    Evidence Plasma protein characterization, SPR, hemolytic assays, native PAGE/SEC, genomic sequencing

    PMID:23728178

    Open questions at the time
    • Did not resolve stoichiometry of mutant multimers at surfaces
    • Causal chain from multimerization to glomerular pathology incomplete
  6. 2016 High

    Mapped the molecular basis of FH antagonism: FHR-1 binds C3b/C3d through an interface identical to CFH SCR19-20 and requires dimerization to compete with both CFH and CFHL-1, defining the steric mechanism of de-regulation.

    Evidence Site-directed mutagenesis, ELISA binding and functional complement assays

    PMID:27814381

    Open questions at the time
    • No co-crystal structure of FHR-1 with C3b
    • Did not quantify competition at native cell surfaces
  7. 2017 High

    Revealed a complement-enhancing role via pentraxins: FHR-1 binds monomeric (not pentameric) CRP through C-terminal domains and amplifies classical and alternative pathway activation on ECM and necrotic cells.

    Evidence ELISA binding, classical/alternative pathway and C3 convertase activation assays

    PMID:28533443

    Open questions at the time
    • In vivo contribution of FHR-1/CRP axis to inflammation not established
  8. 2017 High

    Quantified FHR-1 dimer dynamics, showing homodimers and FHR-1/FHR-2 heterodimers with rapid monomer exchange, absent in homozygous CFHR1-deletion individuals—confirming the dimer as the functional plasma unit.

    Evidence FRET, ELISA with specific antibodies, serum from CFHR1-deletion individuals

    PMID:29093712

    Open questions at the time
    • Functional difference between homo- and heterodimers not resolved
  9. 2018 Medium

    Demonstrated FHR-1 competes with FH on Plasmodium falciparum surfaces, where add-back of FHR-1 impairs C3b inactivation and reduces parasite viability, framing FHR-1 as a host-protective complement amplifier in malaria.

    Evidence FHR-1-deficient serum, recombinant add-back, binding competition and parasite viability assays

    PMID:30455399

    Open questions at the time
    • Single lab, no in vivo malaria model
    • Effect size on parasite control in physiological serum uncertain
  10. 2019 High

    Uncovered a complement-independent inflammatory function: FHR-1 selectively binds necrotic cells and activates the NLRP3 inflammasome in monocytes via the GPCR EMR2 and phospholipase C, with in situ binding at necrotic glomerular and atherosclerotic sites.

    Evidence Monocyte stimulation, NLRP3/IL-1β readouts, EMR2 receptor identification, pathway inhibitors, patient tissue IHC

    PMID:31273197

    Open questions at the time
    • Structural basis of FHR-1–EMR2 engagement undefined
    • Selectivity over FHR-2/FHR-3 mechanistically unexplained
  11. 2020 Medium

    Broadened FHR-1 ligand repertoire to DNA and dead-cell surfaces, where it inhibits FH-DNA binding and recruits CRP and pentraxin 3 to amplify complement on apoptotic/necrotic material.

    Evidence ELISA binding, cofactor activity and complement activation assays on DNA and dead cells

    PMID:32765490

    Open questions at the time
    • Single lab
    • Physiological relevance of DNA binding in vivo unclear
  12. 2020 Medium

    Provided in vivo genetic proof that FHR-1 restrains alternative-pathway activation, as Cfhr1-knockout mice showed enhanced LPS-induced AP activation and more severe sepsis and acute kidney injury.

    Evidence Cfhr1 knockout mouse, LPS sepsis model, complement measurements

    PMID:32636836

    Open questions at the time
    • Murine FHR-E may differ functionally from human FHR-1
    • Single lab
  13. 2021 High

    Explained aHUS mutant pathogenicity at atomic resolution: wild-type FHR-1 lacks sialic-acid binding (preventing host-surface competition with FH), while aHUS mutants acquire it, raising avidity for surface C3 fragments; FHR-1 also binds native C3 to attract it to surfaces and promote activation.

    Evidence NMR, homology modeling, mutagenesis, sialic-acid binding and complement activation assays

    PMID:33651882

    Open questions at the time
    • Full-length FHR-1 surface structure not solved
    • Quantitative threshold of avidity gain for disease unknown
  14. 2021 Medium

    Connected FHR-1 to vascular inflammation, showing it deposits in atherosclerotic plaques, circulates on extracellular vesicles, and induces pro-inflammatory cytokines and tissue factor in monocytes and neutrophils.

    Evidence FHR-1 plasma isolation, plaque IHC, immune-cell stimulation and cytokine assays

    PMID:34795372

    Open questions at the time
    • Receptor/pathway for tissue factor induction not defined here
    • Single lab
  15. 2022 Medium

    Identified ECM proteins (laminin, fibromodulin, osteoadherin, PRELP) as FHR-1 ligands bound via CCP4-5, where FHR-1 competitively displaces FH and enhances alternative-pathway activation on matrix surfaces.

    Evidence ELISA binding, CCP domain mapping, FH cofactor and complement activation assays on ECM

    PMID:35392081

    Open questions at the time
    • In vivo ECM complement dysregulation not tested
    • Single lab
  16. 2022 Medium

    Functionally distinguished aHUS-risk allotype FHR1*B from FHR1*A, showing FHR1*B has higher C3b and necrotic-cell binding, more strongly de-regulates FH, and elicits greater monocyte cytokine secretion—linking sequence variation to both complement and inflammatory gain of function.

    Evidence Recombinant protein expression, homology modeling, C3b/cofactor/convertase and monocyte assays

    PMID:35126388

    Open questions at the time
    • Structural cause of the FHR1*B avidity gain not resolved
    • Single lab
  17. 2014 Medium

    Showed a CFHR1/CFH hybrid protein (FHR1 SCR1-4 plus FH SCR20) acts as a competitive FH antagonist causing hemolysis and increased C5b-9 deposition on endothelial cells, linking gene rearrangements to complement dysregulation.

    Evidence FH-dependent hemolysis assay, endothelial C5b-9 deposition, genomic sequencing

    PMID:24904082

    Open questions at the time
    • Single carrier-derived material
    • Mechanism of the hybrid's surface targeting incomplete
  18. 2024 Medium

    Provided in vivo evidence that FHR-1 limits AP activation during S. aureus infection, as Cfhr1-knockout mice showed excessive C3a, higher bacterial burden, and exacerbated sepsis and lung injury.

    Evidence Cfhr1 knockout mouse, S. aureus infection, complement and bacterial readouts, RNA-seq

    PMID:39128222

    Open questions at the time
    • Murine-to-human FHR-1 functional correspondence assumed
    • Single lab
  19. 2024 Medium

    Implicated FHR-1 in lipid metabolism and atherosclerosis, as muFHR1 deletion in ApoE-/- mice normalized cholesterol, reduced inflammation and plaque, and FHR-1 was shown to direct macrophage oxidized-LDL uptake driving foam cell formation.

    Evidence muFHR1 knockout crossed to ApoE-/-, liver RNAseq, lipid measurements, plaque quantification

    PMID:41583528

    Open questions at the time
    • Molecular mechanism of FHR-1-directed oxLDL uptake not defined
    • Reliance on murine homolog
  20. 2025 Medium

    Extended the FHR-1/EMR2 inflammatory axis to retinal disease, showing FHR-1 accumulates beneath the RPE in AMD, triggers EMR2-dependent calcium signaling and transcriptional changes, and that muFHR1 deletion reduces mononuclear phagocyte invasion and neoangiogenesis.

    Evidence RNAseq, Ca2+ signaling in RPE cells, muFHR1 knockout, laser-induced choroidal neovascularization, IHC

    PMID:40611130

    Open questions at the time
    • Direct human genetic link to AMD via this axis not established
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how the competing complement-regulatory (C5-inhibitory) and complement-enhancing (FH-antagonist) activities of FHR-1 are balanced at specific surfaces in vivo, and whether the dimer/multimer state, allotype, and EMR2-mediated inflammatory signaling are coordinately controlled.
  • No integrated structural model of FHR-1 functions at a defined surface
  • Selectivity determinants for inflammasome activation versus complement modulation unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0060089 molecular transducer activity 2 GO:0003677 DNA binding 1
Localization
GO:0005576 extracellular region 2 GO:0031012 extracellular matrix 2
Pathway
R-HSA-168256 Immune System 4 R-HSA-8953897 Cellular responses to stimuli 2
Partners
C3BCFHCFHL-1CRPEMR2PTX3
Complex memberships
FHR-1 homodimerFHR-1/FHR-2 heterodimer

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 CFHR1 (FHR-1) inhibits complement C5 convertase activity and blocks C5b surface deposition and MAC (membrane attack complex) formation. This activity is distinct from complement factor H (CFH), which regulates the C3 convertase. Both proteins bind to the same or similar sites at cellular surfaces, suggesting sequential and partially competitive roles in complement regulation. In vitro functional assays (C5 convertase activity assays, MAC deposition assays, cell surface binding experiments) Blood High 19528535
2009 A novel CFHR1 polymorphism (CFHR1*B), arising from gene conversion between CFH and CFHR1, associates with aHUS susceptibility. Patients with aHUS lacking CFHR1 (but not CFHR3) present anti-factor H autoantibodies, indicating CFHR1 deficiency specifically drives anti-FH autoantibody generation. The CFHR1*B allotype, with greater sequence similarity to FH, may compete with FH and reduce protection of cellular surfaces. Proteomics strategy (2D-PAGE/MS), sequencing of CFHR1 genomic DNA, functional inference from allotype characterization Blood Medium 19745068
2010 CFHR1 binds to Group A streptococcal collagen-like protein Scl1 via its conserved C-terminal short consensus repeats SCR3-5. Binding of CFHR1 to Scl1 interferes with Factor H-mediated C3 convertase regulation (competitive inhibition), while maintaining terminal complement complex inhibition by CFHR1 at the C5 convertase level. This interaction enables streptococci to evade complement via two distinct surface protein classes. Binding assays (pulldown/ELISA), functional hemolysis/complement regulation assays, domain mutagenesis (ionic strength and heparin competition), bacterial surface binding experiments The Journal of Biological Chemistry High 20855886
2012 CFHR1 (FHR-1) is acquired on Leptospira surfaces via binding to leptospiral immunoglobulin-like (Lig) proteins, facilitating complement evasion. CFHR1 was shown to bind to Lig proteins from human serum alongside FH, FHL-1, and C4BP. Co-incubation binding assays, competition assays, serum-based complement evasion experiments The Journal of Infectious Diseases Medium 22291192
2013 A C3 glomerulopathy-associated mutation in CFHR1 causes duplication of the N-terminal SCRs (conserved in FHR2 and FHR5), resulting in unusually large multimeric FHR complexes. Native FHR1, FHR2, and FHR5 circulate as homo- and hetero-oligomeric complexes mediated by the conserved N-terminal domain. Mutant FHR1 shows increased avidity for C3b, iC3b, and C3dg and enhanced competition with FH in SPR and hemolytic assays. Plasma protein characterization, surface plasmon resonance (SPR), hemolytic assays, size-exclusion chromatography/native PAGE, genomic sequencing The Journal of Clinical Investigation High 23728178
2016 CFHR1 binds to complement components C3b and C3d via a single shared interface identical to that of the two C-terminal domains (SCR19-20) of CFH. CFHR1 dimerization is required for effective binding to C3b and C3d and for competition with CFH. CFHR1 also competes with complement factor H-like protein 1 (CFHL-1/FHL-1) for C3b binding, sterically blocking the N-terminal CFH interaction required for CFH-mediated regulation. Site-directed mutagenesis, ELISA-based binding assays, functional complement assays PloS one High 27814381
2017 FHR-1 binds strongly to monomeric CRP (but not native pentameric CRP) via its C-terminal domains. FHR-1/CRP interactions increased complement activation via both classical and alternative pathways on surfaces such as extracellular matrix and necrotic cells. FHR-1 did not inhibit FH-mediated regulation of solid-phase C3 convertase or terminal complement complex formation induced by zymosan; instead, by binding C3b, FHR-1 allowed C3 convertase formation and enhanced complement activation. ELISA-based binding assays, complement activation assays (classical and alternative pathway), C3 convertase formation assays, competition binding assays Journal of Immunology High 28533443
2017 FHR-1 circulates in human plasma as homodimers and as FHR-1/FHR-2 heterodimers. FHR-1, FHR-2, and FHR-5 homodimerize and FHR-1/FHR-2 heterodimers form, with monomer exchange occurring rapidly as shown by FRET. In individuals with homozygous CFHR1 deletions, FHR-1 homo- and heterodimers are absent. FRET, ELISA with specific antibodies, serum analysis from CFHR1-deletion individuals Frontiers in Immunology High 29093712
2018 FHR-1 competes with Factor H for binding to Plasmodium falciparum surfaces (intraerythrocytic schizonts and free merozoites). In FHR-1-deficient human serum, FH binding to parasite surfaces is increased; addition of recombinant FHR-1 decreases FH binding, impairs C3b inactivation, and reduces parasite viability. FHR-1-deficient human serum experiments, recombinant FHR-1 add-back, parasite viability assays, binding competition assays Journal of Immunology Medium 30455399
2019 FHR1 selectively binds to necrotic cells via its N-terminus. FHR1 (but not FH, FHR2, or FHR3) strongly induces NLRP3 inflammasome activation in blood-derived human monocytes, leading to secretion of IL-1β, TNFα, IL-18, and IL-6. This FHR1-mediated inflammasome activation occurs via the phospholipase C pathway through the G-protein coupled receptor EMR2, independent of complement. FHR1 also binds near necrotic glomerular sites in AAV patients and necrotic areas in atherosclerotic plaques. In vitro monocyte stimulation assays, NLRP3 inflammasome activation (IL-1β secretion), receptor identification (EMR2), signaling pathway inhibitor experiments, immunohistochemistry on patient tissue, in vitro necrotic cell binding assays Nature Communications High 31273197
2020 FHR-1 and FHR-5 bind to both plasmid DNA and human genomic DNA, and inhibit FH-DNA interaction by competing with FH binding. The FHR-1 cofactor activity inhibition was due to reduced FH binding to DNA. Both FHRs cause increased complement activation on DNA. FHR-1 and FHR-5 bind to late apoptotic and necrotic cells and recruit monomeric CRP and pentraxin 3; FHR-pentraxin interactions promote enhanced activation of both classical and alternative complement pathways on dead cells. ELISA-based binding assays, cofactor activity assays, complement activation assays on DNA and dead cell surfaces, competition binding experiments Frontiers in Immunology Medium 32765490
2020 In a Cfhr1 knockout mouse model, murine FHR-1 homolog (FHR-E) deficiency enhanced LPS-induced alternative complement pathway (AP) activation both in vitro and in vivo, and knockout mice exhibited more severe sepsis and acute kidney injury. This establishes that FHR-E/FHR-1 regulates AP activation in vivo in the context of infection. Cfhr1 knockout mouse generation, LPS-induced sepsis model, complement activation measurements, in vitro complement assays Frontiers in Immunology Medium 32636836
2021 FHR-1 lacks the capacity to bind sialic acids (unlike FH), which prevents C3b-binding competition between FH and FHR-1 at host-cell surfaces under normal circumstances. aHUS-associated FHR-1 mutants are pathogenic because they acquire sialic acid-binding capacity, increasing FHR-1 avidity for surface-bound C3-activated fragments and enabling C3b-binding competition with FH. FHR-1 also binds to native C3 (in addition to C3b, iC3b, C3dg), and surface-bound FHR-1 promotes complement activation by attracting native C3 to the cell surface. Biochemical assays, NMR spectroscopy, computational/homology modeling, mutagenesis of FHR-1, sialic acid binding experiments, complement activation assays Blood High 33651882
2021 FHR1 is deposited in atherosclerotic plaques and circulates on extracellular vesicles. Surface-bound FHR-1 induces expression of pro-inflammatory cytokines and tissue factor in monocytes and neutrophils. Isolation of FHR-1 from human plasma, immunohistochemistry of plaques, monocyte/neutrophil stimulation assays, cytokine measurement Scientific Reports Medium 34795372
2022 FHR1 binds to extracellular matrix (ECM) proteins laminin, fibromodulin, osteoadherin, and PRELP through its C-terminal CCP domains 4-5. FHR1 competitively inhibits FH binding to these ECM proteins in a dose-dependent manner, reduces FH cofactor activity, and enhances alternative complement pathway activation on immobilized ECM proteins when exposed to human serum. ELISA-based binding assays, domain-specific binding studies (CCP domain mapping), FH cofactor activity assays, complement activation assays on ECM surfaces Frontiers in Immunology Medium 35392081
2022 The aHUS-associated FHR1 isoform FHR1*B (c.469T, c.475G, c.523C) displays higher capacity for binding C3b and necrotic cells compared to FHR1*A. FHR1*B more strongly inhibits FH-mediated cofactor function (resulting in fewer C3b cleavage products) and more powerfully de-regulates FH inhibition of C3bBb assembly. FHR1*B also triggers higher IL-1β and IL-6 secretion from monocytes than FHR1*A. Recombinant protein expression, homology modeling, C3b binding assays, cofactor activity assays, C3 convertase assays, monocyte stimulation assays Frontiers in Immunology Medium 35126388
2014 A novel hybrid CFHR1/CFH fusion protein (containing first four SCRs of FHR1 and terminal SCR20 of FH) acts as a competitive antagonist of FH in an FH-dependent hemolysis assay, causing sheep erythrocyte lysis. Sera from carriers of the hybrid gene induce more C5b-9 deposition on endothelial cells than control serum. Functional hemolysis assay, C5b-9 deposition assay on endothelial cells, genomic sequencing Journal of the American Society of Nephrology Medium 24904082
2025 FHR1 accumulates below the retinal pigment epithelium (RPE) in AMD donor tissue and in AMD-relevant mouse models. The murine FHR1 receptor EMR2 (EGF-like module-containing mucin-like hormone receptor 1, also known as Emr1 in mice) is expressed on RPE and invading mononuclear phagocytes (MP). FHR1 triggers EMR2-dependent calcium signals and gene expression changes in both human RPE cells and in vivo. Deletion of muFHR1 in mice significantly reduced mononuclear phagocyte invasion and neoangiogenesis in laser-induced choroidal neovascularization. RNAseq, Ca2+ signaling assays in RPE cells, muFHR1 knockout mouse experiments, laser-induced choroidal neovascularization model, immunohistochemistry Journal of Neuroinflammation Medium 40611130
2024 Deletion of murine FHR1 (muFHR1, the mouse homolog of human FHR1) in ApoE-/- mice normalizes cholesterol levels, reduces inflammation, and decreases plaque formation. muFHR1 deletion enhanced lipid conversion in the liver (shown by RNAseq), and FHR1 directs uptake of oxidized LDL by macrophages, supporting foam cell formation and plaque development. muFHR1 knockout mouse generation, cross with ApoE-/- mice, RNAseq analysis of liver, lipid/cholesterol measurements, plaque quantification International Journal of Medical Sciences Medium 41583528
2024 Cfhr1 gene deletion in mice leads to excessive alternative complement pathway (AP) activation following Staphylococcus aureus infection, with significantly increased C3a formation in lung tissues, higher bacterial colony counts in lungs, and exacerbated sepsis and acute lung injury compared to wild-type mice. Cfhr1 knockout mouse model, S. aureus tail vein injection, complement factor measurements, bacterial colony counts, RNA-seq transcriptome analysis Biochemical and Biophysical Research Communications Medium 39128222

Source papers

Stage 0 corpus · 74 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 A common CFH haplotype, with deletion of CFHR1 and CFHR3, is associated with lower risk of age-related macular degeneration. Nature genetics 387 16998489
2007 Deletion of complement factor H-related genes CFHR1 and CFHR3 is associated with atypical hemolytic uremic syndrome. PLoS genetics 291 17367211
2009 Factor H-related protein 1 (CFHR-1) inhibits complement C5 convertase activity and terminal complex formation. Blood 222 19528535
2009 Characterization of complement factor H-related (CFHR) proteins in plasma reveals novel genetic variations of CFHR1 associated with atypical hemolytic uremic syndrome. Blood 175 19745068
2013 C3 glomerulopathy-associated CFHR1 mutation alters FHR oligomerization and complement regulation. The Journal of clinical investigation 162 23728178
2014 Variants in Complement Factor H and Complement Factor H-Related Protein Genes, CFHR3 and CFHR1, Affect Complement Activation in IgA Nephropathy. Journal of the American Society of Nephrology : JASN 134 25205734
2009 The high frequency of complement factor H related CFHR1 gene deletion is restricted to specific subgroups of patients with atypical haemolytic uraemic syndrome. Journal of medical genetics 127 19435718
2012 Leptospiral immunoglobulin-like proteins interact with human complement regulators factor H, FHL-1, FHR-1, and C4BP. The Journal of infectious diseases 120 22291192
2013 Determining the population frequency of the CFHR3/CFHR1 deletion at 1q32. PloS one 106 23613724
2014 A novel atypical hemolytic uremic syndrome-associated hybrid CFHR1/CFH gene encoding a fusion protein that antagonizes factor H-dependent complement regulation. Journal of the American Society of Nephrology : JASN 82 24904082
2013 Genetic influences on plasma CFH and CFHR1 concentrations and their role in susceptibility to age-related macular degeneration. Human molecular genetics 76 23873044
2007 Deletion of CFHR3 and CFHR1 genes in age-related macular degeneration. Human molecular genetics 73 18084039
2016 Fine Mapping Implicates a Deletion of CFHR1 and CFHR3 in Protection from IgA Nephropathy in Han Chinese. Journal of the American Society of Nephrology : JASN 72 26940089
2019 Serum FHR1 binding to necrotic-type cells activates monocytic inflammasome and marks necrotic sites in vasculopathies. Nature communications 61 31273197
2012 Renal transplantation under prophylactic eculizumab in atypical hemolytic uremic syndrome with CFH/CFHR1 hybrid protein. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 60 22494769
2015 Complement factor H, FHR-3 and FHR-1 variants associate in an extended haplotype conferring increased risk of atypical hemolytic uremic syndrome. Molecular immunology 50 26163426
2000 Complement factor H: sequence analysis of 221 kb of human genomic DNA containing the entire fH, fHR-1 and fHR-3 genes. Molecular immunology 49 10781834
2017 FHR-1 Binds to C-Reactive Protein and Enhances Rather than Inhibits Complement Activation. Journal of immunology (Baltimore, Md. : 1950) 47 28533443
2013 A novel hybrid CFHR1/CFH gene causes atypical hemolytic uremic syndrome. Pediatric nephrology (Berlin, Germany) 43 23880784
2010 Binding of the human complement regulators CFHR1 and factor H by streptococcal collagen-like protein 1 (Scl1) via their conserved C termini allows control of the complement cascade at multiple levels. The Journal of biological chemistry 41 20855886
2017 Deletion Variants of CFHR1 and CFHR3 Associate with Mesangial Immune Deposits but Not with Progression of IgA Nephropathy. Journal of the American Society of Nephrology : JASN 40 29114042
1973 Genetic and biochemical investigation of the Escherichia coli mutant hfl-1 which is lysogenized at high frequency by bacteriophage lambda. Journal of bacteriology 39 4352176
2017 Factor H-Related (FHR)-1 and FHR-2 Form Homo- and Heterodimers, while FHR-5 Circulates Only As Homodimer in Human Plasma. Frontiers in immunology 38 29093712
2014 Growth of geographic atrophy on fundus autofluorescence and polymorphisms of CFH, CFB, C3, FHR1-3, and ARMS2 in age-related macular degeneration. JAMA ophthalmology 37 24557084
2012 Relevance of complement factor H-related 1 (CFHR1) genotypes in age-related macular degeneration. Investigative ophthalmology & visual science 37 22247456
2017 A novel CFHR1-CFHR5 hybrid leads to a familial dominant C3 glomerulopathy. Kidney international 36 28729035
2016 Specific regulation of PRMT1 expression by PIAS1 and RKIP in BEAS-2B epithelia cells and HFL-1 fibroblasts in lung inflammation. Scientific reports 33 26911452
2014 Vitamin D Inhibits Expression and Activity of Matrix Metalloproteinase in Human Lung Fibroblasts (HFL-1) Cells. Tuberculosis and respiratory diseases 33 25237378
2009 Successful renal transplantation in factor H autoantibody associated HUS with CFHR1 and 3 deficiency and CFH variant G2850T. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 32 19951285
2013 Eculizumab long-term therapy for pediatric renal transplant in aHUS with CFH/CFHR1 hybrid gene. Pediatric nephrology (Berlin, Germany) 31 23982707
2020 Interaction of the Factor H Family Proteins FHR-1 and FHR-5 With DNA and Dead Cells: Implications for the Regulation of Complement Activation and Opsonization. Frontiers in immunology 29 32765490
2014 The Rbf1, Hfl1 and Dbp4 of Candida albicans regulate common as well as transcription factor-specific mitochondrial and other cell activities. BMC genomics 29 24450762
2022 An Autoantigen Atlas From Human Lung HFL1 Cells Offers Clues to Neurological and Diverse Autoimmune Manifestations of COVID-19. Frontiers in immunology 25 35401574
2021 Molecular bases for the association of FHR-1 with atypical hemolytic uremic syndrome and other diseases. Blood 24 33651882
2016 CFHR1-Modified Neural Stem Cells Ameliorated Brain Injury in a Mouse Model of Neuromyelitis Optica Spectrum Disorders. Journal of immunology (Baltimore, Md. : 1950) 24 27671112
2022 Complement Factor H-Related Proteins FHR1 and FHR5 Interact With Extracellular Matrix Ligands, Reduce Factor H Regulatory Activity and Enhance Complement Activation. Frontiers in immunology 22 35392081
2016 Mapping the Complement Factor H-Related Protein 1 (CFHR1):C3b/C3d Interactions. PloS one 22 27814381
2018 Cutting Edge: FHR-1 Binding Impairs Factor H-Mediated Complement Evasion by the Malaria Parasite Plasmodium falciparum. Journal of immunology (Baltimore, Md. : 1950) 21 30455399
2021 Factor H-related protein 1 (FHR-1) is associated with atherosclerotic cardiovascular disease. Scientific reports 20 34795372
2017 Eculizumab and Belatacept for De Novo Atypical Hemolytic Uremic Syndrome Associated With CFHR3-CFHR1 Deletion in a Kidney Transplant Recipient: A Case Report. Transplantation proceedings 19 28104134
2020 Deficiency of Mouse FHR-1 Homolog, FHR-E, Accelerates Sepsis, and Acute Kidney Injury Through Enhancing the LPS-Induced Alternative Complement Pathway. Frontiers in immunology 18 32636836
2021 Membrane recruitment of Atg8 by Hfl1 facilitates turnover of vacuolar membrane proteins in yeast cells approaching stationary phase. BMC biology 17 34088313
2021 An Autoantigen Atlas from Human Lung HFL1 Cells Offers Clues to Neurological and Diverse Autoimmune Manifestations of COVID-19. bioRxiv : the preprint server for biology 14 33501444
2021 The Transcription Factor C/EBPβ Promotes HFL-1 Cell Migration, Proliferation, and Inflammation by Activating lncRNA HAS2-AS1 in Hypoxia. Frontiers in cell and developmental biology 14 33777961
2019 CFHR1 is a potentially downregulated gene in lung adenocarcinoma. Molecular medicine reports 14 31485643
2016 Complement-Regulatory Proteins CFHR1 and CFHR3 and Patient Response to Anti-CD20 Monoclonal Antibody Therapy. Clinical cancer research : an official journal of the American Association for Cancer Research 14 27528699
2012 Associations of CFH polymorphisms and CFHR1-CFHR3 deletion with blood pressure and hypertension in Chinese population. PloS one 14 22848687
2021 Atypical Hemolytic Uremic Syndrome after ChAdOx1 nCoV-19 Vaccination in a Patient with Homozygous CFHR3/CFHR1 Gene Deletion. Nephron 13 34724668
2022 Diterpenoid alkaloids isolated from Delphinium trichophorum alleviate pulmonary fibrosis via the TGF-β/Smad pathway in 3T6 and HFL-1 cells. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 11 36068772
2017 Analysis of Linear Antibody Epitopes on Factor H and CFHR1 Using Sera of Patients with Autoimmune Atypical Hemolytic Uremic Syndrome. Frontiers in immunology 10 28424685
2023 Cryptotanshinone affects HFL-1 cells proliferation by inhibiting cytokines secretion in RAW264.7 cells and ameliorates inflammation and fibrosis in newborn rats with hyperoxia induced lung injury. Frontiers in pharmacology 9 37560477
2019 Altered Peripheral Blood Leucocyte Phenotype and Responses in Healthy Individuals with Homozygous Deletion of FHR1 and FHR3 Genes. Journal of clinical immunology 8 30945073
2018 A Heterozygous CFHR3-CFHR1 Gene Deletion in a Pediatric Patient With Transplant-associated Thrombotic Microangiopathy Who was Treated With Eculizumab. Journal of pediatric hematology/oncology 8 28991129
2018 Protective effect of methylallyl sulfone in the development of cigarette smoke extract-induced apoptosis in rats and HFL-1 cells. Biochemical and biophysical research communications 8 29524412
2025 Factor-H-related protein 1 (FHR1), a promotor of para-inflammation in age-related macular degeneration. Journal of neuroinflammation 7 40611130
2015 Favorable four-yr outcome after renal transplantation in a patient with complement factor H antibody and CFHR1/CFHR3 gene mutation-associated HUS. Pediatric transplantation 7 26087050
2023 Complete biodegradation of fungicide carboxin and its metabolite aniline by Delftia sp. HFL-1. The Science of the total environment 6 38030002
2020 HYAL1 Is Downregulated in Idiopathic Pulmonary Fibrosis and Inhibits HFL-1 Fibroblast Proliferation When Upregulated. BioMed research international 6 32258117
2017 Effective immunosuppressive management with belatacept and eculizumab in post-transplant aHUS due to a homozygous deletion of CFHR1/CFHR3 and the presence of CFH antibodies. Clinical kidney journal 6 29225802
2022 Copy number variation analysis using next-generation sequencing identifies the CFHR3/CFHR1 deletion in atypical hemolytic uremic syndrome: a case report. Hematology (Amsterdam, Netherlands) 4 35617302
2023 CFH-CFHR1 hybrid genes in two cases of atypical hemolytic uremic syndrome. Journal of human genetics 3 36755127
2023 Structural modelling of human complement FHR1 and two of its synthetic derivatives provides insight into their in-vivo functions. Computational and structural biotechnology journal 3 36851916
2022 Atypical Hemolytic Uremic Syndrome-Associated FHR1 Isoform FHR1*B Enhances Complement Activation and Inflammation. Frontiers in immunology 3 35126388
2021 Exogenous BMP9 promotes lung fibroblast HFL-1 cell activation via ALK1/Smad1/5 signaling in vitro. Experimental and therapeutic medicine 3 34007337
2019 Three months interval therapy of Eculizumab in a patient with atypical hemolytic uremic syndrome with hybrid CFHR1/CFH gene. CEN case reports 3 30715674
2023 Atypical haemolytic uremic syndrome with refractory multiorgan involvement and heterozygous CFHR1/CFHR3 gene deletion. BMC nephrology 2 37147581
2024 CFHR1 involvement in bile duct carcinoma: Insights from a data mining study. Analytical biochemistry 1 38286352
2024 Case report: A family of atypical hemolytic uremic syndrome involving a CFH::CFHR1 fusion gene and CFHR3-1-4-2 gene duplication. Frontiers in immunology 1 38524137
2022 De novo systemic atypical hemolytic uremic syndrome in an ABO-incompatible living kidney transplant recipient with a novel pathogenic CFHR1 gene mutation successfully treated with eculizumab: a case report. Journal of nephrology 1 35852773
2022 An Infant Case of Streptococcus Pneumoniae-Associated Thrombotic Microangiopathy with Heterozygous CFI Mutation and CFHR3-CFHR1 Deletion. The Tohoku journal of experimental medicine 1 36070894
2017 [Study on the CFHR1 level and its genetic polymorphisms in type 2 diabetes mellitus patients]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 1 28604974
2026 Deletion of the Mouse Homolog of Human FHR1 (muFHR1) Alleviates Atherosclerosis in ApoE-/- mice. International journal of medical sciences 0 41583528
2026 Dual pathogenic variants in ADAMTS13 and CFHR1/CFHR3 deletion: divergent thrombotic microangiopathy phenotypes in siblings. Pediatric nephrology (Berlin, Germany) 0 42113272
2024 Cfhr1 gene deficiency exacerbates Staphylococcus aureus-induced sepsis and acute lung injury through complement alternative pathway hyperactivation. Biochemical and biophysical research communications 0 39128222

Missed literature

Know a paper Affinage missed for CFHR1? Flag it for the maintainers and the community.

No submissions yet.