Affinage

CFHR1

Complement factor H-related protein 1 · UniProt Q03591

Length
330 aa
Mass
37.7 kDa
Annotated
2026-04-28
73 papers in source corpus 21 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CFHR1 (FHR-1) is a secreted complement regulatory protein that fine-tunes the balance between complement activation and suppression on cell surfaces, extracellular matrices, and microbial surfaces, while also driving complement-independent sterile inflammation. FHR-1 circulates as homo- and heterodimers (with FHR-2) whose N-terminal dimerization domains are required for effective C3b/C3d binding; its C-terminal SCR3–5 domains share the same C3b-binding interface as CFH SCR19-20, enabling dose-dependent competition with CFH that displaces CFH cofactor activity and promotes alternative pathway amplification on surfaces including ECM components (laminin, fibromodulin), DNA, necrotic cells, pentraxins (monomeric CRP, PTX3), and microbial targets (PMID:27814381, PMID:23728178, PMID:35392081, PMID:32765490, PMID:28533443). While FHR-1 can inhibit C5 convertase and terminal complement complex formation under certain conditions (PMID:19528535), murine knockout studies demonstrate that loss of FHR-1 leads to excessive alternative pathway activation and worsened sepsis-associated organ injury, confirming a net regulatory role in vivo (PMID:32636836, PMID:39128222). Independently of complement, FHR-1 binds necrotic cells via its N-terminus and signals through the GPCR EMR2 to activate the NLRP3 inflammasome via the phospholipase C pathway, driving IL-1β, TNFα, and IL-6 secretion from monocytes, and promoting mononuclear phagocyte invasion and neoangiogenesis in retinal disease models (PMID:31273197, PMID:40611130).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2009 High

    Establishing that FHR-1 acts at the terminal complement pathway: FHR-1 was shown to inhibit C5 convertase and MAC formation independently of CFH's C3 convertase regulation, revealing a distinct level of complement control and raising the question of how FHR-1 and CFH partition regulatory functions on surfaces.

    Evidence In vitro C5 convertase inhibition, C5b deposition, and MAC formation assays with binding competition on cell surfaces

    PMID:19528535

    Open questions at the time
    • Whether FHR-1 C5 convertase inhibition operates in vivo
    • Whether terminal pathway regulation is the dominant activity or context-dependent
    • The structural basis for C5 convertase recognition by FHR-1
  2. 2009 Medium

    Linking CFHR1 deficiency to autoimmune pathology: CFHR1-deficient aHUS patients specifically generated anti-FH autoantibodies, suggesting FHR-1 may serve as an immune tolerance antigen for CFH due to shared epitopes.

    Evidence Proteomics of CFHR proteins in plasma combined with genotype-phenotype correlation in aHUS cohorts

    PMID:19745068

    Open questions at the time
    • Mechanism of tolerance breakdown in CFHR1 deficiency not demonstrated experimentally
    • Correlation does not establish causality — could reflect linked deletions
    • No B-cell or T-cell epitope mapping performed
  3. 2010 High

    Demonstrating microbial surface exploitation: FHR-1 was recruited to group A streptococcal surfaces via Scl1 proteins through its C-terminal SCR3–5, displacing CFH and thereby shifting complement regulation from C3 convertase to terminal pathway level.

    Evidence Pulldown and competition binding assays with domain mutagenesis and complement functional assays on streptococcal surfaces

    PMID:20855886

    Open questions at the time
    • In vivo relevance of FHR-1 recruitment in streptococcal infection not established
    • Whether this mechanism extends to other Gram-positive pathogens
  4. 2013 High

    Revealing that dimerization/oligomerization is functionally critical: native FHR-1 circulates as dimers that enhance avidity for C3b/iC3b/C3dg; a C3G-associated CFHR1 N-terminal duplication created abnormally large multimers with pathologically enhanced CFH competition, establishing that oligomeric state directly controls complement deregulatory potency.

    Evidence SPR, hemolytic assays, and biochemical analysis of patient-derived mutant FHR1 oligomers

    PMID:23728178

    Open questions at the time
    • High-resolution structure of the dimerization interface not determined
    • How oligomeric state is regulated in vivo
  5. 2014 High

    Establishing fusion proteins as competitive antagonists of CFH: a naturally occurring CFHR1/CFH hybrid protein containing FHR-1 N-terminal dimerization domains fused to CFH SCR20 competed with FH and caused complement-mediated hemolysis and C5b-9 deposition on endothelial cells.

    Evidence FH-dependent hemolysis assay and C5b-9 deposition on endothelial cells with patient-derived hybrid protein

    PMID:24904082

    Open questions at the time
    • Prevalence and penetrance of hybrid gene in broader populations
    • Whether hybrid formation requires specific genomic rearrangement hotspots
  6. 2016 High

    Defining the structural basis for CFH competition: mutagenesis showed that FHR-1 dimerization is necessary for C3b/C3d binding, that the binding interface is identical to CFH SCR19-20, and that FHR-1 sterically blocks both C-terminal and N-terminal CFH interactions with C3b, unifying the competitive deregulation model.

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

    PMID:27814381

    Open questions at the time
    • Crystal or cryo-EM structure of FHR-1 dimer bound to C3b not available
    • Relative affinities under physiological conditions on cell surfaces
  7. 2017 High

    Resolving how FHR-1 promotes complement activation on damaged tissues: FHR-1 binds monomeric CRP and permits C3 convertase formation on ECM and necrotic cells, enhancing both classical and alternative pathway activation — contradicting the earlier view that FHR-1 primarily inhibits terminal complement.

    Evidence ELISA binding assays, complement activation assays on ECM and necrotic cell surfaces, C3 convertase formation assay

    PMID:28533443

    Open questions at the time
    • Which activity predominates in vivo — complement inhibition or activation — remains context-dependent
    • Whether CRP conformational state is controlled at injury sites
  8. 2017 High

    Characterizing the dynamics of FHR dimeric pools: FRET demonstrated rapid monomer exchange between FHR-1 homodimers and FHR-1/FHR-2 heterodimers in plasma, and CFHR1-deletion individuals confirmed loss of all FHR-1-containing dimers.

    Evidence FRET, ELISA, and ex vivo serum analysis from CFHR1-deletion individuals

    PMID:29093712

    Open questions at the time
    • Functional differences between FHR-1/1 homodimers and FHR-1/2 heterodimers not defined
    • Whether monomer exchange is regulated or stochastic
  9. 2019 High

    Discovering a complement-independent inflammatory function: FHR-1 binds necrotic cells via its N-terminus and signals through the GPCR EMR2 to activate the NLRP3 inflammasome via the PLC pathway, inducing IL-1β, TNFα, IL-18, and IL-6 secretion from monocytes — a function unique to FHR-1 among FHR family members.

    Evidence In vitro binding, inflammasome activation, cytokine ELISA, EMR2 receptor identification, PLC pathway pharmacological inhibition, patient tissue staining

    PMID:31273197

    Open questions at the time
    • The FHR-1/EMR2 binding interface not structurally defined
    • Whether other cell types respond to FHR-1 via EMR2
    • In vivo contribution of FHR-1–EMR2 axis to sterile inflammation not demonstrated at that time
  10. 2019 Medium

    Extending FHR-1 to atherosclerosis: FHR-1 was found on circulating extracellular vesicles and deposited in atherosclerotic plaques, where surface-bound FHR-1 induced proinflammatory cytokine and tissue factor expression in monocytes and neutrophils.

    Evidence Isolation from plasma EVs, immunostaining of human plaques, cytokine/tissue factor induction assays

    PMID:34795372

    Open questions at the time
    • Causal role of FHR-1 in plaque formation not established by this study alone
    • Whether EV-associated FHR-1 has different activity than soluble FHR-1
  11. 2020 Medium

    Demonstrating in vivo complement regulatory role: Cfhr1 knockout mice showed enhanced alternative pathway activation and more severe sepsis/acute kidney injury upon LPS challenge, establishing that FHR-1 has a net protective, complement-dampening function in vivo during endotoxemia.

    Evidence Cfhr1 knockout mouse model with LPS-induced sepsis/AKI, complement activation assays in vitro and in vivo

    PMID:32636836

    Open questions at the time
    • Mouse FHR-E is not identical to human FHR-1 — species-specific differences in complement regulation
    • Whether the in vivo effect is direct C5 convertase inhibition or indirect via CFH modulation
  12. 2020 High

    Broadening ligand repertoire to DNA and pentraxins: FHR-1 binds DNA, recruits monomeric CRP and PTX3 to dead cells, and inhibits FH binding to DNA, collectively enhancing complement activation via both classical and alternative pathways on apoptotic/necrotic surfaces.

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

    PMID:32765490

    Open questions at the time
    • Whether DNA-bound FHR-1 contributes to lupus-like autoimmunity
    • Relative contributions of CRP vs PTX3 recruitment in vivo
  13. 2021 High

    Resolving why FHR-1 does not normally compete with CFH on host cells: wild-type FHR-1 lacks sialic acid binding capacity, preventing effective competition on sialylated host surfaces; aHUS-associated mutations confer sialic acid binding, enabling pathological CFH displacement and surface complement activation.

    Evidence NMR spectroscopy, biochemical binding assays, computational modeling of FHR-1 mutants, functional complement activation assays

    PMID:33651882

    Open questions at the time
    • Whether sialic acid binding distinguishes pathogenic from benign FHR-1 variants genome-wide
    • Structural mechanism of sialic acid recognition by mutant FHR-1
  14. 2022 High

    Defining ECM as a major surface for FHR-1 activity: FHR-1 binds laminin, fibromodulin, osteoadherin, and PRELP via CCP4-5, displaces FH, and enhances alternative pathway activation with increased C3-fragment, factor B, and C5b-9 deposition on ECM surfaces.

    Evidence ELISA/SPR binding, domain mapping, cofactor activity, and complement activation on immobilized ECM proteins

    PMID:35392081

    Open questions at the time
    • Whether ECM-bound FHR-1 contributes to fibrosis or tissue remodeling
    • In vivo validation of FHR-1 ECM interactions
  15. 2022 Medium

    Establishing that natural FHR-1 isoform variation modulates disease risk: the aHUS-associated FHR1*B isoform shows higher C3b binding, stronger CFH displacement, and greater inflammasome-activating capacity compared to FHR1*A, connecting common polymorphism to quantitative differences in both complement and inflammatory outputs.

    Evidence Recombinant FHR1*A vs *B proteins tested in C3b binding, cofactor, C3 convertase, and cytokine secretion assays

    PMID:35126388

    Open questions at the time
    • Single lab study — independent replication needed
    • Population-level contribution of FHR1*B to aHUS risk not quantified
  16. 2024 Medium

    Connecting FHR-1 to metabolic inflammation: muFHR1 knockout in ApoE-/- mice normalized cholesterol, reduced plaque formation, and decreased foam cell development, with muFHR1 shown to direct oxLDL uptake by macrophages.

    Evidence muFHR1-/- ApoE-/- double knockout mouse model with RNAseq, cholesterol measurements, and plaque quantification

    PMID:41583528

    Open questions at the time
    • Mechanism of FHR-1-mediated oxLDL uptake not defined at receptor level
    • Mouse-to-human translatability of metabolic phenotype uncertain
  17. 2025 Medium

    Validating the FHR-1/EMR2 axis in vivo in retinal disease: FHR-1 accumulates sub-RPE in AMD, signals through EMR2 on RPE and phagocytes to induce Ca2+ flux and transcriptional changes, and muFHR1 deletion significantly reduced phagocyte invasion and neoangiogenesis in laser-induced CNV, establishing a para-inflammatory signaling role in AMD.

    Evidence AMD donor tissue immunostaining, EMR2 receptor identification, Ca2+ signaling in RPE cells, muFHR1 KO mouse in laser-induced CNV model

    PMID:40611130

    Open questions at the time
    • Whether therapeutic FHR-1 blockade or EMR2 antagonism protects against AMD progression
    • Contribution of complement-dependent vs complement-independent FHR-1 effects in the retina

Open questions

Synthesis pass · forward-looking unresolved questions
  • Open question: the context-dependent switch between FHR-1's complement-activating and complement-inhibiting functions, the structural basis of FHR-1/EMR2 signaling, and whether FHR-1 can be therapeutically targeted in complement-mediated and inflammatory diseases remain unresolved.
  • No high-resolution structure of FHR-1 dimer or FHR-1/EMR2 complex available
  • Quantitative partitioning of complement-inhibitory vs complement-activating functions across tissues and disease states not defined
  • No clinical trials targeting FHR-1 or the FHR-1/EMR2 axis reported

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 6 GO:0048018 receptor ligand activity 2
Localization
GO:0005576 extracellular region 5 GO:0031012 extracellular matrix 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-168256 Immune System 10 R-HSA-162582 Signal Transduction 2
Partners
C3BCFHCRPEMR2FHR2PTX3
Complex memberships
FHR-1 homodimerFHR-1/FHR-2 heterodimer

Evidence

Reading pass · 21 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 (terminal complex) formation on cell surfaces, acting distinctly from CFH which regulates at the C3 convertase level; both proteins bind to the same or similar sites on cellular surfaces, with CFHR1 gain of activity presumed to be at the expense of CFH-mediated C3 convertase inhibition. In vitro complement assays (C5 convertase inhibition, C5b deposition assay, MAC formation assay), binding competition studies on cell surfaces Blood High 19528535
2013 Native FHR1, FHR2, and FHR5 circulate in plasma as homo- and hetero-oligomeric complexes mediated by conserved N-terminal SCR domains. A C3G-associated CFHR1 mutation duplicating the N-terminal domain caused unusually large multimeric FHR complexes with increased avidity for C3b, iC3b, and C3dg, and enhanced competition with CFH in surface plasmon resonance studies and hemolytic assays. SPR (surface plasmon resonance), hemolytic assays, biochemical characterization of mutant FHR1 oligomers, plasma protein analysis The Journal of clinical investigation High 23728178
2016 CFHR1 dimerization is necessary for effective binding to C3b and C3d, and for competition with CFH. The C3b/C3d:CFHR1 binding interface is identical to that of CFH SCR19-20 with C3b. CFHR1 also competes with the CFH splice variant CFHL-1 for C3b binding, sterically blocking both C-terminal and N-terminal CFH interactions with C3b. Site-directed mutagenesis, ELISA-based binding assays, functional hemolytic assays PloS one High 27814381
2017 FHR-1 binds to monomeric CRP (but not native pentameric CRP) via its C-terminal domains. FHR-1/CRP interactions increase complement activation via the classical and alternative pathways on extracellular matrix and necrotic cell surfaces. FHR-1 also binds C3b and allows C3 convertase formation, thereby enhancing rather than inhibiting complement activation. FHR-1 did not inhibit terminal complement complex formation induced by zymosan. Binding assays (ELISA), complement activation assays on surfaces (ECM, necrotic cells), C3 convertase formation assay Journal of immunology High 28533443
2017 FHR-1 and FHR-2 form homodimers and FHR-1/FHR-2 heterodimers in human plasma; FHR-5 circulates only as homodimer. FRET analysis demonstrated rapid monomer exchange between FHR dimers. In CFHR1-deletion individuals, FHR-1/1 and FHR-1/2 dimers were absent. FHR-5/5 homodimers showed strong heparin binding affinity. ELISA, FRET, ex vivo serum analysis from deletion individuals, recombinant protein analysis Frontiers in immunology High 29093712
2019 FHR1 selectively binds to necrotic cells via its N-terminus and triggers NLRP3 inflammasome activation in blood-derived human monocytes, leading to secretion of IL-1β, TNFα, IL-18, and IL-6. This signaling is mediated via the G-protein coupled receptor EMR2 through the phospholipase C pathway, independent of complement. FHR1, but not FH, FHR2, or FHR3, drove this inflammatory response. In vitro binding assays, inflammasome activation assay (NLRP3), cytokine secretion (ELISA), receptor identification (EMR2), pharmacological pathway inhibition (PLC pathway), staining of patient tissues Nature communications High 31273197
2021 FHR-1 lacks the capacity to bind sialic acids (unlike CFH), which prevents C3b-binding competition between FH and FHR-1 on host-cell surfaces under normal conditions. aHUS-associated FHR-1 mutants are pathogenic because they have acquired sialic acid-binding capacity, increasing FHR-1 avidity for surface-bound C3-activated fragments and enabling competition with FH. FHR-1 also binds native C3 in addition to C3b, iC3b, and C3dg, and surface-bound FHR-1 promotes complement activation by attracting native C3 to the cell surface. Biochemical assays, immunological assays, NMR spectroscopy, computational modeling of FHR-1 mutants, functional complement activation assays Blood High 33651882
2010 CFHR1 binds to streptococcal Scl1.6 and Scl1.55 proteins via its conserved C-terminal SCR3-5 attachment region; binding is affected by ionic strength and heparin. CFHR1 binding to streptococcal surfaces is at the expense of CFH-mediated C3 convertase regulatory function but provides terminal complement control (C5 convertase/MAC level). CFH mutations associated with aHUS blocked CFHR1 interaction with Scl1 proteins. Pulldown/binding assays, complement functional assays (C3 convertase regulation), mutagenesis of binding domains, ionic strength/heparin competition The Journal of biological chemistry High 20855886
2020 FHR-1 and FHR-5 bind to plasmid DNA and human genomic DNA, inhibiting FH binding to DNA and reducing FH cofactor activity. Both FHRs also bind to late apoptotic and necrotic cells, recruit monomeric CRP and pentraxin 3, and FHR-pentraxin interactions promote enhanced activation of both classical and alternative complement pathways on dead cells when exposed to human serum. Binding assays (ELISA, pulldown), complement activation assays on DNA and dead cells, cofactor activity assay Frontiers in immunology High 32765490
2022 FHR1 binds extracellular matrix components laminin, fibromodulin, osteoadherin, and PRELP through its C-terminal CCP domains 4-5. FHR1 inhibits FH binding to these ECM ligands in a dose-dependent manner, reducing FH cofactor activity, and enhances alternative complement pathway activation on immobilized ECM proteins, resulting in increased C3-fragment, factor B, and C5b-9 deposition. Binding assays (ELISA/SPR), cofactor activity assay, complement activation assay on immobilized ECM proteins, domain mapping Frontiers in immunology High 35392081
2014 A novel CFHR1/CFH hybrid fusion protein containing the first four SCRs of FHR1 and the terminal SCR20 of CFH acts as a competitive antagonist of FH. In an FH-dependent hemolysis assay, the hybrid protein caused sheep erythrocyte lysis, and sera from carriers induced more C5b-9 deposition on endothelial cells than control serum. FH-dependent hemolysis assay, C5b-9 deposition assay on endothelial cells, purification of hybrid protein from patient serum Journal of the American Society of Nephrology : JASN High 24904082
2022 The aHUS-associated FHR1*B isoform (CFHR1*B haplotype) exhibits higher C3b-binding capacity and stronger binding to necrotic cells than FHR1*A. FHR1*B shows stronger interference with FH-mediated cofactor function (less C3b cleavage) and stronger deregulation of FH inhibition of C3bBb assembly. FHR1*B also triggers higher IL-1β and IL-6 secretion from monocytes than FHR1*A. Homology modeling, recombinant protein expression, C3b binding assays, cofactor assay, C3 convertase assay, cytokine secretion assay Frontiers in immunology Medium 35126388
2018 FHR-1 competes with FH for binding to Plasmodium falciparum surfaces (intraerythrocytic schizonts and merozoites). FHR-1 accumulates on parasite surfaces and impairs C3b inactivation and parasite viability; FHR-1-deficient serum showed increased FH binding to parasites, and adding recombinant FHR-1 decreased FH binding. Binding competition assays with FHR-1-deficient serum and recombinant FHR-1, C3b inactivation assay, parasite viability assay Journal of immunology Medium 30455399
2009 Leptospiral immunoglobulin-like (Lig) proteins mediate acquisition of FHR-1 from human serum onto the Leptospira surface, contributing to bacterial complement evasion. Competition assays showed FH and C4BP have distinct binding sites on Lig proteins. Serum acquisition assays, pulldown, competition binding assays The Journal of infectious diseases Medium 22291192
2020 Deletion of mouse Cfhr1 (FHR-E, the murine homolog of human FHR-1) enhanced LPS-induced alternative complement pathway activation both in vitro and in vivo, and Cfhr1 knockout mice exhibited more severe sepsis and acute kidney injury in response to LPS challenge, demonstrating that FHR-E/FHR-1 regulates the alternative pathway in vivo. Cfhr1 knockout mouse model, LPS-induced sepsis/AKI model, complement activation assays in vitro and in vivo Frontiers in immunology Medium 32636836
2025 FHR1 accumulates below the retinal pigment epithelium (RPE) in AMD. FHR1 signals through the receptor EMR2 (EGF-like module-containing mucin-like hormone receptor 1) on RPE and mononuclear phagocytes (MPs) to induce Ca2+ signaling and gene expression changes. muFHR1 deletion in mice significantly reduced mononuclear phagocyte invasion and neoangiogenesis in laser-induced choroidal neovascularization (CNV) model, establishing an EMR2-dependent FHR1 signaling pathway promoting para-inflammation. AMD donor tissue immunostaining, murine AMD models (RNAseq), EMR2 receptor identification, Ca2+ signaling assay in RPE cells, muFHR1 KO mouse in laser-induced CNV model Journal of neuroinflammation Medium 40611130
2016 CFHR1-modified neural stem cells (NSCs) blocked complement activation cascade and inhibited membrane attack complex formation in a neuromyelitis optica spectrum disorder model, protecting endogenous and transplanted NSC-differentiated astrocytes from immune-mediated damage. Engineered NSC transplantation in NMOSD model, complement activation assay, MAC formation assay Journal of immunology Medium 27671112
2024 Deletion of muFHR1 (mouse homolog of FHR-1) in ApoE-/- mice normalized cholesterol levels, reduced inflammation and plaque formation. muFHR1 deletion enhanced lipid conversion in the liver (RNAseq), and muFHR1 was found to direct oxLDL uptake by macrophages, supporting foam cell formation and plaque development. muFHR1-/- ApoE-/- double knockout mouse model, RNAseq, cholesterol measurements, plaque quantification International journal of medical sciences Medium 41583528
2019 FHR-1 circulates on extracellular vesicles and is deposited in atherosclerotic plaques. Surface-bound FHR-1 induces expression of pro-inflammatory cytokines and tissue factor in monocytes and neutrophils. Isolation of FHR-1 from plasma/extracellular vesicles, immunostaining of plaques, cytokine/tissue factor induction assays in monocytes and neutrophils Scientific reports Medium 34795372
2009 Patients lacking CFHR1 (but not those lacking CFHR3 alone) present with anti-FH autoantibodies, suggesting that CFHR1 deficiency specifically promotes generation of anti-CFH autoantibodies, possibly due to lack of CFHR1 as an immune tolerance antigen sharing epitopes with CFH. Proteomics strategy to analyze CFHR proteins in plasma, genotype-phenotype correlation in aHUS cohorts Blood Medium 19745068
2024 Cfhr1 gene knockout in mice led to excessive alternative complement pathway activation and enhanced C3a formation in lung tissues following S. aureus infection, resulting in higher bacterial loads in lungs and exacerbated sepsis-induced acute lung injury. Cfhr1-knockout mouse model, S. aureus i.v. infection model, C3a measurement, bacterial CFU counts, cytokine/complement factor measurements, RNA-seq Biochemical and biophysical research communications Medium 39128222

Source papers

Stage 0 corpus · 73 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 386 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 221 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 132 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 119 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
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
2019 Serum FHR1 binding to necrotic-type cells activates monocytic inflammasome and marks necrotic sites in vasculopathies. Nature communications 59 31273197
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 49 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 39 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
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
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 36 24557084
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 19 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
2021 Membrane recruitment of Atg8 by Hfl1 facilitates turnover of vacuolar membrane proteins in yeast cells approaching stationary phase. BMC biology 17 34088313
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 17 32636836
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
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
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 9 36068772
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 8 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
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
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
2025 Factor-H-related protein 1 (FHR1), a promotor of para-inflammation in age-related macular degeneration. Journal of neuroinflammation 5 40611130
2023 Complete biodegradation of fungicide carboxin and its metabolite aniline by Delftia sp. HFL-1. The Science of the total environment 5 38030002
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
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