Affinage

CFH

Complement factor H · UniProt P08603

Round 2 corrected
Length
1231 aa
Mass
139.1 kDa
Annotated
2026-04-28
130 papers in source corpus 21 papers cited in narrative 18 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Complement factor H (CFH) is a soluble 20-CCP-domain plasma glycoprotein that serves as the principal negative regulator of the alternative complement pathway, restraining amplification both in the fluid phase and on host cell surfaces. Its N-terminal domains (SCR1–4) mediate C3b binding, cofactor activity for factor I–mediated C3b inactivation, and decay-acceleration of the C3 convertase C3bBb, while C-terminal domains (SCR19–20) discriminate self from non-self by recognizing polyanion markers such as sialic acid and heparan sulfate on host surfaces (PMID:15163532, PMID:20580090). Loss-of-function mutations in the C-terminal surface-recognition domains cause atypical hemolytic uremic syndrome (aHUS), whereas variants impairing fluid-phase regulation predispose to C3 glomerulopathy, and the common Y402H polymorphism in SCR7 impairs binding to heparin, C-reactive protein, and the lipid peroxidation product malondialdehyde, conferring strong risk for age-related macular degeneration (PMID:9551389, PMID:15761122, PMID:21979047, PMID:19297022). Pathogens including Neisseria meningitidis and Candida albicans recruit CFH to their surfaces via specific CCP-domain interactions to evade complement-mediated killing, and an alternatively spliced variant FHL-1 (SCR1–7) functions as the predominant complement regulator at Bruch's membrane (PMID:16785547, PMID:17959597, PMID:33178228).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1988 High

    Determining the complete primary structure of CFH revealed a modular 20-CCP-repeat architecture and evidence for alternative splicing, establishing the structural framework for all subsequent domain-function studies.

    Evidence cDNA cloning and sequencing of overlapping clones covering the full-length 1213-amino-acid protein

    PMID:2963625

    Open questions at the time
    • Three-dimensional structure of individual CCP domains and full-length CFH not yet resolved
    • Functional roles of individual CCP domains not mapped
  2. 2004 High

    Biochemical reconstitution and domain-deletion mutagenesis established that CFH controls the alternative pathway through three distinct activities—factor I cofactor activity, C3 convertase decay acceleration, and polyanion-dependent host-surface recognition—mapped to separable CCP domains.

    Evidence Synthesis of in vitro reconstitution, binding assays, and domain-deletion mutagenesis from multiple laboratories

    PMID:15163532

    Open questions at the time
    • Precise stoichiometry and kinetics of CFH–C3b interaction on physiological surfaces not fully defined
    • Relative contributions of each activity in vivo not resolved
  3. 1998 High

    Identification of CFH mutations in familial and sporadic HUS provided the first causal genetic link between defective alternative pathway regulation and thrombotic microangiopathy, showing that both loss-of-expression (frameshift) and C-terminal missense variants drive disease.

    Evidence Linkage analysis at 1q32 followed by direct CFH gene mutation screening in HUS families

    PMID:9551389

    Open questions at the time
    • Spectrum of causative mutations incomplete
    • Mechanism by which C-terminal mutations specifically predispose to endothelial damage not elucidated
  4. 2005 High

    Genome-wide association identified Y402H in SCR7 as a major AMD risk variant, implicating complement dysregulation in macular degeneration and pinpointing the heparin/CRP-binding region as functionally critical for retinal protection.

    Evidence GWAS (116,204 SNPs) with resequencing in AMD case-control cohorts; independently replicated across four studies

    PMID:15761120 PMID:15761121 PMID:15761122 PMID:15870199

    Open questions at the time
    • Molecular mechanism by which Y402H alters local complement regulation at Bruch's membrane not defined
    • Whether the variant acts through altered CRP binding, heparin binding, or both remained unclear
  5. 2006 High

    Combined pathogen-interaction and genotype-phenotype studies demonstrated that CFH domain specificity determines both disease type and microbial exploitation: C-terminal SCR19–20 mutations cause aHUS via loss of surface protection, and bacteria such as N. meningitidis hijack CFH to their surfaces via specific protein–protein interactions to evade complement killing.

    Evidence Genetic screening of 156 HUS patients with functional characterization of mutant proteins; GNA1870 deletion mutant, flow cytometry, and serum bactericidal assays for meningococcal fH binding

    PMID:16621965 PMID:16785547

    Open questions at the time
    • Full repertoire of microbial CFH-binding proteins not catalogued
    • Structural basis of CFH recruitment to bacterial surfaces not resolved at atomic level
  6. 2009 High

    Systematic genotype-phenotype correlation resolved the paradox of how CFH variants cause different diseases: N-terminal dysfunction impairs fluid-phase C3b regulation causing MPGN/C3 glomerulopathy, while C-terminal dysfunction abrogates host-surface recognition causing aHUS.

    Evidence Functional studies of disease-associated CFH variants measuring C3b binding, cofactor activity, and surface binding across large patient cohorts

    PMID:19297022

    Open questions at the time
    • Incomplete penetrance and environmental modifiers not explained
    • Role of CFH-related proteins (CFHRs) in modifying disease phenotype only partially understood
  7. 2010 High

    Anti-CFH autoantibodies targeting SCR19–20 were shown to functionally mimic C-terminal loss-of-function mutations, causing aHUS almost exclusively in patients with homozygous CFHR1/CFHR3 deletion, revealing a genetic susceptibility to autoimmune complement dysregulation.

    Evidence Autoantibody epitope mapping by ELISA, functional surface-binding inhibition assays, and genetic deletion analysis in patient cohorts

    PMID:19190803 PMID:20157737

    Open questions at the time
    • Mechanism by which CFHR1 deletion breaks immune tolerance to CFH not established
    • Whether autoantibodies also impair fluid-phase CFH activity not fully tested
  8. 2011 High

    Discovery that CFH is a major plasma MDA-binding protein that blocks MDA-induced macrophage uptake and inflammation provided a complement-independent protective function and mechanistically explained the AMD-risk Y402H variant, which has markedly reduced MDA binding.

    Evidence In vitro MDA-binding and macrophage uptake assays with recombinant CFH; in vivo mouse inflammation model; comparative binding of Y402 versus H402 variants

    PMID:21979047

    Open questions at the time
    • In vivo relevance of MDA-binding in human retina not directly demonstrated
    • Whether MDA-binding operates independently of or synergistically with complement regulation in AMD not resolved
  9. 2018 High

    Large-scale structural genomic analysis of the CFH-CFHR locus identified recurrent hybrid gene formation and confirmed bipolar clustering of rare disease mutations—N-terminal for AMD, C-terminal for aHUS—under positive selection, revealing ongoing evolutionary pressures shaping domain-specific regulation.

    Evidence High-quality sequencing of ~360-kbp locus across six primate species; structural variant analysis in >2,400 individuals; burden testing in >5,000 AMD cases/controls

    PMID:29686068

    Open questions at the time
    • Functional consequences of most hybrid CFH-CFHR proteins not tested biochemically
    • Selective pressures driving CFHR copy-number variation not identified
  10. 2020 Medium

    Characterization of the alternative splice variant FHL-1 (SCR1–7) as the predominant complement regulator at Bruch's membrane established tissue-specific division of labor between CFH and FHL-1 and showed that pathogens and tumors can selectively exploit FHL-1 for immune evasion.

    Evidence Synthesis of splice variant functional assays, Bruch's membrane localization studies, and microbial/tumor binding analyses

    PMID:33178228

    Open questions at the time
    • Mechanisms controlling relative CFH versus FHL-1 expression in specific tissues not fully defined
    • Whether FHL-1 loss alone is sufficient for AMD pathology not tested
  11. 2021 Medium

    Endogenous CFH in RPE cells was shown to modulate local complement and cytokine expression through NF-κB signaling, demonstrating that CFH has cell-autonomous anti-inflammatory functions beyond its classical role as a plasma complement regulator.

    Evidence CFH siRNA silencing in hTERT-RPE1 cells; cytokine and complement protein quantification; NF-κB pathway inhibition experiments

    PMID:34445430

    Open questions at the time
    • Whether intracellular CFH directly engages NF-κB pathway components or acts indirectly through autocrine complement signaling unknown
    • Relevance of RPE-derived CFH versus liver-derived plasma CFH in AMD pathogenesis not resolved in vivo

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis for how full-length CFH simultaneously engages C3b and host-surface polyanions in a physiological membrane context, and how intracellular CFH functions are integrated with canonical plasma complement regulation, remain unresolved.
  • No high-resolution structure of full-length CFH bound to C3b on a membrane surface
  • Intracellular signaling mechanisms of CFH in RPE and other cells not defined
  • Therapeutic strategies to selectively restore surface-specific CFH function in aHUS or AMD not clinically validated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0008289 lipid binding 3 GO:0140096 catalytic activity, acting on a protein 3
Localization
GO:0005576 extracellular region 4 GO:0031012 extracellular matrix 2
Pathway
R-HSA-168256 Immune System 7 R-HSA-1643685 Disease 5
Partners
C3BCFBCFICRPFHBP

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1988 CFH (complement factor H) is a 1213-amino-acid protein composed of 20 homologous ~60-amino-acid complement control protein (CCP/SCR) repeat units; cDNA sequencing revealed an 18-residue leader sequence and a tyrosine/histidine polymorphism in the seventh repeat unit, and evidence for alternative splicing producing at least two mRNA species. cDNA cloning and sequencing of three overlapping clones; protein sequence analysis The Biochemical journal High 2963625
1998 Mutations in the CFH gene (including a frameshift/premature stop causing half-normal serum factor H levels, and a point mutation in exon 20 causing an Arg-to-Gly change) are causally linked to familial and sporadic hemolytic uremic syndrome (HUS), implicating defective alternative pathway complement regulation in HUS pathogenesis. Genetic linkage analysis (microsatellite markers at 1q32) followed by direct mutation analysis of the CFH gene in HUS patients and families Kidney international High 9551389
2004 CFH is an essential soluble complement regulatory protein that controls the alternative pathway in plasma and on cell surfaces by acting as a cofactor for factor I-mediated cleavage of C3b, by accelerating decay of the C3 convertase C3bBb, and by recognizing polyanion markers on host cells; distinct functional domains within the 20 CCP units mediate C3b binding, decay-acceleration, and surface recognition. Review synthesizing biochemical reconstitution, domain-deletion mutagenesis, and binding studies from multiple labs Molecular immunology High 15163532
2005 A common Y402H polymorphism in CFH's seventh CCP domain (which binds heparin and C-reactive protein) is strongly associated with AMD risk (OR ~7.4 for homozygotes), identifying CFH's heparin/CRP-binding domain as functionally critical for macular protection. Genome-wide SNP association study (116,204 SNPs, 96 cases/50 controls) followed by resequencing to identify the coding variant; functional domain mapping Science (New York, N.Y.) High 15761120 15761121 15761122 15870199
2006 CFH (factor H) accumulates within drusen of the retinal pigment epithelium and is synthesized by RPE cells; the Y402H risk variant is located in a region mediating heparin and C-reactive protein binding, and multiple CFH haplotypes confer elevated or reduced AMD risk through effects on alternative complement pathway regulation at Bruch's membrane. Immunohistochemical localization of CFH in drusen; genetic association with functional haplotype analysis in ~900 AMD cases and ~400 controls Proceedings of the National Academy of Sciences of the United States of America High 15870199
2006 Neisseria meningitidis outer-membrane lipoprotein GNA1870 (fHbp) binds human complement factor H (CFH) via direct protein-protein interaction; this binding recruits CFH to the bacterial surface, attenuates C3 deposition, and enhances serum resistance. Deletion of GNA1870 abolishes fH binding and increases C3 deposition and bacterial killing. GNA1870 deletion mutant generation; flow cytometry measuring fH binding; C3 deposition assays; serum bactericidal assays; anti-GNA1870 mAb blocking experiments; mass spectrometry identification Journal of immunology (Baltimore, Md. : 1950) High 16785547
2006 Mutations in CFH (found in 15–30% of aHUS patients) impair complement regulation at host cell surfaces, predisposing to uncontrolled alternative pathway activation and endothelial damage; CFH mutations were identified in 30.1% of non-Shiga-toxin HUS patients, with mutations in the C-terminal SCR20 domain associated with poorest prognosis and highest disease recurrence after transplantation. Genetic screening of 156 non-Stx-HUS patients for CFH (and MCP, factor I) mutations; functional characterization of mutant proteins (C3b binding, expression levels); clinical outcome correlation Blood High 16621965
2007 Candida albicans surface phosphoglycerate mutase (CaGpm1p) binds human CFH via CCP domains SCR6-7 and SCR19-20 (two distinct contact regions), and also binds FHL-1 via SCR6-7; surface-bound CFH retains cofactor activity for factor I-mediated C3b cleavage, enabling immune evasion. Protein array screening of 4088 S. cerevisiae proteins; recombinant CaGpm1p expression and pulldown; flow cytometry; C3b cleavage cofactor assays; gpm1(-/-) mutant generation The Journal of biological chemistry High 17959597
2009 The spectrum of diseases caused by CFH variants depends on differential effects on plasma-phase versus surface-bound CFH function: variants impairing systemic fluid-phase regulation predispose to MPGN/C3 glomerulopathy, while variants specifically disrupting C-terminal surface-recognition domains (SCR19-20) predispose to aHUS by preventing CFH from protecting host cell surfaces. Genotype-phenotype correlation across large patient cohorts; functional studies of CFH variants examining C3b binding, factor I cofactor activity, and surface-binding capacity Molecular immunology High 19297022
2010 CFH controls the alternative complement pathway by acting as a competitive inhibitor of the C3 convertase (C3bBb): it binds C3b on host cell surfaces decorated with polyanions (sialic acid, heparan sulfate), acts as cofactor for factor I to inactivate C3b, and accelerates decay of C3bBb; pathogenic mutations in CFH disrupt these activities through reduced protein expression or dysfunctional surface recognition. Review synthesizing genetic screening, functional protein assays (cofactor activity, decay acceleration, surface binding), and mutation analysis across multiple patient cohorts Pediatric nephrology (Berlin, Germany) High 20526633
2010 IgG autoantibodies against CFH (targeting the C-terminal SCR19-20 domain) block CFH surface recognition function, mimicking gain-of-loss mutations at this domain and causing atypical HUS; these autoantibodies occur almost exclusively in patients with homozygous deletion of CFHR1/CFHR3 (the DEAP-HUS subgroup), suggesting CFHR1 normally competes with these autoantibodies or modulates immune tolerance. Autoantibody characterization by ELISA and epitope mapping; genetic deletion analysis by PCR/Southern blot; functional studies of CFH surface-binding inhibition Pediatric nephrology (Berlin, Germany) High 19190803 20157737
2011 CFH is a major plasma binding protein for malondialdehyde (MDA), a common lipid peroxidation product; CFH binds MDA-modified proteins, blocks their uptake by macrophages, and suppresses MDA-induced proinflammatory effects in vivo. The AMD-associated H402 polymorphism markedly reduces CFH's ability to bind MDA, providing a mechanistic link between this variant and AMD pathogenesis via impaired oxidative stress responses. In vitro MDA-binding assays with recombinant CFH; macrophage uptake inhibition assays; in vivo mouse inflammation model; comparative binding assays of Y402 vs H402 CFH variants Nature High 21979047
2012 miR-125b and miR-146a, which are upregulated in Alzheimer's disease brain and in NF-κB-activated neuronal-glial cells, directly target CFH mRNA and significantly reduce CFH protein expression; combinatorial NF-κB signaling drives these miRNAs to downregulate CFH in the context of neuroinflammation. miRNA expression profiling in post-mortem AD brain tissue and primary HNG cell culture; miRNA target prediction and validation; NF-κB inhibitor experiments; ANOVA-based quantification of CFH expression Molecular neurobiology Medium 22302353
2015 CFH loss of function in liver tumor-initiating cells promotes cancer stemness: knockdown of CFH abolishes tumorsphere formation and induces differentiation, while overexpression stimulates stemness factor expression and in vivo tumor growth; mechanistically, CFH maintains stemness through regulation of LSF-1 transcription factor expression. Primary tumorsphere culture; NanoString CD antigen gene expression; CFH siRNA knockdown and overexpression; in vivo xenograft assays; LSF-1 expression analysis Cancer letters Medium 26723877
2018 Rare structural variants (SVs) in the CFH-CFHR locus — including CFH::CFHR1 hybrid genes (caused by recurrent genomic rearrangements sharing a common 4.8-kbp ancestral CFHR promoter segment) — create fusion proteins with altered complement regulatory activity; bipolar clustering of rare nonsynonymous mutations in aHUS patients maps to C-terminal SCR domains (surface recognition) and in AMD patients maps to N-terminal domains (fluid-phase regulation), confirming domain-specific functional roles under positive selection. High-quality sequencing of ~360-kbp locus in six primate lineages; structural variant analysis in >2,400 individuals; burden testing in >5,000 AMD cases/controls; comparative genomics and selection analysis Proceedings of the National Academy of Sciences of the United States of America High 29686068
2020 Factor H-like protein 1 (FHL-1), an alternative splice variant of CFH comprising the first 7 N-terminal CCP domains of CFH, has regulatory activity comparable to full-length CFH and is the predominant complement regulator on Bruch's membrane (a critical site for AMD). FHL-1 is specifically recruited by certain microorganisms for complement evasion, and some cancers upregulate FHL-1 for immune evasion, indicating tissue-specific roles distinct from CFH. Review synthesizing splice variant characterization, functional complement regulation assays, localization studies in Bruch's membrane, microbial binding studies, and cancer tissue analysis Frontiers in immunology Medium 33178228
2021 Endogenous CFH expressed by RPE cells modulates complement regulation and inflammatory cytokine production independently of external complement sources; CFH silencing in hTERT-RPE1 cells increases IL-6, IL-8, GM-CSF, C3, and CFB while decreasing C5, and the NF-κB pathway is identified as the major pathway through which CFH loss drives these inflammatory and complement changes. CFH siRNA silencing in human hTERT-RPE1 cells; cytokine/complement protein quantification by ELISA and proteomics; NF-κB pathway inhibitor experiments; western blotting International journal of molecular sciences Medium 34445430
2010 Complement factor H is a soluble regulator essential for controlling alternative pathway activation: it recognizes polyanion markers (e.g., sialic acid, heparan sulfate) on host cell surfaces via its C-terminal domains (SCR19-20) to provide surface-specific protection, while N-terminal domains (SCR1-4) mediate C3b binding, factor I cofactor activity, and C3 convertase decay acceleration in the fluid phase. Review synthesizing structural domain studies, binding assays, mutagenesis, and disease-variant functional analysis Molecular immunology High 20580090

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Complement factor H polymorphism in age-related macular degeneration. Science (New York, N.Y.) 3310 15761122
2005 Complement factor H polymorphism and age-related macular degeneration. Science (New York, N.Y.) 1965 15761121
2005 Complement factor H variant increases the risk of age-related macular degeneration. Science (New York, N.Y.) 1959 15761120
2005 A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration. Proceedings of the National Academy of Sciences of the United States of America 1646 15870199
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2010 Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype. Clinical journal of the American Society of Nephrology : CJASN 773 20595690
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2013 Seven new loci associated with age-related macular degeneration. Nature genetics 649 23455636
2005 Hypothetical LOC387715 is a second major susceptibility gene for age-related macular degeneration, contributing independently of complement factor H to disease risk. Human molecular genetics 640 16174643
2006 Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome. Blood 555 16621965
2011 Genome-wide association study identifies susceptibility loci for IgA nephropathy. Nature genetics 522 21399633
2013 Immunology of age-related macular degeneration. Nature reviews. Immunology 514 23702979
1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 492 8125298
2006 Common variation in three genes, including a noncoding variant in CFH, strongly influences risk of age-related macular degeneration. Nature genetics 489 16936732
2004 The human complement factor H: functional roles, genetic variations and disease associations. Molecular immunology 447 15163532
2011 Complement factor H binds malondialdehyde epitopes and protects from oxidative stress. Nature 445 21979047
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2010 Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration. Proceedings of the National Academy of Sciences of the United States of America 433 20385819
1998 Genetic studies into inherited and sporadic hemolytic uremic syndrome. Kidney international 390 9551389
2010 Genome-wide association study of advanced age-related macular degeneration identifies a role of the hepatic lipase gene (LIPC). Proceedings of the National Academy of Sciences of the United States of America 376 20385826
2005 Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. Journal of proteome research 350 16335952
2007 Variation in complement factor 3 is associated with risk of age-related macular degeneration. Nature genetics 344 17767156
2006 The meningococcal vaccine candidate GNA1870 binds the complement regulatory protein factor H and enhances serum resistance. Journal of immunology (Baltimore, Md. : 1950) 330 16785547
2010 Complement control protein factor H: the good, the bad, and the inadequate. Molecular immunology 319 20580090
2008 Systemic complement activation in age-related macular degeneration. PloS one 310 18596911
1988 The complete amino acid sequence of human complement factor H. The Biochemical journal 309 2963625
2012 STEC-HUS, atypical HUS and TTP are all diseases of complement activation. Nature reviews. Nephrology 290 22986360
2022 Heart Failure Drug Treatment-Inertia, Titration, and Discontinuation: A Multinational Observational Study (EVOLUTION HF). JACC. Heart failure 247 36202739
2017 HUS and atypical HUS. Blood 206 28416508
2009 Mutations of the FHL1 gene cause Emery-Dreifuss muscular dystrophy. American journal of human genetics 176 19716112
2012 Renal and neurological involvement in typical Shiga toxin-associated HUS. Nature reviews. Nephrology 162 22986362
2012 Regulation of complement factor H (CFH) by multiple miRNAs in Alzheimer's disease (AD) brain. Molecular neurobiology 133 22302353
2011 Alternative complement pathway assessment in patients with atypical HUS. Journal of immunological methods 122 21215749
2010 Genetics and complement in atypical HUS. Pediatric nephrology (Berlin, Germany) 115 20526633
2020 Sacubitril/Valsartan: Neprilysin Inhibition 5 Years After PARADIGM-HF. JACC. Heart failure 112 33004114
2007 Gpm1p is a factor H-, FHL-1-, and plasminogen-binding surface protein of Candida albicans. The Journal of biological chemistry 106 17959597
2008 Association analysis of CFH, C2, BF, and HTRA1 gene polymorphisms in Chinese patients with polypoidal choroidal vasculopathy. Investigative ophthalmology & visual science 95 18515590
2013 CFH and ARMS2 genetic polymorphisms predict response to antioxidants and zinc in patients with age-related macular degeneration. Ophthalmology 91 23972322
2007 Persistent expression of hF.IX After tolerance induction by in utero or neonatal administration of AAV-1-F.IX in hemophilia B mice. Molecular therapy : the journal of the American Society of Gene Therapy 86 17565352
2009 The spectrum of phenotypes caused by variants in the CFH gene. Molecular immunology 80 19297022
2009 Clinical, histological and genetic characterization of reducing body myopathy caused by mutations in FHL1. Brain : a journal of neurology 78 19181672
2013 Genetic influences on plasma CFH and CFHR1 concentrations and their role in susceptibility to age-related macular degeneration. Human molecular genetics 76 23873044
2006 Analysis of CFH, TLR4, and APOE polymorphism in India suggests the Tyr402His variant of CFH to be a global marker for age-related macular degeneration. Investigative ophthalmology & visual science 75 16936080
1999 The LIM proteins FHL1 and FHL3 are expressed differently in skeletal muscle. Biochemical and biophysical research communications 74 10049693
2021 Proteomic and Mechanistic Analysis of Spironolactone in Patients at Risk for HF. JACC. Heart failure 71 33549556
2018 Extrarenal manifestations of the hemolytic uremic syndrome associated with Shiga toxin-producing Escherichia coli (STEC HUS). Pediatric nephrology (Berlin, Germany) 65 30382336
2011 Downregulation and growth inhibitory role of FHL1 in lung cancer. International journal of cancer 65 21702045
2009 Autoantibodies in haemolytic uraemic syndrome (HUS). Thrombosis and haemostasis 64 19190803
2010 DEAP-HUS: deficiency of CFHR plasma proteins and autoantibody-positive form of hemolytic uremic syndrome. Pediatric nephrology (Berlin, Germany) 63 20157737
2009 Consequences of mutations within the C terminus of the FHL1 gene. Neurology 60 19687455
2015 CFH Variants Affect Structural and Functional Brain Changes and Genetic Risk of Alzheimer's Disease. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 55 26243271
2014 5'RNA-Seq identifies Fhl1 as a genetic modifier in cardiomyopathy. The Journal of clinical investigation 55 24509080
2009 Treatment options for HUS secondary to Escherichia coli O157:H7. Kidney international. Supplement 55 19180140
2015 Complement proteins C7 and CFH control the stemness of liver cancer cells via LSF-1. Cancer letters 54 26723877
2006 SRC uses Cas to suppress Fhl1 in order to promote nonanchored growth and migration of tumor cells. Cancer research 52 16452211
2020 Serum potassium in the PARADIGM-HF trial. European journal of heart failure 51 32809261
2018 Recurrent structural variation, clustered sites of selection, and disease risk for the complement factor H (CFH) gene family. Proceedings of the National Academy of Sciences of the United States of America 51 29686068
2010 Contractures and hypertrophic cardiomyopathy in a novel FHL1 mutation. Annals of neurology 50 20186852
2019 MRAs in Elderly HF Patients: Individual Patient-Data Meta-Analysis of RALES, EMPHASIS-HF, and TOPCAT. JACC. Heart failure 46 31779922
2011 FHL1 interacts with oestrogen receptors and regulates breast cancer cell growth. Journal of cellular and molecular medicine 46 19840196
2001 Characterization of tissue-specific LIM domain protein (FHL1C) which is an alternatively spliced isoform of a human LIM-only protein (FHL1). Journal of cellular biochemistry 44 11400158
2004 Mutations in CD46, a complement regulatory protein, predispose to atypical HUS. Trends in molecular medicine 41 15121049
2018 Pathogenic role of inflammatory response during Shiga toxin-associated hemolytic uremic syndrome (HUS). Pediatric nephrology (Berlin, Germany) 39 29372302
2013 DGKE and atypical HUS. Nature genetics 39 23619787
2018 Circular RNA Complement Factor H (CFH) Promotes Glioma Progression by Sponging miR-149 and Regulating AKT1. Medical science monitor : international medical journal of experimental and clinical research 38 30111766
2010 Joint effect of cigarette smoking and CFH and LOC387715/HTRA1 polymorphisms on polypoidal choroidal vasculopathy. Investigative ophthalmology & visual science 38 20688737
2015 Development of autoantibodies against muscle-specific FHL1 in severe inflammatory myopathies. The Journal of clinical investigation 37 26551678
2021 CFH Loss in Human RPE Cells Leads to Inflammation and Complement System Dysregulation via the NF-κB Pathway. International journal of molecular sciences 36 34445430
1999 Characterization of a brain-specific nuclear LIM domain protein (FHL1B) which is an alternatively spliced variant of FHL1. Gene 36 10524257
2010 CFH, VEGF, and PEDF genotypes and the response to intravitreous injection of bevacizumab for the treatment of age-related macular degeneration. Journal of ocular biology, diseases, and informatics 35 21811649
2008 Clinical significance of loss of Fhl1 expression in human gastric cancer. Annals of surgical oncology 34 18465173
2021 Protective chromosome 1q32 haplotypes mitigate risk for age-related macular degeneration associated with the CFH-CFHR5 and ARMS2/HTRA1 loci. Human genomics 33 34563268
2017 The effects of sacubitril/valsartan on coronary outcomes in PARADIGM-HF. American heart journal 33 28577679
2013 Association of CFH and CFB gene polymorphisms with retinopathy in type 2 diabetic patients. Mediators of inflammation 33 23864767
2013 Successful treatment of DEAP-HUS with eculizumab. Pediatric nephrology (Berlin, Germany) 32 24249282
2009 Pathological aspects of membranoproliferative glomerulonephritis (MPGN) and haemolytic uraemic syndrome (HUS) / thrombocytic thrombopenic purpura (TTP). Thrombosis and haemostasis 31 19190808
2019 Data-Independent Acquisition for the Orbitrap Q Exactive HF: A Tutorial. Journal of proteome research 30 30557026
2017 Thrombotic Microangiopathies (TTP, HUS, HELLP). Hematology/oncology clinics of North America 30 29078925
2017 Genetic variation in CFH predicts phenytoin-induced maculopapular exanthema in European-descent patients. Neurology 30 29288229
2006 Altered expression of FHL1, CARP, TSC-22 and P311 provide insights into complex transcriptional regulation in pacing-induced atrial fibrillation. Biochimica et biophysica acta 30 17174532
2016 Natural resistance to Meningococcal Disease related to CFH loci: Meta-analysis of genome-wide association studies. Scientific reports 28 27805046
2014 Thrombotic microangiopathies (TTP, HUS, HELLP). Emergency medicine clinics of North America 27 25060255
2005 Negative control of keratinocyte differentiation by Rho/CRIK signaling coupled with up-regulation of KyoT1/2 (FHL1) expression. Proceedings of the National Academy of Sciences of the United States of America 27 16061799
2015 FHL1 activates myostatin signalling in skeletal muscle and promotes atrophy. FEBS open bio 26 26504741
2018 Src-mediated phosphorylation converts FHL1 from tumor suppressor to tumor promoter. The Journal of cell biology 25 29434030
2011 Reducing body myopathy and other FHL1-related muscular disorders. Seminars in pediatric neurology 25 22172421
2006 Synthesis, characterization and DNA binding of magnesium-ciprofloxacin (cfH) complex [Mg(cf)2] * 2.5H2O. Journal of inorganic biochemistry 25 16876251
2021 CFH and CFHR Copy Number Variations in C3 Glomerulopathy and Immune Complex-Mediated Membranoproliferative Glomerulonephritis. Frontiers in genetics 24 34211499
2014 FPR1 interacts with CFH, HTRA1 and smoking in exudative age-related macular degeneration and polypoidal choroidal vasculopathy. Eye (London, England) 24 25277308
2009 Severe atypical HUS caused by CFH S1191L--case presentation and review of treatment options. Pediatric nephrology (Berlin, Germany) 24 19856002
2019 FHL1 regulates myoblast differentiation and autophagy through its interaction with LC3. Journal of cellular physiology 23 31637727
2017 Influence of CFH gene on symptom severity of schizophrenia. Neuropsychiatric disease and treatment 23 28293111
2014 FHL1 mutants that cause clinically distinct human myopathies form protein aggregates and impair myoblast differentiation. Journal of cell science 23 24634512
2000 Pathophysiology and treatment of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS). International journal of hematology 23 10905050
2017 A novel, multiplexed targeted mass spectrometry assay for quantification of complement factor H (CFH) variants and CFH-related proteins 1-5 in human plasma. Proteomics 21 27647805
2017 Epigenetic analysis of FHL1 tumor suppressor gene in human liver cancer. Oncology letters 21 29113254
2015 Estrogen enhances activity of Wnt signaling during osteogenesis by inducing Fhl1 expression. Journal of cellular biochemistry 21 25676585
2023 VE-822 upregulates the deubiquitinase OTUD1 to stabilize FHL1 to inhibit the progression of lung adenocarcinoma. Cellular oncology (Dordrecht, Netherlands) 19 36929488
2021 Risk of Atypical HUS Among Family Members of Patients Carrying Complement Regulatory Gene Abnormality. Kidney international reports 19 34169201
2021 FHL1 Inhibits the Progression of Colorectal Cancer by Regulating the Wnt/β-Catenin Signaling Pathway. Journal of Cancer 19 34335951
2013 Dysregulation of FHL1 spliceforms due to an indel mutation produces an Emery-Dreifuss muscular dystrophy plus phenotype. Neurogenetics 18 23456229
2023 CFH and CFHR structural variants in atypical Hemolytic Uremic Syndrome: Prevalence, genomic characterization and impact on outcome. Frontiers in immunology 17 36793547
2020 Tuning the Functionality by Splicing: Factor H and Its Alternative Splice Variant FHL-1 Share a Gene but Not All Functions. Frontiers in immunology 17 33178228
2016 Protective coding variants in CFH and PELI3 and a variant near CTRB1 are associated with age-related macular degeneration†. Human molecular genetics 17 28011711
2013 AT1 blockade abolishes left ventricular hypertrophy in heterozygous cMyBP-C null mice: role of FHL1. Fundamental & clinical pharmacology 17 23600722
2016 Critical Questions about PARADIGM-HF and the Future. Acta Cardiologica Sinica 16 27471351
2015 FHL1 inhibits the growth of tongue squamous cell carcinoma cells via G1/S cell cycle arrest. Molecular medicine reports 16 26017856
2014 CFH haplotypes and ARMS2, C2, C3, and CFB alleles show association with susceptibility to age-related macular degeneration in Mexicans. Molecular vision 16 24453474
2020 Pathogenic functions and diagnostic utility of cytokines/chemokines in EHEC-HUS. Pediatrics international : official journal of the Japan Pediatric Society 15 31742829
2018 A zebrafish model for FHL1-opathy reveals loss-of-function effects of human FHL1 mutations. Neuromuscular disorders : NMD 15 29735270
2018 Aberrant Protein Turn-Over Associated With Myofibrillar Disorganization in FHL1 Knockout Mice. Frontiers in genetics 15 30083183
2001 Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS): the new thinking. Journal of thrombosis and thrombolysis 15 11577265
2023 FHL1 promotes chikungunya and o'nyong-nyong virus infection and pathogenesis with implications for alphavirus vaccine design. Nature communications 14 37884534
2020 Association of CRP levels with ARMS2 and CFH variants in age-related macular degeneration. International ophthalmology 14 32507953
2018 IGF2-derived miR-483-3p associated with Hirschsprung's disease by targeting FHL1. Journal of cellular and molecular medicine 14 30073757
2012 Associations of CFH polymorphisms and CFHR1-CFHR3 deletion with blood pressure and hypertension in Chinese population. PloS one 14 22848687
2016 X-linked FHL1 as a novel therapeutic target for head and neck squamous cell carcinoma. Oncotarget 13 26908444
2015 Inhibition of FHL1 inhibits cigarette smoke extract-induced proliferation in pulmonary arterial smooth muscle cells. Molecular medicine reports 13 25975448
2013 CFH (rs1410996), HTRA1 (rs112000638) and ARMS2 (rs10490923) gene polymorphisms are associated with AMD risk in Spanish patients. Ophthalmic genetics 13 23534868
2013 Identification of FHL1 as a therapeutic target for Duchenne muscular dystrophy. Human molecular genetics 13 24087791
2024 Efficient and markerless gene integration with SlugCas9-HF in Kluyveromyces marxianus. Communications biology 12 38956406
2021 Maternal smoking during pregnancy aggravated muscle phenotype in FHL1-/y offspring mice similar to congenital clubfoot through P2RX7-mediated pyroptosis. Toxicology letters 12 33872746
2014 X-linked Recessive Distal Myopathy With Hypertrophic Cardiomyopathy Caused by a Novel Mutation in the FHL1 Gene. Journal of child neurology 12 25246303
2013 Association analysis of CFH and ARMS2 gene polymorphisms in a Brazilian cohort with age-related macular degeneration. Ophthalmic research 12 23867343
2010 Downregulation of FHL1 expression in thoracic aortic dissection: implications in aortic wall remodeling and pathogenesis of thoracic aortic dissection. Annals of vascular surgery 12 21126853
2002 Forkhead-associated domains of the tobacco NtFHA1 transcription activator and the yeast Fhl1 forkhead transcription factor are functionally conserved. The Journal of biological chemistry 12 12149245