Property Summary

NCBI Gene PubMed Count 102
PubMed Score 268.22
PubTator Score 377.27

Knowledge Summary

Patent

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TINX Plot

  Disease (8)

Disease Target Count Z-score Confidence
Macular degeneration 44 0.0 2.0
Disease Target Count Z-score Confidence
Complement factor I deficiency 1 0.0 5.0

Expression

  Differential Expression (24)

Disease log2 FC p
nephrosclerosis -1.234 1.7e-02
urothelial carcinoma -3.300 4.9e-06
malignant mesothelioma -7.000 3.3e-10
Barrett's esophagus 1.200 4.3e-02
astrocytoma 1.200 3.4e-05
glioblastoma 3.700 8.4e-04
posterior fossa group A ependymoma 4.900 1.2e-17
periodontitis 1.100 3.5e-26
active ulcerative colitis 3.656 4.9e-03
pancreatic ductal adenocarcinoma liver m... -2.682 4.2e-03
non-small cell lung cancer -1.030 1.3e-05
lung cancer -1.900 2.4e-05
active Crohn's disease 2.754 6.5e-03
interstitial cystitis 1.400 3.0e-05
cystic fibrosis 1.500 9.8e-04
adult high grade glioma 3.200 2.7e-05
group 3 medulloblastoma 1.600 6.9e-04
pilocytic astrocytoma 5.100 1.5e-15
aldosterone-producing adenoma -2.252 1.4e-02
subependymal giant cell astrocytoma 4.743 1.2e-03
lung carcinoma -2.000 2.6e-18
Breast cancer -2.800 3.3e-16
ovarian cancer -4.600 1.2e-15
pituitary cancer -1.900 7.6e-05

 IMPC Phenotype (1)

Protein-protein Interaction (7)

Gene RIF (72)

PMID Text
26900322 Our results indicate that CFI polymorphisms are not significantly associated with VKH syndrome.
26767664 Patients with advanced atrophic AMD carried these rare variants more frequently than patients with neovascular AMD (11 of 93 [11.8%] vs 40 of 835 [4.8%]; P = .04).
26312598 In this study, the odds of AMD were highest in those with deficient vitamin D status and 2 risk alleles for the CFH and CFI genotypes, suggesting a synergistic effect between vitamin D status and complement cascade protein function.
25986072 A missense variant (p.V412M) in CFI was discovered in two Tunisian Jewish families with early-onset age-related macular degeneration.
25803806 Regulatory components of the alternative complement pathway in endothelial cell cytoplasm, factor H and factor I, are not packaged in Weibel-Palade bodies.
25788521 Low FI levels are strongly associated with rare CFI variants and age-related macular degeneration.
25618258 High expression of complement factor I is associated with recurrence in breast cancer.
25394898 CFI genetic variants played an important role in the development of NSCLC in Chinese population.
25352734 The CFI p.Gly119Arg mutation was identified in 7/521 age-related macular degeneration cases compared to 1/627 age-matched controls; this mutation confers a high risk of disease.
25188723 The mutations in the regulators CFH, CFI and MCP involve loss-of-function, whereas those for C3 involve gain-of-function.
25184960 results provide evidence for the role of CFI in the progression of cSCC and identify it as a potential therapeutic target in this nonmelanoma skin cancer
25075123 This study has revealed a significant association between acute anterior uveitis (AAU) and CFI-rs7356506, suggesting that CFI is involved in the pathogenesis of AAU
24983375 iC3b level, a proteolytically inactive form of C3b, was lower in HCV infected patient sera, reflecting impairment of both C3 convertase and Factor I activity.
24732209 Neither of the two SNPs most studied (rs10033900 or rs2285714) in the CFI gene was a risk factor for developing neovascular age-related macular degeneration or polypoidal choroidal vasculopathy in a Chinese population.
24642830 association between rs10033900 and age-related macular degeneration risk in Han Chinese population
24142231 Recurrent aseptic meningo-encephalitis is a rare clinical presentation of complete FI deficiency.
24036952 We found that 7.8% of advanced age-related macular degeneration cases compared to 2.3% of controls are carriers of rare missense CFI variants.
23731345 Mutations in complement factor I protein is associated with end-stage renal disease in a patient with hemolytic uremic syndrome caused by infections by Escherichia coli strains producing Shiga-like toxins.
23722394 rs1136287 in CFI is less likely to be associated in in extremely myopic Japanese individuals.
23688582 An STR polymorphism in intron 7 of human CFI gene on chromosome 4q in 11 Asian populations indicated that Group H alleles in exon 11 of the CFI gene were almost entirely confined to East Asian populations, making it useful in forensic anthropology.
23685748 these findings demonstrate that rare, highly penetrant mutations in CFI contribute to the genetic burden of age-related macular degeneration.
23519521 Case Report: patient with atypical haemolytic uremic syndrome with combined membrane cofactor protein CD46 and complement factor I mutations undergoing successful kidney transplantation.
22926405 Acute hemorrhagic leukoencephalitis (AHLE) is an unreported, rare phenotype for partial complement factor I deficiency.
22710145 we report four novel mutations and the first large gene deletion in the CFI locus.
22678500 One SNP (rs10033900) in the CFI gene, which encodes a protein involved in the inflammatory pathway, was significantly associated with myopic choroidal neovascularization in multivariate analysis after correction for multiple testing.
22594569 The alternative pathway of complement may play a role in the pathogenesis of HELLP syndrome.
22514678 Since FI requires cofactors for its activity we also investigated the binding of purified cofactors C4BP and FH and found acquisition of both proteins, which retained their activity in FI mediated degradation of C3b and C4b.
22393059 all analyzed cofactors form similar trimolecular complexes with FI and C3b/C4b, and the accessibility of FIMAC and SP domains is crucial for the function of FI
22258234 factor I were significantly diminished early after trauma.
22223611 Results question whether complement factor I autoantibodies per se predispose to atypical hemolytic uremic syndrome.
21936007 Forster resonance energy transfer was used to investigate the 10 muM K(D) (210 kD) complex between the N-terminal region of the soluble complement regulator, factor H (FH1-4), and the key activation-specific complement fragment, C3b.
21768352 Data show that FI is in a proteolytically inactive form, demonstrating that it circulates in a zymogen-like state.
21316765 Study describes the molecular and functional consequences of two novel mutations of FI.
20888482 Observational study of gene-disease association. (HuGE Navigator)
20513133 Study identified novel mutations in CFH, CFHR5, CFI, CFB and C3 in American patients with atypical hemolytic uremic syndrome.
20513133 Observational study of gene-disease association. (HuGE Navigator)
20385819 Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
20379614 Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
20332099 Observational study of gene-disease association. (HuGE Navigator)
20106822 Observational study of gene-disease association. (HuGE Navigator)
20087399 Role of a common variant near the complement factor I gene in susceptibility to age-related macular degeneration.
20087399 Observational study of gene-disease association. (HuGE Navigator)
20059470 Observational study of gene-disease association. (HuGE Navigator)
20044478 the FIMAC domain appears to harbor the main binding sites important for the ability of FI to degrade C4b and C3b
20016463 In a large cohort of 202 patients with aHUS, we identified 23 patients carrying exonic mutations in CFI
19877009 mutations in complement factor I affect both secretion and function of factor I, which leads to impaired regulation of the complement system in atypical hemolytic uremic syndrome.
19861685 Association of factor H autoantibodies with deletions of CFHR1, CFHR3, CFHR4, and with mutations in CFH, CFI, CD46, and C3 in patients with atypical hemolytic uremic syndrome.
19693526 Observational study of genotype prevalence. (HuGE Navigator)
19661236 Observational study of gene-disease association. (HuGE Navigator)
19065647 This is the first study that investigates, at the functional level, the consequences of molecular defects identified in patients with full complement factor I deficiency.
18825487 one of two polymorphic suballeles responsible for CFI A is Japanese-specific.
18825487 Observational study of genotype prevalence. (HuGE Navigator)
18805611 renal transplant recipient developed recurrent hemolytic uremic syndrome 1 month after transplantation associated with factor I mutation
18701018 Pint mutations in patients with type 2 diabetes and their families were studied. mitochondrial genes including np3316, np3394 and np3426 in the ND1 region and np3243 in the tRNA(Leu(UUR))were screened.
18685559 This analysis identified a single nucleotide polymorphism just 3' of complement factor I on chromosome 4 showing significant association (P<10(-7)) with age-related macular degeneration.
18658028 An abnormal control of the complement alternative pathway is a risk factor for the occurrence of HELLP syndrome.
18566438 Abeta activates the complement system within drusen by blocking the function of factor I leading to a low-grade, chronic inflammation in subretinal tissues
18544012 clumping factor A (ClfA) was identified as a specific protein bound by factor I; the shed ClfA fragment increased factor I cleavage of C3b into inactive C3b
18374984 The biochemical and genetic characterization in two Spanish families with complete Factor I deficiency, is described.
17599974 Age <3 mo at onset seems to be characteristic of CFH and IF mutation-associated atypical hemolytic uremic syndrome
17597211 The nature of the functional defect in atypical hemolytic uremic syndrome-associated CFI mutations, is examined.
17548110 Non-small cell lung cancer (NSCLC) cells produce soluble complement inhibitors factor I (FI) and C4b-binding protein (C4BP).
17482181 Impairment of the mechanisms involved in the regulation of activation of complement system factor iC3b may be important in the pathogenesis of endometriosis and endometriosis-associated infertility.
17320177 keratinocytes are capable of synthesizing factor I, and that this synthesis is regulated by IFN-gamma
17067565 CFI precursor could aid in the diagnosis and indicate the advancement of gastric cancer
17055788 both forms of factor I (fI) have very similar proteolytic activities against C3(NH(3)) indicating that the charged glycans of fI do not influence the fI-cofactor-substrate interactions
16920989 factor I in concert with CR1 on E and factor H in serum due to their cofactor activity are likely to be important contributors
16621965 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
16386793 Mutations in the complement regulators factor H, membrane cofactor protein (MCP), and factor I are associated with atypical hemolytic uremic syndrome.
15835912 fI and the serine protease domain were found to have similar amidolytic activities but strikingly different proteolytic activities on C3(NH(3)).
15210795 Human complement factor I does not require cofactors for cleavage of synthetic substrates.
14967308 the last 45 amino acid of the heavy chain, including a disulfide bridge area, did not participate in the serine protease function of factor I

AA Sequence

MKLLHVFLLFLCFHLRFCKVTYTSQEDLVEKKCLAKKYTHLSCDKVFCQPWQRCIEGTCVCKLPYQCPKN      1 - 70
GTAVCATNRRSFPTYCQQKSLECLHPGTKFLNNGTCTAEGKFSVSLKHGNTDSEGIVEVKLVDQDKTMFI     71 - 140
CKSSWSMREANVACLDLGFQQGADTQRRFKLSDLSINSTECLHVHCRGLETSLAECTFTKRRTMGYQDFA    141 - 210
DVVCYTQKADSPMDDFFQCVNGKYISQMKACDGINDCGDQSDELCCKACQGKGFHCKSGVCIPSQYQCNG    211 - 280
EVDCITGEDEVGCAGFASVTQEETEILTADMDAERRRIKSLLPKLSCGVKNRMHIRRKRIVGGKRAQLGD    281 - 350
LPWQVAIKDASGITCGGIYIGGCWILTAAHCLRASKTHRYQIWTTVVDWIHPDLKRIVIEYVDRIIFHEN    351 - 420
YNAGTYQNDIALIEMKKDGNKKDCELPRSIPACVPWSPYLFQPNDTCIVSGWGREKDNERVFSLQWGEVK    421 - 490
LISNCSKFYGNRFYEKEMECAGTYDGSIDACKGDSGGPLVCMDANNVTYVWGVVSWGENCGKPEFPGVYT    491 - 560
KVANYFDWISYHVGRPFISQYNV                                                   561 - 583
//

Text Mined References (107)

PMID Year Title
26900322 2016 CFI-rs7356506 polymorphisms associated with Vogt-Koyanagi-Harada syndrome.
26767664 2016 Rare Genetic Variants Associated With Development of Age-Related Macular Degeneration.
26312598 2015 Association between vitamin D status and age-related macular degeneration by genetic risk.
25986072 2015 Rare genetic variants in Tunisian Jewish patients suffering from age-related macular degeneration.
25803806 2015 Regulatory components of the alternative complement pathway in endothelial cell cytoplasm, factor H and factor I, are not packaged in Weibel-Palade bodies.
25788521 2015 Rare genetic variants in the CFI gene are associated with advanced age-related macular degeneration and commonly result in reduced serum factor I levels.
25618258 2015 Local expression of complement factor I in breast cancer cells correlates with poor survival and recurrence.
25394898 2015 Tag SNPs of CFI contributed to the susceptibility for non-small cell lung cancer in Chinese population.
25352734 2014 Complement factor I and age-related macular degeneration.
25188723 2014 New functional and structural insights from updated mutational databases for complement factor H, Factor I, membrane cofactor protein and C3.
25184960 2015 Complement factor I promotes progression of cutaneous squamous cell carcinoma.
25075123 2014 CFI-rs7356506 is a genetic protective factor for acute anterior uveitis in Chinese patients.
24983375 2014 Inhibition of c3 convertase activity by hepatitis C virus as an additional lesion in the regulation of complement components.
24732209 2014 Complement factor I polymorphism is not associated with neovascular age-related macular degeneration and polypoidal choroidal vasculopathy in a chinese population.
24642830 2014 Common variant rs10033900 near the complement factor I gene is associated with age-related macular degeneration risk in Han Chinese population.
24275569 2014 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
24204828 2013 Genome-wide contribution of genotype by environment interaction to variation of diabetes-related traits.
24142231 2013 Complete factor I deficiency due to dysfunctional factor I with recurrent aseptic meningo-encephalitis.
24036952 2013 Rare variants in CFI, C3 and C9 are associated with high risk of advanced age-related macular degeneration.
23731345 2013 Two patients with history of STEC-HUS, posttransplant recurrence and complement gene mutations.
23722394 2013 Evaluation of pigment epithelium-derived factor and complement factor I polymorphisms as a cause of choroidal neovascularization in highly myopic eyes.
23688582 2013 A hypervariable STR polymorphism in the CFI gene: southern origin of East Asian-specific group H alleles.
23685748 2013 A functional variant in the CFI gene confers a high risk of age-related macular degeneration.
23533145 2013 In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.
23519521 2013 Successful long-term outcome after renal transplantation in a patient with atypical haemolytic uremic syndrome with combined membrane cofactor protein CD46 and complement factor I mutations.
23455636 2013 Seven new loci associated with age-related macular degeneration.
23376485 2013 Proteomic analysis of podocyte exosome-enriched fraction from normal human urine.
23235567 2013 Atypical postinfectious glomerulonephritis is associated with abnormalities in the alternative pathway of complement.
22926405 2013 Mutations of complement factor I and potential mechanisms of neuroinflammation in acute hemorrhagic leukoencephalitis.
22710145 2012 Complement factor I deficiency: a not so rare immune defect: characterization of new mutations and the first large gene deletion.
22705344 2012 Heritability and genome-wide association study to assess genetic differences between advanced age-related macular degeneration subtypes.
22678500 2012 Genetic factors for choroidal neovascularization associated with high myopia.
22594569 2012 The genetics of the alternative pathway of complement in the pathogenesis of HELLP syndrome.
22514678 2012 Acquisition of complement inhibitor serine protease factor I and its cofactors C4b-binding protein and factor H by Prevotella intermedia.
22393059 2012 Analysis of binding sites on complement factor I using artificial N-linked glycosylation.
22258234 2012 Early complementopathy after multiple injuries in humans.
22223611 2012 Factor I autoantibodies in patients with atypical hemolytic uremic syndrome: disease-associated or an epiphenomenon?
21936007 2011 Use of time-resolved FRET to validate crystal structure of complement regulatory complex between C3b and factor H (N terminus).
21768352 2011 Structural basis for complement factor I control and its disease-associated sequence polymorphisms.
21665990 2011 Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration.
21316765 2011 Molecular characterization of two novel cases of complete complement inhibitor Factor I deficiency.
20888482 2010 Serum lipid biomarkers and hepatic lipase gene associations with age-related macular degeneration.
20513133 2010 Mutations in alternative pathway complement proteins in American patients with atypical hemolytic uremic syndrome.
20385826 2010 Genome-wide association study of advanced age-related macular degeneration identifies a role of the hepatic lipase gene (LIPC).
20385819 2010 Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration.
20379614 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
20332099 2010 A systematic gene-based screen of chr4q22-q32 identifies association of a novel susceptibility gene, DKK2, with the quantitative trait of alcohol dependence symptom counts.
20106822 2010 Genetic disorders in complement (regulating) genes in patients with atypical haemolytic uraemic syndrome (aHUS).
20087399 2010 Additional evidence to support the role of a common variant near the complement factor I gene in susceptibility to age-related macular degeneration.
20059470 2010 Epidemiological approach to identifying genetic predispositions for atypical hemolytic uremic syndrome.
20044478 2010 Analysis of binding sites on complement factor I that are required for its activity.
20016463 2010 Mutations in components of complement influence the outcome of Factor I-associated atypical hemolytic uremic syndrome.
19877009 2010 Mutations in complement factor I as found in atypical hemolytic uremic syndrome lead to either altered secretion or altered function of factor I.
19861685 2010 Association of factor H autoantibodies with deletions of CFHR1, CFHR3, CFHR4, and with mutations in CFH, CFI, CD46, and C3 in patients with atypical hemolytic uremic syndrome.
19838169 2009 Enrichment of glycopeptides for glycan structure and attachment site identification.
19693526 2011 A hypervariable STR polymorphism in the complement factor I (CFI) gene: Asian-specific alleles.
19661236 2009 Plasma complement components and activation fragments: associations with age-related macular degeneration genotypes and phenotypes.
19423168 2009 Characterization of shark complement factor I gene(s): genomic analysis of a novel shark-specific sequence.
19159218 2009 Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry.
19139490 2009 A strategy for precise and large scale identification of core fucosylated glycoproteins.
19065647 2009 Genetic, molecular and functional analyses of complement factor I deficiency.
19056867 2009 Large-scale proteomics and phosphoproteomics of urinary exosomes.
18825487 2008 Molecular basis of complement factor I (CFI) polymorphism: one of two polymorphic suballeles responsible for CFI A is Japanese-specific.
18805611 2009 Recurrent atypical hemolytic uremic syndrome associated with factor I mutation in a living related renal transplant recipient.
18701018 2008 Mitochondrial gene mutations and type 2 diabetes in Chinese families.
18685559 2009 Variation near complement factor I is associated with risk of advanced AMD.
18658028 2008 Factor H, membrane cofactor protein, and factor I mutations in patients with hemolysis, elevated liver enzymes, and low platelet count syndrome.
18566438 2008 Altered function of factor I caused by amyloid beta: implication for pathogenesis of age-related macular degeneration from Drusen.
18544012 2008 Staphylococcus aureus clumping factor A binds to complement regulator factor I and increases factor I cleavage of C3b.
18374984 2008 Molecular characterization of Complement Factor I deficiency in two Spanish families.
18029348 2008 Toward a confocal subcellular atlas of the human proteome.
17599974 2007 Differential impact of complement mutations on clinical characteristics in atypical hemolytic uremic syndrome.
17597211 2008 Characterization of mutations in complement factor I (CFI) associated with hemolytic uremic syndrome.
17548110 2008 Non-small cell lung cancer cells produce a functional set of complement factor I and its soluble cofactors.
17482181 2007 Levels of complement components iC3b, C3c, C4, and SC5b-9 in peritoneal fluid and serum of infertile women with endometriosis.
17320177 2007 Human keratinocytes produce the complement inhibitor factor I: Synthesis is regulated by interferon-gamma.
17106690 2007 A missense mutation in factor I (IF) predisposes to atypical haemolytic uraemic syndrome.
17067565 2007 Down-regulated expression of complement factor I: a potential suppressive protein for gastric cancer identified by serum proteome analysis.
17055788 2006 Human complement factor I glycosylation: structural and functional characterisation of the N-linked oligosaccharides.
17018561 2007 Primary glomerulonephritis with isolated C3 deposits: a new entity which shares common genetic risk factors with haemolytic uraemic syndrome.
16920989 2006 Factor I-mediated processing of complement fragments on HIV immune complexes targets HIV to CR2-expressing B cells and facilitates B cell-mediated transmission of opsonized HIV to T cells.
16621965 2006 Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome.
16502470 2006 Human colostrum: identification of minor proteins in the aqueous phase by proteomics.
16386793 2006 Insights into hemolytic uremic syndrome: segregation of three independent predisposition factors in a large, multiple affected pedigree.
16335952 Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry.
16237761 2005 Screening of hepatocyte proteins binding to F protein of hepatitis C virus by yeast two-hybrid system.
15835912 2005 The catalytically active serine protease domain of human complement factor I.
15815621 2005 Generation and annotation of the DNA sequences of human chromosomes 2 and 4.
15342556 2004 Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions.
15210795 2004 Human complement factor I does not require cofactors for cleavage of synthetic substrates.
15173250 2004 Complement factor I: a susceptibility gene for atypical haemolytic uraemic syndrome.
14967308 2004 Only the light chain is sufficient for the serine protease function of the membrane bound form of factor I on a xeno-surface.
14761935 2004 Differential gene expression profile of human tonsil high endothelial cells: implications for lymphocyte trafficking.
14760718 2004 Screening for N-glycosylated proteins by liquid chromatography mass spectrometry.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12562389 2003 Molecular characterization of homozygous hereditary factor I deficiency.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
9605165 1998 Interaction of vaccinia virus complement control protein with human complement proteins: factor I-mediated degradation of C3b to iC3b1 inactivates the alternative complement pathway.
9479036 1998 Cloning and characterization of the promoter for the human complement factor I (C3b/C4b inactivator) gene.
9291131 1997 Interactions between human complement components factor H, factor I and C3b.
8613545 1996 The molecular basis of hereditary complement factor I deficiency.
8604219 1996 cDNA cloning, sequencing and chromosomal assignment of the gene for mouse complement factor I (C3b/C4b inactivator): identification of a species specific divergent segment in factor I.
7672128 1995 Beta-sheet secondary structure of an LDL receptor domain from complement factor I by consensus structure predictions and spectroscopy.
2956252 1987 Human complement factor I: analysis of cDNA-derived primary structure and assignment of its gene to chromosome 4.
2954545 1987 Characterization of primary amino acid sequence of human complement control protein factor I from an analysis of cDNA clones.
2563353 1989 Mapping of the human complement factor I gene to 4q25.
1401896 1992 Ultrastructures and interactions of complement factors H and I.