Gene: CFH

Alternate names for this Gene: AHUS1|AMBP1|ARMD4|ARMS1|CFHL3|FH|FHL1|HF|HF1|HF2|HUS

Gene Summary: This gene is a member of the Regulator of Complement Activation (RCA) gene cluster and encodes a protein with twenty short consensus repeat (SCR) domains. This protein is secreted into the bloodstream and has an essential role in the regulation of complement activation, restricting this innate defense mechanism to microbial infections. Mutations in this gene have been associated with hemolytic-uremic syndrome (HUS) and chronic hypocomplementemic nephropathy. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.

Gene is located in Chromosome: 1

Location in Chromosome : 1q31.3

Description of this Gene: complement factor H

Type of Gene: protein-coding

rs1061147 in CFH gene and Age related macular degeneration PMID 23326517 2013 Insights into the genetic architecture of early stage age-related macular degeneration: a genome-wide association study meta-analysis.

PMID 21665990 2011 Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration.

PMID 20385826 2010 Genome-wide association study of advanced age-related macular degeneration identifies a role of the hepatic lipase gene (LIPC).

PMID 22705344 2012 Heritability and genome-wide association study to assess genetic differences between advanced age-related macular degeneration subtypes.

PMID 23577725 2013 Genetic factors in nonsmokers with age-related macular degeneration revealed through genome-wide gene-environment interaction analysis.

PMID 29346644 2018 Genome-wide analysis of disease progression in age-related macular degeneration.

PMID 23455636 2013 Seven new loci associated with age-related macular degeneration.

PMID 20385819 2010 Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration.

PMID 22125219 2011 Sifting the wheat from the chaff: prioritizing GWAS results by identifying consistency across analytical methods.

PMID 22694956 2012 Genome-wide association study of age-related macular degeneration identifies associated variants in the TNXB-FKBPL-NOTCH4 region of chromosome 6p21.3.

PMID 26691988 2016 A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

PMID 20861866 2010 Genome-wide association identifies SKIV2L and MYRIP as protective factors for age-related macular degeneration.

PMID 15761122 2005 Complement factor H polymorphism in age-related macular degeneration.

PMID 21909106 2011 In addition to CFH (rs800292, P = 4.23 × 10(-15)) and ARMS2 (rs3750847, P = 8.67 × 10(-29)) loci, we identified two new susceptibility loci for exudative AMD: TNFRSF10A-LOC389641 on chromosome 8p21 (rs13278062, combined P = 1.03 × 10(-12), odds ratio = 0.73) and REST-C4orf14-POLR2B-IGFBP7 on chromosome 4q12 (rs1713985, combined P = 2.34 × 10(-8), odds ratio = 1.30).

PMID 28703135 2017 We confirmed the association of age-related maculopathy susceptibility 2 (ARMS2) rs10490924 (P=7.38 × 10<sup>-17</sup>), HTRA1 rs11200638 (P=5.47 × 10<sup>-17</sup>) and complement factor H gene (CFH) rs800292 (P=2.53 × 10<sup>-8</sup>) with neovascular AMD, all loci passing the genome-wide significance level (P<5.22 × 10<sup>-8</sup>).

rs1061170 in CFH gene and Blood Protein Measurement PMID 29875488 2018 Genomic atlas of the human plasma proteome.

PMID 30072576 2018 Co-regulatory networks of human serum proteins link genetics to disease.

rs3753394 in CFH gene and C4 complement assay (procedure) PMID 23028341 2012 Genome-wide association study for serum complement C3 and C4 levels in healthy Chinese subjects.

rs10465586 in CFH gene and Chronic Obstructive Airway Disease PMID 26634245 2015 A genome-wide association study identifies risk loci for spirometric measures among smokers of European and African ancestry.

rs1410996 in CFH gene and Coagulation factor measurement PMID 23381943 2013 Ischemic stroke is associated with the ABO locus: the EuroCLOT study.

rs3753394 in CFH gene and Complement C3 Measurement PMID 23028341 2012 Genome-wide association study for serum complement C3 and C4 levels in healthy Chinese subjects.

rs575109631 in CFH gene and Complement Factor H Deficiency PMID 14978182 2004 Heterozygous and homozygous factor h deficiencies associated with hemolytic uremic syndrome or membranoproliferative glomerulonephritis: report and genetic analysis of 16 cases.

PMID 11170896 2001 Factor H mutations in hemolytic uremic syndrome cluster in exons 18-20, a domain important for host cell recognition.

PMID 16612335 2006 Deletion of Lys224 in regulatory domain 4 of Factor H reveals a novel pathomechanism for dense deposit disease (MPGN II).

PMID 9312129 1997 Human factor H deficiency. Mutations in framework cysteine residues and block in H protein secretion and intracellular catabolism.

PMID 11158219 2001 The molecular basis of familial hemolytic uremic syndrome: mutation analysis of factor H gene reveals a hot spot in short consensus repeat 20.

PMID 12020532 2002 Combined kidney and liver transplantation for familial haemolytic uraemic syndrome.

PMID 11170895 2001 Clustering of missense mutations in the C-terminal region of factor H in atypical hemolytic uremic syndrome.

PMID 10803850 2000 Molecular basis for factor H and FHL-1 deficiency in an Italian family.

rs1048663 in CFH gene and Complement factor H measurement PMID 28240269 2017 Connecting genetic risk to disease end points through the human blood plasma proteome.

rs1061170 in CFH gene and Exudative age-related macular degeneration PMID 22705344 2012 Heritability and genome-wide association study to assess genetic differences between advanced age-related macular degeneration subtypes.

PMID 25629512 2015 New loci and coding variants confer risk for age-related macular degeneration in East Asians.

PMID 26691988 2016 A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

PMID 28703135 2017 Genome-wide association study of neovascular age-related macular degeneration in the Thai population.

rs2274700 in CFH gene and Fuchs Endothelial Dystrophy PMID 28358029 2017 Genome-wide association study identifies three novel loci in Fuchs endothelial corneal dystrophy.

rs1061170 in CFH gene and Geographic Atrophy PMID 22705344 2012 Heritability and genome-wide association study to assess genetic differences between advanced age-related macular degeneration subtypes.

PMID 26691988 2016 A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

rs121913051 in CFH gene and HEMOLYTIC UREMIC SYNDROME, ATYPICAL, SUSCEPTIBILITY TO, 1 PMID 19846853 2009 Atypical hemolytic-uremic syndrome.

PMID 19821824 2010 Clinical practice guidelines for the management of atypical haemolytic uraemic syndrome in the United Kingdom.

PMID 9551389 1998 Genetic studies into inherited and sporadic hemolytic uremic syndrome.

PMID 10762557 2000 Complement factor H gene mutation associated with autosomal recessive atypical hemolytic uremic syndrome.

PMID 10577907 1999 Complement factor H gene mutation associated with autosomal recessive atypical hemolytic uremic syndrome.

PMID 14583443 2003 Complement factor H mutations and gene polymorphisms in haemolytic uraemic syndrome: the C-257T, the A2089G and the G2881T polymorphisms are strongly associated with the disease.

PMID 20513133 2010 Mutations in alternative pathway complement proteins in American patients with atypical hemolytic uremic syndrome.

PMID 11851332 2002 Molecular modelling of the C-terminal domains of factor H of human complement: a correlation between haemolytic uraemic syndrome and a predicted heparin binding site.

PMID 12960213 2003 Haemolytic uraemic syndrome and mutations of the factor H gene: a registry-based study of German speaking countries.

PMID 14978182 2004 Heterozygous and homozygous factor h deficiencies associated with hemolytic uremic syndrome or membranoproliferative glomerulonephritis: report and genetic analysis of 16 cases.

rs419137 in CFH gene and Hemopexin measurement PMID 28240269 2017 Connecting genetic risk to disease end points through the human blood plasma proteome.

rs6677604 in CFH gene and IGA Glomerulonephritis PMID 25305756 2014 Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens.

rs6677604 in CFH gene and Kidney Diseases PMID 21399633 2011 Genome-wide association study identifies susceptibility loci for IgA nephropathy.

rs121913059 in CFH gene and MACULAR DEGENERATION, AGE-RELATED, 4 (disorder) PMID 25814826 2015 Analysis of rare variants in the CFH gene in patients with the cuticular drusen subtype of age-related macular degeneration.

PMID 22019782 2011 A rare penetrant mutation in CFH confers high risk of age-related macular degeneration.

PMID 24036949 2013 Identification of a rare coding variant in complement 3 associated with age-related macular degeneration.

PMID 12697737 2003 Mutations in factor H reduce binding affinity to C3b and heparin and surface attachment to endothelial cells in hemolytic uremic syndrome.

PMID 24498017 2014 Three new genetic loci (R1210C in CFH, variants in COL8A1 and RAD51B) are independently related to progression to advanced macular degeneration.

rs800292 in CFH gene and Matrix Metalloproteinase 8 Measurement PMID 29212897 2017 In functional experiments, activation of the alternative pathway of complement in the carriers of rs800292 minor allele (Ile62 in factor H) led to decreased release of MMP-8 from neutrophils compared with the major allele (Val62 in factor H).

rs505102 in CFH gene and Myeloperoxidase Measurement PMID 23620142 2013 A locus on chromosome 1q31.1 containing the complement factor H (CFH) gene was strongly associated with serum MPO levels in 9305 subjects of European ancestry (lead SNP rs800292; P = 4.89 × 10(-41)) and in 1690 AA subjects (rs505102; P = 1.05 × 10(-8)).

PMID 23620142 2013 Genome-wide and gene-centric analyses of circulating myeloperoxidase levels in the charge and care consortia.

PMID 23620142 2013 A locus on chromosome 1q31.1 containing the complement factor H (CFH) gene was strongly associated with serum MPO levels in 9305 subjects of European ancestry (lead SNP rs800292; P = 4.89 × 10(-41)) and in 1690 AA subjects (rs505102; P = 1.05 × 10(-8)).

rs10737680 in CFH gene and Vital capacity PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs505102 in CFH gene and Waist-Hip Ratio PMID 30575882 2018 Association of Genetic Variants Related to Gluteofemoral vs Abdominal Fat Distribution With Type 2 Diabetes, Coronary Disease, and Cardiovascular Risk Factors.

rs1061170 in CFH gene and exudative macular degeneration PMID 22705344 2012 Heritability and genome-wide association study to assess genetic differences between advanced age-related macular degeneration subtypes.

PMID 25629512 2015 New loci and coding variants confer risk for age-related macular degeneration in East Asians.

PMID 26691988 2016 A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

PMID 28703135 2017 Genome-wide association study of neovascular age-related macular degeneration in the Thai population.

rs10465586 in CFH gene and response to bronchodilator PMID 26634245 2015 A genome-wide association study identifies risk loci for spirometric measures among smokers of European and African ancestry.

rs10737680 in CFH gene and von Willebrand's factor (lab test) PMID 23381943 2013 Ischemic stroke is associated with the ABO locus: the EuroCLOT study.