CFH complement factor H [Homo sapiens] - Gene

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Summary

Official Symbol: CFHprovided by HGNC
Official Full Name: complement factor Hprovided by HGNC
Primary source: HGNC:4883
Locus tag: RP1-177P10.1
See related: Ensembl:ENSG00000000971; HPRD:00601; MIM:134370; Vega:OTTHUMG00000035607
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: FH; HF; HF1; HF2; HUS; FHL1; AHUS1; AMBP1; ARMD4; ARMS1; CFHL3; MGC88246
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. [provided by RefSeq, Oct 2011]

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Genomic context

Location :: 1q32

Sequence :: Chromosome: 1; NC_000001.10 (196621008..196716634)

See CFH in Epigenomics, MapViewer

Chromosome 1 - NC_000001.10 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

Up-regulated miRNA-146a targets several inflammation-related mRNAs, including those encoding complement factor-H (CFH) and interleukin-1 receptor associated kinase-1 (IRAK-1), resulting in significant decreases in their expression in Alzheimer brain.
Title: Differential expression of miRNA-146a-regulated inflammatory genes in human primary neural, astroglial and microglial cells.
The strongest associations replicated in both cohorts were found for four SNPs within CD46 (p-value<10(-3)) and five SNPs within CFH (p-value<5x10(-3)).
Title: Common genetic variants in complement genes other than CFH, CD46 and the CFHRs are not associated with aHUS.
Immunopathological deficits associated with Down's syndrome can, in part, be explained by a generalized miRNA-155-mediated downregulation of complement factor H that may contribute to both brain and systemic immune pathology.
Title: miRNA-155 upregulation and complement factor H deficits in Down's syndrome.
NC4 Domain of cartilage-specific collagen IX inhibits complement directly due to attenuation of membrane attack formation and indirectly through binding and enhancing activity of complement inhibitors C4B-binding protein and factor H.
Title: NC4 Domain of cartilage-specific collagen IX inhibits complement directly due to attenuation of membrane attack formation and indirectly through binding and enhancing activity of complement inhibitors C4B-binding protein and factor H.
CFH I890 and L1007 are repeatedly associated with atypical hemolytic uremic syndrome and also found in dense deposit disease and age-related macular degeneration. Here we report an extensive genetic and functional analysis of these CFH variants.
Title: Complement factor H variants I890 and L1007 while commonly associated with atypical hemolytic uremic syndrome are polymorphisms with no functional significance.
new crystal structure of the S1191L mutant of FH19-20 complexed with an activation-specific complement fragment, C3d, was nearly identical to that of the wild-type FH19-20:C3d complex, consistent with mutants binding to C3b with wild-type-like affinity
Title: Structural and functional characterization of the product of disease-related factor H gene conversion.
There was significant difference between CFH genotypes in the age-related macular degeneration group, TT 21.8%, TC 48.3%, and CC 29.9%, and in the control subjects, TT 45% (p=0.003), TC 41% (p=0.0001), and CC 14%
Title: Age-related macular degeneration and association of CFH Y402H and LOC387715 A69S polymorphisms in a Turkish population.
Our investigation of the gene-environment interaction involved in age-related macular degeneration revealed a relationship between a plasma biomarker of oxidative stress, CySS, and CFH genotype.
Title: Plasma biomarkers of oxidative stress and genetic variants in age-related macular degeneration.
The findings support our previous work showing raised serum fH in patients with progressive MS, and results predict that CSF fH levels will be raised rather than reduced in active disease.
Title: Complement regulator factor H in multiple sclerosis.
After combined photodynamic therapy with intravitreal bevacizumab treatment, LOC387715 TT and HTRA1 AA genotype had poorer outcomes at 12 months, suggesting a pharmacogenetic relationship.
Title: LOC387715/HTRA1 variants and the response to combined photodynamic therapy with intravitreal bevacizumab for polypoidal choroidal vasculopathy.

Submit: New GeneRIF Correction See all (329)

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Phenotypes

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

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

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

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

Genome-wide association study identifies susceptibility loci for IgA nephropathy.

Genome-wide association study identifies variants in the CFH region associated with host susceptibility to meningococcal disease.

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

Dense deposit disease (DDD)/membranoproliferative glomerulonephritis type II (MPGNII) is characterized by onset of hematuria and/or proteinuria, acute nephritic syndrome, or nephrotic syndrome. It most frequently affects children between ages five and 15 years. Spontaneous remissions are uncommon and about 50% of affected individuals develop end-stage renal disease (ESRD) within ten years of diagnosis. DDD/MPGNII can be associated with acquired partial lipodystrophy (APL). Drusen, whitish-yellow deposits within Bruch's membrane of the retina often develop in the second decade of life; they initially have little impact on vision, but cause vision problems from subretinal neovascular membranes, macular detachment, and central serous retinopathy in about 10% of affected individuals.

Diagnosis Testing

The definitive diagnosis of DDD/MPGNII requires electron microscopy and immunofluorescence studies of a renal biopsy. Sequence variants in the genes CFH, CFHR5, C3, and LMNA have been implicated in the pathogenesis of DDD/MPGNII, a complex genetic disease that is rarely inherited in a simple Mendelian fashion.

Genetic Counseling

DDD/MPGNII is a complex genetic disease that is rarely inherited in a simple Mendelian fashion. Multiple affected persons within a single nuclear family are only reported occasionally; in these instances, parental consanguinity is common. In persons with DDD/MPGNII in whom two pathologic mutations can be identified in CFH, inheritance is autosomal recessive. However, in most persons with DDD/MPGNII, two pathologic mutations cannot be identified and risks to family members are not known.

References

PMID: 20301598

Myocardial infarction, susceptibility to

MIM: 134370

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HIV-1 protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	Inhibition of DAF or use of factor H depleted sera significantly increases C3 deposition on recombinant HIV-1 gp120 coated CD4 cells	PubMed
	env	Direct interaction of complement factor H with the C1 domain (amino acids 105-119) of HIV-1 gp120 is found in sera from AIDS patients	PubMed
Envelope transmembrane glycoprotein gp41	env	Four areas in HIV-1 gp41 (aa 561-585, 587-605, 615-635, 651-675) interact with human factor H	PubMed
	env	Preincubation of HIV-1 gp41 with either factor H or properdin, and of HIV-1 gp120 with C3b or C4b affect the interaction between HIV-1 gp41 and gp120	PubMed

Go to the HIV-1, Human Protein Interaction Database

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Interactions

Products	Interactant	Other Gene	Source	Pubs	Description
P08603	P35318	ADM	HPRD	PubMed
P08603	P01024	C3	HPRD	PubMed
P08603	Q03591	CFHR1	HPRD	PubMed
P08603	P05156	CFI	HPRD	PubMed
P08603	P02741	CRP	HPRD	PubMed
P08603	Q13316	DMP1	HPRD	PubMed
P08603	P11215	ITGAM	HPRD	PubMed
P08603	P26022	PTX3	HPRD	PubMed
P08603	P14151	SELL	HPRD	PubMed
P08603	P07996	THBS1	HPRD	PubMed
BioGRID:109324	BioGRID:107179	C3	BioGRID	PubMed	Reconstituted Complex
BioGRID:109324	BioGRID:107791	CRP	BioGRID	PubMed	Reconstituted Complex
BioGRID:109324	BioGRID:33985	GPM1	BioGRID	PubMed	Far Western
BioGRID:109324	BioGRID:109142	GRB2	BioGRID	PubMed	Two-hybrid
BioGRID:109324	BioGRID:32102	HEM12	BioGRID	PubMed	Far Western
BioGRID:109324	BioGRID:33444	HIP1	BioGRID	PubMed	Far Western
BioGRID:109324	BioGRID:32674	NCL1	BioGRID	PubMed	Far Western
BioGRID:109324	BioGRID:112302	SELL	BioGRID	PubMed	Reconstituted Complex

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General gene information

Markers

D11S2921 (e-PCR)
- UniSTS:152074

SHGC-76080 (e-PCR)
- UniSTS:13837

G43547 (e-PCR)
- UniSTS:95001

AL009841 (e-PCR)
- UniSTS:57896

SGC31488 (e-PCR)
- UniSTS:62003

D1S2816 (e-PCR), detects polymorphism
- UniSTS:78395

L18426 (e-PCR)
- UniSTS:34648

D1S1423 (e-PCR)
- UniSTS:149619

D1S3541 (e-PCR)
- UniSTS:76944

G16258 (e-PCR)
- UniSTS:12734

G44722 (e-PCR)
- UniSTS:95197

Genotypes

See CFH SNP Geneview Report
See CFH SNP Genotype Report
See CFH SNP Variation Viewer Report

Homology

Homologs of the CFH gene: The CFH gene is conserved in chimpanzee, , dog, cow, mouse, rat, chicken, and zebrafish.
Map Viewer (Mouse, Rat)

Pathways from BioSystems

Complement and coagulation cascades, organism-specific biosystem (from KEGG)
Complement and coagulation cascades, organism-specific biosystemThe complement system is a proteolytic cascade in blood plasma and a mediator of innate immunity, a nonspecific defense mechanism against pathogens. There are three pathways of complement activation:...
Complement and coagulation cascades, conserved biosystem (from KEGG)
Complement and coagulation cascades, conserved biosystemThe complement system is a proteolytic cascade in blood plasma and a mediator of innate immunity, a nonspecific defense mechanism against pathogens. There are three pathways of complement activation:...
Complement cascade, organism-specific biosystem (from REACTOME)
Complement cascade, organism-specific biosystemThe complement system is a biochemical cascade, so named because it 'complements' the ability of antibodies to clear pathogens. It is part of the innate immune system. Complement system proteins circ...
Immune System, organism-specific biosystem (from REACTOME)
Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
Innate Immune System, organism-specific biosystem (from REACTOME)
Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
Regulation of Complement cascade, organism-specific biosystem (from REACTOME)
Regulation of Complement cascade, organism-specific biosystemTwo inherent features of complement activation make its regulation very important: 1. There is an inherent positive feedback loop because the product of C3 activation forms part of an enzyme that cau...
Staphylococcus aureus infection, organism-specific biosystem (from KEGG)
Staphylococcus aureus infection, organism-specific biosystemStaphylococcus aureus can cause multiple forms of infections ranging from superficial skin infections to food poisoning and life-threatening infections. The organism has several ways to divert the ef...
Staphylococcus aureus infection, conserved biosystem (from KEGG)
Staphylococcus aureus infection, conserved biosystemStaphylococcus aureus can cause multiple forms of infections ranging from superficial skin infections to food poisoning and life-threatening infections. The organism has several ways to divert the ef...

Gene Ontology Provided by GOA

Process	Evidence Code	Pubs
complement activation	TAS Traceable Author Statement more info	PubMed
complement activation, alternative pathway	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
extracellular region	IEA Inferred from Electronic Annotation more info
extracellular space	TAS Traceable Author Statement more info	PubMed

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General protein information

Preferred Names: complement factor H

Names: complement factor H; beta-1H; factor H; factor H-like 1; beta-1-H-globulin; H factor 1 (complement); H factor 2 (complement); adrenomedullin binding protein; complement factor H, isoform b; age-related maculopathy susceptibility 1

NP_000177.2

EC 4.2.1.2

NP_001014975.1

EC 4.2.1.2

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_007259.1 RefSeqGene

Range

4868..100494

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_47

mRNA and Protein(s)

NM_000186.3 → NP_000177.2 complement factor H isoform a precursor

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (a).

Source sequence(s)

AL049744, BC142699, BM842566, BP324193, Y00716

Consensus CDS

CCDS1385.1

UniProtKB/Swiss-Prot

P08603

Related

ENSP00000356399, OTTHUMP00000033598, ENST00000367429, OTTHUMT00000086412

Conserved Domains (5) summary

cd00033
Location:146 – 206
Blast Score: 130

CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system

PHA02817
Location:320 – 444
Blast Score: 117

PHA02817; EEV Host range protein; Provisional

PHA02831
Location:744 – 915
Blast Score: 117

PHA02831; EEV host range protein; Provisional

PHA02927
Location:989 – 1230
Blast Score: 202

PHA02927; secreted complement-binding protein; Provisional

cl00043
Location:267 – 320
Blast Score: 87

CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system
NM_001014975.2 → NP_001014975.1 complement factor H isoform b precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) utilizes an alternate terminal exon which results in an early stop codon. The resulting protein (isoform b, also known as the "factor H-like 1" or "FHL-1" isoform) has a distinct C-terminus and is shorter than isoform a.

Source sequence(s)

AL049744, BC073982, BM842566

Consensus CDS

CCDS53452.1

UniProtKB/TrEMBL

F8WDX4

Related

ENSP00000402656, ENST00000439155

Conserved Domains (3) summary

cd00033
Location:146 – 206
Blast Score: 130

CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system

PHA02817
Location:320 – 449
Blast Score: 120

PHA02817; EEV Host range protein; Provisional

cl00043
Location:267 – 320
Blast Score: 88

CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000001.10 Reference GRCh37.p5 Primary Assembly

Range

196621008..196716634

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000133.1 Alternate HuRef

Range

167862965..167958566

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AL049744.8	CAI19672.1
		CAI19673.1
genomic	CH471067.1	EAW91260.1
		EAW91261.1
genomic	DQ233256.1	ABB02180.1
genomic	U56979.1	AAB01987.1
genomic	Z29665.1	CAA82763.1
mRNA	AI568119.1	None
mRNA	AK124051.1	None
mRNA	AK225649.1	None
mRNA	AK226113.1	None
mRNA	AK291395.1	BAF84084.1
mRNA	BC012610.1	None
mRNA	BC037285.2	AAH37285.1
mRNA	BC073982.1	None
mRNA	BC110643.1	AAI10644.1
mRNA	BC142699.1	AAI42700.1
mRNA	BM842566.1	None
mRNA	BP324193.1	None
mRNA	M12383.1	AAA52013.1
mRNA	M17517.1	AAA52016.1
mRNA	M65294.1	AAA35948.1
mRNA	X04697.1	CAB41739.1
mRNA	X07523.1	CAA30403.1
mRNA	Y00716.1	CAA68704.1
other-genetic	JF432152.1	ADZ15369.1

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
P08603.4	GenPept	UniProtKB/Swiss-Prot:P08603
Q14006	GenPept	UniProtKB/TrEMBL:Q14006
Q5TFM2	GenPept	UniProtKB/TrEMBL:Q5TFM2

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Additional Links

Epigenomics
MIM 134370
CFHbase: Mutation registry for Factor H deficiency (previously known as HF1base) CFHbase/
GeneTests for MIM: 134370
Resource of Asian Primary Immunodeficiency Diseases (RAPID) AGID_43
UCSC UCSC
UniGene Hs.363396