CFH complement factor H [Homo sapiens (human)] - Gene

Summary

Official Symbol: CFHprovided by HGNC
Official Full Name: complement factor Hprovided by HGNC
Primary source: HGNC:HGNC:4883
See related: Ensembl:ENSG00000000971 MIM:134370; AllianceGenome:HGNC:4883
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
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]
Expression: Biased expression in liver (RPKM 390.3), gall bladder (RPKM 78.0) and 9 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1q31.3

Exon count:: 23

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (196652043..196747504)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (195998386..196093925)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (196621173..196716634)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Protective role of complement factor H against the development of preeclampsia.
Title: Protective role of complement factor H against the development of preeclampsia.
Gliosis-dependent expression of complement factor H truncated variants attenuates retinal neurodegeneration following ischemic injury.
Title: Gliosis-dependent expression of complement factor H truncated variants attenuates retinal neurodegeneration following ischemic injury.
Association of KDR (rs2071559, rs1870377), CFH (rs1061170, rs1410996) genes variants and serum levels with pituitary adenoma.
Title: Association of KDR (rs2071559, rs1870377), CFH (rs1061170, rs1410996) genes variants and serum levels with pituitary adenoma.
Mesangial C3 Deposition, Complement-Associated Variant, and Disease Progression in IgA Nephropathy.
Title: Mesangial C3 Deposition, Complement-Associated Variant, and Disease Progression in IgA Nephropathy.
Complement factor H attenuates TNF-alpha-induced inflammation by upregulating EIF3C in rheumatoid arthritis.
Title: Complement factor H attenuates TNF-α-induced inflammation by upregulating EIF3C in rheumatoid arthritis.
Identification of complement factor H variants that predispose to pre-eclampsia: A genetic and functional study.
Title: Identification of complement factor H variants that predispose to pre-eclampsia: A genetic and functional study.
Reduced binding of apoE4 to complement factor H promotes amyloid-beta oligomerization and neuroinflammation.
Title: Reduced binding of apoE4 to complement factor H promotes amyloid-β oligomerization and neuroinflammation.
CFH-CFHR1 hybrid genes in two cases of atypical hemolytic uremic syndrome.
Title: CFH-CFHR1 hybrid genes in two cases of atypical hemolytic uremic syndrome.
Low level of complement factor H increases the risk of cancer-related death in patients with small-cell lung cancer.
Title: Low level of complement factor H increases the risk of cancer-related death in patients with small-cell lung cancer.
Rare germline complement factor H variants in patients with paroxysmal nocturnal hemoglobinuria.
Title: Rare germline complement factor H variants in patients with paroxysmal nocturnal hemoglobinuria.

Submit: New GeneRIF Correction See all GeneRIFs (709)

Phenotypes

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

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Age related macular degeneration 4 MedGen: C1853147 OMIM: 610698 GeneReviews: Not available	Compare labs
Basal laminar drusen MedGen: C0730295 OMIM: 126700 GeneReviews: Not available	Compare labs
Factor H deficiency MedGen: C0398777 OMIM: 609814 GeneReviews: C3 Glomerulopathy	Compare labs
Hemolytic uremic syndrome, atypical, susceptibility to, 1 MedGen: C2749604 OMIM: 235400 GeneReviews: Genetic Atypical Hemolytic-Uremic Syndrome	Compare labs

EBI GWAS Catalog

Description
Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration. EBI GWAS Catalog EBI GWAS CatalogPubMed
Complement factor H polymorphism in age-related macular degeneration. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic factors in nonsmokers with age-related macular degeneration revealed through genome-wide gene-environment interaction analysis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide and gene-centric analyses of circulating myeloperoxidase levels in the charge and care consortia. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association identifies SKIV2L and MYRIP as protective factors for age-related macular degeneration. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study for serum complement C3 and C4 levels in healthy Chinese subjects. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies susceptibility loci for IgA nephropathy. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies variants in the CFH region associated with host susceptibility to meningococcal disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of advanced age-related macular degeneration identifies a role of the hepatic lipase gene (LIPC). EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of age-related macular degeneration identifies associated variants in the TNXB-FKBPL-NOTCH4 region of chromosome 6p21.3. EBI GWAS Catalog EBI GWAS CatalogPubMed
Heritability and genome-wide association study to assess genetic differences between advanced age-related macular degeneration subtypes. EBI GWAS Catalog EBI GWAS CatalogPubMed
Insights into the genetic architecture of early stage age-related macular degeneration: a genome-wide association study meta-analysis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Ischemic stroke is associated with the ABO locus: the EuroCLOT study. EBI GWAS Catalog EBI GWAS CatalogPubMed
Seven new loci associated with age-related macular degeneration. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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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 Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

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

D1S3541 (e-PCR)
- UniSTS:76944

G16258 (e-PCR)
- UniSTS:12734

G44722 (e-PCR)
- UniSTS:95197

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables complement component C3b binding	IBA Inferred from Biological aspect of Ancestor more info
enables heparan sulfate proteoglycan binding	IDA Inferred from Direct Assay more info	PubMed
enables heparin binding	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in complement activation	IBA Inferred from Biological aspect of Ancestor more info
involved_in complement activation	IDA Inferred from Direct Assay more info	PubMed
involved_in complement activation, alternative pathway	IEA Inferred from Electronic Annotation more info
involved_in proteolysis	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within regulation of complement activation	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of complement activation, alternative pathway	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within regulation of complement-dependent cytotoxicity	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in blood microparticle	HDA more info	PubMed
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular space	NAS Non-traceable Author Statement more info	PubMed
part_of serine-type endopeptidase complex	IPI Inferred from Physical Interaction more info	PubMed
located_in symbiont cell surface	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: complement factor H

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

NP_000177.2

EC 4.2.1.2

NP_001014975.1

EC 4.2.1.2

NCBI Reference Sequences (RefSeq)

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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_000186.4 → NP_000177.2 complement factor H isoform a precursor

See identical proteins and their annotated locations for NP_000177.2

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

A5PL14, P08603, P78435, Q14570, Q2TAZ5, Q38G77, Q5TFM3, Q8N708, Q9NU86

Related

ENSP00000356399.4, ENST00000367429.9

Conserved Domains (4) summary

cd00033
Location:1109 → 1163

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

smart00032
Location:146 → 205

CCP; Domain abundant in complement control proteins; SUSHI repeat; short complement-like repeat (SCR)

PHA02927
Location:10 → 262

PHA02927; secreted complement-binding protein; Provisional

pfam00084
Location:811 → 864

Sushi; Sushi repeat (SCR repeat)
NM_001014975.3 → 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

A0A0D9SG88, A0A8Q3WM71

Related

ENSP00000487250.1, ENST00000630130.2

Conserved Domains (4) summary

cd00033
Location:85 → 142

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

smart00032
Location:146 → 205

CCP; Domain abundant in complement control proteins; SUSHI repeat; short complement-like repeat (SCR)

PHA02927
Location:10 → 262

PHA02927; secreted complement-binding protein; Provisional

pfam00084
Location:325 → 384

Sushi; Sushi repeat (SCR repeat)