Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Orphanet	Ensembl
	HGNC	UniGene	Nucleotide	OMIM		UCSC

Home Page

FLASH GENE

Symbol

CFH

contributors: shn/pgu - updated : 20-04-2018

HGNC name	complement factor H
HGNC id	4883

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	ARMD4 age-related macular degeneration 4 HUS hemolytic-uremic syndrome, atypical
Location	1q31.3      Physical location : 196.621.007 - 196.716.631
Synonym name	H factor 1 (complement)
	factor H-like 1
	beta-1H
	beta-1-H-globulin
	H factor 2 (complement)
	complement factor H, isoform b
	adrenomedullin binding protein 1
Synonym symbol(s)	FH, HF, HF1, HF2, FHL1, AHUS1, ARMS1, CFHL3, MGC88246, AMBP1

DNA

TYPE	functioning gene
STRUCTURE	95.63 kb     22 Exon(s)

regulatory sequence	Binding site
text structure	exons 18-20 is a domain important for host recognition
	three binding sites for C3b

MAPPING

cloned

Y

linked

Y

status

confirmed

Map	cen - D1S2757 - D1S2794 - CFH - D1S2840 - D1S413 - qter

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000186 22 splicing 4200 NP_000177 155 1231 - 2002 11851332 also called transcript variant 1/isoform a 20 SUSHI domains NM_001014975 10 splicing 1835 NP_001014975 48 449 - 2002 11851332 also called transcript variant 2 an alternate exon resulting in an early stop codon 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

EXPRESSION

Type	ubiquitous

constitutive of

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart         Digestive intestine small intestine     highly   liver       highly Reproductive female system uterus       Respiratory respiratory tract trachea     highly Urinary bladder       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial secretory glandular     Muscular striatum skeletal

cell lineage
cell lines
fluid/secretion	plasma

at STAGE

physiological period

fetal

Text

spleen

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

twenty short concensus repeat (SCR, sushi) domains

conjugated

GlycoP

HOMOLOGY

interspecies	ortholog to cfh, Danio rerio
	ortholog to Cfh, Rattus norvegicus
	ortholog to Cfh, Mus musculus
	ortholog to CFH, Pan trogloytes

Homologene

FAMILY

CATEGORY

immunity/defense , regulatory

SUBCELLULAR LOCALIZATION	extracellular
text	secreted

basic FUNCTION	involved in the regulation of complement activation and protection of cellular surfaces from complement activation (restricting this innate defense mechanism to microbial infections)
	an adhesion ligand for human neutrophils but not for eosinophils
	is one essential complement inhibitor that binds to the acute phase reactant C-reactive protein
	acting as a cofactor with factor I also known as C3b inactivator
	it regulates the activity of C3 convertases, such as C4b2a
	critically required for the long-term functional health of the retina
	mediates anti-inflammatory housekeeping functions by protecting self cells from complement activation
	major regulator of the complement system and protects host tissues from complement-mediated damage

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

immunity/defense

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	complement factor I, CF1 and C3B (
	alphaMbeta2 (CD11b/CD18) (
	selectin L, SELL (
	C-reactive protein, CRP (
	binding the complement C3b in competition with Bb in the assembly of C3 convertase and downregulating proteins of the alternative pathway in the complement system
	dermatan sulfate-binding protein
	Adrenomedullin, AM (
	integrin-binding sialoprotein, IBSP; secreted phosphoprotein 1, SPP1 (
	phosphoglycerate mutase (ScGpm1p) (
	pentraxin 3 long, PTX3 (
	interacting with ADIPOQ (adiponectin controls activation of the terminal complement pathway by binding CFH)(
	reciprocal synergistic effects of ADM and CFH (
	role of IL27 in regulating complement activation through up-regulation of CFH, suggesting that defects in IL27 signaling or expression may contribute to the reduction of CFH expression in the retina of patients with AMD
	CFHR1 competes with complement factor H-like protein 1 (CFH) for binding to C3b
	CFH can bind pro-inflammatory monomeric CRP (mCRP) as well as the circulating pentameric form
	serum concentrations of CFH are genetically regulated by a locus within CFHR3

cell & other

platelets

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

HUS , ARMD4

Susceptibility

to age-related macular degeneration (AMD) (see ARMDS4) to atypical hemolytic and uremic syndromewith nephropathy to membranoproliferative glomerulonephritis type II(dense deposit disease) to meningococcal disease (MD) to (IgA) vasculitis with nephritis (IgAVN), and IgA nephropathy (IgAN)

Variant & Polymorphism SNP , repeat , other	Y402H located in SCR7 coupled with a modifiable lifestyle factor such as cigarette smoking confers a significantly higher risk of age-related macular degeneration
	SNPs within complement factor H (CFH) rs1065489
	than either factor alone
	A2089G or G2881T increasing the risk of atypical hemolytic and uremic syndrome
	SNP increasing the risk of macular degeneration (in association with ERCC6 SNPs)
	SNP increasing the risk of membranoproliferative glomerulonephritis type II(dense deposit disease)
	CFH Tyr402His is not a major risk factor for overall early AMD in this Latino population, but may play a role in susceptibility to phenotypes of early AMD likely to progress to late AMD
	SNP rs1410996 moderately increased the risk of exudative age-related macular degeneration in a Chinese population
	SNPs within complement factor H (CFH) rs1065489 associated with host susceptibility to meningococcal disease
	rs800292 is a potential marker for typical neovascularization (
	mutation causing the R1210C alteration is associated with age-related macular degeneration, but also associated with a rare renal glomerular disease
	genetic variation in CFH (rs6677604) is involved in the phenotype of complement activation in both IgAVN and IgAN
	CFHR3 SNP provides protection from MD (rs75703017), by decreasing the concentration of CFH in the blood
	rs800292 is associated with AMD

Candidate gene
Marker
Therapy target	renal injury is completely reversed in Cfh(-/-) mice, affected with Membranoproliferative glomerulonephritis, pretreated with an anti-murine C5 antibody
	ADM/CFH is a novel therapy target for safe and effective therapy of patients with hemorrhagic shock, sepsis, and ischemic injury

ANIMAL & CELL MODELS

	mice deficient in complement factor H develop membranoproliferative glomerulonephritis
	cfh(-/-) MICE exhibit significantly reduced visual acuity and rod response amplitudes on electroretinography, an increase in autofluorescent subretinal deposits, an accumulation of complement C3 in the neural retina and a thinning of Bruch's membrane