CFH
Domain
Sushi 1-3 domain represents the minimal unit capable of cofactor activity (PubMed:18252712). The property to discriminate self surfaces from non-self surfaces depends on the C-terminal region made of Sushis 19-20 (PubMed:21285368).
Function
Glycoprotein that plays an essential role in maintaining a well-balanced immune response by modulating complement activation. Acts as a soluble inhibitor of complement, where its binding to self markers such as glycan structures prevents complement activation and amplification on cell surfaces (PubMed:21285368, PubMed:25402769). Accelerates the decay of the complement alternative pathway (AP) C3 convertase C3bBb, thus preventing local formation of more C3b, the central player of the complement amplification loop (PubMed:19503104, PubMed:26700768). As a cofactor of the serine protease factor I, CFH also regulates proteolytic degradation of already-deposited C3b (PubMed:18252712, PubMed:23332154, PubMed:28671664). In addition, mediates several cellular responses through interaction with specific receptors. For example, interacts with CR3/ITGAM receptor and thereby mediates the adhesion of human neutrophils to different pathogens. In turn, these pathogens are phagocytosed and destroyed (PubMed:20008295, PubMed:9558116).
(Microbial infection) In the mosquito midgut, binds to the surface of parasite P.falciparum gametocytes and protects the parasite from alternative complement pathway-mediated elimination.
Involvement in disease
Basal laminar drusen
BLD
Drusen are extracellular deposits that accumulate below the retinal pigment epithelium on Bruch membrane. Basal laminar drusen refers to an early adult-onset drusen phenotype that shows a pattern of uniform small, slightly raised yellow subretinal nodules randomly scattered in the macula. In later stages, these drusen often become more numerous, with clustered groups of drusen scattered throughout the retina. In time these small basal laminar drusen may expand and ultimately lead to a serous pigment epithelial detachment of the macula that may result in vision loss.
None
The gene represented in this entry is involved in disease pathogenesis.
Complement factor H deficiency
CFHD
A disorder that can manifest as several different phenotypes, including asymptomatic, recurrent bacterial infections, and renal failure. Laboratory features usually include decreased serum levels of factor H, complement component C3, and a decrease in other terminal complement components, indicating activation of the alternative complement pathway. It is associated with a number of renal diseases with variable clinical presentation and progression, including membranoproliferative glomerulonephritis and atypical hemolytic uremic syndrome.
None
The disease is caused by variants affecting the gene represented in this entry.
Hemolytic uremic syndrome, atypical, 1
AHUS1
An atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease.
None
Disease susceptibility is associated with variants affecting the gene represented in this entry. Other genes may play a role in modifying the phenotype.
Macular degeneration, age-related, 4
ARMD4
A form of age-related macular degeneration, a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane.
None
Disease susceptibility is associated with variants affecting the gene represented in this entry.
Post-translational modifications
Sulfated on tyrosine residues.
According to a report, Asn-217 is not glycosylated (PubMed:17591618). Another study observed glycosylation at this position (PubMed:19139490).
Tissue Specificity
Expressed in the retinal pigment epithelium (at protein level) (PubMed:25136834). CFH is one of the most abundant complement components in blood where the liver is the major source of CFH protein in vivo. in addition, CFH is secreted by additional cell types including monocytes, fibroblasts, or endothelial cells (PubMed:2139673, PubMed:25136834, PubMed:2968404, PubMed:6444659).
Cellular localization
- Secreted
- (Microbial infection) In the mosquito midgut, localizes to P.falciparum (NF54 strain) macrogamete and young zygote cell membranes.
Alternative names
HF, HF1, HF2, CFH, Complement factor H, H factor 1