CFH Gene - Complement Factor H
Key regulator of the alternative complement pathway, associated with age-related macular degeneration and atypical hemolytic uremic syndrome
Gene Information Card
| Symbol | CFH |
|---|---|
| Full Name | Complement Factor H |
| Gene Type | Protein coding |
| Chromosomal Location | 1q31.3 |
| NCBI Gene ID | 3075 ncbi.nlm.nih.gov/gene/3075 |
| Ensembl ID | ENSG00000000971 |
| UniProt ID | P08603 |
| OMIM ID | 134370 |
| HGNC ID | 4883 |
| Aliases | AHUS1, AMBP1, CFHL3, FH, FHL1, HF, HF1, HF2, HUS |
Description
The CFH gene encodes complement factor H, a soluble glycoprotein that regulates the alternative complement pathway. Factor H binds to C3b, accelerates the decay of the C3 convertase (C3bBb), and acts as a cofactor for factor I-mediated cleavage of C3b. It is essential for protecting host cells from complement-mediated damage. Mutations and polymorphisms in CFH are strongly associated with age-related macular degeneration (AMD) and atypical hemolytic uremic syndrome (aHUS).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Age-related macular degeneration (AMD) | Polymorphisms (e.g., Y402H) reduce factor H binding to C-reactive protein and glycosaminoglycans, leading to uncontrolled complement activation on retinal pigment epithelium. | NCBI Gene, OMIM, ClinVar |
| Atypical hemolytic uremic syndrome (aHUS) | Loss-of-function mutations impair factor H's ability to regulate complement on endothelial surfaces, resulting in thrombotic microangiopathy. | NCBI Gene, OMIM, ClinVar |
| C3 glomerulopathy (C3G) | Deficiency or dysfunction of factor H leads to uncontrolled C3 activation and deposition in glomeruli. | NCBI Gene, OMIM |
| Hemolytic uremic syndrome, atypical, susceptibility to | Heterozygous mutations in CFH predispose to aHUS. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 100.0 | High |
| Plasma | N/A | High (secreted) |
| Kidney | 10.0 | Medium |
| Retina | 5.0 | Low |
| Brain | 3.0 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 100.0 | High expression |
| ARPE-19 (retinal pigment epithelium) | 5.0 | Low expression |
| HEK293 (embryonic kidney) | 8.0 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1204C>T (p.Arg402His) | SNP (rs1061170) | ~30% in European populations | Reduced binding to C-reactive protein and heparin; risk factor for AMD |
| c.3572C>T (p.Ser1191Leu) | Missense | Rare | Associated with aHUS; impairs C3b binding and cofactor activity |
| c.2850G>T (p.Trp950Cys) | Missense | Rare | Causes aHUS; disrupts C-terminal domain function |
| c.94C>T (p.Arg32*) | Nonsense | Rare | Complete loss of function; associated with C3 glomerulopathy |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations (e.g., p.Trp950Cys, p.Arg32*) impair C3b binding, cofactor activity, or secretion, leading to aHUS or C3G.
Gain of Function (GOF)
Not described for CFH.
Dominant Negative (DN)
Heterozygous missense mutations (e.g., p.Ser1191Leu) can interfere with wild-type factor H function, contributing to aHUS.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Complement and coagulation cascades (KEGG: hsa04610)
• Alternative complement pathway (Reactome: R-HSA-173736)
• Regulation of complement cascade (Reactome: R-HSA-977606)
Protein Summary
Complement factor H is a 155 kDa glycoprotein composed of 20 short consensus repeats (SCRs) also known as complement control protein (CCP) modules. It is primarily synthesized in the liver and circulates in plasma. Factor H binds to C3b and host cell surfaces via sialic acid and glycosaminoglycans, preventing complement activation on self-tissues. Its C-terminal domains (SCRs 19-20) are critical for surface recognition, while N-terminal domains (SCRs 1-4) mediate cofactor and decay-accelerating activities. Mutations in the C-terminal region are common in aHUS, while the Y402H polymorphism in SCR 7 is a major risk factor for AMD.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CFHR4 Knockout HEK293 Cell Line | EDJ-KQ3499 | Human | 10877 | Details Get a Quote |
| CFHR2 Knockout HEK293 Cell Line | EDJ-KQ4859 | Human | 3080 | Details Get a Quote |
| CFHR5 Knockout HEK293 Cell Line | EDJ-KQ8908 | Human | 81494 | Details Get a Quote |
| CFH Knockout HEK293 Cell Line | EDJ-KQ50344 | Human | 3075 | Details Get a Quote |
| CFHR1 Knockout HEK293 Cell Line | EDJ-KQ50345 | Human | 3078 | Details Get a Quote |
| CFHR3 Knockout HEK293 Cell Line | EDJ-KQ51013 | Human | 10878 | Details Get a Quote |
| CFH Knockout HeLa Cell Line | EDJ-KQ53510 | Human | 3075 | Details Get a Quote |
| CFHR1 Knockout HeLa Cell Line | EDJ-KQ53511 | Human | 3078 | Details Get a Quote |
| CFHR2 Knockout HeLa Cell Line | EDJ-KQ53512 | Human | 3080 | Details Get a Quote |
| CFHR4 Knockout HeLa Cell Line | EDJ-KQ55509 | Human | 10877 | Details Get a Quote |
| CFHR3 Knockout HeLa Cell Line | EDJ-KQ55510 | Human | 10878 | Details Get a Quote |
| CFHR5 Knockout HeLa Cell Line | EDJ-KQ57390 | Human | 81494 | Details Get a Quote |
| CFH Knockout A-549 Cell Line | EDJ-KQ61979 | Human | 3075 | Details Get a Quote |
| CFHR1 Knockout A-549 Cell Line | EDJ-KQ61980 | Human | 3078 | Details Get a Quote |
| CFHR2 Knockout A-549 Cell Line | EDJ-KQ61981 | Human | 3080 | Details Get a Quote |
Displaying Records 1 To 15 Of 28 Records
