CFHR5 Gene: Complement Factor H Related 5
Genetic and Functional Insights into CFHR5 in Complement Regulation and Disease
Gene Information Card
| Symbol | CFHR5 |
|---|---|
| Full Name | complement factor H related 5 |
| Gene Type | protein coding |
| Chromosomal Location | 1q31.3 |
| NCBI Gene ID | 81494 ncbi.nlm.nih.gov/gene/81494 |
| Ensembl ID | ENSG00000134321 |
| UniProt ID | Q9BXR6 |
| OMIM ID | 608593 |
| HGNC ID | 24679 |
| Aliases | CFHL5, FHR5, FLJ00368 |
Description
CFHR5 (complement factor H related 5) is a protein-coding gene located on chromosome 1q31.3. It encodes a member of the complement factor H protein family, which plays a role in the regulation of the alternative complement pathway. CFHR5 is primarily expressed in the liver and secreted into the bloodstream. The protein binds to complement components C3b and C3d, modulating complement activation. Mutations and copy number variations in CFHR5 are associated with atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathy, and age-related macular degeneration (AMD).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Atypical hemolytic uremic syndrome (aHUS) | CFHR5 mutations lead to dysregulation of the alternative complement pathway, resulting in uncontrolled complement activation on endothelial cells. | ClinVar, OMIM |
| C3 glomerulopathy | CFHR5 variants, including internal duplications, impair complement regulation, leading to C3 deposition in glomeruli. | OMIM, NCBI |
| Age-related macular degeneration (AMD) | CFHR5 polymorphisms influence complement factor H activity, contributing to AMD risk. | NCBI, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Kidney | 3.2 | Medium |
| Lung | 1.8 | Low |
| Heart | 1.1 | Low |
| Brain | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 15.3 | High expression |
| HEK293 (embryonic kidney) | 4.1 | Moderate expression |
| A549 (lung) | 2.0 | Low expression |
| K562 (leukemia) | 0.8 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.481G>A (p.Gly161Arg) | Missense | Rare | Alters C3b binding affinity, associated with aHUS |
| c.635A>G (p.Gln212Arg) | Missense | Rare | Impaired complement regulation, linked to C3 glomerulopathy |
| c.742C>T (p.Arg248Trp) | Missense | Rare | Reduced factor H binding, associated with AMD |
| Internal duplication (exon 2-3) | Copy number variation | Rare | Gain-of-function, increased C3b binding, linked to C3 glomerulopathy |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Gly161Arg) that reduce C3b binding or complement regulatory activity.
Gain of Function (GOF)
Internal duplications (e.g., exon 2-3 duplication) that enhance C3b binding and complement activation.
Dominant Negative (DN)
Not well documented for CFHR5; most mutations act through haploinsufficiency or gain-of-function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Complement and coagulation cascades (KEGG: hsa04610)
• Alternative complement pathway (Reactome: R-HSA-173736)
Protein Summary
CFHR5 encodes complement factor H related 5, a 65 kDa secreted glycoprotein composed of 9 short consensus repeats (SCRs). It binds to complement components C3b and C3d, acting as a regulator of the alternative complement pathway. CFHR5 competes with factor H for C3b binding, modulating complement activation on surfaces. The protein is primarily synthesized in the liver and circulates in plasma. Dysregulation of CFHR5 due to mutations or copy number variations contributes to complement-mediated diseases such as aHUS, C3 glomerulopathy, and AMD.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CFHR5 Knockout HEK293 Cell Line | EDJ-KQ8908 | Human | 81494 | Details Get a Quote |
| CFHR5 Knockout HeLa Cell Line | EDJ-KQ57390 | Human | 81494 | Details Get a Quote |
| CFHR5 Knockout A-549 Cell Line | EDJ-KQ65896 | Human | 81494 | Details Get a Quote |
| CFHR5 Knockout HCT 116 Cell Line | EDJ-KQ74323 | Human | 81494 | Details Get a Quote |
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