ArticleBioscience reports2014
New functional and structural insights from updated mutational databases for complement factor H, Factor I, membrane cofactor protein and C3.
Article in Bioscience reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 74 citations in OpenAlex.
- A key regulator of missing-self innate immunity is polymorphic and under diversifying selection.Molecular biology and evolution · 2026Article
- A young woman with membranoproliferative glomerulonephritis and persistent hypocomplementemia: a case report.BMC nephrology · 2026Article
- Evidence for the Pathogenicity of aMedicina (Kaunas, Lithuania) · 2025Article
- Genetic Susceptibility in Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease: A Case-Control Study.International journal of molecular sciences · 2025Article
- Non-canonical roles of CFH in retinal pigment epithelial cells revealed by dysfunctional rare CFH variants.Stem cell reports · 2025Article
- Antibody recognition of complement factor H reveals a flexible loop involved in atypical hemolytic uremic syndrome pathogenesis.The Journal of biological chemistry · 2022Article
- Genetic justification of severe COVID-19 using a rigorous algorithm.Clinical immunology (Orlando, Fla.) · 2021Article
- Complement Inhibitors in Age-Related Macular Degeneration: A Potential Therapeutic Option.Journal of immunology research · 2021Review
- A Novel Homozygous In-Frame Deletion in Complement Factor 3 Underlies Early-Onset Autosomal Recessive Atypical Hemolytic Uremic Syndrome - Case Report.Frontiers in immunology · 2021Article
- The solution structure of the complement deregulator FHR5 reveals a compact dimer and provides new insights into CFHR5 nephropathy.The Journal of biological chemistry · 2020Article
- A Dimerization Site at SCR-17/18 in Factor H Clarifies a New Mechanism for Complement Regulatory Control.Frontiers in immunology · 2020Article
- Atypical hemolytic uremic syndrome: a syndrome in need of clarity.Clinical kidney journal · 2019Article
- Deleterious Impact of a NovelFrontiers in genetics · 2019Article
- Rare Functional Variants in Complement Genes and Anti-FH Autoantibodies-Associated aHUS.Frontiers in immunology · 2019Article
- Two distinct conformations of factor H regulate discrete complement-binding functions in the fluid phase and at cell surfaces.The Journal of biological chemistry · 2018Article
- Genotype-phenotype correlations of low-frequency variants in the complement system in renal disease and age-related macular degeneration.Clinical genetics · 2018Article
- Delivery of CR2-fH Using AAV Vector Therapy as Treatment Strategy in the Mouse Model of Choroidal Neovascularization.Molecular therapy. Methods & clinical development · 2018Article
- Statistical Validation of Rare Complement Variants Provides Insights into the Molecular Basis of Atypical Hemolytic Uremic Syndrome and C3 Glomerulopathy.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Regulator-dependent mechanisms of C3b processing by factor I allow differentiation of immune responses.Nature structural & molecular biology · 2017Article
- Matchout deuterium labelling of proteins for small-angle neutron scattering studies using prokaryotic and eukaryotic expression systems and high cell-density cultures.European biophysics journal : EBJ · 2017Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aHUS (atypical haemolytic uraemic syndrome), AMD (age-related macular degeneration) and other diseases are associated with defective AP (alternative pathway) regulation. CFH (complement factor H), CFI (complement factor I), MCP (membrane cofactor protein) and C3 exhibited the most disease-associated genetic alterations in the AP. Our interactive structural database for these was updated with a total of 324 genetic alterations. A consensus structure for the SCR (short complement regulator) domain showed that the majority (37%) of SCR mutations occurred at its hypervariable loop and its four conserved Cys residues. Mapping 113 missense mutations onto the CFH structure showed that over half occurred in the C-terminal domains SCR-15 to -20. In particular, SCR-20 with the highest total of affected residues is associated with binding to C3d and heparin-like oligosaccharides. No clustering of 49 missense mutations in CFI was seen. In MCP, SCR-3 was the most affected by 23 missense mutations. In C3, the neighbouring thioester and MG (macroglobulin) domains exhibited most of 47 missense mutations. The mutations in the regulators CFH, CFI and MCP involve loss-of-function, whereas those for C3 involve gain-of-function. This combined update emphasizes the importance of the complement AP in inflammatory disease, clarifies the functionally important regions in these proteins, and will facilitate diagnosis and therapy.
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