ArticleJournal of the American Society of Nephrology : JASN2014
Complement factor B mutations in atypical hemolytic uremic syndrome-disease-relevant or benign?
Article in Journal of the American Society of Nephrology : JASN, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.
- Anti-Factor B Antibodies and Acute Postinfectious GN in Children.Journal of the American Society of Nephrology : JASN · 2020Pooled it
- Trial
- Article
- Atypical Hemolytic Uremic Syndrome: A Review of Complement Dysregulation, Genetic Susceptibility and Multiorgan Involvement.Journal of clinical medicine · 2025Review
- Factor B as a therapeutic target for the treatment of complement-mediated diseases.Frontiers in immunology · 2025Review
- The Inhibitory Effects of a Factor B-Binding DNA Aptamer Family Supersede the Gain of Function of Factor B Variants Associated with Atypical Hemolytic Uremic Syndrome.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Anti-factor B antibodies in atypical hemolytic uremic syndrome.Pediatric nephrology (Berlin, Germany) · 2024Article
- Atypical hemolytic uremic syndrome: genetically-based insights into pathogenesis through an analysis of the complement regulator CD46.Annals of blood · 2023Article
- Targeted genotyping of COVID-19 patients reveals a signature of complement C3 and factor B coding SNPs associated with severe infection.Immunobiology · 2023Article
- C3-dependent effector functions of complement.Immunological reviews · 2023Review
- Genetic investigation of Nordic patients with complement-mediated kidney diseases.Frontiers in immunology · 2023Article
- AnFrontiers in immunology · 2023Article
- Kidney diseases.Immunological reviews · 2023Review
- Alternative pathway diagnostics.Immunological reviews · 2023Review
- Structure determination of an unstable macromolecular complex enabled by nanobody-peptide bridging.Protein science : a publication of the Protein Society · 2022Article
- Targeted Genotyping of MIS-C Patients Reveals a Potential Alternative Pathway Mediated Complement Dysregulation during COVID-19 Infection.Current issues in molecular biology · 2022Article
- In Silico Designed Gain-of-Function Variants of Complement C2 Support Cytocidal Activity of Anticancer Monoclonal Antibodies.Cancers · 2022Article
- Complement Blockade Is a Promising Therapeutic Approach in a Subset of Critically Ill Adult Patients with Complement-Mediated Hemolytic Uremic Syndromes.Journal of clinical medicine · 2022Review
- Modeling C3 glomerulopathies: C3 convertase regulation on an extracellular matrix surface.Frontiers in immunology · 2022Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 6 institutions in 4 countries.
Funding
Abstract
Atypical hemolytic uremic syndrome (aHUS) is a genetic ultrarare renal disease associated with overactivation of the alternative pathway of complement. Four gain-of-function mutations that form a hyperactive or deregulated C3 convertase have been identified in Factor B (FB) ligand binding sites. Here, we studied the functional consequences of 10 FB genetic changes recently identified from different aHUS cohorts. Using several tests for alternative C3 and C5 convertase formation and regulation, we identified two gain-of-function and potentially disease-relevant mutations that formed either an overactive convertase (M433I) or a convertase resistant to decay by FH (K298Q). One mutation (R178Q) produced a partially cleaved protein with no ligand binding or functional activity. Seven genetic changes led to near-normal or only slightly reduced ligand binding and functional activity compared with the most common polymorphism at position 7, R7. Notably, none of the algorithms used to predict the disease relevance of FB mutations agreed completely with the experimental data, suggesting that in silico approaches should be undertaken with caution. These data, combined with previously published results, suggest that 9 of 15 FB genetic changes identified in patients with aHUS are unrelated to disease pathogenesis. This study highlights that functional assessment of identified nucleotide changes in FB is mandatory to confirm disease association.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.