ArticleJournal of the American Society of Nephrology : JASN2016
Rare Variants in the Complement Factor H-Related Protein 5 Gene Contribute to Genetic Susceptibility to IgA Nephropathy.
Article in Journal of the American Society of Nephrology : JASN, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
38 citing papers in PubMed, 68 citations in OpenAlex.
- Association of Complement Genetics with Outcomes in IgA Nephropathy.Clinical journal of the American Society of Nephrology : CJASN · 2026Article
- Complement-Mediated Kidney Diseases: Role of Alternative Pathway in Glomerular Inflammation.Kidney international reports · 2026Review
- Complement proteins associated with circulatory and glomerular IgA-containing immune complexes in patients with IgA nephropathy.Scientific reports · 2025Article
- Review
- IgA Nephropathy With Membranoproliferative Pattern and Resistance to Immunosuppressive Therapy in Two Patients With Cofactor I Pathogenic Variant.Nephrology (Carlton, Vic.) · 2025Article
- The human factor H protein family - an update.Frontiers in immunology · 2024Review
- Heterozygous mutations in factor H aggravate pathological damage in a stable IgA deposition model induced byFrontiers in immunology · 2024Article
- The role of complement in kidney disease.Nature reviews. Nephrology · 2023Review
- Review
- Molecular insight in intrarenal inflammation affecting four main types of cells in nephrons in IgA nephropathy.Frontiers in medicine · 2023Review
- Urinary complement profile in IgA nephropathy and its correlation with the clinical and pathological characteristics.Frontiers in immunology · 2023Article
- Kidney diseases.Immunological reviews · 2023Review
- The Role of Complement in Microangiopathic Lesions of IgA Nephropathy.Kidney international reports · 2022Article
- Complement Factor H-Related Proteins FHR1 and FHR5 Interact With Extracellular Matrix Ligands, Reduce Factor H Regulatory Activity and Enhance Complement Activation.Frontiers in immunology · 2022Article
- Article
- The Contribution of Complement to the Pathogenesis of IgA Nephropathy: Are Complement-Targeted Therapies Moving from Rare Disorders to More Common Diseases?Journal of clinical medicine · 2021Review
- Is IgA nephropathy the same disease in different parts of the world?Seminars in immunopathology · 2021Review
- Complement activation in IgA nephropathy.Seminars in immunopathology · 2021Review
- Management of IgA Vasculitis with Nephritis.Paediatric drugs · 2021Review
- Complement catalyzing glomerular diseases.Cell and tissue research · 2021Review
Corrections and comments
- Commented on by
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A recent genome-wide association study of IgA nephropathy (IgAN) identified 1q32, which contains multiple complement regulatory genes, including the complement factor H (CFH) gene and the complement factor H-related (CFHRs) genes, as an IgAN susceptibility locus. Abnormal complement activation caused by a mutation in CFHR5 was shown to cause CFHR5 nephropathy, which shares many characteristics with IgAN. To explore the genetic effect of variants in CFHR5 on IgAN susceptibility, we recruited 500 patients with IgAN and 576 healthy controls for genetic analysis. We sequenced all exons and their intronic flanking regions as well as the untranslated regions of CFHR5 and compared the frequencies of identified variants using the sequence kernel association test. We identified 32 variants in CFHR5, including 28 rare and four common variants. The distribution of rare variants in CFHR5 in patients with IgAN differed significantly from that in controls (P=0.002). Among the rare variants, in silico programs predicted nine as potential functional variants, which we then assessed in functional assays. Compared with wild-type CFHR5, three recombinant CFHR5 proteins, CFHR5-M (c.508G>A/p.Val170Met), CFHR5-S (c.533A>G/p.Asn178Ser), and CFHR5-D (c.822A>T/p.Glu274Asp), showed significantly higher C3b binding capacity (CFHR5-M: 109.67%±3.54%; P=0.02; CFHR5-S: 174.27%±9.78%; P<0.001; CFHR5-D: 127.25%±1.75%; P<0.001), whereas another recombinant CFHR5 (c.776T>A/p.Leu259Termination) showed less C3b binding (56.89%±0.57%; P<0.001). Our study found that rare variants in CFHR5 may contribute to the genetic susceptibility to IgAN, which suggests that CFHR5 is an IgAN susceptibility gene.
Indexed as
Identifiers
What OpenQuestion holds
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.