ArticleHuman molecular genetics2020
Effect of rare coding variants in the CFI gene on Factor I expression levels.
Article in Human molecular genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Complete Complement Factor I (CFI) deficiency: a systematic review of forty-nine patients including three novel cases.BMC immunology · 2025Pooled it
- Functional Analysis of Variants in Complement Factor I Identified in Age-Related Macular Degeneration and Atypical Hemolytic Uremic Syndrome.Frontiers in immunology · 2021Trial
- Geographic Atrophy in Patients with Age-Related Macular Degeneration Is Associated with Rare Variants in Complement Factor H and Complement Factor I.Ophthalmology science · 2026Article
- Recurrence of C3 Glomerulopathy and Immune Complex-Mediated Membranoproliferative Glomerulonephritis After Kidney Transplantation: Challenges and Opportunities.Kidney international reports · 2026Review
- Article
- Complement factor I deficiency-associated neuroinflammatory disease among Old Order Amish.The Journal of allergy and clinical immunology · 2025Article
- The role of complement factor I rare genetic variants in age related macular degeneration in Finland.Human molecular genetics · 2025Article
- High prevalence of the hotspot complement factor I p.Ile357Met pathogenic variant in Tunisian atypical hemolytic uremic syndrome patients: report of three new cases and review of the literature.Frontiers in immunology · 2025Review
- C3 glomerulopathy is highly prevalent in French Polynesia.Journal of translational autoimmunity · 2024Article
- Comprehensive functional characterization of complement factor I rare variant genotypes identified in the SCOPE geographic atrophy cohort.The Journal of biological chemistry · 2024Article
- The Relationship between Complements and Age-Related Macular Degeneration and Its Pathogenesis.Journal of ophthalmology · 2024Review
- Whole Genome Sequencing Identifies Novel Common and Low-Frequency Variants Associated With Age-Related Macular Degeneration.Investigative ophthalmology & visual science · 2023Article
- Complement Factor I Gene Variant as a Treatable Cause of Recurrent Aseptic Neutrophilic Meningitis: A Case Report.Neurology(R) neuroimmunology & neuroinflammation · 2023Article
- Article
- Genotypic analysis of a large cohort of patients with suspected atypical hemolytic uremic syndrome.Journal of molecular medicine (Berlin, Germany) · 2023Article
- Functional evaluation of complement factor I variants by immunoassays and SDS-PAGE.Frontiers in immunology · 2023Article
- Genetic investigation of Nordic patients with complement-mediated kidney diseases.Frontiers in immunology · 2023Article
- Systems genomics in age-related macular degeneration.Experimental eye research · 2022Article
- Functional analysis of rare genetic variants in complement factor I in advanced age-related macular degeneration.Human molecular genetics · 2022Article
- Rare complement factor I variants associated with reduced macular thickness and age-related macular degeneration in the UK Biobank.Human molecular genetics · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Factor I (FI) is one of the main inhibitors of complement activity, and numerous rare coding variants have been reported in patients with age-related macular degeneration, atypical hemolytic uremic syndrome and C3 glomerulopathy. Since many of these variants are of unknown clinical significance, this study aimed to determine the effect of rare coding variants in the complement factor I (CFI) gene on FI expression. We measured FI levels in plasma samples of carriers of rare coding variants and in vitro in the supernatants of epithelial cells expressing recombinant FI. FI levels were measured in 177 plasma samples of 155 individuals, carrying 24 different rare coding variants in CFI. In carriers of the variants p.Gly119Arg, p.Leu131Arg, p.Gly188Ala and c.772G>A (r.685_773del), significantly reduced FI plasma levels were detected. Furthermore, recombinant FI expression levels were determined for 126 rare coding variants. Of these variants 68 (54%) resulted in significantly reduced FI expression in supernatant compared to wildtype (WT). The recombinant protein expression levels correlated significantly with the FI level in plasma of carriers of CFI variants. In this study, we performed the most comprehensive FI expression level analysis of rare coding variants in CFI to date. More than half of CFI variants lead to reduced FI expression, which might impair complement regulation in vivo. Our study will aid the interpretation of rare coding CFI variants identified in clinical practice, which is in particular important in light of patient inclusion in ongoing clinical trials for CFI gene supplementation in AMD.
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.