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Membranoproliferative glomerulonephritis including C3 glomerulopathy v3.9 CFH Ida Ertmanska changed review comment from: PMID: 37615951 Meuleman et al., 2023
Cohort of 398 French patients with C3 glomerulopathy ( n =296) or Ig-MPGN ( n =102). 53 rare variants were identified, including variants in CFI, C3, and 30 variants in (57%) in CFH. 20/30 CFH variants were absent from gnomAD, and 24 were classified as Pathogenic according to ACMG criteria. Presence of a rare variant was associated with poor kidney survival. Plasma FH levels were low in 20 families, and normal in 10. 6/38 individuals were homozygous, 32 were heterozygous for CFH variants. Based on histology data, C3 glomerulopathy was confirmed in 32 patients, and Ig-MPGN in 6 individuals with CFH variants. Kidney failure (leading to dialysis or transplant) occured in 21/38 patients at time of report.
Authors acknowledge the Levine et al., 2020 study that found no enrichment, but dispute the methodology: "In this large series, 45% of patients with Ig-MPGN had a low C4 level, suggesting that secondary forms with the activation of the classical pathway may have been included in the study." - low C4 points to secondary MPGN, rather than complement dysregulation driving disease.

PMID: 34211499 Piras et al., 2021
Authors state approx 20% of cases are familial. MLPA study of patients with C3G (n = 103) and IC-MPGN (n = 96). Detected a deletion of the entire CFH, CFHR3, and CFHR1 in one patient with IC-MPGN, as well as CNVs in other CFH-related genes.

PMID: 31919107 Levine et al., 2020
Analysis of WGS data of 165 primary membranoproliferative GN cases and 10k controls from the UK. Authors found that the MPGN cohort was not enriched for rare variants in complement factors compared to the control group. Hence, they pose that "rather than resulting from a primary genetic disorder of complement alternative pathway regulation, in most cases PMG is actually an autoimmune disease."

The association between CFH and AR C3 glomerulonephritis has been classified as Definitive in ClinGen (Feb 2024). The gene is also associated with Semi Dominant atypical hemolytic-uremic syndrome (Definitive, July 2023). ClinGen accessed 4th June 2026.; to: PMID: 37615951 Meuleman et al., 2023
Cohort of 398 French patients with C3 glomerulopathy ( n =296) or Ig-MPGN ( n =102). 53 rare variants were identified, including variants in CFI, C3, and 30 variants in (57%) in CFH. 20/30 CFH variants were absent from gnomAD, and 24 were classified as Pathogenic according to ACMG criteria. Presence of a rare variant was associated with poor kidney survival. Plasma FH levels were low in 20 families, and normal in 10. 6/38 individuals were homozygous, 32 were heterozygous for CFH variants. Based on histology data, C3 glomerulopathy was confirmed in 32 patients, and Ig-MPGN in 6 individuals with CFH variants. Kidney failure (leading to dialysis or transplant) occured in 21/38 patients at time of report.
Authors acknowledge the Levine et al., 2020 study that found no enrichment, but dispute the methodology: "In this large series, 45% of patients with Ig-MPGN had a low C4 level, suggesting that secondary forms with the activation of the classical pathway may have been included in the study." - low C4 points to secondary MPGN, rather than complement dysregulation driving disease.

PMID: 31919107 Levine et al., 2020
Analysis of WGS data of 165 primary membranoproliferative GN cases and 10k controls from the UK. Authors found that the MPGN cohort was not enriched for rare variants in complement factors compared to the control group. Hence, they pose that "rather than resulting from a primary genetic disorder of complement alternative pathway regulation, in most cases PMG is actually an autoimmune disease."

The association between CFH and AR C3 glomerulonephritis has been classified as Definitive in ClinGen (Feb 2024). The gene is also associated with Semi Dominant atypical hemolytic-uremic syndrome (Definitive, July 2023). ClinGen accessed 4th June 2026.
Membranoproliferative glomerulonephritis including C3 glomerulopathy v3.9 CFH Ida Ertmanska changed review comment from: PMID: 37615951 Meuleman et al., 2023
Cohort of 398 French patients with C3 glomerulopathy ( n =296) or Ig-MPGN ( n =102). 53 rare variants were identified, including variants in CFI, C3, and 30 variants in (57%) in CFH. 20/30 CFH variants were absent from gnomAD, and 24 were classified as Pathogenic according to ACMG criteria. Presence of a rare variant was associated with poor kidney survival. Plasma FH levels were low in 20 families, and normal in 10. 6/38 individuals were homozygous, 32 were heterozygous for CFH variants. Based on histology data, C3 glomerulopathy was confirmed in 32 patients, and Ig-MPGN in 6 individuals with CFH variants. Kidney failure (leading to dialysis or transplant) occured in 21/38 patients at time of report.

PMID: 31919107 Levine et al., 2020
Analysis of WGS data of 165 primary membranoproliferative GN cases and 10k controls from the UK. Authors found that the MPGN cohort was not enriched for rare variants in complement factors compared to the control group. Hence, they pose that "rather than resulting from a primary genetic disorder of complement alternative pathway regulation, in most cases PMG is actually an autoimmune disease."

The association between CFH and AR C3 glomerulonephritis has been classified as Definitive in ClinGen (Feb 2024). The gene is also associated with Semi Dominant atypical hemolytic-uremic syndrome (Definitive, July 2023). ClinGen accessed 4th June 2026.; to: PMID: 37615951 Meuleman et al., 2023
Cohort of 398 French patients with C3 glomerulopathy ( n =296) or Ig-MPGN ( n =102). 53 rare variants were identified, including variants in CFI, C3, and 30 variants in (57%) in CFH. 20/30 CFH variants were absent from gnomAD, and 24 were classified as Pathogenic according to ACMG criteria. Presence of a rare variant was associated with poor kidney survival. Plasma FH levels were low in 20 families, and normal in 10. 6/38 individuals were homozygous, 32 were heterozygous for CFH variants. Based on histology data, C3 glomerulopathy was confirmed in 32 patients, and Ig-MPGN in 6 individuals with CFH variants. Kidney failure (leading to dialysis or transplant) occured in 21/38 patients at time of report.
Authors acknowledge the Levine et al., 2020 study that found no enrichment, but dispute the methodology: "In this large series, 45% of patients with Ig-MPGN had a low C4 level, suggesting that secondary forms with the activation of the classical pathway may have been included in the study." - low C4 points to secondary MPGN, rather than complement dysregulation driving disease.

PMID: 34211499 Piras et al., 2021
Authors state approx 20% of cases are familial. MLPA study of patients with C3G (n = 103) and IC-MPGN (n = 96). Detected a deletion of the entire CFH, CFHR3, and CFHR1 in one patient with IC-MPGN, as well as CNVs in other CFH-related genes.

PMID: 31919107 Levine et al., 2020
Analysis of WGS data of 165 primary membranoproliferative GN cases and 10k controls from the UK. Authors found that the MPGN cohort was not enriched for rare variants in complement factors compared to the control group. Hence, they pose that "rather than resulting from a primary genetic disorder of complement alternative pathway regulation, in most cases PMG is actually an autoimmune disease."

The association between CFH and AR C3 glomerulonephritis has been classified as Definitive in ClinGen (Feb 2024). The gene is also associated with Semi Dominant atypical hemolytic-uremic syndrome (Definitive, July 2023). ClinGen accessed 4th June 2026.
Membranoproliferative glomerulonephritis including C3 glomerulopathy v1.5 CFHR1 Anna de Burca reviewed gene: CFHR1: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: ; Phenotypes: ; Mode of inheritance: None
Membranoproliferative glomerulonephritis including C3 glomerulopathy CFHR1 Arianna Tucci marked CFHR1 as ready
Membranoproliferative glomerulonephritis including C3 glomerulopathy CFHR1 Louise Daugherty classified CFHR1 as green
Membranoproliferative glomerulonephritis including C3 glomerulopathy CFHR1 BRIDGE consortium reviewed CFHR1
Membranoproliferative glomerulonephritis including C3 glomerulopathy CFHR1 Louise Daugherty reviewed CFHR1