STRs in panel
Prev Next
Regions in panel
Prev Next

Membranoproliferative glomerulonephritis

Gene: C3

Green List (high evidence)

C3 (complement C3)
EnsemblGeneIds (GRCh38): ENSG00000125730
EnsemblGeneIds (GRCh37): ENSG00000125730
OMIM: 120700, Gene2Phenotype
C3 is in 9 panels

5 reviews

Daniel Gale (UCL)

Green List (high evidence)

A very small number (~2 I am aware of) of mutations that activate C3 (i.e. reduce its regulation by complement alternative pathway regulators) have been linked to familial C3 glomerulopathy (one with DDD, one with C3GN). Loss of function variants might be associated with reduced circulating C3 levels but DO NOT CAUSE MPGN or C3 glomerulopathy.
Created: 10 Jan 2020, 10:08 a.m. | Last Modified: 10 Jan 2020, 10:08 a.m.
Panel Version: 2.2

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
C3 glomerulopathy; Membranoproliferative glomerulonephritis; renal insufficiency; proteinuria

Publications

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Variants in this GENE are reported as part of current diagnostic practice

David Kavanagh (Newcastle upon Tyne NHS hospitals trust)

Green List (high evidence)

Gain of function mutations associated with familial C3G/MPGN
Created: 6 Aug 2019, 10:04 a.m. | Last Modified: 6 Aug 2019, 10:04 a.m.
Panel Version: 1.6

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
C3G; MPGN

Publications

Mode of pathogenicity
Other

Eleanor Williams (Genomics England Curator)

I don't know

Comment on mode of pathogenicity: Gain of function mutations associated with familial C3G/MPGN
Created: 23 Mar 2020, 11:02 a.m. | Last Modified: 23 Mar 2020, 11:02 a.m.
Panel Version: 2.5
Green review by Daniel Gale agrees with Green rating and gain of function mode of pathogenicity. Should change the Mode of Pathogenicity to make it clear that Loss of function variants are not associated with the disease phenotype.
Created: 29 Jan 2020, 10:59 p.m. | Last Modified: 29 Jan 2020, 10:59 p.m.
Panel Version: 2.2
Comment on list classification: 2 cases plus functional data and expert review green.
Created: 14 Aug 2019, 6:11 p.m. | Last Modified: 14 Aug 2019, 6:11 p.m.
Panel Version: 1.10
Comment on mode of pathogenicity: Gain of function
Created: 14 Aug 2019, 6:11 p.m. | Last Modified: 14 Aug 2019, 6:11 p.m.
Panel Version: 1.8
Associated with C3 deficiency (#613779) and {Hemolytic uremic syndrome, atypical, susceptibility to, 5} (#612925) in OMIM.

PMID: 20852386 - Martínez-Barricarte et al 2010 - report a case a mother and her two identical twin sons with Dense deposit disease (DDD) caused by a heterozygous variant in the C3 gene. The mutation, c.2767_2774delACGGTG (C3923ΔDG) in exon 21, results in a mutated protein (C3923ΔDG) lacking 2 amino acids (Asp923 and Gly924) in the MG7 domain of C3. The deletion was only present in affected family members. Functional studies suggest a gain of function.

PMID: 26471127 - Chauvet et al 2016 - report functional characterization of a C3 mutation identified in two brothers with C3GN (C3 glomerulopathy). Both carry the same c.2327T>C heterozygous mutation in the C3 gene, leading to p.I756T. The mutation was not found in the 1000 genomes or EVS databases. In vitro the C3 mutation exhibited decreased binding to CR1, resulting in less CR1-dependent cleavage of C3b by factor 1.
Created: 14 Aug 2019, 6:09 p.m. | Last Modified: 14 Aug 2019, 6:09 p.m.
Panel Version: 1.6
This gene was part of an initial gene list collated by Valerie Wilson, The National Renal Complement Therapeutics Centre, February 2019 on behalf of Yorkshire and North East GLH for the GMS Renal Specialist Test Group; Gene Symbol submitted: C3; Suggested initial gene rating: none provided;
Created: 12 Feb 2019, 12:13 p.m.

Arianna Tucci (Genomics England Curator)

Comment when marking as ready: Marked as red as the evidence of association with the isolated phenotype is limited.
Created: 15 Dec 2017, 3:59 p.m.

BRIDGE consortium (NIHRBR-RD)

Red List (low evidence)

Novel gene currently associated to atypical haemolytic uraemic syndrome (aHUS), but are thought to be also causative for MPGN. PMID: 18796626 study of patients with atypical haemolytic uraemic syndrome, not PMG. Because of the variable expressivity of some complement gene mutations, we have included the genes known to cause (and in routine clinical testing in) the mechanistically related, extremely rare disease atypical Haemolytic Uraemic Syndrome (aHUS). There is now good evidence that mutations that are associated with aHUS can be found in patients with Primary MPGN/C3G (see Servais et al PMID: 22456601). Therefore known or clearly pathogenic mutations previously associated with aHUS would be presumed to be causative in patients with PMG where this is the clinical presentation.
Created: 5 Jun 2017, 3:35 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Haemolytic uraemic syndrome; aHUS; Hemolytic uremic syndrome, atypical, susceptibility to, 5,612925; C3 glomerulopathy; C3G; C3 deficiency, 613779; Immune complex MPGN; IC-MPGN

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • NHS GMS
  • Expert list
Phenotypes
  • Haemolytic uraemic syndrome
  • aHUS
  • Hemolytic uremic syndrome, atypical, susceptibility to, 5,612925
  • C3 glomerulopathy
  • C3G
  • C3 deficiency, 613779
  • Immune complex MPGN
  • IC-MPGN
OMIM
120700
Clinvar variants
Variants in C3
Penetrance
Complete
Publications
Mode of Pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Panels with this gene

History Filter Activity

23 Mar 2020, Gel status: 3

Set mode of pathogenicity

Eleanor Williams (Genomics England Curator)

Mode of pathogenicity for gene: C3 was changed from Other to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

14 Aug 2019, Gel status: 3

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: c3 has been classified as Green List (High Evidence).

14 Aug 2019, Gel status: 1

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: C3 were set to 24172683; 20852386; 18796626; 21902819

14 Aug 2019, Gel status: 1

Set mode of pathogenicity

Eleanor Williams (Genomics England Curator)

Mode of pathogenicity for gene: C3 was changed from to Other

14 Aug 2019, Gel status: 1

Set mode of inheritance

Eleanor Williams (Genomics England Curator)

Mode of inheritance for gene: C3 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

12 Feb 2019, Gel status: 1

Added New Source

Eleanor Williams (Genomics England Curator)

Source NHS GMS was added to C3.

15 Dec 2017, Gel status: 1

Panel promoted to version 1.0

Louise Daugherty (Genomics England Curator)

15th December 2017. Panel reviews were assessed, and panel was revised according to reviews and further curation by Arianna Tucci and Louise Daugherty

15 Dec 2017, Gel status: 1

Gene classified by Genomics England curator

Arianna Tucci (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

5 Jun 2017, Gel status: 0

Created

Anonymous ()

C3 was created by Anonymous

5 Jun 2017, Gel status: 0

Added New Source

Anonymous ()

C3 was added to Primary Membranoproliferative Glomerulonephritispanel. Sources: Expert list