Proteinuria
Gene: APOL1
Comment on list classification: Assigning amber status, because this is a susceptibility alleleCreated: 20 Jun 2022, 7:55 a.m. | Last Modified: 20 Jun 2022, 7:55 a.m.
Panel Version: 0.205
Assigned Definitive gene-disease validity by the ClinGen Glomerulopathy GCEP - Classification - 09/28/2021
Increased risk of kidney and glomerular diseases in persons carrying two of the risk alleles in this gene: G1/G1, G2/G2 and compound heterozygous G1/G2.
PMID: 20647424 - first study to identify G1 & G2 alleles associated with risk of renal disease. Comparing participants with zero or 1 risk allele of APOL1 to participants with 2 risk alleles provided an odds ratio for FSGS of 10.5 (CI, 6.0-18.4). This analysis supported a completely recessive pattern of inheritance.
PMID: 25993319 - only G1 and G2 confer renal risk, and other common and rare APOL1 missense variants, including the archaic G3 haplotype, do not contribute to sporadic FSGS and HIVAN
rs73885319 (G1) OR 9.66, p=9.97E-25
rs60910145 (G1) OR 9.75, p=9.04E-24
rs71785313 (G2) OR 5.69, p=3.39E-06
2 APOL1 risk alleles OR 18.31, p=3.31E-58
PMID: 34350953 - recessive gain-of-function toxicity mouse model recapitulates human kidney disease
G1:
p.Ser342Gly, AFR/AA gnomAD v2.1 AF 0.2276 (5,671/24,920 alleles, 687 homozygotes)
p.Ile384Met, AFR/AA gnomAD v2.1 AF 0.2278 (5,487/24,082 alleles, 662 homozygotes)
G2:
p.Asn388_Tyr389del, AFR/AA gnomAD v2.1 AF 0.1402(3,402/24,268 alleles, 224 homozygotes)Created: 20 Jun 2022, 7:53 a.m. | Last Modified: 20 Jun 2022, 7:53 a.m.
Panel Version: 0.204
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
focal segmental glomerulosclerosis 4, susceptibility to MONDO:0012931
Publications
Mode of pathogenicity
Other
PMID: 33517446 - Ge et al 2021 - demonstrate a mouse model to study APOL1 risk variants associated susceptibility to NFAT-mediated FSGS. They provide evidence that APOL1 G1 induced glomerular lipid accumulation correlates with loss of renal function and confirm that APOL1 G1/G2 risk variant is associated with mitochondrial dysfunction.Created: 4 May 2021, 3:02 p.m. | Last Modified: 4 May 2021, 3:02 p.m.
Panel Version: 0.7488
Phenotypes
{Focal Segmental Glomerulosclerosis 4, Susceptibility to} OMIM:612551; {End-stage renal disease, nondiabetic, susceptibility to} OMIM:612551
Publications
In keeping with Genomics England, as susceptibility allele we should not be testing for this.Created: 9 Jan 2020, 3:24 a.m. | Last Modified: 9 Jan 2020, 3:24 a.m.
Panel Version: 0.68
Susceptibility alleles:
APOL1, SER342GLY, ILE384MET (rs73885319, rs60910145): linkage disequilibrium
APOL1, 6-BP DEL, N388/Y389 (rs71785313)Created: 19 Dec 2019, 11:44 p.m. | Last Modified: 19 Dec 2019, 11:44 p.m.
Panel Version: 0.9
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
{Glomerulosclerosis, focal segmental, 4, susceptibility to}, MIM#612551
Publications
Mode of inheritance for gene: APOL1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Mode of pathogenicity for gene: APOL1 was changed from to Other
Publications for gene: APOL1 were set to 20647424; 24206458; 20635188
Gene: apol1 has been classified as Amber List (Moderate Evidence).
Gene: apol1 has been classified as Red List (Low Evidence).
Gene: apol1 has been classified as Amber List (Moderate Evidence).
Gene: apol1 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: APOL1 were changed from to {Glomerulosclerosis, focal segmental, 4, susceptibility to}, MIM#612551
Publications for gene: APOL1 were set to
Mode of inheritance for gene: APOL1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Gene: apol1 has been classified as Amber List (Moderate Evidence).
gene: APOL1 was added gene: APOL1 was added to Nephrotic Syndrome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: APOL1 was set to Unknown