Proteinuric renal disease

Gene: APOL1

Green List (high evidence)

This gene has been submitted for consideration for a new clinical indication in order to genotype patients with recent African ancestry who are being assessed for suitability to be a living kidney donor. A British Transplantation Society (BTS) group is also working in parallel to develop clinical and ethical guidance to support this clinical pathway for living kidney donors. Well defined high-risk alleles have been reported in the literature to confer a significantly increased risk of developing chronic kidney disease. Therefore there is a clinical drive to include this gene on the R159 proteinuric renal disease panel in order to provide additional genotypic information for patients with African ancestry, whose clinical course may be affected by the presence of these high-risk alleles.

Created: 29 Jan 2021, 5:53 p.m. | Last Modified: 29 Jan 2021, 5:53 p.m.

Panel Version: 2.44

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
chronic kidney disease

Publications

• 23766536

Mode of pathogenicity
Other

I don't know

After NHSGenomic Medicine Service consideration, the rating of this gene has not been changed.

Created: 7 Mar 2022, 11:37 p.m. | Last Modified: 7 Mar 2022, 11:37 p.m.

Panel Version: 2.66

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, 2:58 p.m. | Last Modified: 4 May 2021, 2:58 p.m.

Panel Version: 2.48

Comment on list classification: Changing the rating from red to amber, following review and proposal for green by Natalie Forrester. It should be considered for green rating following GMS review.

Created: 2 Feb 2021, 11:31 a.m. | Last Modified: 2 Feb 2021, 11:31 a.m.

Panel Version: 2.48

This gene was part of an initial gene list collated by Elizabeth Watson, North Bristol NHS Trust, February 2019 on behalf of the GMS Renal Specialist Test Group. Gene Symbol submitted: APOL1; Suggested initial gene rating: amber; Evidence for inclusion: none provided; Other comments: Polymorphisms common in African population associated with susceptibility to renal disease. In 70 gene SRNS panel. Local agreement not to report variants in this gene pending national review of clinical utility of testing in this gene.

Created: 4 Feb 2019, 10:41 a.m.

Mode of inheritance
Unknown

Phenotypes
Focal Segmental Glomerulosclerosis 4, Susceptibility to #612551

Publications

• 33517446

I don't know

Currently on UK diagnostic panel. Increased susceptibility to FSGS. No positive cases over 300 tested

Created: 19 Oct 2015, 1:44 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

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

Red List (low evidence)

Common variants in ApoL1 found in people with recent African ancestry confer innate defence against trypanosomiasis. The same alleles are associated with ~10-fold increased risk of proteinuric renal disease and kidney failure. Rare variants in this gene have not been linked to kidney disease.

Created: 7 Oct 2015, 10:33 a.m.

Mode of inheritance
Other

Phenotypes
FSGS; proteinuria; renal failure

Publications

• PubMed: 20647424

Mode of pathogenicity
Other