Kidney disease-associated APOL1 variants have dose-dependent, dominant toxic gain-of-function
Background Two coding renal risk variants (RRVs) of the APOL1 gene (G1 and G2) are
associated with large increases in CKD rates among populations of recent African descent,
but the underlying molecular mechanisms are unknown. Mammalian cell culture models are
widely used to study cytotoxicity of RRVs, but results have been contradictory. It remains
unclear whether cytotoxicity is RRV-dependent or driven solely by variant-independent
overexpression. It is also unknown whether expression of the reference APOL1 allele, the …
associated with large increases in CKD rates among populations of recent African descent,
but the underlying molecular mechanisms are unknown. Mammalian cell culture models are
widely used to study cytotoxicity of RRVs, but results have been contradictory. It remains
unclear whether cytotoxicity is RRV-dependent or driven solely by variant-independent
overexpression. It is also unknown whether expression of the reference APOL1 allele, the …