APOL1 and APOL1-Associated Kidney Disease: A Common Disease, an Unusual Disease Gene – Proceedings of the Henry Shavelle Professorship

Background: Genetic variants in APOL1 are a major contributor to the increased risk of kidney disease in people of recent African ancestry. Summary: Two alleles in the APOL1 gene, referred to as G1 and G2, confer increased risk of kidney disease under a recessive model of risk inheritance. Disease risk is inherited as a recessive trait: People with genotypes G1/G1, G2/G2, and G1/G2 (i.e., a risk allele from each parent) have increased risk for what we refer to here as APOL1-associated kidney disease. In the USA, about 13% of the self-identified African-American population has a high-risk genotype. As we discuss below, APOL1 is an unusual disease gene. Most studies to date have suggested that the G1 and G2 variants have toxic, gain-of-function effects on the encoded protein. Key Message: In this article, we review key concepts critical to understanding APOL1-associated kidney disease, emphasizing ways in which it is highly atypical for a human disease-causing gene.