Genetic variants in the CD59 gene: An exploratory study of large genome databases

CD59 is a GPI-anchored glycoprotein on the surface of many cell types. It inhibits the assembly of the membrane attack complex, thus preventing complement-mediated cell lysis. Lack of a functional CD59 protein causes recurrent ischemic strokes, neuropathy, and chronic hemolysis. We aimed at a comprehensive analysis of the CD59 gene from publicly available databases to identify variants and evaluate their pathophysiologic potential.

Variants in the CD59 coding sequence of exons 4, 5, and 6 and their splice sites were systematically compiled from 4 major populations across 6 whole-genome and whole-exome databases. The PredictSNP algorithm assessed the functional impact of non-synonymous variants.

Among 488,592 individuals, 160 distinct alleles were identified in 6881 subjects (0.7%). Among 93 alleles with non-synonymous variants, 43 were classified as deleterious and 49 (2 variants encoded the same amino acid change) as neutral by PredictSNP. Additional variants included: 53 synonymous, 9 deletions/duplications, 3 splice site, and 2 nonsense. Among the 14 non-synonymous variants reported in patient samples, 9 were classified as deleterious (64.3%) and 5 as neutral (35.7%).

We collated a list of CD59 variants, which were classified as neutral or deleterious by PredictSNP, from genome databases. These results can be applied to identify individuals with possible latent CD59 deficiency symptoms, such as hemolytic transfusion reactions. In conjunction with clinical data, these CD59 variants can guide personalized clinical decisions.