Analysis of coding variants in the human FTO gene from the gnomAD database

Abstract

Single nucleotide polymorphisms (SNPs) in the first intron of the FTO gene reported in 2007 continue to be the known variants with the greatest effect on adiposity in different human populations. Coding variants in the FTO gene, on the other hand, have been little explored, although data from complete sequencing of the exomes of various populations are available in public databases and provide an excellent opportunity to investigate potential functional variants in FTO. In this context, this study aimed to track nonsynonymous variants in the exons of the FTO gene in different population groups employing the gnomAD database and analyze the potential functional impact of these variants on the FTO protein using five publicly available pathogenicity prediction programs. The findings revealed 345 rare mutations, of which 321 are missense (93%), 19 are stop gained (5.6%) and five mutations are located in the splice region (1.4%). Of these, 134 (38.8%) were classified as pathogenic, 144 (41.7%) as benign and 67 (19.5%) as unknown. The available data, however, suggest that these variants are probably not associated with BMI and obesity, but instead, with other diseases. Functional studies are, therefore, required to identify the role of these variants in disease genesis.