Figure 1.

Genetic variation of the Proglucagon peptide hormone gene. (A) Human germline genetic variation diversity of the proglucagon gene GCG located on chromosome (2q24.2) with expression mainly in the pancreas and the small intestine (see gtexportal.org for expression data). Cleavage enzymes differently cleave the proglucagon precursor into distinct peptides. (B) Cross-sectional mutational landscape aggregated from three independent genomic sequencing efforts including gnomAD [122,439 exomes/13,304 genomes, excluding individuals also found in TOPMed (12)], UK Biobank [200,629 exomes (13)], and TOPMed [132,345 genomes (14)] leading to a total set of 184 unique missense variants spanning 117 positions found in a total set of 468,717 unique individuals ( SI2 ). (C) Allele frequency (AF) spectrum of variants found in one, two, or all three cohorts respectively. The threshold for singletons, i.e., variants only carried by a single individual within a given cohort, are highlighted.