Fig. 2. Schematic diagram of the ACO1 protein domain structure.

Central core domains 1 (yellow) and 2 (green), domain 3 (blue), linker (gray), and domain 4 (red) (based on Walden et al.²⁵). Red lollipops represent cysteine residues required for iron–sulfur binding and aconitase function. Blue lollipops represent the amino acids required for binding to the iron-response element found on mRNA transcripts of various proteins required for stable erythropoiesis. Black arrows represent the sex rare coding variants we report associating with hemoglobin concentration. The axis is the numbers of each of the total 889 amino acids of ACO1. Protein reference: NP_001265281.1.