Impact of class 2 or 3 KLF1 variants on clinical severity of hemoglobinopathies. (A) Three major hematologic indices— mean cell volume (MCV), HbA₂, and HbF—in controls and α- or β-thalassemia trait individuals with (wt/var) or without (wt/wt) class 2 or 3 KLF1 variants. Values are mean ± standard deviation, derived from Liu et al⁷  and Yu et al.⁵⁵  (B) Effects of class 2 or 3 KLF1 variants on globin chain balance in healthy controls (normal) and α- or β-thalassemia patients. Significant recovery of globin chain balance is observed only when β-thalassemia is co-inherited with a class 2 or 3 KLF1 variant. α-like denotes ζ- and α-globin chains, and β-like denotes ε-, γ-, δ-, and β-globin chains. wt, wild type; var, variant.