Hb S-São Paulo: A new sickling hemoglobin with stable polymers and decreased oxygen affinity

► A new human β-globin variant was found: Hb S-São Paulo [HBB:c.20A > T p.Glu6Val; c.196A > G p.Lys65Glu]. ► The double-mutant caused clinical features of sickle cell disease in a heterozygote. ► In addition to sickling properties, Hb S-São Paulo also showed reduced O2 affinity. ► Molecular dynamics suggested that the Lys65 → Glu replacement favors the T-state. ► The second substitution appears to stabilize the Hb S-SP polymer formed.