Hemoglobin subunit beta, sickle variant (HbS)

Hemoglobin subunit beta, sickle variant—commonly known as **hemoglobin S** or **HbS**—is a mutant form of the normal adult β-globin chain caused by a single point mutation in the HBB gene. This mutation results in substitution of valine for glutamic acid at position 6 on the β-chain. When present in homozygous form (*HbSS*), it causes **sickle cell disease**, an inherited disorder characterized by abnormal "sickled" red blood cells that are rigid and prone to blocking small vessels. This leads to chronic anemia, recurrent pain episodes ("crises"), increased risk for infection due to splenic dysfunction, organ damage from repeated ischemia-reperfusion injury, and reduced life expectancy if untreated. Treatments target either increasing non-sickling forms of hemoglobin or directly inhibiting polymerization/aggregation processes that cause cellular deformation.

Other names

Sickle hemoglobinHemoglobin SHbSSickle cell hemoglobinβ^S-globin

Inhibition of polymerization of deoxygenated HbS (e.g., voxelotor stabilizes the oxygenated state of HbS to prevent sickling) Induction of fetal hemoglobin production to dilute the concentration of HbS in red blood cells (hydroxyurea) Reduction of oxidative stress in red blood cells (L-glutamine)