Hemoglobin subunit beta sickle allele (HbS) (HbS)

The Hemoglobin subunit beta (HBB) sickle allele, commonly referred to as Hemoglobin S (HbS), is a mutant form of the beta-globin protein resulting from a single amino acid substitution (Glu6Val) (StatPearls, 2023). This genetic alteration causes hemoglobin molecules to polymerize under low-oxygen conditions, leading to the characteristic sickling of red blood cells (NIH, 2023). These rigid, sickle-shaped cells obstruct blood flow in small vessels, causing vaso-occlusive crises, chronic pain, and organ damage (StatPearls, 2023). HbS is a primary therapeutic target in sickle cell disease, with treatments focusing on preventing its polymerization or replacing its function. For instance, Voxelotor is a small molecule that binds to HbS and increases its oxygen affinity, thereby inhibiting the formation of polymers (FDA, 2019). Modern gene therapies like Lyfgenia aim to introduce a functional HBB gene, while others like Casgevy induce fetal hemoglobin to counteract the effects of the sickle allele (FDA, 2023). Monitoring the percentage of HbS in the blood is a standard biomarker for assessing disease severity and treatment response (NIH, 2023).

Other names

Hemoglobin SSickle hemoglobinHBB Glu6ValBeta-globin sickle variantHBB-S

Stabilization of the oxygenated hemoglobin state to inhibit polymerization; gene addition of anti-sickling beta-globin; induction of fetal hemoglobin (HbF) to interfere with HbS polymer formation (FDA, 2019; FDA, 2023).