Hemoglobin subunit alpha (HBA) (HBA)

Hemoglobin subunit alpha (HBA) is a fundamental protein component of the hemoglobin tetramer, which is responsible for oxygen transport in red blood cells. In adult humans, two alpha-globin chains combine with two beta-globin chains to form Hemoglobin A (HbA), facilitating the reversible binding of oxygen in the lungs and its delivery to peripheral tissues (UniProt: P69905). Beyond gas exchange, HBA is involved in the regulation of nitric oxide bioavailability, thereby influencing vascular tone and blood pressure (PubMed: 23123848). Mutations or deletions in the HBA1 and HBA2 genes lead to alpha-thalassemia, a spectrum of disorders characterized by impaired hemoglobin production, microcytic anemia, and potential fetal hydrops in severe cases (StatPearls: NBK442005). Historically viewed primarily as a structural protein, HBA has become a specific therapeutic target with the development of drugs like Voxelotor. This molecule binds covalently to the N-terminal valine of the alpha-chain, increasing the oxygen affinity of sickle hemoglobin and preventing the polymerization that leads to red blood cell sickling (NEJM: 2019;381:509-519). Current research also focuses on gene therapy and gene editing techniques to restore HBA function in patients with hereditary anemias (Molecular Therapy: 2021).

Other names

Alpha-globinHemoglobin alpha chainHBA1HBA2Hemoglobin alpha-1Hemoglobin alpha-2

Pharmacological modulation of oxygen affinity through covalent binding to the alpha-subunit N-terminal valine to stabilize the oxygenated hemoglobin state; replacement or editing of functional HBA1/HBA2 genes via lentiviral vectors or CRISPR/Cas9; and induction of fetal hemoglobin which incorporates alpha-globin chains.