Hemoglobin subunit alpha 1 and Hemoglobin subunit alpha 2 gene loci (HBA1/HBA2)

The HBA1 and HBA2 gene loci, located on chromosome 16p13.3, encode the alpha-globin chains that are essential components of adult (HbA) and fetal (HbF) hemoglobin [1.3.1, 1.4.1]. These genes are nearly identical and work together to produce the alpha-globin subunits that pair with beta-globin or gamma-globin to form functional heterotetrameric hemoglobin molecules responsible for oxygen transport [1.3.1, 1.4.3]. Mutations or deletions in these loci lead to alpha-thalassemia, a group of inherited blood disorders characterized by reduced alpha-globin production, resulting in anemia and the formation of unstable hemoglobin tetramers like HbH or Hb Bart [1.3.3, 1.3.4]. In therapeutic contexts, these loci are primary targets for gene therapy and CRISPR-based gene editing aimed at restoring alpha-globin levels or balancing the globin chain ratio in patients with thalassemia [1.2.1, 1.4.2]. Additionally, downregulating alpha-globin expression by targeting its enhancers, such as MCS-R2, is being explored as a strategy to ameliorate the severity of beta-thalassemia [1.4.2].

Other names

Alpha-globin gene clusterHBA1HBA2Alpha-globin locusHemoglobin alpha chain genes

Therapeutic strategies involve gene replacement using viral vectors to restore alpha-globin production, or CRISPR-mediated gene editing to correct specific mutations or delete regulatory enhancers (e.g., MCS-R2) to modulate globin chain balance [1.2.1, 1.4.2].