Hemoglobin subunit alpha 2 (HBA2) genomic locus (HBA2)

The Hemoglobin subunit alpha 2 (HBA2) genomic locus, located within the alpha-globin cluster on chromosome 16, encodes a critical protein component of adult hemoglobin (HbA) (NCBI Gene: 3040). In hematopoietic stem and progenitor cells (HSPCs), this locus is a primary target for gene editing therapies designed to treat beta-thalassemia (Pavani et al., 2021, PubMed: 33536637). The disease is characterized by a lack of beta-globin chains, which results in an excess of alpha-globin chains that precipitate and cause oxidative damage to erythroid precursors (Mettananda et al., 2015, PubMed: 26123394). By employing CRISPR-Cas9 or other gene-editing tools to disrupt the HBA2 locus, researchers aim to reduce alpha-globin production, thereby restoring the stoichiometric balance between alpha and beta chains (UniProt: P69905). This therapeutic approach seeks to improve red blood cell survival and alleviate the symptoms of chronic anemia and ineffective erythropoiesis.

Other names

Alpha-2 globin geneHBA2 locusHemoglobin alpha-2 chain geneHBA-T2

Targeted genomic disruption or silencing of the HBA2 gene or its regulatory elements to reduce alpha-globin chain production, thereby restoring the stoichiometric balance between alpha and beta globin chains in patients with beta-thalassemia (Pavani et al., 2021, PubMed: 33536637).