Alpha-globin gene (encompassing HBA1 and HBA2) (HBA1/HBA2)

The **alpha-globin gene locus consists of two highly homologous genes, HBA1 and HBA2, both encoding the alpha-globin protein, a crucial structural component of hemoglobin in red blood cells**[1][6]. These genes are located on chromosome 16p13.3 and are essential for the correct assembly of hemoglobin tetramers (2 alpha + 2 beta chains in adults, or 2 alpha + 2 gamma chains in fetuses). Hemoglobin enables oxygen transport from the lungs to tissues throughout the body. Genetic defects in HBA1 or HBA2 can lead to quantitative or qualitative disorders of hemoglobin—most notably the alpha-thalassemia syndromes, including severe fetal hydrops (Hb Bart syndrome), moderate anemia (HbH disease), or silent carrier states, depending on the number of mutant or deleted alleles[1][6]. Disruption or deliberate gene editing at the HBA1 or HBA2 locus in hematopoietic stem cells is currently being explored as a therapeutic approach for correcting hemoglobinopathies such as thalassemia, by either silencing, replacing, or supplementing globin gene expression[3][5][7]. High sequence identity (~97%) between HBA1 and HBA2 complicates genetic analysis but enables redundant function in erythropoiesis[4]. Both genes are not receptors or enzymes but structural protein-encoding loci essential for erythrocyte physiology and inherited as part of the globin gene family.

Other names

α-globin geneHemoglobin alpha-1 geneHemoglobin alpha-2 geneHBAHemoglobin subunit alpha

Direct modulation via gene editing to correct alpha-globin/hemoglobin disorders (e.g., CRISPR knock-in/out approaches)[3][5][7] Indirect modulation via agents that alter globin chain synthesis balance (e.g., increase fetal hemoglobin)[6]