Globin gene (HBB/HBA)

The globin genes comprise two main clusters, the alpha-globin cluster on chromosome 16 and the beta-globin cluster on chromosome 11, which encode the protein subunits of hemoglobin. Hemoglobin is the primary metalloprotein in red blood cells responsible for transporting oxygen from the lungs to peripheral tissues and returning carbon dioxide (Source: UniProt, NIH). During human development, these genes undergo a tightly regulated switching process from embryonic to fetal (HbF) and finally to adult (HbA) hemoglobin. Mutations in these genes, particularly the HBB gene, lead to prevalent genetic disorders known as hemoglobinopathies, including sickle cell disease and beta-thalassemia, which cause chronic anemia and multi-organ damage (Source: StatPearls). Therapeutic interventions target these genes through various modalities to restore functional hemoglobin levels. Small molecules like hydroxyurea induce the expression of fetal globin to compensate for defective adult forms, while novel gene therapies utilize lentiviral vectors to add functional genes or CRISPR-based editing to silence repressors like BCL11A, thereby restoring healthy hemoglobin production (Source: FDA, Nature Reviews).

Other names

Hemoglobin geneHBBHBA1HBA2HBG1HBG2HBDHBE1Beta-globin locusAlpha-globin locus

Induction of fetal hemoglobin (HbF) expression; Allosteric stabilization of the oxygenated state of hemoglobin; Lentiviral-mediated gene addition of functional globin; CRISPR-Cas9 disruption of the BCL11A erythroid-specific enhancer to reactivate gamma-globin expression.