Hemoglobin subunit beta (HBB) gene locus (HBB)

The Hemoglobin subunit beta (HBB) gene locus encodes the beta-globin protein, which combines with alpha-globin to form adult hemoglobin (HbA), the primary oxygen carrier in human erythrocytes (NCBI Gene ID 3043). Sickle cell disease is caused by a homozygous A-to-T transversion in the HBB gene, resulting in a glutamic acid to valine substitution at position 6 (Glu6Val) of the beta-globin chain (PubMed: 25205356). This mutation produces hemoglobin S (HbS), which polymerizes when deoxygenated, leading to erythrocyte sickling, vaso-occlusion, and chronic hemolytic anemia. The HBB locus is the focus of advanced genetic therapies, such as lovotibeglogene autotemcel, which utilizes a lentiviral vector to integrate a functional beta-globin gene into hematopoietic stem cells (FDA, 2023). Other approaches involve small molecules like voxelotor that bind to the HBB protein to increase oxygen affinity and prevent HbS polymerization (FDA, 2019). Understanding and manipulating the HBB locus is essential for developing curative treatments for sickle cell disease and related hemoglobinopathies like beta-thalassemia (NIH, 2023).

Other names

Beta-globin geneHBB locusHemoglobin beta chain geneSickle cell gene

Gene addition via lentiviral vector to provide functional beta-globin; gene editing to induce fetal hemoglobin expression; allosteric modulation of hemoglobin to prevent polymerization.