Hemoglobin subunit beta (HBB) gene (HBB)

The HBB gene encodes the beta-globin subunit of hemoglobin, the protein in red blood cells responsible for oxygen transport (UniProt P68871). A specific point mutation in this gene (Glu6Val, rs334) causes sickle cell disease, where abnormal hemoglobin S (HbS) molecules polymerize, leading to red blood cell deformation and vascular occlusion (MedlinePlus Genetics). The genomic DNA at this pathogenic locus is a major target for curative genetic therapies, including gene addition and gene editing. Gene addition therapies, such as lovotibeglogene autotemcel, use viral vectors to introduce functional HBB sequences into hematopoietic stem cells (FDA, 2023). Direct gene editing approaches, including CRISPR/Cas9-mediated correction, aim to repair the mutation at the endogenous HBB locus (DeWitt et al., 2016). These interventions are designed to restore the production of functional hemoglobin and alleviate the clinical manifestations of sickle cell disease and beta-thalassemia.

Other names

Beta-globin geneHemoglobin beta chain geneHBB locusrs334 locusSickle cell mutation site

Gene addition or direct gene correction via viral vectors or CRISPR-based genome editing to restore functional beta-globin production.