Hemoglobin subunit beta gene sickle mutation locus (HBB)

The Hemoglobin subunit beta (HBB) gene sickle mutation locus is a critical genomic site on chromosome 11 (11p15.4) that encodes the beta-globin component of adult hemoglobin (UniProt, 2024). The locus is defined by a single nucleotide substitution (A to T) at the sixth codon of the HBB gene, known as the rs334 mutation (NIH, 2023). This mutation results in the production of sickle hemoglobin (HbS), which polymerizes under low oxygen tension, causing red blood cells to assume a rigid, sickle shape (StatPearls, 2024). These deformed cells lead to hemolytic anemia, painful vaso-occlusive crises, and progressive organ damage in individuals with sickle cell disease (SCD) (PubMed, 2023). As a therapeutic target, this locus is the focus of gene-editing technologies like CRISPR/Cas9, which aim to correct the mutation directly in hematopoietic stem cells (Nature Medicine, 2022). Other approaches involve gene addition of functional HBB variants or the induction of fetal hemoglobin to mitigate the effects of the mutated locus (FDA, 2023). Successful modification of this target represents a potentially curative strategy for patients with SCD (NEJM, 2021).

Other names

Beta-globin geneHBBSickle cell locusrs334Glu6Val mutation siteHemoglobin subunit beta

Direct genomic correction of the rs334 mutation via homology-directed repair, lentiviral-mediated gene addition of anti-sickling beta-globin variants, or CRISPR-mediated disruption of modifiers to induce fetal hemoglobin (PubMed, 2023; FDA, 2023).