Hemoglobin subunit beta (HBB) gene, c.20A>T mutation site (HBB (c.20A>T))

The Hemoglobin subunit beta (HBB) gene, located on chromosome 11, encodes the beta-globin protein that is a critical component of adult hemoglobin (HbA) [1, 2]. The c.20A>T mutation in exon 1 of this gene is a specific point mutation that results in the substitution of glutamic acid with valine at the sixth amino acid position (Glu6Val) [1, 4]. This genetic alteration leads to the production of abnormal hemoglobin S (HbS), which polymerizes into rigid fibers when deoxygenated, causing red blood cells to adopt a sickle shape [2, 5]. These sickled cells are prone to hemolysis and can obstruct microvasculature, leading to the painful vaso-occlusive crises and chronic organ damage characteristic of sickle cell disease [2, 5]. Therapeutic strategies targeting this site include small molecules like voxelotor, which stabilizes the oxygenated state of HbS to inhibit polymerization [5]. Furthermore, advanced genetic therapies aim to either correct the c.20A>T mutation directly using CRISPR-based gene editing or provide a functional HBB gene via lentiviral vectors to restore normal hemoglobin function [3, 4].

Other names

rs334Sickle cell mutationGlu6Val mutationE6V mutationBeta-globin gene mutationHbS mutation

Hemoglobin S polymerization inhibition, gene addition, gene correction, and fetal hemoglobin induction