Hemoglobin subunit beta (HBB) codon 26 genomic locus (HBB codon 26)

The HBB codon 26 genomic locus is a specific site within the hemoglobin subunit beta gene (NCBI Gene ID: 3043) located on chromosome 11. A point mutation at this position, specifically a G-to-A transition (c.79G>A), results in the substitution of glutamic acid with lysine (Glu26Lys), which produces the Hemoglobin E (HbE) variant (Thein, 2013). This mutation is clinically significant because it creates a cryptic splice site that interferes with normal mRNA processing, leading to a reduction in beta-globin chain production and a phenotype similar to beta-thalassemia (Weatherall, 2010). As a therapeutic target, this locus is the focus of precision genome editing technologies, such as CRISPR-Cas9 and base editors, which aim to correct the mutation in hematopoietic stem cells (Liang et al., 2017). Successful correction of the HBB codon 26 locus can restore the production of normal adult hemoglobin (HbA) and potentially cure HbE/beta-thalassemia, a major health burden in Southeast Asia (Mettananda et al., 2015). Current research efforts are directed toward improving the efficiency and specificity of these genetic interventions to minimize off-target risks (Newby et al., 2021).

Other names

Hemoglobin E mutation siteHBB:c.79G>AGlu26Lys locusHbE locusBeta-globin codon 26

Correction of the c.79G>A mutation via precise nucleotide substitution or homology-directed repair to restore normal HBB expression and hemoglobin function (Liang et al., 2017).