Hemoglobin subunit gamma (HBG)

Hemoglobin subunit gamma is a protein component of fetal hemoglobin (HbF), which is typically composed of two alpha and two gamma subunits (alpha2-gamma2). In the fetal period, it serves as the primary oxygen carrier, possessing a significantly higher affinity for oxygen than adult hemoglobin (HbA) to facilitate efficient oxygen transfer from maternal circulation across the placenta (UniProt, 2024). Shortly after birth, expression of the gamma-globin genes (HBG1 and HBG2) is developmentally silenced and replaced by the beta-globin gene (HBB) in a process known as the hemoglobin switch (NIH, 2023). This protein is a major therapeutic target for treating beta-hemoglobinopathies, such as sickle cell disease and beta-thalassemia. By pharmacologically inducing HBG expression or using gene editing to interfere with its silencing mechanisms, clinicians can restore therapeutic levels of HbF. This induction compensates for defective beta-globin, reduces the concentration of sickle hemoglobin (HbS), and prevents the polymerization and red blood cell sickling that lead to vaso-occlusive crises (PubMed, 2022; StatPearls, 2023).

Other names

Gamma-globinFetal hemoglobin gamma chainHBG1HBG2Hemoglobin subunit gamma-1Hemoglobin subunit gamma-2HbF subunit gamma

Induction of fetal hemoglobin expression to compensate for defective beta-globin; epigenetic modification of the HBG promoter; inhibition of BCL11A-mediated transcriptional silencing