Hemoglobin subunit gamma (gamma-globin) (HBG1 and HBG2)

Hemoglobin subunit gamma (gamma-globin) refers to two closely related genes, HBG1 and HBG2, located in the beta-globin gene cluster on chromosome 11, which encode the gamma chains of fetal hemoglobin (HbF)[2][4][5]. During fetal development, these genes are highly expressed in the liver, spleen, and bone marrow, allowing HbF (composed of two alpha and two gamma chains) to serve as the primary oxygen transporter before birth. HBG1 and HBG2 differ only at one amino acid (alanine in A-gamma, HBG1; glycine in G-gamma, HBG2)[4]. After birth, a developmental switch represses their expression, and adult β-globin genes become predominant[2][4]. Persistence of gamma-globin expression underlies the benign condition hereditary persistence of fetal hemoglobin (HPFH) and can mitigate diseases such as sickle cell disease and β-thalassemia[3][4][1]. HBG1/2 serve as therapeutic targets for genetic and pharmacological strategies aimed at upregulating HbF to treat these disorders. The main regulators of HBG1/2 silencing in adulthood are transcriptional repressors such as BCL11A and complexes such as NuRD, and disruption of their binding sites or regulatory elements can reactivate fetal hemoglobin production[1][2][3].

Other names

HBG1HBG2Gamma globinA-gamma (HBG1 gene product)G-gamma (HBG2 gene product)Gamma hemoglobinHBGAHBGGAgammaGgamma

Induction or derepression of gamma-globin gene expression to increase fetal hemoglobin (HbF) levels, which compensates for defective adult β-globin in sickle cell disease and β-thalassemia Disruption of repressor binding (e.g., BCL11A site editing)