HBG2

HBG2 is a human gene that encodes the gamma-2 chain of fetal hemoglobin (HbF). It is one of two gamma-globin genes, the other being HBG1. Both HBG1 and HBG2 are located in the beta-globin gene cluster on chromosome 11 (11p15.4) and are primarily active during fetal development, pairing with alpha-globin to form HbF (α2γ2).

Expression of HBG2, along with HBG1, is developmentally regulated. HbF is the predominant form of hemoglobin before birth and is largely replaced by adult hemoglobin (HbA, α2β2) after birth. HbF has a higher affinity for oxygen than HbA, which supports efficient transfer of oxygen from the mother to the fetus. In adulthood, gamma-globin expression declines, but can be reactivated in certain conditions or in response to therapeutic interventions.

Genomic and regulatory context: HBG2 resides in the beta-globin gene cluster together with HBE1 (epsilon), HBG1 (gamma-1), HBD (delta), and HBB (beta). Variations in the regulation of HBG2 and the gamma-globin genes contribute to interindividual differences in HbF levels. Polymorphisms in promoter regions, such as those associated with the XmnI site at -158, can influence HbF expression. Trans-acting factors, including BCL11A and KLF1, also play important roles in silencing gamma-globin after birth and can be targeted to increase HbF.

Clinical relevance: Elevated HbF due to persistent gamma-globin expression can ameliorate symptoms in certain hemoglobinopathies, notably sickle cell disease and beta-thalassemia. As a result, HBG2 and the broader gamma-globin genes are targets of research and therapeutic strategies aiming to induce HbF production.