HBG1

HBG1 is a protein-coding gene in humans that encodes the gamma-globin chain of fetal hemoglobin (HbF). It is one of two gamma-globin genes in the beta-globin gene cluster, along with HBG2, and is located on chromosome 11p15.4. The gamma-globin proteins pair with alpha-globin chains to form HbF, which is the main hemoglobin present during fetal development.

During embryonic and fetal development, HBG1 is actively transcribed, producing gamma-globin mRNA that is translated into the Gγ chain. After birth, transcription of gamma-globin declines, and HbF levels fall to a small fraction of total hemoglobin, with HbA (adult Hb containing beta-globin) predominating.

Gene regulation: HBG1 expression is governed by the beta-globin locus control region and local regulatory elements. Trans-acting factors such as BCL11A, KLF1, GATA1, and NF-E2 contribute to silencing of gamma-globin postnatally, while certain mutations or natural genetic variants (as in hereditary persistence of fetal Hb, HPFH) maintain or reinduce gamma-globin expression. Epigenetic modifications and chromatin accessibility at the locus also influence expression.

Clinical relevance: Elevated HbF due to persistent or reactivated HBG1 expression can ameliorate symptoms in diseases like beta-thalassemia and sickle cell disease. Ongoing research explores pharmacologic and genetic strategies to induce HbF by upregulating HBG1/HBG2.