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Gamma-globin expression upregulation (HBG1, HBG2)
- Target
- HBG1, HBG2
- Molecular classification
- Protein (globin family), Other ("globin chain of fetal hemoglobin")
01
Overview
Gamma-globin is one of the protein chains that make up fetal hemoglobin (HbF). The HBG1 and HBG2 genes encode these chains, which partner with alpha-globin chains for effective oxygen transport in fetuses. After birth, gamma-globin expression largely ceases as beta-globin takes over in adult hemoglobin. Persistence or reactivation of gamma-globin production is therapeutically beneficial in beta-globin disorders such as beta-thalassemia and sickle cell disease, as fetal hemoglobin can compensate for dysfunctional or deficient adult hemoglobin. Pharmacological or genetic upregulation of gamma-globin expression is a major therapeutic aim in these conditions.
- Other names
- gamma hemoglobingamma-globinAgamma (HBG1)Ggamma (HBG2)HBGGhereditary persistence of fetal hemoglobin
02
Mechanism of action
DNA methyltransferase inhibition (epigenetic upregulation). Induction of fetal hemoglobin via gene modulation. Increased gamma-globin compensates for deficient beta-globin.
03
Biological functions
Oxygen transportDevelopmental hemoglobin switchingCompensation in beta-thalassemia and sickle cell disease
04
Disease associations
Beta-thalassemiaSickle cell diseaseNeonatal anemiaHereditary persistence of fetal hemoglobin (HPFH)
05
Safety considerations
Overproduction of gamma-globin is generally benignSome gamma-globin variants may cause neonatal hemolytic anemia, cyanosis, or methemoglobinemia
06
Interacting drugs
Hydroxyurea (induces HbF/gamma-globin expression)
2 more in the full profile.
07
Biomarkers
Percentage of HbF in bloodSpecific genetic variants in HBG1, HBG2
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