Hemoglobin subunit beta (variant C) (HbC) (HbC)

Hemoglobin subunit beta (variant C), commonly known as Hemoglobin C (HbC), is an abnormal structural variant of adult hemoglobin (HbA) resulting from a specific point mutation in the HBB gene [Ref: StatPearls, Hemoglobin C Disease]. This mutation involves the substitution of glutamic acid with lysine at the sixth position of the beta-globin chain (β6 Glu→Lys), which alters the protein's solubility and charge [Ref: UniProt, P68871]. In its deoxygenated state, HbC tends to form intracellular crystals within red blood cells, leading to increased cellular rigidity and a shortened erythrocyte lifespan [Ref: NIH, MedlinePlus]. Clinically, individuals homozygous for the mutation (HbCC) present with mild chronic hemolytic anemia and splenomegaly, while those with the heterozygous trait (HbAC) are generally asymptomatic [Ref: Merck Manual]. HbC is also a critical component of Hemoglobin SC disease, where it interacts with Hemoglobin S to cause vaso-occlusive complications [Ref: ASH, Sickle Cell Disease]. Therapeutic management often involves the use of hydroxyurea to induce fetal hemoglobin (HbF), which interferes with the crystallization process and improves red cell survival [Ref: PubMed, PMID: 28233471]. Additionally, allosteric modulators like voxelotor are utilized to increase oxygen affinity, thereby stabilizing the hemoglobin molecule and reducing pathological polymer or crystal formation [Ref: FDA, Voxelotor Label].

Other names

Hemoglobin CHb CHBB C-variantBeta-6-Lysine hemoglobinHBB

Induction of fetal hemoglobin synthesis and allosteric modulation of hemoglobin oxygen affinity