Molecular Classification
Gene, Protein (once translated), Disease-causing gene variant
Other Names
Hemoglobin subunit beta, Hemoglobin beta gene, β-globin, HBB
Disease Roles
Hemoglobinopathies (e.g., sickle cell disease, beta-thalassemia)AnemiaVaso-occlusive crises

Beta-globin gene Overview

The beta-globin gene (HBB) encodes the beta-globin subunit of hemoglobin, which is vital for oxygen transport in red blood cells. The sickle cell disease mutation occurs at codon 6, changing the amino acid from glutamic acid (Glu) to valine (Val) (Glu6Val, E6V), resulting in hemoglobin S. This causes hemoglobin molecules to polymerize in low oxygen conditions, distorting red blood cells into a sickle shape and leading to chronic anemia, vaso-occlusion, pain, and organ damage. The HBB gene is a validated therapeutic target for pharmacologic and gene therapy approaches, and monitoring the mutation status is essential for diagnosis and patient management. Correction of the sickle cell mutation in HBB via gene therapy is an active area of research with promising safety and efficacy profiles.

Mechanism of Action

Gene editing/correction: Replaces or repairs the faulty nucleotide (e.g., A>T for Glu6Val). Induction of fetal hemoglobin: Increases production of HbF, which dilutes mutant beta-globin and reduces sickling events. Polymerization inhibition: Agents that prevent hemoglobin S polymerization indirectly reduce sickling.

Biological Functions

Oxygen transport (as a subunit of hemoglobin)
Erythrocyte (red blood cell) structure and function
Mutation impacts polymerization properties and red blood cell deformation

Disease Associations

Hemoglobinopathies (e.g., sickle cell disease, beta-thalassemia)
Anemia
Vaso-occlusive crises
Organ ischemia and damage (as secondary consequences of sickle cell disease)

Safety Considerations

  • Off-target effects from gene editing (including potential unwanted chromosomal rearrangements)
  • Immune reactions to gene therapy vectors
  • Risks of bone marrow transplantation (e.g., graft-versus-host disease, infection, organ damage)
  • Increased risk of vaso-occlusive events if therapy fails or worsens sickling
  • Long-term unknowns with new genetic therapies

Interacting Drugs

Hydroxyurea (hydroxycarbamide, increases fetal hemoglobin and alters sickling risk)
L-glutamine
Voxelotor (targets hemoglobin oxygen affinity)
Crizanlizumab (targets P-selectin, not HBB itself but relevant in clinical context)
Various gene therapies or editing agents (e.g., Cas9/gRNA constructs, lentiviral and rAAV6 gene therapy molecules)

Associated Biomarkers

Biomarker
Hemoglobin S (HbS) fraction
Fetal hemoglobin (HbF) level
Presence of HBB Glu6Val mutation (by sequencing)
Hemoglobin C or E (for compound heterozygous states)
Red cell indices (anemia, reticulocyte count)