Overview
The HBB gene encodes the beta chain of hemoglobin, the protein in red blood cells responsible for transporting oxygen throughout the body. Mutations in this gene are the cause of some of the most common hereditary diseases worldwide.
11p15.4 (Chromosome 11)
Hereditary Diseases
Autosomal recessive
Variable (up to 1:50 in high-risk areas)
Function & Significance
The HBB gene provides the instructions for building the beta-globin protein. Two beta-globin proteins combine with two alpha-globin proteins to form a hemoglobin A (HbA) complex.
Hemoglobin binds oxygen in the lungs and releases it in the tissues. Without functional HBB, the oxygen supply to the body can be massively impaired.
🚀 Gene Therapy Breakthrough
HBB is the first gene for which CRISPR gene therapies (Casgevy®, Lyfgenia®) were approved in 2023 to cure sickle cell anemia.
Associated Diseases
Mutations in the HBB gene lead to so-called hemoglobinopathies:
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🩸 Sickle Cell Anemia (HbS)
Point mutation leads to deformed erythrocytes and vascular occlusions.
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🩸 Beta-Thalassemia
Decreased production of beta-globin leads to severe anemia.
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🩸 Hemoglobin C & E Diseases
Variants that often occur in combination with HbS or thalassemia.
🧬 Relevant SNPs
Clinically significant variants in the HBB gene:
11:5227002
/
Significance: HbS (Sickle cell mutation). Carriers (AT) have malaria protection; homozygous carriers (TT) develop sickle cell anemia.
11:5225464
/
Significance: IVS1-110 splice mutation. One of the most common causes of beta-thalassemia in the Mediterranean region.
⚕️ Clinical Management
Treatment includes blood transfusions, hydroxyurea, or, if eligible, the new gene therapies. Newborn screening is standard in many countries.
📚 Data Sources
- OMIM: #141900 – Hemoglobin Subunit Beta
- dbSNP: rs334, rs713040 – SNP Database (NCBI)
- PubMed: HBB Gene Therapy Trials (2023/24)
Biological Function
Associated Conditions
Analyzed Markers
HbS (Glu6Val) - Pathogenic for Sickle Cell Anemia. Homozygous: severe anemia, pain crises. Heterozygous: Malaria protection.
IVS1-110 G>A - Pathogenic for Beta-Thalassemia. Most common mutation in the Mediterranean region.