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HBA2
hemoglobin subunit alpha 2
The HBA2 gene provides instructions for synthesising alpha-globin, a crucial protein subunit of haemoglobin, which is responsible for oxygen transport in the blood. Haemoglobin, found in red blood cells, facilitates oxygen delivery throughout the body.
HBA2 is located on the short (p) arm of chromosome 16, at band 16p13.3. Arm ratio per GRCh38 - banding schematic.
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Overview
The HBA2 gene is one of two genes, alongside HBA1, that direct the production of alpha-globin, a protein essential for the correct formation of haemoglobin. Haemoglobin is the primary protein in red blood cells, playing a critical role in transporting oxygen from the lungs to the body's tissues and cells.
Variations within the HBA2 gene can alter the production or structure of alpha-globin, which may lead to reduced oxygen-carrying capacity in the blood. These genetic changes are associated with conditions collectively known as alpha-thalassaemia, affecting how effectively the body can distribute oxygen.
What the gene does
The HBA2 gene provides the genetic blueprint for producing alpha-globin. This protein is a fundamental subunit of haemoglobin, a complex protein responsible for binding and transporting oxygen within the bloodstream. Each functional haemoglobin molecule is typically composed of four protein subunits: two alpha-globin units and two units of another globin type.
Alpha-globin is incorporated into both foetal haemoglobin, which is active before birth and shortly afterwards, and adult haemoglobin, which predominates throughout life. Each of these globin subunits associates with an iron-containing molecule called haem. These haem molecules are crucial for enabling red blood cells to efficiently pick up oxygen in the lungs and release it into the body's tissues. A complete haemoglobin protein can carry four oxygen molecules, one per haem group, giving blood its characteristic bright red colour when oxygenated.
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Chromosome location
The HBA2 gene is situated on the short (p) arm of chromosome 16, specifically at position 13.3 (16p13.3). It is located in close proximity to the HBA1 gene within a region known as the alpha-globin locus. This genomic arrangement means that HBA1 and HBA2 are nearly identical and often inherited together.
Protein structure
The HBA2 gene encodes a protein that is 142 amino acids long. The mature protein features a prominent Globin domain spanning amino acids 2-142. This domain is characteristic of proteins involved in oxygen transport and is responsible for binding the haem molecule, which is essential for oxygen carriage.
Key variants
Variants in the HBA2 gene can range from small changes in the DNA sequence to larger deletions involving part or all of the gene. These genetic alterations can impact the production, stability, or function of the alpha-globin protein. The clinical consequences of HBA2 variants vary, depending on the specific nature of the change and its effect on alpha-globin synthesis.
Sample of pathogenic variants
2 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
GRCh37/hg19 16p13.3(chr16:223124-223599)x1 | - | Pathogenic | ★☆☆☆ | not provided |
Single allele | - | Pathogenic | - | alpha Thalassemia |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Pathogenic variants in the HBA2 gene are primarily associated with various forms of alpha-thalassaemia. These include Alpha-thalassaemia (Hb Bart's hydrops), a severe condition, and the milder Alpha-thalassaemia trait. These conditions arise from reduced or absent production of alpha-globin, leading to an imbalance in the globin chains that make up haemoglobin and consequently, impaired oxygen transport.
- Alpha-thalassaemia (Hb Bart's hydrops)
- Alpha-thalassaemia trait Dedicated page coming soon
Inheritance pattern
Conditions caused by pathogenic HBA2 variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
In the UK, the HBA2 gene is evaluated on several NHS Genomic Medicine Service national panels. These include panels for Cytopenias and congenital anaemias, Foetal anomalies, Foetal hydrops, Hereditary Erythrocytosis, Rare anaemia, Sickle cell, thalassaemia and other haemoglobinopathies, and Sickle cell, thalassaemia and other haemoglobinopathies trait or carrier testing. This indicates its recognised clinical importance within the NHS for diagnosing and managing related conditions.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main role of the HBA2 gene?
The HBA2 gene provides instructions for making alpha-globin, a protein subunit necessary for the formation of haemoglobin. Haemoglobin is found in red blood cells and is responsible for transporting oxygen throughout the body.
What happens if there is a variant in the HBA2 gene?
Variants in the HBA2 gene can lead to reduced or absent production of alpha-globin. This imbalance can cause conditions known as alpha-thalassaemia, which affect the blood's ability to carry oxygen efficiently.
Is the HBA2 gene related to other genes?
Yes, the HBA2 gene is closely related to the HBA1 gene. Both genes encode alpha-globin and are located near each other on chromosome 16, often working together to ensure proper haemoglobin function.
References
- Higgs DR, Weatherall DJ. The alpha thalassaemias. Cellular and molecular life sciences : CMLS. 2009. PMID: 19020805
- Ribeiro DM, Sonati MF. Regulation of human alpha-globin gene expression and alpha-thalassemia. Genetics and molecular research : GMR. 2008. PMID: 19048483
- Harteveld CL, Kriek M, Bijlsma EK. Refinement of the genetic cause of ATR-16. Human genetics. 2007. PMID: 17598130
- Zhang HB, Liu DP, Liang CC. The control of expression of the alpha-globin gene cluster. International journal of hematology. 2002. PMID: 12512836
- Adam MP, Bick S, Mirzaa GM. Alpha-Thalassemia. 1993. PMID: 20301608