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GeneE
26 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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HBA2
hemoglobin subunit alpha 2
Chromosome 16 · 16p13.3
NCBI Gene: 3040Ensembl: ENSG00000188536.14HGNC: HGNC:4823UniProt: D1MGQ2
341PubMed Papers
23Diseases
2Drugs
168Pathogenic Variants
FUNCTIONAL ROLE
Transporter
RESEARCH IMPACT
Highly StudiedTrendingVariant-Rich
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
✓ Swiss-Prot Reviewed
hemoglobin H diseaseAlpha-thalassemiaAutosomal dominant methemoglobinemiaalpha thalassemia spectrum
✦AI Summary

HBA2 encodes the alpha-2 globin chain, a critical component of adult hemoglobin. As part of the α-globin gene cluster on chromosome 16, HBA2 is essential for normal hemoglobin synthesis and oxygen transport 1. Mutations in HBA2 cause α-thalassemia, characterized by reduced or absent alpha-globin chain production, leading to severe anemia, microcytic hypochromic red blood cells, and transfusion dependence in severe cases 23. HbA2, the minor hemoglobin tetramer containing alpha and delta chains, normally comprises 2-3% of total hemoglobin and serves as a diagnostic marker for β-thalassemia carriers (elevated to 6-7%) 45. Notably, HbA2 prevents polymerization of deoxy-sickle hemoglobin, suggesting potential therapeutic value in sickle cell disease 4. HBA2 mutations show considerable phenotypic variability due to coinheritance with other globin gene defects 6. Clinical diagnosis relies on hemoglobin electrophoresis and molecular analysis 27. Recent advances in lentiviral vector-based gene therapy demonstrate promising restoration of α-globin expression and hemoglobin levels in alpha-thalassemia major 3.

Sources cited
1
HBA2 mutations cause hemoglobin variants with increased oxygen affinity leading to congenital erythrocytosis; HBA2 is part of α-globin genes
PMID: 29741264
2
α-thalassemia results from defective α-globin chain production; HbA2 determination is used in diagnostic testing for thalassemia carriers
PMID: 27183541
3
Alpha thalassemia major is caused by absence of all four α-globin genes (HBA2/1); lentiviral gene therapy using HBA2 restores α-globin expression and hemoglobin levels
PMID: 40967220
4
HbA2 is a tetramer of α- and δ-globin chains forming 2-3% of total hemoglobin; HbA2 prevents polymerization of deoxy-sickle hemoglobin and could benefit sickle cell disease
PMID: 26104837
5
HbA2 normally accounts for 2.5-3.3% of total hemoglobin; elevated to 6-7% in β-thalassemia carriers
PMID: 23027585
6
β-thalassemia carriers show elevated HbA2 with considerable phenotypic variability from coinheritance with α- and δ-globin gene mutations
PMID: 27123947
7
Reduced HbA2 is associated with α-thalassemia; abnormal HbA2 levels detected by hemoglobin electrophoresis aid diagnosis
PMID: 37356947
Disease Associationsⓘ23
hemoglobin H diseaseOpen Targets
0.75Strong
Alpha-thalassemiaOpen Targets
0.75Strong
Autosomal dominant methemoglobinemiaOpen Targets
0.71Strong
alpha thalassemia spectrumOpen Targets
0.71Strong
Heinz body anemiaOpen Targets
0.69Moderate
primary familial polycythemia due to EPO receptor mutationOpen Targets
0.60Moderate
sickle cell diseaseOpen Targets
0.58Moderate
bacterial diseaseOpen Targets
0.46Moderate
hemoglobin M diseaseOpen Targets
0.39Weak
Hb Bart's hydrops fetalisOpen Targets
0.38Weak
anemia (phenotype)Open Targets
0.38Weak
neoplasmOpen Targets
0.37Weak
anemiaOpen Targets
0.37Weak
autosomal dominant secondary polycythemiaOpen Targets
0.37Weak
lung cancerOpen Targets
0.28Weak
breast cancerOpen Targets
0.26Weak
metastatic malignant neoplasmOpen Targets
0.26Weak
unstable hemoglobin diseaseOpen Targets
0.18Weak
genetic disorderOpen Targets
0.17Weak
ThalassemiaOpen Targets
0.15Weak
Alpha-thalassemiaUniProt
Heinz body anemiasUniProt
Hemoglobin H diseaseUniProt
Pathogenic Variants168
NM_000517.6(HBA2):c.118dup (p.Thr40fs)Pathogenic
not provided|alpha Thalassemia
★★☆☆2026→ Residue 40
NM_000517.6(HBA2):c.45G>A (p.Trp15Ter)Pathogenic
not provided|alpha Thalassemia
★★☆☆2026→ Residue 15
NM_000517.6(HBA2):c.300+1G>ALikely pathogenic
not provided|alpha Thalassemia
★★☆☆2026
NM_000517.6(HBA2):c.95+1G>APathogenic
not provided|not specified|alpha Thalassemia
★★☆☆2026
NM_000517.4(HBA2):c.427T>A (p.Ter143Lys)Pathogenic
HEMOGLOBIN ICARIA|Hemoglobin H disease, nondeletional|not provided|alpha Thalassemia|beta Thalassemia
★★☆☆2026→ Residue 143
NM_000517.6(HBA2):c.200T>C (p.Leu67Pro)Pathogenic
HEMOGLOBIN DARTMOUTH|not provided|alpha Thalassemia
★★☆☆2025→ Residue 67
NM_000517.6(HBA2):c.377T>C (p.Leu126Pro)Pathogenic
Hemoglobin Quong Sze|alpha Thalassemia|not provided|Erythrocytosis, familial, 7;Heinz body anemia;Hemoglobin H disease;alpha Thalassemia
★★☆☆2025→ Residue 126
NM_000517.6(HBA2):c.373T>C (p.Ser125Pro)Pathogenic
not provided|alpha Thalassemia
★★☆☆2025→ Residue 125
NM_000517.6(HBA2):c.178G>C (p.Gly60Arg)Likely pathogenic
HEMOGLOBIN ZURICH ALBISRIEDEN|Alpha-thalassemia, Dutch type|alpha Thalassemia|not provided
★★☆☆2025→ Residue 60
NM_000517.4(HBA2):c.142G>C (p.Asp48His)Pathogenic
HEMOGLOBIN L (FERRARA)|HEMOGLOBIN SINAI|HEMOGLOBIN HASHARON|HEMOGLOBIN SEALY|alpha Thalassemia|not provided|Erythrocytosis, familial, 7;Heinz body anemia;Hemoglobin H disease;alpha Thalassemia
★★☆☆2025→ Residue 48
NM_000517.6(HBA2):c.*92A>GPathogenic
Alpha-thalassemia-2, nondeletional|Hemoglobin H disease, nondeletional|not provided|alpha Thalassemia|Erythrocytosis, familial, 7;Heinz body anemia;Hemoglobin H disease;alpha Thalassemia|Hemoglobin H disease|beta Thalassemia
★★☆☆2025
NM_000517.6(HBA2):c.283G>T (p.Asp95Tyr)Pathogenic
not provided|alpha Thalassemia
★★☆☆2025→ Residue 95
NM_000517.6(HBA2):c.96-2A>GPathogenic
Alpha-thalassemia, Dutch type|not provided|Erythrocytosis, familial, 7;Heinz body anemia;Hemoglobin H disease;alpha Thalassemia|alpha Thalassemia
★★☆☆2025
NM_000517.6(HBA2):c.345del (p.Ala116fs)Pathogenic
not provided|alpha Thalassemia
★★☆☆2025→ Residue 116
NM_000517.6(HBA2):c.69del (p.Glu24fs)Pathogenic
not provided|alpha Thalassemia|Hemoglobin H disease;alpha Thalassemia;Heinz body anemia;Erythrocytosis, familial, 7
★★☆☆2025→ Residue 24
NM_000517.6(HBA2):c.75T>G (p.Tyr25Ter)Pathogenic
alpha Thalassemia|not provided|alpha Thalassemia;Erythrocytosis, familial, 7;Heinz body anemia;Hemoglobin H disease
★★☆☆2025→ Residue 25
NM_000517.6(HBA2):c.89T>C (p.Leu30Pro)Pathogenic
HEMOGLOBIN AGRINIO|Hemoglobin H disease, nondeletional|not provided|alpha Thalassemia
★★☆☆2025→ Residue 30
NM_000517.6(HBA2):c.377T>G (p.Leu126Arg)Pathogenic
HEMOGLOBIN PLASENCIA|not provided|alpha Thalassemia|Erythrocytosis, familial, 7;Heinz body anemia;Hemoglobin H disease;alpha Thalassemia
★★☆☆2025→ Residue 126
NM_000517.6(HBA2):c.314G>A (p.Cys105Tyr)Pathogenic
HEMOGLOBIN SALLANCHES|Hemoglobin H disease, nondeletional|alpha Thalassemia|not provided|Hemoglobin H disease|Erythrocytosis, familial, 7;Heinz body anemia;Hemoglobin H disease;alpha Thalassemia
★★☆☆2025→ Residue 105
NM_000517.6(HBA2):c.428A>C (p.Ter143Ser)Pathogenic
HEMOGLOBIN KOYA DORA|not provided|alpha Thalassemia|Erythrocytosis, familial, 7;Heinz body anemia;Hemoglobin H disease;alpha Thalassemia
★★☆☆2025→ Residue 143
View on ClinVar ↗
Drug Targets2
EFAPROXIRALApproved
Hemoglobin HbA negative modulator
neoplasm
VOXELOTORApproved
Hemoglobin HbA positive modulator
sickle cell disease
Related Genes
RPS11Protein interaction100%RPS27Protein interaction100%RPS26Protein interaction100%RPS29Protein interaction100%RPS15AProtein interaction100%RPS14Protein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
21%
Liver
10%
Brain
6%
Ovary
1%
Heart
0%
Gene Interaction Network
Click a node to explore
HBA2RPS11RPS27RPS26RPS29RPS15ARPS14
PROTEIN STRUCTURE
Preparing viewer…
PDB2W72 · 1.07 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.87LoF Tolerant
pLIⓘ
0.04Tolerant
Observed/Expected LoF1.04 [0.44–1.87]
RankingsWhere HBA2 stands among ~20K protein-coding genes
  • #941of 20,598
    Most Researched341 · top 5%
  • #530of 1,025
    FDA-Approved Drug Targets2
  • #441of 5,498
    Most Pathogenic Variants168 · top 10%
  • #16,992of 17,882
    Most Constrained (LOEUF)1.87
Genes detectedHBA2
Sources retrieved26 papers
Response time—
📄 Sources
26▼
1
Laboratory diagnosis of thalassemia.
PMID: 27183541
Int J Lab Hematol · 2016
1.00
2
HbA2 : biology, clinical relevance and a possible target for ameliorating sickle cell disease.
PMID: 26104837
Br J Haematol · 2015
0.90
3
Analytical goals for the determination of HbA₂.
PMID: 23027585
Clin Chem Lab Med · 2013
0.80
4
Thalassemia in the laboratory: pearls, pitfalls, and promises.
PMID: 30138112
Clin Chem Lab Med · 2018
0.72
5
Diverse hematological phenotypes of β-thalassemia carriers.
PMID: 27123947
Ann N Y Acad Sci · 2016
0.70