Alpha Thalassemia: genes and variants

Genes linked to Alpha Thalassemia

• HBA1: Hemoglobin subunit alpha

  It contributes alpha-globin chains that pair with beta-like globins to carry oxygen in red blood cells. Deletion or inactivation reduces alpha-globin production and causes alpha-thalassemia, with severity determined by the number and function of affected alpha-globin genes.

  10 disease-causing and 14 uncertain variants in HBA1 are linked to Alpha Thalassemia.

• HBB: Hemoglobin subunit beta

  Beta-globin, one of the two major protein chains in adult hemoglobin. Hemoglobin uses these chains to transport oxygen from the lungs to tissues, and HBB variants are associated with sickle-cell disease and beta-thalassemia.

  0 disease-causing and 2 uncertain variants in HBB are linked to Alpha Thalassemia.

Known disease-causing variants in Alpha Thalassemia

Which prediction tools work for Alpha Thalassemia

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• SIFT: 91 out of 100
• CATVariant: 86 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• MetaLR: 84 out of 100 (learned from overlapping clinical labels, so this is optimistic)

Same protein, different disease

• Erythrocytosis, familial, 6 is also caused by HBA1 variants; they fall partly in the same places as the Alpha Thalassemia variants (16 disease-causing).
• Heinz body anemia is also caused by HBA1 variants; they fall mostly in different places as the Alpha Thalassemia variants (7 disease-causing).
• Hemoglobin H disease is also caused by HBA1 variants; they fall partly in the same places as the Alpha Thalassemia variants (6 disease-causing).

Diseases related to Alpha Thalassemia

• Erythrocytosis, familial, 6, also linked to HBA1 and HBB
• Heinz body anemia, also linked to HBA1 and HBB
• Malaria, also linked to HBB
• Beta thalassemia, also linked to HBB
• Atypical hemolytic-uremic syndrome, also linked to HBB
• Beta-thalassemia HBB/LCRB, also linked to HBB
• Hemoglobinopathy, also linked to HBB
• Dominant beta-thalassemia, also linked to HBB
• METHEMOGLOBINEMIA, BETA TYPE, also linked to HBB
• Hemoglobin H disease, also linked to HBA1
• Primary familial polycythemia due to EPO receptor mutation, also linked to HBA1
• Hemolytic anemia, also linked to HBB

Frequently asked questions

Which genes are linked to Alpha Thalassemia?

In CATVariant, Alpha Thalassemia is linked to 2 analyzed proteins: HBA1 (Hemoglobin subunit alpha) and HBB (Hemoglobin subunit beta).

How many genetic variants are linked to Alpha Thalassemia?

38 variants: 10 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 16 are of uncertain significance or have conflicting reports.

Which uncertain variants in Alpha Thalassemia look disease-causing?

None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.

Which variant effect predictor works best for Alpha Thalassemia?

Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.91, based on 9 disease-causing and 32 harmless variants).

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.

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