Hemoglobinopathy: genes and variants

Genes linked to Hemoglobinopathy

• 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.

  12 disease-causing and 1 uncertain variants in HBB are linked to Hemoglobinopathy.

Known disease-causing variants in Hemoglobinopathy

Which prediction tools work for Hemoglobinopathy

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

• AlphaMissense: 80 out of 100
• CATVariant: 74 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 67 out of 100
• ESM1b (LLR): 54 out of 100

Same protein, different disease

• Erythrocytosis, familial, 6 is also caused by HBB variants; they fall partly in the same places as the Hemoglobinopathy variants (31 disease-causing).
• Beta thalassemia is also caused by HBB variants; they fall partly in the same places as the Hemoglobinopathy variants (21 disease-causing).
• Beta-thalassemia HBB/LCRB is also caused by HBB variants; they fall partly in the same places as the Hemoglobinopathy variants (18 disease-causing).
• Heinz body anemia is also caused by HBB variants; they fall partly in the same places as the Hemoglobinopathy variants (12 disease-causing).
• Dominant beta-thalassemia is also caused by HBB variants; they fall partly in the same places as the Hemoglobinopathy variants (11 disease-causing).

Diseases related to Hemoglobinopathy

• Erythrocytosis, familial, 6, also linked to HBB
• Malaria, also linked to HBB
• Beta thalassemia, also linked to HBB
• Heinz body anemia, also linked to HBB
• Atypical hemolytic-uremic syndrome, also linked to HBB
• Beta-thalassemia HBB/LCRB, also linked to HBB
• Dominant beta-thalassemia, also linked to HBB
• Alpha Thalassemia, also linked to HBB
• METHEMOGLOBINEMIA, BETA TYPE, also linked to HBB
• Hemolytic anemia, also linked to HBB

Frequently asked questions

Which genes are linked to Hemoglobinopathy?

In CATVariant, Hemoglobinopathy is linked to 1 analyzed protein: HBB (Hemoglobin subunit beta).

How many genetic variants are linked to Hemoglobinopathy?

16 variants: 12 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 1 are of uncertain significance or have conflicting reports.

Which uncertain variants in Hemoglobinopathy 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 Hemoglobinopathy?

Among tools not trained on clinical labels, AlphaMissense separates this disease's known disease-causing variants from harmless ones best (AUROC 0.80, based on 12 disease-causing and 19 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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