Hemoglobin M disease: genes and variants
Explore variant evidence for Hemoglobin M disease across 2 analyzed proteins (HBB, HBA1). Linked ClinVar records include 10 pathogenic or likely pathogenic variants, 2 variants of uncertain significance and 3 with conflicting classifications.
Coverage includes proteins already analyzed in CATVariant, not every gene involved in this condition. Database links are associations, not an assessment of clinical gene–disease validity. Computable evidence prioritizes variants for expert review and does not reclassify them. Source labels are pooled across this disease family.
Data updated 2026-10-10. Automated aggregation, not a clinical review date.
Download variant evidence (CSV)
Genes linked to Hemoglobin M disease
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.
10 ClinVar pathogenic / likely pathogenic and 5 uncertain variants in HBB have source records linked to Hemoglobin M disease. Association strength is not clinical gene validity.
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.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in HBA1 have source records linked to Hemoglobin M disease. Association strength is not clinical gene validity.
ClinVar pathogenic and likely pathogenic variants linked to Hemoglobin M disease
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| HBB R31K | 31 | Globin | Pathogenic / likely pathogenic (★★) |
| HBB E122K | 122 | Globin | Pathogenic / likely pathogenic (★★) |
| HBB E122Q | 122 | Globin | Pathogenic / likely pathogenic (★★) |
| HBB H64N | 64 | Globin | Pathogenic / likely pathogenic (★★) |
| HBB L69F | 69 | Globin | Pathogenic / likely pathogenic (★★) |
| HBB N109K | 109 | Globin | Pathogenic / likely pathogenic (★★) |
| HBB M1T | 1 | Pathogenic / likely pathogenic (★★) | |
| HBB A54T | 54 | Globin | Pathogenic / likely pathogenic (★) |
| HBB L107Q | 107 | Globin | Pathogenic / likely pathogenic (★) |
| HBB V68E | 68 | Globin | Pathogenic / likely pathogenic |
Which prediction tools work for Hemoglobin M disease
Observed separation of ClinVar pathogenic / likely pathogenic from benign / likely benign variants (AUROC × 100). This benchmark is not a clinical recommendation.
- CATVariant: 86 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- AlphaMissense: 76 out of 100
- ESM1b (LLR): 63 out of 100
Same protein, different disease
- Erythrocytosis, familial, 6 also has ClinVar records linked to HBB variants; they fall mostly in different places as the Hemoglobin M disease variants (31 pathogenic / likely pathogenic).
- Beta thalassemia also has ClinVar records linked to HBB variants; they fall mostly in different places as the Hemoglobin M disease variants (21 pathogenic / likely pathogenic).
- Beta-thalassemia HBB/LCRB also has ClinVar records linked to HBB variants; they fall mostly in different places as the Hemoglobin M disease variants (18 pathogenic / likely pathogenic).
- Heinz body anemia also has ClinVar records linked to HBB variants; they fall mostly in different places as the Hemoglobin M disease variants (12 pathogenic / likely pathogenic).
- Hemoglobinopathy also has ClinVar records linked to HBB variants; they fall partly in the same places as the Hemoglobin M disease variants (12 pathogenic / likely pathogenic).
Diseases related to Hemoglobin M disease
- Erythrocytosis, familial, 6, also linked to HBA1 and HBB
- Heinz body anemia, also linked to HBA1 and HBB
- Alpha Thalassemia, 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
- Hemoglobin H disease, also linked to HBA1
- Primary familial polycythemia due to EPO receptor mutation, also linked to HBA1
Frequently asked questions
Which genes have records linked to Hemoglobin M disease?
This view contains 2 analyzed proteins: HBB, HBA1. Links come from clinical records and association databases. They do not imply that every listed gene is a validated cause, and missing genes may not yet be analyzed.
What do the clinical classifications mean?
Linked records include 10 pathogenic or likely pathogenic variants, 2 variants of uncertain significance and 3 with conflicting classifications. Labels summarize source records; multi-condition records may not make a separate assertion for this disease. Check the original record and review status.
Does the evidence score change a VUS classification?
No. 0 VUS or conflicting variants reach the likely-pathogenic points range on the computable criteria available here. This is a research prioritization signal, not a clinical classification. Patient, family and other required evidence may be missing.
Can I download the variant evidence?
Download the CSV for all 35 variants in the selected disease scope, including clinical labels, review status, evidence criteria, predictor scores, functional measurements and population frequency where available.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from eligible public CATVariant analyses 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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