Erythrocytosis, familial, 6: genes and variants
Explore variant evidence for Erythrocytosis, familial, 6 across 3 analyzed proteins (HBB, HBA1, EPAS1). Linked ClinVar records include 52 pathogenic or likely pathogenic variants, 24 variants of uncertain significance and 22 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.
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Genes linked to Erythrocytosis, familial, 6
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.
31 ClinVar pathogenic / likely pathogenic and 16 uncertain variants in HBB have source records linked to Erythrocytosis, familial, 6. 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.
16 ClinVar pathogenic / likely pathogenic and 1 uncertain variants in HBA1 have source records linked to Erythrocytosis, familial, 6. Association strength is not clinical gene validity.
EPAS1: Endothelial PAS domain-containing protein 1
When stabilized by hypoxia, it activates hypoxia-responsive genes controlling erythropoiesis, angiogenesis, iron metabolism, and cellular adaptation to low oxygen. Activating variants can cause familial erythrocytosis, while somatic dysregulation is central to clear-cell renal carcinoma and some paragangliomas.
5 ClinVar pathogenic / likely pathogenic and 29 uncertain variants in EPAS1 have source records linked to Erythrocytosis, familial, 6. Association strength is not clinical gene validity.
Where Erythrocytosis, familial, 6 variants cluster
- EPAS1 NTAD (positions 496–542): 5 of 5 ClinVar pathogenic / likely pathogenic variants, 18.5× more than its size predicts.
ClinVar pathogenic and likely pathogenic variants linked to Erythrocytosis, familial, 6
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| EPAS1 M535T | 535 | NTAD | Pathogenic / likely pathogenic (★★) |
| EPAS1 G537R | 537 | NTAD | Pathogenic / likely pathogenic (★★) |
| HBB R31T | 31 | Globin | Pathogenic / likely pathogenic (★★) |
| HBA1 M1V | 1 | Pathogenic / likely pathogenic (★★) | |
| HBA1 M1T | 1 | Pathogenic / likely pathogenic (★★) | |
| HBA1 G60D | 60 | Globin | Pathogenic / likely pathogenic (★★) |
| HBB L69F | 69 | Globin | Pathogenic / likely pathogenic (★★) |
| HBA1 M33I | 33 | Globin | Pathogenic / likely pathogenic (★★) |
| HBA1 A111D | 111 | Globin | Pathogenic / likely pathogenic (★★) |
| HBA1 P120S | 120 | Globin | Pathogenic / likely pathogenic (★★) |
| HBA1 L130P | 130 | Globin | Pathogenic / likely pathogenic (★★) |
| HBB M1R | 1 | Pathogenic / likely pathogenic (★★) | |
| HBB V35F | 35 | Globin | Pathogenic / likely pathogenic (★★) |
| HBB L115P | 115 | Globin | Pathogenic / likely pathogenic (★★) |
| HBB V21M | 21 | Globin | Pathogenic / likely pathogenic (★★) |
| HBB E122K | 122 | Globin | Pathogenic / likely pathogenic (★★) |
| HBB D100Y | 100 | Globin | Pathogenic / likely pathogenic (★) |
| EPAS1 P534L | 534 | NTAD | Pathogenic / likely pathogenic (★) |
| HBA1 R32K | 32 | Globin | Pathogenic / likely pathogenic (★) |
| HBB F46C | 46 | Globin | Pathogenic / likely pathogenic (★) |
| EPAS1 M535V | 535 | NTAD | Pathogenic / likely pathogenic |
| EPAS1 G537W | 537 | NTAD | Pathogenic / likely pathogenic |
| HBA1 R142L | 142 | Globin | Pathogenic / likely pathogenic |
| HBA1 R142C | 142 | Globin | Pathogenic / likely pathogenic |
| HBA1 R142H | 142 | Globin | Pathogenic / likely pathogenic |
| HBA1 Y141H | 141 | Globin | Pathogenic / likely pathogenic |
| HBB D100G | 100 | Globin | Pathogenic / likely pathogenic |
| HBB D100V | 100 | Globin | Pathogenic / likely pathogenic |
| HBB D100H | 100 | Globin | Pathogenic / likely pathogenic |
| HBB D100A | 100 | Globin | Pathogenic / likely pathogenic |
| HBB D100N | 100 | Globin | Pathogenic / likely pathogenic |
| HBB E102K | 102 | Globin | Pathogenic / likely pathogenic |
| HBB E102G | 102 | Globin | Pathogenic / likely pathogenic |
| HBB E102D | 102 | Globin | Pathogenic / likely pathogenic |
| HBB H147D | 147 | Globin | Pathogenic / likely pathogenic |
| HBB H147L | 147 | Globin | Pathogenic / likely pathogenic |
| HBB S90R | 90 | Globin | Pathogenic / likely pathogenic |
| HBB L69H | 69 | Globin | Pathogenic / likely pathogenic |
| HBB K83N | 83 | Globin | Pathogenic / likely pathogenic |
| HBB K83T | 83 | Globin | Pathogenic / likely pathogenic |
| HBB S90N | 90 | Globin | Pathogenic / likely pathogenic |
| HBB H98Q | 98 | Globin | Pathogenic / likely pathogenic |
| HBB P101L | 101 | Globin | Pathogenic / likely pathogenic |
| HBB F104L | 104 | Globin | Pathogenic / likely pathogenic |
| HBA1 A89S | 89 | Globin | Pathogenic / likely pathogenic |
| HBA1 R93Q | 93 | Globin | Pathogenic / likely pathogenic |
| HBA1 D127H | 127 | Globin | Pathogenic / likely pathogenic |
| HBB H144Q | 144 | Globin | Pathogenic / likely pathogenic |
| HBA1 K41M | 41 | Globin | Pathogenic / likely pathogenic |
| HBB D95H | 95 | Globin | Pathogenic / likely pathogenic |
| HBB A141T | 141 | Globin | Pathogenic / likely pathogenic |
| HBB V24F | 24 | Globin | Pathogenic / likely pathogenic |
Uncertain variants prioritized for review in Erythrocytosis, familial, 6
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| HBB D100E | 100 | Globin | Conflicting reports (★) | +6: 11 other pathogenic changes within 3 positions; D100G at the same position is pathogenic; REVEL 0.891 |
Which prediction tools work for Erythrocytosis, familial, 6
Observed separation of ClinVar pathogenic / likely pathogenic from benign / likely benign variants (AUROC × 100). This benchmark is not a clinical recommendation.
- REVEL: 92 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- AlphaMissense: 91 out of 100
- CATVariant: 90 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- PolyPhen-2: 88 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- MutPred2: 88 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 86 out of 100
- MetaLR: 84 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CADD: 81 out of 100
- ESM1b (LLR): 68 out of 100
- phyloP: 62 out of 100
Same protein, different disease
- Beta thalassemia also has ClinVar records linked to HBB variants; they fall partly in the same places as the Erythrocytosis, familial, 6 variants (21 pathogenic / likely pathogenic).
- Beta-thalassemia HBB/LCRB also has ClinVar records linked to HBB variants; they fall in the same places as the Erythrocytosis, familial, 6 variants (18 pathogenic / likely pathogenic).
- Heinz body anemia also has ClinVar records linked to HBB variants; they fall in the same places as the Erythrocytosis, familial, 6 variants (12 pathogenic / likely pathogenic).
- Hemoglobinopathy also has ClinVar records linked to HBB variants; they fall partly in the same places as the Erythrocytosis, familial, 6 variants (12 pathogenic / likely pathogenic).
- Dominant beta-thalassemia also has ClinVar records linked to HBB variants; they fall partly in the same places as the Erythrocytosis, familial, 6 variants (11 pathogenic / likely pathogenic).
- Alpha Thalassemia also has ClinVar records linked to HBA1 variants; they fall in the same places as the Erythrocytosis, familial, 6 variants (10 pathogenic / likely pathogenic).
Diseases related to Erythrocytosis, familial, 6
- Heinz body anemia, also linked to HBA1 and HBB
- Alpha Thalassemia, also linked to HBA1 and HBB
- Hemoglobin M disease, also linked to HBA1 and HBB
- Von Hippel-Lindau disease, also linked to EPAS1
- 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
- Renal cell carcinoma, also linked to EPAS1
Frequently asked questions
Which genes have records linked to Erythrocytosis, familial, 6?
This view contains 3 analyzed proteins: HBB, HBA1, EPAS1. 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 52 pathogenic or likely pathogenic variants, 24 variants of uncertain significance and 22 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. 1 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 120 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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