Chuvash polycythemia: genes and variants

Genes linked to Chuvash polycythemia

• VHL: von Hippel-Lindau disease tumor suppressor

  It targets hydroxylated HIF-alpha proteins for ubiquitin-mediated degradation when oxygen is sufficient, keeping hypoxia-response programs suppressed. Loss of function stabilizes HIF signaling and causes von Hippel-Lindau tumor-predisposition syndrome while also driving most clear-cell renal carcinomas.

  116 disease-causing and 455 uncertain variants in VHL are linked to Chuvash polycythemia.

Where Chuvash polycythemia variants cluster

• VHL Involved in binding to CCT complex (positions 100–155): 48 of 116 disease-causing changes, 1.6× more than its size predicts.
• VHL Interaction with Elongin BC complex (positions 157–166): 14 of 116 disease-causing changes, 2.6× more than its size predicts.

Known disease-causing variants in Chuvash polycythemia

Showing 60 of 116.

Uncertain variants in Chuvash polycythemia that look disease-causing

Which prediction tools work for Chuvash polycythemia

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

• CATVariant: 90 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• REVEL: 88 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CADD: 88 out of 100
• PolyPhen-2: 87 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• MetaLR: 85 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• phyloP: 77 out of 100
• SIFT: 72 out of 100

Same protein, different disease

• Von Hippel-Lindau syndrome is also caused by VHL variants; they fall in the same places as the Chuvash polycythemia variants (147 disease-causing).
• Pheochromocytoma is also caused by VHL variants; they fall in the same places as the Chuvash polycythemia variants (4 disease-causing).

Diseases related to Chuvash polycythemia

• Von Hippel-Lindau syndrome, also linked to VHL
• Pheochromocytoma, also linked to VHL
• Inherited phaeochromocytoma and paraganglioma excluding NF1, also linked to VHL
• Nonpapillary renal cell carcinoma, also linked to VHL
• Renal cell carcinoma, also linked to VHL

Frequently asked questions

Which genes are linked to Chuvash polycythemia?

In CATVariant, Chuvash polycythemia is linked to 1 analyzed protein: VHL (von Hippel-Lindau disease tumor suppressor).

How many genetic variants are linked to Chuvash polycythemia?

576 variants: 116 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 455 are of uncertain significance or have conflicting reports.

Which uncertain variants in Chuvash polycythemia look disease-causing?

9 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example VHL R200W, VHL V130I, VHL R64H, VHL I151V and VHL R82C. These are leads for expert review, not diagnoses.

Which variant effect predictor works best for Chuvash polycythemia?

Among tools not trained on clinical labels, CADD separates this disease's known disease-causing variants from harmless ones best (AUROC 0.88, based on 29 disease-causing and 16 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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