Werner syndrome: genes and variants
Werner syndrome is linked to 1 analyzed protein (WRN). 7 DNA variants are known to cause it; 1,671 more are uncertain, and 2 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Werner syndrome
WRN: Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN
It combines DNA helicase and exonuclease activities to maintain replication forks, telomeres, and genome stability. Biallelic loss-of-function variants cause Werner syndrome, an adult-onset progeroid disorder with premature aging, metabolic disease, atherosclerosis, and increased cancer risk.
7 disease-causing and 1,671 uncertain variants in WRN are linked to Werner syndrome.
Where Werner syndrome variants cluster
- WRN Helicase ATP-binding (positions 558–724): 3 of 7 disease-causing changes, 3.7× more than its size predicts.
- WRN Interaction with WRNIP1 (positions 2–277): 3 of 7 disease-causing changes, 2.2× more than its size predicts.
Known disease-causing variants in Werner syndrome
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| WRN G574R | 574 | Helicase ATP-binding | Disease-causing (★★) |
| WRN S707G | 707 | Helicase ATP-binding | Disease-causing (★★) |
| WRN K37N | 37 | Interaction with WRNIP1 | Disease-causing (★) |
| WRN K577M | 577 | Helicase ATP-binding | Disease-causing |
| WRN K125N | 125 | 3'-5' exonuclease | Disease-causing |
| WRN K135E | 135 | 3'-5' exonuclease | Disease-causing |
| WRN Q1229L | 1229 | HRDC | Disease-causing |
Uncertain variants in Werner syndrome that look disease-causing
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| WRN G574E | 574 | Helicase ATP-binding | Uncertain (★) | +7: 2 other pathogenic changes within 3 positions; G574R at the same position is pathogenic; seen in 6.6e-06 of gnomAD DNA copies; REVEL 0.773 |
| WRN G574V | 574 | Helicase ATP-binding | Uncertain (★) | +6: 2 other pathogenic changes within 3 positions; G574R at the same position is pathogenic; seen in 2.8e-06 of gnomAD DNA copies; REVEL 0.760 |
Diseases related to Werner syndrome
- Ovarian cancer, also linked to WRN
- Wiskott-Aldrich syndrome, also linked to WRN
Frequently asked questions
Which genes are linked to Werner syndrome?
In CATVariant, Werner syndrome is linked to 1 analyzed protein: WRN (Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN).
How many genetic variants are linked to Werner syndrome?
1,779 variants: 7 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 1,671 are of uncertain significance or have conflicting reports.
Which uncertain variants in Werner syndrome look disease-causing?
2 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example WRN G574E and WRN G574V. These are leads for expert review, not diagnoses.
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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