Peutz-Jeghers syndrome: genes and variants
Peutz-Jeghers syndrome is linked to 1 analyzed protein (STK11). 24 DNA variants are known to cause it; 729 more are uncertain, and 3 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Peutz-Jeghers syndrome
STK11: Serine/threonine-protein kinase STK11
It activates AMPK-family kinases to coordinate cellular energy sensing, polarity, and growth restraint. Germline loss-of-function variants cause Peutz-Jeghers syndrome and its associated cancer predisposition, while somatic loss is common in lung and other cancers.
24 disease-causing and 729 uncertain variants in STK11 are linked to Peutz-Jeghers syndrome.
Known disease-causing variants in Peutz-Jeghers syndrome
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| STK11 R297S | 297 | Protein kinase | Disease-causing (★★) |
| STK11 R304P | 304 | Protein kinase | Disease-causing (★★) |
| STK11 N181S | 181 | Protein kinase | Disease-causing (★★) |
| STK11 N181K | 181 | Protein kinase | Disease-causing (★★) |
| STK11 R304W | 304 | Protein kinase | Disease-causing (★★) |
| STK11 W308C | 308 | Protein kinase | Disease-causing (★★) |
| STK11 N181E | 181 | Protein kinase | Disease-causing (★★) |
| STK11 D194N | 194 | Protein kinase | Disease-causing (★★) |
| STK11 H306Y | 306 | Protein kinase | Disease-causing (★★) |
| STK11 W308L | 308 | Protein kinase | Disease-causing (★★) |
| STK11 G163R | 163 | Protein kinase | Disease-causing (★★) |
| STK11 D176N | 176 | Protein kinase | Disease-causing (★★) |
| STK11 D194E | 194 | Protein kinase | Disease-causing (★★) |
| STK11 C132R | 132 | Protein kinase | Disease-causing (★★) |
| STK11 P179R | 179 | Protein kinase | Disease-causing (★★) |
| STK11 S240W | 240 | Protein kinase | Disease-causing (★★) |
| STK11 L67P | 67 | Protein kinase | Disease-causing (★★) |
| STK11 R297G | 297 | Protein kinase | Disease-causing (★) |
| STK11 N181D | 181 | Protein kinase | Disease-causing (★) |
| STK11 H174P | 174 | Protein kinase | Disease-causing (★) |
| STK11 I177N | 177 | Protein kinase | Disease-causing (★) |
| STK11 W239C | 239 | Protein kinase | Disease-causing (★) |
| STK11 G242R | 242 | Protein kinase | Disease-causing (★) |
| STK11 L140P | 140 | Protein kinase | Disease-causing (★) |
Uncertain variants in Peutz-Jeghers syndrome that look disease-causing
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| STK11 S240L | 240 | Protein kinase | Uncertain (★★) | +6: 3 other pathogenic changes within 3 positions; S240W at the same position is pathogenic; REVEL 0.965 |
| STK11 G242V | 242 | Protein kinase | Uncertain (★) | +6: 3 other pathogenic changes within 3 positions; G242R at the same position is pathogenic; REVEL 0.970 |
| STK11 H306R | 306 | Protein kinase | Uncertain (★) | +6: 5 other pathogenic changes within 3 positions; H306Y at the same position is pathogenic; REVEL 0.843 |
Which prediction tools work for Peutz-Jeghers syndrome
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- SIFT: 100 out of 100
Diseases related to Peutz-Jeghers syndrome
- Non-small cell lung carcinoma, also linked to STK11
- Breast-ovarian cancer, familial, susceptibility to, 1, also linked to STK11
- Melanoma, cutaneous malignant, susceptibility to, 8, also linked to STK11
- Lung adenocarcinoma, also linked to STK11
- Breast and/or ovarian cancer, also linked to STK11
- Familial pancreatic carcinoma, also linked to STK11
- Carcinoma of pancreas, also linked to STK11
- Malignant tumor of testis, also linked to STK11
- Germ cell tumor of testis, also linked to STK11
Frequently asked questions
Which genes are linked to Peutz-Jeghers syndrome?
In CATVariant, Peutz-Jeghers syndrome is linked to 1 analyzed protein: STK11 (Serine/threonine-protein kinase STK11).
How many genetic variants are linked to Peutz-Jeghers syndrome?
775 variants: 24 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 729 are of uncertain significance or have conflicting reports.
Which uncertain variants in Peutz-Jeghers syndrome look disease-causing?
3 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example STK11 S240L, STK11 G242V and STK11 H306R. These are leads for expert review, not diagnoses.
Which variant effect predictor works best for Peutz-Jeghers syndrome?
Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 1.00, based on 18 disease-causing and 12 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.
Download every variant as CSV · Browse all diseases · Methods · About the Center