PTEN hamartoma tumor syndrome: genes and variants

Genes linked to PTEN hamartoma tumor syndrome

• PTEN: Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN

  A lipid and protein phosphatase that removes phosphate groups from signaling molecules, especially PIP3. By opposing the PI3K-AKT pathway, it limits cell growth and survival signals, and PTEN variants are associated with Cowden syndrome and multiple cancers.

  147 disease-causing and 550 uncertain variants in PTEN are linked to PTEN hamartoma tumor syndrome.

Where PTEN hamartoma tumor syndrome variants cluster

• PTEN Phosphatase tensin-type (positions 14–185): 114 of 147 disease-causing changes, 1.8× more than its size predicts.

Known disease-causing variants in PTEN hamartoma tumor syndrome

Showing 60 of 147.

Uncertain variants in PTEN hamartoma tumor syndrome that look disease-causing

Which prediction tools work for PTEN hamartoma tumor syndrome

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

• ESM1b (LLR): 100 out of 100
• CATVariant: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• AlphaMissense: 100 out of 100
• SIFT: 96 out of 100
• DMS / MaveDB: 58 out of 100

Same protein, different disease

• Cowden syndrome is also caused by PTEN variants; they fall in the same places as the PTEN hamartoma tumor syndrome variants (41 disease-causing).
• Macrocephaly-autism syndrome is also caused by PTEN variants; they fall in the same places as the PTEN hamartoma tumor syndrome variants (13 disease-causing).
• Familial meningioma is also caused by PTEN variants; they fall in the same places as the PTEN hamartoma tumor syndrome variants (3 disease-causing).

Diseases related to PTEN hamartoma tumor syndrome

• Cowden syndrome, also linked to PTEN
• Familial cancer of breast, also linked to PTEN
• Macrocephaly-autism syndrome, also linked to PTEN
• Glioma susceptibility 1, also linked to PTEN
• Familial meningioma, also linked to PTEN
• Prostate cancer, also linked to PTEN
• Endometrial carcinoma, also linked to PTEN
• Thyroid cancer, nonmedullary, 2, also linked to PTEN
• Melanoma, also linked to PTEN
• Familial prostate cancer, also linked to PTEN

Frequently asked questions

Which genes are linked to PTEN hamartoma tumor syndrome?

In CATVariant, PTEN hamartoma tumor syndrome is linked to 1 analyzed protein: PTEN (Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN).

How many genetic variants are linked to PTEN hamartoma tumor syndrome?

722 variants: 147 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 550 are of uncertain significance or have conflicting reports.

Which uncertain variants in PTEN hamartoma tumor syndrome look disease-causing?

18 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example PTEN G165E, PTEN C71F, PTEN R173S, PTEN D22Y and PTEN Y46C. These are leads for expert review, not diagnoses.

Which variant effect predictor works best for PTEN hamartoma tumor syndrome?

Among tools not trained on clinical labels, ESM1b (LLR) separates this disease's known disease-causing variants from harmless ones best (AUROC 1.00, based on 147 disease-causing and 8 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