PTEN
Chr 10ADphosphatase and tensin homolog
Also known as: 10q23del, BZS, CWS1, DEC, GLM2, MHAM, MMAC1, PTEN1
This gene encodes a dual-specificity phosphatase that functions primarily as a lipid phosphatase, dephosphorylating PIP3 to negatively regulate the PI3K-AKT signaling pathway critical for cell growth, survival, and neuronal development. Germline mutations cause autosomal dominant conditions including Cowden syndrome, macrocephaly/autism syndrome, and Lhermitte-Duclos disease, predominantly through loss-of-function resulting in excessive PI3K-AKT pathway activation. The protein plays essential roles in neuronal migration, dendritic development, synaptic plasticity, and regulation of cell size and proliferation.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Highly missense-constrained (top ~0.1%)
Tumor suppressor phosphatase. LOF (haploinsufficiency) causes PHTS (Cowden, Bannayan-Riley-Ruvalcaba). This is a classic tumor suppressor with LOF mechanism; the DN prediction does not reflect the established biology.
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative, gain-of-function and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
PTEN · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
ScreenIng of Genetic Susceptibility Genes for Breast Cancer Patients in CHinese communiTies
RECRUITINGHypofractionated, Dose Escalation Radiotherapy for High Risk Adenocarcinoma of the Prostate
ACTIVE NOT RECRUITINGCanadian Profiling and Targeted Agent Utilization Trial (CAPTUR)
RECRUITINGMolecular and Functional Imaging in Monogenic PD.
RECRUITINGDouble-Blind Trial of Everolimus for Improving Social Abilities in PTEN Germline Mutations
NOT YET RECRUITINGPrevalence Of Germline Gene Mutations In Patients With Myeloproliferative Neoplasms With Family History
NOT YET RECRUITINGDetection of Minimal Residual Disease Post-prostatectomy
RECRUITINGComparative Study of Radiotherapy Treatments to Treat High Risk Prostate Cancer Patients
ACTIVE NOT RECRUITINGGenetic Testing in Screening Patients With Stage IB-IIIA Non-small Cell Lung Cancer That Has Been or Will Be Removed by Surgery (The ALCHEMIST Screening Trial)
ACTIVE NOT RECRUITINGAn Intervention to Increase Genetic Testing in Families Who May Share a Gene Mutation Related to Cancer Risk and An Intervention to Help Patients and Their Primary Care Providers Stay Up-to-date About Uncertain Genetic Test Results
RECRUITINGVideo Capsule Examination in Patients With Lynch Syndrome
RECRUITINGFamilial Investigations of Childhood Cancer Predisposition
RECRUITINGExternal Resources
Links to major genomics databases and tools