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GeneE
50 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
PTEN
phosphatase and tensin homolog
Chromosome 10 Β· 10q23.31
NCBI Gene: 5728Ensembl: ENSG00000171862.16HGNC: HGNC:9588UniProt: F6KD01
2,819PubMed Papers
7Diseases
0Drugs
1,254Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneTumor Suppressor
RESEARCH IMPACT
Highly StudiedVariant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
ubiquitin-specific protease bindingphosphatidylinositol-3-phosphate phosphatase activityprotein dephosphorylationapical plasma membraneCowden syndrome 1Lhermitte-Duclos diseaseSquamous cell carcinoma of the head and neckEndometrial cancer
✦AI Summary

PTEN is a dual-specificity phosphatase that functions as a critical tumor suppressor through multiple mechanisms. Cytoplasmic PTEN antagonizes the PI3K/AKT/mTOR signaling pathway to suppress cellular proliferation and survival 1. Beyond cytoplasmic functions, PTEN exhibits important nuclear roles in genome maintenance, DNA repair, cell-cycle control, and chr10 remodeling through interactions with histone H1 and regulation of gene expression 23. PTEN also regulates angiogenesis by suppressing HIF-1Ξ± and the PI3K/AKT pathway, with downregulation occurring in 30-40% of melanomas 4. PTEN regulation involves complex post-translational modifications. Neddylation under high glucose conditions promotes nuclear accumulation of PTEN, which unexpectedly promotes cell proliferation by dephosphorylating FASN to enhance fatty acid synthesisβ€”revealing a tumor-promoting role for nuclear neddylated PTEN 5. Ubiquitination and deubiquitination by enzymes like USP7, USP10, and USP13 dynamically regulate PTEN stability and subcellular localization 6. PTEN loss correlates with advanced disease, chemotherapy resistance, and poor survival across multiple cancers including lymphoma, hepatocellular carcinoma, and melanoma 17. Stromal PTEN inactivation additionally correlates with worse cancer outcomes, highlighting non-cell-autonomous tumor suppression 8. Germline PTEN mutations cause Cowden syndrome and related disorders with increased cancer susceptibility.

Sources cited
1
PTEN antagonizes PI3K signaling, regulates genomic instability and DNA repair, and loss is associated with advanced disease and poor survival
PMID: 26655726
2
Nuclear PTEN is indispensable for genomic stability and controls chromatin dynamics through histone H1 interactions
PMID: 31570373
3
Nuclear PTEN functions in genome maintenance, DNA repair, cell-cycle control, gene expression, and DNA replication
PMID: 31712221
4
PTEN downregulation occurs in 30-40% of melanomas and regulates angiogenesis through PI3K/AKT pathway inhibition and HIF-1Ξ± suppression
PMID: 38338464
5
Neddylation promotes nuclear PTEN accumulation and unexpectedly promotes cell proliferation by dephosphorylating FASN to enhance fatty acid synthesis
PMID: 33299139
6
Deubiquitinating enzymes including USP7, USP10, and USP13 regulate PTEN stability and subcellular localization
PMID: 36385557
7
PTEN expression is significantly lower in hepatocellular carcinoma compared to paracancerous tissues
PMID: 25613699
8
PTEN inactivation in stromal cells of tumor microenvironment correlates with worse outcomes in human cancers
PMID: 31427286
Disease Associationsβ“˜7
Cowden syndrome 1UniProt
Endometrial cancerUniProt
Glioma 2UniProt
Lhermitte-Duclos diseaseUniProt
Macrocephaly/autism syndromeUniProt
Prostate cancerUniProt
Squamous cell carcinoma of the head and neckUniProt
Pathogenic Variants1,254
NM_000314.8(PTEN):c.331T>C (p.Trp111Arg)Pathogenic
not provided|PTEN hamartoma tumor syndrome|Cowden syndrome 1|Hereditary cancer-predisposing syndrome|Autosomal dominant PTEN-related disorders|Neoplasm
β˜…β˜…β˜…β˜†2025β†’ Residue 111
NM_000314.8(PTEN):c.100G>C (p.Ala34Pro)Pathogenic
Hereditary cancer-predisposing syndrome|Cowden syndrome 1|PTEN hamartoma tumor syndrome
β˜…β˜…β˜…β˜†2025β†’ Residue 34
NM_000314.8(PTEN):c.802-2delPathogenic
PTEN hamartoma tumor syndrome|not provided
β˜…β˜…β˜…β˜†2025
NM_000314.8(PTEN):c.964A>T (p.Lys322Ter)Likely pathogenic
Hereditary cancer-predisposing syndrome|not provided|PTEN hamartoma tumor syndrome
β˜…β˜…β˜…β˜†2025β†’ Residue 322
NM_000314.8(PTEN):c.599T>C (p.Phe200Ser)Likely pathogenic
not provided|PTEN hamartoma tumor syndrome|Cowden syndrome 1
β˜…β˜…β˜…β˜†2025β†’ Residue 200
NM_000314.8(PTEN):c.802-2A>TPathogenic
Hereditary cancer-predisposing syndrome|not provided|Cowden syndrome 1|PTEN hamartoma tumor syndrome|PTEN-related disorder|Malignant tumor of esophagus|Thymoma
β˜…β˜…β˜…β˜†2025
NM_000314.8(PTEN):c.209T>C (p.Leu70Pro)Likely pathogenic
Cowden syndrome 1|PTEN hamartoma tumor syndrome|Macrocephaly-autism syndrome;Glioma susceptibility 2;Cowden syndrome 1;Familial meningioma;Prostate cancer|Hereditary cancer-predisposing syndrome|Diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype
β˜…β˜…β˜…β˜†2025β†’ Residue 70
NM_000314.8(PTEN):c.477G>T (p.Arg159Ser)Likely pathogenic
PTEN hamartoma tumor syndrome|Neoplasm
β˜…β˜…β˜…β˜†2025β†’ Residue 159
NM_000314.8(PTEN):c.761_765del (p.Lys254fs)Likely pathogenic
Prostate cancer, somatic|PTEN hamartoma tumor syndrome|Neoplasm
β˜…β˜…β˜…β˜†2025β†’ Residue 254
NM_000314.8(PTEN):c.355G>T (p.Val119Phe)Likely pathogenic
Hereditary cancer-predisposing syndrome|PTEN hamartoma tumor syndrome|PTEN-related disorder
β˜…β˜…β˜…β˜†2025β†’ Residue 119
NM_000314.8(PTEN):c.801G>T (p.Lys267Asn)Pathogenic
PTEN hamartoma tumor syndrome|not provided|Hereditary cancer-predisposing syndrome|Segmental outgrowth-lipomatosis-arteriovenous malformation-epidermal nevus syndrome;Cowden syndrome
β˜…β˜…β˜…β˜†2025β†’ Residue 267
NM_000314.8(PTEN):c.80-1G>CPathogenic
not provided|PTEN hamartoma tumor syndrome
β˜…β˜…β˜…β˜†2025
NM_000314.8(PTEN):c.314G>A (p.Cys105Tyr)Pathogenic
Hereditary cancer-predisposing syndrome|not provided|PTEN hamartoma tumor syndrome
β˜…β˜…β˜…β˜†2025β†’ Residue 105
NM_000314.8(PTEN):c.959T>C (p.Leu320Ser)Likely pathogenic
PTEN hamartoma tumor syndrome|not provided|Hereditary cancer-predisposing syndrome|Cowden syndrome 1
β˜…β˜…β˜…β˜†2025β†’ Residue 320
NM_000314.8(PTEN):c.530A>G (p.Tyr177Cys)Likely pathogenic
PTEN hamartoma tumor syndrome|Hereditary cancer-predisposing syndrome|not provided
β˜…β˜…β˜…β˜†2025β†’ Residue 177
NM_000314.8(PTEN):c.564T>A (p.Tyr188Ter)Likely pathogenic
Prostate cancer, somatic|PTEN hamartoma tumor syndrome
β˜…β˜…β˜…β˜†2025β†’ Residue 188
NM_000314.8(PTEN):c.520T>A (p.Tyr174Asn)Likely pathogenic
Hereditary cancer-predisposing syndrome|PTEN hamartoma tumor syndrome
β˜…β˜…β˜…β˜†2025β†’ Residue 174
NM_000314.8(PTEN):c.633C>G (p.Cys211Trp)Pathogenic
not provided|Hereditary cancer-predisposing syndrome|PTEN hamartoma tumor syndrome
β˜…β˜…β˜…β˜†2025β†’ Residue 211
NM_000314.8(PTEN):c.476G>A (p.Arg159Lys)Pathogenic
PTEN hamartoma tumor syndrome|not provided|Prostate cancer, hereditary, 1
β˜…β˜…β˜…β˜†2025β†’ Residue 159
NM_000314.8(PTEN):c.1027-1852A>GLikely pathogenic
Hereditary cancer-predisposing syndrome|PTEN hamartoma tumor syndrome
β˜…β˜…β˜…β˜†2025
View on ClinVar β†—
Related Genes
IDH1Protein interaction100%UBE3AProtein interaction100%USP7Protein interaction100%TERTProtein interaction100%EGFRProtein interaction99%SPOPProtein interaction99%
Tissue Expression

No tissue expression data available for this gene.

Gene Interaction Network
Click a node to explore
PTENIDH1UBE3AUSP7TERTEGFRSPOP
PROTEIN STRUCTURE
Preparing viewer…
PDB8X3S Β· 1.87 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.69LoF Tolerant
pLIβ“˜
0.05Tolerant
Observed/Expected LoF0.46 [0.31–0.69]
RankingsWhere PTEN stands among ~20K protein-coding genes
  • #23of 20,598
    Most Researched2,819 Β· top 1%
  • #24of 5,498
    Most Pathogenic Variants1,254 Β· top 1%
  • #5,127of 17,882
    Most Constrained (LOEUF)0.69
Genes detectedPTEN
Sources retrieved50 papers
Response timeβ€”
πŸ“„ Sources
50β–Ό
1
Neddylation of PTEN regulates its nuclear import and promotes tumor development.
PMID: 33299139
Cell Res Β· 2021
1.00
2
PTEN Nuclear Functions.
PMID: 31712221
Cold Spring Harb Perspect Med Β· 2020
0.90
3
PTEN and FOXO3 expression in the prenatal and postnatal human ovary.
PMID: 32424736
J Assist Reprod Genet Β· 2020
0.88
4
PTEN in Hereditary and Sporadic Cancer.
PMID: 31570378
Cold Spring Harb Perspect Med Β· 2020
0.82
5
PTEN in the Stroma.
PMID: 31427286
Cold Spring Harb Perspect Med Β· 2019
0.80