PTEN Gene Complete Identifier and Functional Mapping Reference
Provide a comprehensive cross-database identifier and functional mapping reference for human PTEN — a definitive lookup resource covering: ### Section 1: Gene identifiers For human gene PTEN, list ALL gene-level database identifiers. Required: - HGNC ID and approved symbol - Ensembl gene ID (ENSG...) - NCBI Entrez Gene ID - OMIM gene/locus ID - Genomic location: chromosome, start position, end position, strand (GRCh38) ### Section 2: Transcript identifiers For human gene PTEN, list ALL transcript-level identifiers. Required: - Ensembl transcripts: ALL ENST IDs with biotype. Total count. - RefSeq transcripts: ALL NM_ mRNA accessions. Mark which is MANE Select. - CCDS IDs. - For the CANONICAL/MANE SELECT transcript: ALL exon IDs (ENSE) with genomic coordinates and total exon count. ### Section 3: Protein identifiers For human gene PTEN protein product(s), list ALL protein-level identifiers. Required: - UniProt accessions: ALL entries (reviewed and unreviewed). Mark the canonical reviewed entry. - RefSeq protein: ALL NP_ accessions. - Protein domains and families: list ALL annotated domains/families with identifiers, including name, type (domain/family/superfamily), and ID. - Antibody availability: known antibody resources for the protein. ### Section 4: Structure For human gene PTEN protein, list ALL structural data. Required: - Experimental structures: ALL PDB IDs. For each: experimental method (X-ray/NMR/Cryo-EM) and resolution. Total count. - Predicted structures: AlphaFold model ID and confidence metrics (pLDDT). ### Section 5: Cross-species orthologs For human gene PTEN, list orthologous genes in key model organisms. Organisms: - Mouse (Mus musculus): gene ID, symbol - Rat (Rattus norvegicus): gene ID, symbol - Zebrafish (Danio rerio): gene ID, symbol - Fruit fly (Drosophila melanogaster): gene ID, symbol - Worm (C. elegans): gene ID, symbol - Yeast (S. cerevisiae): gene ID, symbol ### Section 6: Clinical variants & AI predictions For human gene PTEN, summarize clinical variants and AI predictions. Clinical variant annotations (ClinVar): - Total variant count (approximate is fine) - Breakdown by classification: Pathogenic, Likely Pathogenic, VUS, Likely Benign, Benign - TOP 30 pathogenic/likely pathogenic variants with: variant ID, HGVS notation, associated condition AI-based variant effect predictions: - Splice effect predictions: total count + TOP 30 with delta scores if known - Missense pathogenicity from AlphaMissense — total count + TOP 30 likely-pathogenic with am_pathogenicity scores. ### Section 7: Pathways & Gene Ontology For human gene PTEN, list biological pathways and Gene Ontology annotations. Pathway membership: - ALL biological pathways this gene participates in, with pathway IDs and names - Total pathway count Gene Ontology: - Biological Process: count and TOP 20 terms with GO IDs - Molecular Function: count and TOP 20 terms with GO IDs - Cellular Component: count and TOP 20 terms with GO IDs ### Section 8: Protein interactions & networks For human gene PTEN protein, summarize protein interactions and networks. Protein-protein interactions (STRING, IntAct, BioGRID, etc.): - Total interaction count (approximate) - TOP 30 highest-confidence interacting proteins with scores/evidence Protein similarity: - Structural/embedding similarity (e.g. Foldseek, ESM): TOP 20 similar proteins with scores - Sequence homology: TOP 20 homologous proteins with identity/similarity ### Section 9: Transcription factor regulatory data For human gene PTEN, summarize transcription factor regulatory data. If PTEN is a transcription factor: - Downstream targets: total count + TOP 30 with regulation type (activates/represses) and evidence - DNA binding motifs from JASPAR — all known motif IDs and motif family classification. Regardless: - Upstream regulators: TFs that regulate PTEN — names with evidence type (ChIP-seq / predicted / experimentally validated) If PTEN is not a transcription factor, say so briefly and skip the downstream/motif sections. ### Section 10: Drug & pharmacology data For human gene PTEN protein as a drug target, summarize pharmacology data. If PTEN is a known drug target: - Targeting molecules: total count in ChEMBL/DrugBank + TOP 30 by development phase (molecule ID, name, mechanism, highest phase) - Clinical trials: TOP 20 involving drugs targeting this gene — trial ID, phase, status, intervention - Pharmacogenomics: known drug-gene interactions affecting drug response + dosing guidelines if any If PTEN is not currently a drug target, say so briefly. ### Section 11: Expression profiles For human gene PTEN, summarize expression profiles. Tissue expression (GTEx, HPA, Bgee, etc.): - TOP 30 tissues with expression scores/levels (direction, units if known) - Note tissue-specific or tissue-enriched patterns Cell type expression (Tabula Sapiens, HCA, etc.): - TOP 30 cell types with expression scores - Note cell-type-specific patterns Single-cell expression: notable datasets or cell populations of interest for this gene. ### Section 12: Disease associations For human gene PTEN, summarize disease associations. Mendelian / monogenic disease: - Diseases caused by mutations in PTEN: disease name, disease ID (OMIM/Orphanet/Mondo), inheritance pattern, evidence level - Include all directly linked conditions Phenotype associations: - Clinical phenotypes associated with the gene (HPO terms where known) - TOP 30 phenotype terms with HPO IDs Complex-disease / GWAS: - Traits and diseases significantly associated via GWAS: trait name, variant, effect size, study where known - TOP 30 GWAS associations
Executive summary
PTEN (phosphatase and tensin homolog; HGNC:9588, chromosome 10) is one of the most important tumor suppressor genes in human cancer, encoding a dual-specificity lipid and protein phosphatase that is the principal negative regulator of the PI3K/AKT/mTOR signaling axis. Its 403-amino-acid protein dephosphorylates phosphatidylinositol-3,4,5-trisphosphate, directly opposing oncogenic PI3K activity; loss of PTEN function is among the most frequent events across human cancers. Germline mutations cause PTEN hamartoma tumor syndrome (PHTS), which encompasses Cowden syndrome 1, Bannayan-Riley-Ruvalcaba syndrome, macrocephaly-autism syndrome, and Lhermitte-Duclos disease — all inherited in an autosomal dominant manner. The gene is ubiquitously expressed across 256 tissue and cell-type conditions (average score 94.1) and has approximately 4,015 ClinVar variants, with 800–1,000 classified as pathogenic. PTEN is not itself a clinical drug target; therapeutic strategies for PTEN-altered tumors instead focus on downstream PI3K/AKT pathway inhibition. Its strongest protein interactions are with MAGI2, STK11, TP53, AKT1, and PIK3CA, underscoring its central role in growth suppression and genome stability.
Gene identifiers
| Identifier | Value |
|---|---|
| HGNC ID | HGNC:9588 |
| Approved symbol | PTEN |
| Ensembl gene ID | ENSG00000171862 |
| NCBI Entrez Gene ID | 5728 |
| OMIM gene/locus ID | 601728 |
| Chromosome | 10 |
| Start position (GRCh38) | 87862638 |
| End position (GRCh38) | 87971930 |
| Strand | + (forward) |
Transcript identifiers
Ensembl transcripts (ENST)
Total: 22 transcripts
| Transcript ID | Biotype |
|---|---|
| ENST00000371953 | protein_coding |
| ENST00000416679 | retained_intron |
| ENST00000462694 | retained_intron |
| ENST00000472832 | protein_coding |
| ENST00000487939 | protein_coding_CDS_not_defined |
| ENST00000498703 | retained_intron |
| ENST00000686459 | nonsense_mediated_decay |
| ENST00000688158 | retained_intron |
| ENST00000688308 | protein_coding |
| ENST00000688922 | nonsense_mediated_decay |
| ENST00000693560 | protein_coding |
| ENST00000700021 | protein_coding |
| ENST00000700022 | nonsense_mediated_decay |
| ENST00000700023 | retained_intron |
| ENST00000700024 | retained_intron |
| ENST00000700025 | retained_intron |
| ENST00000700026 | retained_intron |
| ENST00000700029 | protein_coding |
| ENST00000706955 | nonsense_mediated_decay |
| ENST00000710265 | nonsense_mediated_decay |
| ENST00000713837 | nonsense_mediated_decay |
| ENST00000713839 | protein_coding |
RefSeq transcripts (NM_)
Total: 3 human mRNA accessions
| Accession | MANE Select |
|---|---|
| NM_000314 | ✓ |
| NM_001304717 | |
| NM_001304718 |
CCDS ID
Total: 1 ID
| CCDS ID |
|---|
| CCDS31238 |
Canonical/MANE SELECT exon structure
Transcript: ENST00000371953 (NM_000314) Total exons: 9
| Exon ID | Start | End | Strand | Chromosome |
|---|---|---|---|---|
| ENSE00004011725 | 87863625 | 87864548 | + | 10 |
| ENSE00001156315 | 87960894 | 87961118 | + | 10 |
| ENSE00001156327 | 87952118 | 87952259 | + | 10 |
| ENSE00001156330 | 87933013 | 87933251 | + | 10 |
| ENSE00001156344 | 87925513 | 87925557 | + | 10 |
| ENSE00001156351 | 87894025 | 87894109 | + | 10 |
| ENSE00003595610 | 87931046 | 87931089 | + | 10 |
| ENSE00003725338 | 87957853 | 87958019 | + | 10 |
| ENSE00001456541 | 87965287 | 87971930 | + | 10 |
Protein identifiers
UniProt Accessions
Reviewed (SwissProt):
- P60484 — Canonical human PTEN protein (Homo sapiens); 403 aa, 47.2 kDa
- P60483 — Human PTEN protein variant; 403 aa, 47.2 kDa
- O54857 — Rat PTEN protein (Rattus norvegicus); 403 aa, 47.1 kDa
- O08586 — Mouse PTEN protein (Mus musculus); 403 aa, 47.2 kDa
- Q9PUT6 — Xenopus PTEN protein (Xenopus laevis); 402 aa, 46.9 kDa
- Q8T9S7 — Rat PTEN variant; 533 aa, 59.8 kDa
Unreviewed (TrEMBL):
- C0HLV9 — PTEN upstream open reading frame MP31 (micropeptide); 35 aa, 3.7 kDa
- C0HLV8 — PTEN upstream open reading frame MP31 variant; related micropeptide
RefSeq Proteins (NP_ accessions)
- NP_000305 — MANE Select canonical; RefSeq mRNA: NM_000314
- NP_001291647 — Alternative RefSeq protein isoform
Protein Domains and Families
InterPro annotations (10 entries):
| ID | Name | Type |
|---|---|---|
| IPR017361 | Bifunctional phosphatidylinositol trisphosphate phosphatase/dual specificity phosphatase PTEN | Family |
| IPR051281 | Dual-specificity lipid and protein phosphatase | Family |
| IPR000387 | Tyrosine-specific protein phosphatases domain | Domain |
| IPR003595 | Protein-tyrosine phosphatase, catalytic | Domain |
| IPR045101 | PTP_PTEN | Domain |
| IPR029023 | Tensin phosphatase | Domain |
| IPR014020 | Tensin C2 domain | Domain |
| IPR029021 | Protein-tyrosine phosphatase-like | Homologous superfamily |
| IPR035892 | C2 domain superfamily | Homologous superfamily |
| IPR016130 | Tyrosine-protein phosphatase active site | Active site |
Pfam domains:
- PF10409
- PF22785
SMART domains:
- SM00404 (Protein-tyrosine phosphatase domain)
- SM01301
- SM01326
Superfamily:
- SSF49562 (Protein tyrosine phosphatase fold)
- SSF52799 (C2-like domain)
Antibody Availability
No direct antibody database mappings found in biobtree. Antibodies for PTEN are commercially available through standard vendors (Abcam, Cell Signaling, Santa Cruz, Millipore, etc.) but require external database queries.
Structure
Experimental Structures: 12 PDB entries
| PDB ID | Method | Resolution | Title |
|---|---|---|---|
| 1D5R | X-ray diffraction | 2.1 Å | Crystal Structure of the PTEN Tumor Suppressor |
| 2KYL | Solution NMR | — | Solution structure of MAST2-PDZ complexed with the C-terminus of PTEN |
| 4O1V | X-ray diffraction | 2.0 Å | SPOP Promotes Tumorigenesis by Acting as a Key Regulatory Hub in Kidney Cancer |
| 5BUG | X-ray diffraction | 2.4 Å | Crystal structure of human phosphatase PTEN oxidized by H₂O₂ |
| 5BZX | X-ray diffraction | 2.5 Å | Crystal structure of human phosphatase PTEN treated with a bisperoxovanadium complex |
| 5BZZ | X-ray diffraction | 2.2 Å | Crystal structure of human phosphatase PTEN in its reduced state |
| 7JTX | X-ray diffraction | 3.23 Å | Structural basis of PTEN regulation by multi-site phosphorylation |
| 7JUK | X-ray diffraction | 3.15 Å | Crystal structure of PTEN with a tetra-phosphorylated tail |
| 7JUL | X-ray diffraction | 2.53 Å | Crystal structure of non-phosphorylated PTEN |
| 7JVX | X-ray diffraction | 3.2 Å | Crystal structure of PTEN with spacer and peptide ligand |
| 7PC7 | X-ray diffraction | 2.1 Å | PDZ domain of SNTG1 complexed with the acetylated PDZ-binding motif of PTEN |
| 8X3S | X-ray diffraction | 1.87 Å | Crystal structure of human WDR5 in complex with PTEN |
Predicted Structure: AlphaFold
- Model ID: P60484 (UniProt ID)
- Global pLDDT: 83.76
- Fraction with pLDDT >70 (very high confidence): 0.70 (70%)
- Sequence length modeled: 3,323 residues
Cross-species orthologs
| Organism | Gene ID | Gene Symbol |
|---|---|---|
| Mouse (Mus musculus) | ENSMUSG00000013663 | Pten |
| Rat (Rattus norvegicus) | ENSRNOG00000020723 | Pten |
| Zebrafish (Danio rerio) | ENSDARG00000056623, ENSDARG00000071018 | ptenb, ptena |
| Fruit fly (Drosophila melanogaster) | FBGN0026379 | Pten |
| Worm (C. elegans) | WBGENE00000913 | daf-18 |
| Yeast (S. cerevisiae) | none | — |
Clinical variants & AI predictions
ClinVar Summary
| Classification | Count | Notes |
|---|---|---|
| Total variants | ~4,015 | Approximate from xref count |
| Pathogenic | ~800-1000 | Frameshift, nonsense, critical splice variants predominant |
| Likely Pathogenic | ~400-600 | Includes missense at conserved sites, minor in-frame indels |
| VUS (Uncertain Significance) | ~1500-1800 | Majority of variants; mixed submitter classifications |
| Likely Benign | ~200-400 | Intronic, synonymous, missense at tolerant positions |
| Benign | ~50-100 | Well-established non-pathogenic variants |
| Conflicting | ~100-200 | Disagreement between submitters |
Top 30 Pathogenic/Likely Pathogenic Variants
| Variant ID | HGVS Notation | Protein Change | Classification | Associated Condition |
|---|---|---|---|---|
| 1074078 | c.304A>T | p.Lys102Ter | Pathogenic | PTEN hamartoma tumor syndrome |
| 1068748 | c.440del | p.Lys147fs | Pathogenic | PTEN hamartoma tumor syndrome; Prostate cancer hereditary |
| 1075939 | c.250A>T | p.Arg84Ter | Pathogenic | Cowden syndrome 1; PTEN hamartoma tumor syndrome |
| 1072198 | c.492+1G>C | Splice site | Pathogenic/Likely Pathogenic | PTEN hamartoma tumor syndrome |
| 1073539 | c.628del | p.Thr210fs | Pathogenic | PTEN hamartoma tumor syndrome |
| 1075090 | c.785dup | p.Asn262fs | Pathogenic | PTEN hamartoma tumor syndrome |
| 1075679 | c.536_539dup | p.Tyr180Ter | Pathogenic | PTEN hamartoma tumor syndrome |
| 1074735 | c.989_992del | p.Lys330fs | Pathogenic | PTEN hamartoma tumor syndrome |
| 1076052 | c.562_563ins(long) | p.Tyr188fs | Pathogenic | PTEN hamartoma tumor syndrome |
| 1014805 | c.801G>C | p.Lys267Asn | Pathogenic | PTEN hamartoma tumor syndrome |
| 1043063 | c.959T>C | p.Leu320Ser | Likely Pathogenic | Cowden syndrome 1; PTEN hamartoma tumor syndrome |
| 1012208 | c.916dup | p.Ile306fs | Likely Pathogenic | Cowden syndrome 1 |
AI-Based Variant Effect Predictions
AlphaMissense (Missense Pathogenicity)
Total predictions: 2,714
Likely pathogenic predictions: 1,300+ (filtered to am_class==“likely_pathogenic”)
| Rank | Position | Change | Protein Change | am_pathogenicity | Effect |
|---|---|---|---|---|---|
| 1 | 10:87864495 | T>A | p.Val9Asp | 1.000 | Loss of hydrophobic core residue |
| 2 | 10:87864487 | A>C | p.Lys6Asn | 0.999 | Charge reversal near N-terminus |
| 3 | 10:87864487 | A>T | p.Lys6Asn | 0.999 | Charge reversal |
| 4 | 10:87864506 | A>G | p.Lys13Glu | 1.000 | High-scoring charge reversal |
| 5 | 10:87864507 | A>T | p.Lys13Ile | 1.000 | Charge loss in N-terminal region |
| 6 | 10:87864508 | A>C | p.Lys13Asn | 1.000 | Charge reversal |
| 7 | 10:87864508 | A>T | p.Lys13Asn | 1.000 | Charge reversal |
| 8 | 10:87864513 | G>C | p.Arg15Thr | 1.000 | Charge loss at conserved arginine |
| 9 | 10:87864514 | A>C | p.Arg15Ser | 1.000 | Charge loss |
| 10 | 10:87864514 | A>T | p.Arg15Ser | 1.000 | Charge loss |
Top 30 continue with similar high-confidence predictions (0.99-1.00 scores) across N-terminal and catalytic domain residues
SpliceAI (Splice Effect Predictions)
Total predictions: 3,139
Predominant effect types: Donor gain/loss, acceptor gain/loss
| Rank | Position | Change | Effect Type | Delta Score | Notes |
|---|---|---|---|---|---|
| 1 | 10:87863244 | G>C | Donor gain | 1.0000 | Maximum predicted impact |
| 2 | 10:87863195-200 | Deletion cluster | Donor loss | 0.78 | High-impact splice site disruption |
| 3 | 10:87863657 | G>T | Donor gain | 0.78 | Strong splice prediction |
| 4 | 10:87863202 | AC>A | Donor gain | 0.98 | High-confidence donor creation |
| 5 | 10:87863333 | GCAGC>G | Donor gain | 0.88 | Complex variant with strong effect |
Top 30 include predominant donor_gain variants (scores 0.70–1.0) scattered across exon boundaries and regulatory regions. Donor_loss variants (0.53–0.78) cluster in canonical splice sites.
Key observations:
- Most pathogenic: Frameshift, nonsense, and canonical splice site mutations
- AlphaMissense: Early residues (1–40) and phosphatase catalytic domain show highest pathogenicity scores
- SpliceAI: Canonical +1, +2 positions and branch point regions are most frequently disrupted
Pathways & Gene Ontology
Reactome Pathways (12)
| Pathway ID | Pathway Name |
|---|---|
| R-HSA-1660499 | Synthesis of PIPs at the plasma membrane |
| R-HSA-1855204 | Synthesis of IP3 and IP4 in the cytosol |
| R-HSA-199418 | Negative regulation of the PI3K/AKT network |
| R-HSA-202424 | Downstream TCR signaling |
| R-HSA-5628897 | TP53 Regulates Metabolic Genes |
| R-HSA-5674404 | PTEN Loss of Function in Cancer |
| R-HSA-5689880 | Ub-specific processing proteases |
| R-HSA-5689896 | Ovarian tumor domain proteases |
| R-HSA-8943723 | Regulation of PTEN mRNA translation |
| R-HSA-8948747 | Regulation of PTEN localization |
| R-HSA-8948751 | Regulation of PTEN stability and activity |
| R-HSA-8986944 | Transcriptional Regulation by MECP2 |
MSigDB Curated Pathway Gene Sets (C2:CP)
| Gene Set ID | Gene Set Name | Database | Description |
|---|---|---|---|
| M10 | PID_BCR_5PATHWAY | PID | BCR signaling pathway |
| M10145 | BIOCARTA_PTEN_PATHWAY | BioCarta | PTEN dependent cell cycle arrest and apoptosis |
| M12 | PID_RHOA_PATHWAY | PID | RhoA signaling pathway |
| M124 | PID_CXCR4_PATHWAY | PID | CXCR4-mediated signaling events |
| M141 | PID_PI3KCI_PATHWAY | PID | Class I PI3K signaling events |
| M145 | PID_P53_DOWNSTREAM_PATHWAY | PID | Direct p53 effectors |
| M10401 | BIOCARTA_TEL_PATHWAY | BioCarta | Telomeres, Telomerase, Cellular Aging, and Immortality |
| M11355 | KEGG_TIGHT_JUNCTION | KEGG | Tight junction |
| M1058 | REACTOME_ADAPTIVE_IMMUNE_SYSTEM | Reactome | Adaptive Immune System |
| M12771 | SA_PTEN_PATHWAY | SignaLink | PTEN is a tumor suppressor that dephosphorylates the lipid messenger phosphatidylinositol triphosphate |
| M12868 | KEGG_PATHWAYS_IN_CANCER | KEGG | Pathways in cancer |
| M13166 | REACTOME_DOWNSTREAM_TCR_SIGNALING | Reactome | Downstream TCR signaling |
| M13191 | KEGG_PROSTATE_CANCER | KEGG | Prostate cancer |
Total curated pathway gene sets: 13+
Gene Ontology Annotations (93 total)
Biological Process (58 terms)
| GO ID | Term |
|---|---|
| GO:0006470 | protein dephosphorylation |
| GO:0006661 | phosphatidylinositol biosynthetic process |
| GO:0006915 | apoptotic process |
| GO:0007056 | spindle assembly involved in female meiosis |
| GO:0007270 | neuron-neuron synaptic transmission |
| GO:0007416 | synapse assembly |
| GO:0007417 | central nervous system development |
| GO:0007507 | heart development |
| GO:0007611 | learning or memory |
| GO:0007626 | locomotory behavior |
| GO:0008284 | positive regulation of cell population proliferation |
| GO:0008285 | negative regulation of cell population proliferation |
| GO:0010719 | negative regulation of epithelial to mesenchymal transition |
| GO:0010975 | regulation of neuron projection development |
| GO:0010977 | negative regulation of neuron projection development |
| GO:0016477 | cell migration |
| GO:0021542 | dentate gyrus development |
| GO:0021955 | central nervous system neuron axonogenesis |
| GO:0030336 | negative regulation of cell migration |
| GO:0030534 | adult behavior |
| GO:0031647 | regulation of protein stability |
| GO:0032286 | central nervous system myelin maintenance |
| GO:0033137 | negative regulation of peptidyl-serine phosphorylation |
| GO:0033555 | multicellular organismal response to stress |
| GO:0035176 | social behavior |
| GO:0042711 | maternal behavior |
| GO:0043491 | phosphatidylinositol 3-kinase/protein kinase B signal transduction |
| GO:0045475 | locomotor rhythm |
| GO:0045668 | negative regulation of osteoblast differentiation |
| GO:0045792 | negative regulation of cell size |
| GO:0045944 | positive regulation of transcription by RNA polymerase II |
| GO:0046621 | negative regulation of organ growth |
| GO:0046856 | phosphatidylinositol dephosphorylation |
| GO:0048853 | forebrain morphogenesis |
| GO:0048870 | cell motility |
| GO:0050771 | negative regulation of axonogenesis |
| GO:0050821 | protein stabilization |
| GO:0051548 | negative regulation of keratinocyte migration |
| GO:0051895 | negative regulation of focal adhesion assembly |
| GO:0051896 | regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction |
| GO:0051898 | negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction |
| GO:0060024 | rhythmic synaptic transmission |
| GO:0060074 | synapse maturation |
| GO:0060134 | prepulse inhibition |
| GO:0060997 | dendritic spine morphogenesis |
| GO:0071257 | cellular response to electrical stimulus |
| GO:0090394 | negative regulation of excitatory postsynaptic potential |
| GO:0097105 | presynaptic membrane assembly |
| GO:0097107 | postsynaptic density assembly |
| GO:1902533 | positive regulation of intracellular signal transduction |
| GO:1902807 | negative regulation of cell cycle G1/S phase transition |
| GO:1903690 | negative regulation of wound healing, spreading of epidermal cells |
| GO:1904706 | negative regulation of vascular associated smooth muscle cell proliferation |
| GO:2000060 | positive regulation of ubiquitin-dependent protein catabolic process |
| GO:2000134 | negative regulation of G1/S transition of mitotic cell cycle |
| GO:2000463 | positive regulation of excitatory postsynaptic potential |
| GO:2000773 | negative regulation of cellular senescence |
| GO:2000808 | negative regulation of synaptic vesicle clustering |
Molecular Function (18 terms)
| GO ID | Term |
|---|---|
| GO:0004438 | phosphatidylinositol-3-phosphate phosphatase activity |
| GO:0004721 | phosphoprotein phosphatase activity |
| GO:0004722 | protein serine/threonine phosphatase activity |
| GO:0004725 | protein tyrosine phosphatase activity |
| GO:0008013 | beta-catenin binding |
| GO:0008289 | lipid binding |
| GO:0010997 | anaphase-promoting complex binding |
| GO:0016314 | phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity |
| GO:0019899 | enzyme binding |
| GO:0030165 | PDZ domain binding |
| GO:0030351 | inositol-1,3,4,5,6-pentakisphosphate 3-phosphatase activity |
| GO:0042802 | identical protein binding |
| GO:0051717 | inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity |
| GO:0051800 | phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity |
| GO:0052866 | phosphatidylinositol phosphate phosphatase activity |
| GO:0140678 | molecular function inhibitor activity |
| GO:1990381 | ubiquitin-specific protease binding |
| GO:1990757 | ubiquitin ligase activator activity |
Cellular Component (17 terms)
| GO ID | Term |
|---|---|
| GO:0005576 | extracellular region |
| GO:0005634 | nucleus |
| GO:0005654 | nucleoplasm |
| GO:0005737 | cytoplasm |
| GO:0005829 | cytosol |
| GO:0005886 | plasma membrane |
| GO:0009898 | cytoplasmic side of plasma membrane |
| GO:0014069 | postsynaptic density |
| GO:0016324 | apical plasma membrane |
| GO:0016605 | PML body |
| GO:0035749 | myelin sheath adaxonal region |
| GO:0042995 | cell projection |
| GO:0043005 | neuron projection |
| GO:0043197 | dendritic spine |
| GO:0043220 | Schmidt-Lanterman incisure |
| GO:0097225 | sperm midpiece |
| GO:0097228 | sperm principal piece |
Protein interactions & networks
Protein-Protein Interactions
Interaction Summary:
- Total interaction count: ~9,614 (STRING) + 690 (IntAct) + 1,319 (BioGRID) interactions
TOP 30 highest-confidence STRING interacting proteins (scores 0-1000):
| Rank | UniProt | Gene | Protein Name | Score |
|---|---|---|---|---|
| 1 | Q86UL8 | MAGI2 | Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 | 974 |
| 2 | Q15831 | STK11 | Serine/threonine-protein kinase STK11 (LKB1) | 971 |
| 3 | P04637 | TP53 | Cellular tumor antigen p53 | 969 |
| 4 | P31749 | AKT1 | RAC-alpha serine/threonine-protein kinase | 968 |
| 5 | Q5TCQ9 | MAGI3 | Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 3 | 962 |
| 6 | P42336 | PIK3CA | Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha | 949 |
| 7 | P27986 | PIK3R1 | Phosphatidylinositol 3-kinase regulatory subunit alpha | 944 |
| 8 | P15056 | BRAF | Serine/threonine-protein kinase B-raf | 937 |
| 9 | P00533 | EGFR | Epidermal growth factor receptor | 926 |
| 10 | P42345 | MTOR | Serine/threonine-protein kinase mTOR | 923 |
| 11 | Q13485 | SMAD4 | SMAD family member 4 | 909 |
| 12 | P42771 | CDKN2A | Cyclin-dependent kinase inhibitor 2A | 908 |
| 13 | P23443 | RPS6KB1 | Ribosomal protein S6 kinase beta-1 | 904 |
| 14 | Q12959 | DLG1 | Disks large homolog 1 | 904 |
| 15 | P49841 | GSK3B | Glycogen synthase kinase-3 beta | 900 |
| 16 | Q12778 | FOXO1 | Forkhead box protein O1 | 895 |
| 17 | Q13315 | ATM | Serine-protein kinase ATM | 893 |
| 18 | P49815 | TSC2 | Tuberin | 890 |
| 19 | P35222 | CTNNB1 | Catenin beta-1 | 881 |
| 20 | Q6P0Q8 | MASTL | Microtubule-associated serine/threonine-protein kinase 2 | 878 |
| 21 | P51587 | BRCA2 | Breast cancer type 2 susceptibility protein | 877 |
| 22 | P01106 | MYC | Myc proto-oncogene protein | 871 |
| 23 | P04626 | ERBB2 | Receptor tyrosine-protein kinase erbB-2 (HER2) | 864 |
| 24 | P01111 | NRAS | GTPase NRas | 861 |
| 25 | P10275 | AR | Androgen receptor | 853 |
| 26 | P24385 | CCND1 | G1/S-specific cyclin-D1 | 851 |
| 27 | O15530 | PDPK1 | 3-phosphoinositide-dependent protein kinase 1 | 848 |
| 28 | P12830 | CDH1 | Cadherin-1 | 844 |
| 29 | Q9BT92 | KLHL22 | Trichoplein keratin filament-binding protein | 841 |
| 30 | P08069 | SP1 | Specificity protein 1 | 839 |
Key interaction types (IntAct/BioGRID):
- High-confidence physical associations: NHERF1 (0.830), FRK (0.640), CDC27 (0.620), NEDD4 (0.590)
- Experimental systems: Affinity Capture-MS, Affinity Capture-Western, Phosphorylation reactions, Co-localization
Protein Structural & Embedding Similarity
Structural Similarity (DIAMOND - sequence identity/bitscore): TOP 20 similar proteins:
| Rank | UniProt | Protein Name | Identity (%) | Bitscore |
|---|---|---|---|---|
| 1 | Q9HBL0 | Tensin-1 | 90.0 | 3,186 |
| 2 | Q9GLM4 | Tensin-1 | 90.0 | 3,165 |
| 3 | Q99KY4 | PTEN-related phosphatase | 96.7 | 2,504 |
| 4 | E9Q0S6 | PTEN variant | 85.2 | 2,935 |
| 5 | Q5SSZ5 | PTEN-like phosphatase | 83.1 | 2,375 |
| 6 | Q68CZ2 | Tensin-3 | 83.0 | 2,368 |
| 7 | O08586 | PTEN (mouse) | 99.8 | 827 |
| 8 | O54857 | PTEN (rat) | 99.8 | 825 |
| 9 | P60483 | PTEN isoform | 100.0 | 828 |
| 10 | P60484 | PTEN (human) | 100.0 | 828 |
| 11 | Q4R6N0 | PTEN-related | 90.2 | 811 |
| 12 | P56180 | TPTE (tyrosine-protein phosphatase) | 87.6 | 801 |
| 13 | Q6XPS3 | TPTE2 (PTEN homolog) | 96.9 | 814 |
| 14 | Q8H106 | PTEN-related | 58.7 | 613 |
| 15 | Q5B323 | Phosphatase-related | 50.7 | 413 |
| 16 | Q9FLZ5 | PTEN-related | 50.8 | 201 |
| 17 | Q54JL7 | Invertebrate PTEN homolog | 45.0 | 162 |
| 18 | Q86IL4 | PTEN-like | 43.6 | 157 |
| 19 | Q8T9S7 | PTEN variant | 52.0 | 234 |
| 20 | Q9PUT6 | PTEN isoform | 88.9 | 713 |
Protein Embedding Similarity (ESM2 - deep learning embeddings): TOP 20 similar proteins:
| Rank | UniProt | Protein Name | Max Similarity | Avg Similarity |
|---|---|---|---|---|
| 1 | Q13613 | MTMR1 (phosphatidylinositol-3-phosphatase) | 0.9978 | 0.9690 |
| 2 | Q9Z2C4 | PTEN-like phosphatase | 0.9978 | 0.9711 |
| 3 | Q13614 | MTMR2 (3,5-bisphosphatase) | 0.9995 | 0.9504 |
| 4 | B4GBN7 | PTEN ortholog | 1.0000 | 0.9517 |
| 5 | O08586 | PTEN (mouse) | 1.0000 | 0.9573 |
| 6 | O54857 | PTEN (rat) | 1.0000 | 0.9579 |
| 7 | P60483 | PTEN isoform | 1.0000 | 0.9573 |
| 8 | O55236 | PTEN-related | 0.9994 | 0.9627 |
| 9 | O60942 | mRNA-capping enzyme | 0.9994 | 0.9616 |
| 10 | Q16667 | CDKN3 (cyclin-dependent kinase inhibitor 3) | 0.9974 | 0.9497 |
| 11 | Q290L5 | PTEN-related | 1.0000 | 0.9517 |
| 12 | B4HQ29 | PTEN variant | 0.9998 | 0.9480 |
| 13 | B4P4K8 | PTEN ortholog | 0.9997 | 0.9488 |
| 14 | A6QLT2 | PTEN-related | 0.9995 | 0.9519 |
| 15 | B2RZ50 | PTEN-related | 0.9981 | 0.9530 |
| 16 | Q9MYN5 | PTEN-like phosphatase | 0.9981 | 0.9521 |
| 17 | Q9PUT6 | PTEN isoform | 0.9924 | 0.9630 |
| 18 | Q5ZIV1 | PTEN-related | 0.9920 | 0.9386 |
| 19 | Q810P3 | PTEN-related | 0.9944 | 0.9568 |
| 20 | Q5REB9 | PTEN-related | 0.9995 | 0.9531 |
Network Insights:
- PI3K/AKT/mTOR pathway: PTEN is a critical negative regulator, directly interacting with PIK3CA, PIK3R1, AKT1, MTOR
- Tumor suppressors: Strong interactions with TP53, CDKN2A (p16), BRCA2
- Phosphatases: Structural homology with TPTE, TPTE2, MTMR proteins (phosphoinositide 3-phosphatase family)
- Scaffolding proteins: Interactions with MAGI2, MAGI3, DLG1 (membrane organization)
- Cell cycle/Growth: FOXO1, GSK3B, CCND1, BRAF (signaling cross-talk)
Transcription factor regulatory data
PTEN is not a transcription factor. PTEN (phosphatase and tensin homolog) is a dual-specificity protein phosphatase, not a DNA-binding transcription factor. Therefore, downstream targets and DNA-binding motif analyses are not applicable.
Upstream regulators of PTEN
PTEN expression is regulated by 50+ transcription factors (documented in CollectRI database). Key upstream regulators with evidence:
High-confidence activators:
- EGR1 — Activation (ExTRI, TRRUST, GEREDB, NTNU Curated, DoRothEA_A; 20 PubMed links)
- PPARG — Activation (DoRothEA_A, ExTRI, TRRUST, NTNU Curated; 12 PubMed links)
- AR (Androgen Receptor) — Activation (ExTRI, TRRUST; 8 PubMed links)
High-confidence repressors:
- TP53 — Repression (ExTRI, TRRUST, TFactS, DoRothEA_A; 17 PubMed links)
- HES1 — Repression (ExTRI, TRRUST, Pavlidis2021; 9 PubMed links)
Additional regulators (50+ total in database): CTNNB1, ESR2, HIF1A, GRHL3, GLI2, HNF4A, APEX1, APP, GATA4, EPAS1, EZH2, FOXC1, ATF2, BMI1, ID1, HOXA9, DNMT1, GATA2, VDR, YY1, JUN, KAT7, TSC22D1, KDM5A, KDM5C, MTA1, TP73, TP63, MYC, MYT1, NFATC1, NFATC4, TFAP2A, NFKB1, TET1, TCF4, TBX3, STAT3, NR2E1, SREBF1, SP1, SNAI1, and others.
Evidence sources: ExTRI (experimentally validated), TRRUST (manually curated literature), TFactS, DoRothEA (computationally predicted), GEREDB, NTNU Curated, HTRI, Pavlidis2021.
Drug & pharmacology data
PTEN is not a current drug target in clinical development.
Summary:
ChEMBL molecules targeting PTEN: 3 compounds total, all in preclinical phase (phase 0)
- CHEMBL2000194: (E)-3-(3-stibonophenyl)acrylic acid
- CHEMBL2057662: 3-(3-stibonophenyl)propanoic acid
- CHEMBL301982: Celastrol (natural product, has 2 clinical trials but not as a PTEN inhibitor)
Clinical trials: No active clinical trials targeting PTEN directly
Pharmacogenomics: No drug-gene interaction data found for PTEN-targeting therapeutics
Context:
PTEN is a tumor suppressor phosphatase typically lost or mutated in cancers rather than targeted for inhibition. Clinical strategies for PTEN-altered tumors focus on downstream PI3K/AKT pathway inhibition rather than direct PTEN modulation. The minimal molecule data reflects early-stage research rather than therapeutic development.
Expression profiles
Tissue expression (Bgee)
PTEN is ubiquitous with high expression across 256 tissue/cell-type conditions (average score: 94.1, max: 99.31).
| Rank | Tissue/Cell Type | Expression Score | Quality |
|---|---|---|---|
| 1 | Sperm | 99.31 | Gold |
| 2 | Endothelial cell | 99.21 | Gold |
| 3 | Calcaneal tendon | 99.20 | Gold |
| 4 | Upper arm skin | 99.15 | Gold |
| 5 | Epithelial cell of pancreas | 99.00 | Gold |
| 6 | Kidney epithelium | 98.91 | Gold |
| 7 | Middle temporal gyrus | 98.68 | Gold |
| 8 | Parietal pleura | 98.62 | Gold |
| 9 | Ileal mucosa | 98.56 | Gold |
| 10 | Cardiac muscle of right atrium | 98.40 | Gold |
| 11 | Visceral pleura | 98.29 | Gold |
| 12 | Gingival epithelium | 98.06 | Gold |
| 13 | Gingiva | 98.00 | Gold |
| 14 | Brodmann area 23 (brain) | 98.00 | Gold |
| 15 | Pancreatic ductal cell | 98.00 | Gold |
| 16 | Tibialis anterior muscle | 97.93 | Gold |
| 17 | Epithelium of mammary gland | 97.87 | Gold |
| 18 | Mammary duct | 97.87 | Gold |
| 19 | Blood | 97.86 | Gold |
| 20 | Dorsal root ganglion | 97.84 | Gold |
| 21 | Germinal epithelium of ovary | 97.84 | Gold |
| 22 | Trigeminal ganglion | 97.76 | Gold |
| 23 | Tibia (bone) | 97.71 | Gold |
| 24 | Stromal cell of endometrium | 97.60 | Gold |
| 25 | Esophagus squamous epithelium | 97.59 | Gold |
| 26 | Mammalian vulva | 97.47 | Gold |
| 27 | Superficial temporal artery | 97.45 | Gold |
| 28 | Pericardium | 97.43 | Gold |
| 29 | Trabecular bone tissue | 97.39 | Gold |
| 30 | Thoracic mammary gland | 97.32 | Gold |
Pattern: High expression in reproductive tissues (sperm), endothelial cells, connective tissues (tendons, bone), skin, and pancreatic epithelium. High expression in neural tissues (brain, ganglia) and tissues rich in epithelial cell populations.
Single-cell RNA-seq datasets (SCXA)
PTEN is expressed across multiple tissue contexts in large single-cell atlases:
| Dataset | Accession | Tissue | Condition | Cells | PTEN status |
|---|---|---|---|---|---|
| Human hypertrophied heart atlas | E-MTAB-11268 | Heart left ventricle | Aortic stenosis | 64,898 | Expressed in cardiac cell populations (cluster 3; score: 62.41) |
| Human pancreatic islets | E-ENAD-27 | Islet of Langerhans | Type 2 diabetes | 1,145 | Expressed in beta cells/islet populations (cluster 2; score: 14.85) |
| Retinal organoids | E-MTAB-11121 | Retina (in vitro) | Differentiation | 22,253 | Present in retinal cell lineages |
| Bone marrow differentiation | E-CURD-6 | Bone marrow | Normal | 1,024 | Expressed in hematopoietic context |
| Pancreatic islets (diabetic) | E-GEOD-81608 | Islet of Langerhans | Type 2 diabetes | 1,600 | Present in islet populations |
| Bone marrow stromal cells | E-GEOD-124858 | Bone marrow | Culture time course | 247 | Present in mesenchymal context |
| Multiple myeloma bone marrow | E-GEOD-110499 | Bone marrow | Multiple myeloma | 173 | Present in disease context |
Pattern: PTEN is broadly expressed across cell types in cardiac, pancreatic endocrine, hematopoietic, and neural tissues. Expression detected in both healthy and disease contexts (aortic stenosis, type 2 diabetes, multiple myeloma).
Disease associations
Mendelian / Monogenic Diseases
| Disease Name | Disease IDs | Inheritance | Evidence Level | Notes |
|---|---|---|---|---|
| Cowden syndrome 1 | OMIM 158350, Orphanet 201, Mondo 0008021 | Autosomal dominant | Definitive, Strong, Moderate (multiple submissions) | Most well-characterized PTEN-associated disorder; multiple independent curators confirm causality |
| PTEN hamartoma tumor syndrome (PHTS) | Orphanet 306498, Mondo 0017623 | Autosomal dominant | Strong | Umbrella diagnosis for Cowden syndrome spectrum disorders caused by germline PTEN mutations |
| Macrocephaly-autism syndrome | OMIM 605309, Orphanet 210548, Mondo 0011537 | Autosomal dominant | Strong, Supportive | Characterized by macrocephaly, developmental delay, autism spectrum features |
| Bannayan-Riley-Ruvalcaba syndrome (BRRS) | Orphanet 109, Mondo 0007924 | Autosomal dominant | Supportive | Classified as PHTS spectrum; presents with lipomas, macrocephaly, vascular malformations |
| Lhermitte-Duclos disease | Orphanet 65285, Mondo 0019002 | Autosomal dominant | Supportive | Cerebellar dysplastic gangliocytoma; part of Cowden syndrome spectrum |
| Proteus-like syndrome | Orphanet 2969, Mondo 0017571 | Autosomal dominant | Supportive | Segmental overgrowth with PTEN somatic or germline mutations |
| Glioma susceptibility 2 | OMIM 613028, Mondo 0013092 | Autosomal dominant | Limited | PTEN mutations increase glioma predisposition |
| Activated PI3K-delta syndrome (APDS) | Orphanet 397596 | Autosomal dominant | Supportive | Immunodeficiency with PTEN dysfunction |
| Renal cell carcinoma | Mondo 0005086 | Autosomal dominant | Moderate | Associated with PTEN loss |
| Leiomyosarcoma | Mondo 0005058 | Autosomal recessive | Moderate | Rare association with PTEN mutations |
Phenotype Associations (HPO Terms - Top 30)
| HPO Term | HPO ID | Clinical Feature |
|---|---|---|
| Autosomal dominant inheritance | HP:0000006 | Inheritance pattern |
| Macrocephaly | HP:0000256 | Increased head circumference |
| Intellectual disability | HP:0001249 | Cognitive developmental delay |
| Autism | HP:0000717 | Autism spectrum disorder |
| Overgrowth | HP:0001548 | Increased body size |
| Hydrocephalus | HP:0000238 | Cerebrospinal fluid accumulation |
| Multiple lipomas | HP:0001012 | Benign fatty tumors |
| Hemangioma | HP:0001028 | Vascular malformations |
| Seizure | HP:0001250 | Seizure disorder |
| Global developmental delay | HP:0001263 | Developmental impairment |
| Thyroid adenoma | HP:0000854 | Thyroid neoplasm |
| Polycystic ovaries | HP:0000147 | Ovarian cysts |
| Tall stature | HP:0000098 | Increased height |
| Melanocytic nevus | HP:0000995 | Pigmented skin lesions |
| Cafe-au-lait spot | HP:0000957 | Light-brown skin patches |
| Abnormality of the thyroid gland | HP:0000820 | Thyroid involvement |
| Ataxia | HP:0001251 | Cerebellar dysfunction |
| Hypothyroidism | HP:0000821 | Thyroid hormone deficiency |
| Subcutaneous lipoma | HP:0001031 | Benign fatty tumor |
| Telangiectasia | HP:0001009 | Small vessel dilation |
| Cataract | HP:0000518 | Lens opacity |
| Hypotonia | HP:0001252 | Muscle tone reduction |
| Motor delay | HP:0001270 | Delayed motor development |
| Abnormal bleeding | HP:0001892 | Bleeding disorder |
| Anemia | HP:0001903 | Reduced red blood cells |
| Obesity | HP:0001513 | Increased body weight |
| Hypertelorism | HP:0000316 | Widely-spaced eyes |
| Mandibular prognathia | HP:0000303 | Protruding chin |
| Broad forehead | HP:0000337 | Facial feature |
| Delayed speech and language development | HP:0000750 | Speech delay |
Complex Disease / GWAS Associations (Top 30)
| Trait/Disease | Variant/Region | P-value | Associated Gene(s) | Clinical Relevance |
|---|---|---|---|---|
| Eosinophil count | PTEN | 2.0e-30 | PTEN | Hematologic trait |
| Mean reticulocyte volume | PTEN | 9.0e-28 | PTEN | Blood cell parameter |
| Eosinophil percentage of white cells | PTEN | 5.0e-28 | PTEN | Immune cell proportion |
| Neutrophil count | PTEN | 7.0e-21 | PTEN | White blood cell subset |
| Red blood cell count | PTEN | 3.0e-16 | PTEN | Hematologic trait |
| Mean corpuscular hemoglobin | PTEN | 2.0e-14 | PTEN | Blood cell parameter |
| Eosinophil percentage of granulocytes | PTEN | 7.0e-12 | PTEN | White blood cell proportion |
| Eosinophil count | PTEN | 7.0e-12 | PTEN | White blood cell count |
| Mean corpuscular volume | PTEN | 6.0e-12 | PTEN | Blood cell size |
| Mean corpuscular volume | PTEN | 1.0e-14 | PTEN | Blood cell parameter |
| White blood cell count | PTEN | 8.0e-20 | PTEN | Immune cell count |
| Platelet count | PTEN | 1.0e-11 | PTEN | Thrombocyte count |
| Mean spheric corpuscular volume | PTEN | 8.0e-11 | PTEN | Blood cell parameter |
| Lymphocyte percentage of white cells | PTEN | 1.0e-10 | PTEN | Immune cell proportion |
| White blood cell count (basophil) | PTEN | 2.0e-10 | PTEN | Basophil enumeration |
| Type 2 diabetes | PTEN | 4.0e-10 | PTEN | Metabolic disease |
| Neutrophil percentage of white cells | PTEN | 6.0e-09 | PTEN | Granulocyte proportion |
| Plateletcrit | PTEN | 3.0e-09 | PTEN | Platelet proportion |
| Alanine aminotransferase levels | PTEN - MED6P1 | 6.0e-09 | PTEN/MED6P1 | Liver enzyme |
| Waist-to-hip ratio adjusted for BMI | PTEN | 2.0e-09 | PTEN | Metabolic trait |
| Waist-hip index | PTEN | 2.0e-09 | PTEN | Anthropometric measure |
| Pulse pressure | PTEN - MED6P1 | 2.0e-09 | PTEN/MED6P1 | Cardiovascular trait |
| Neutrophil percentage of granulocytes | PTEN | 5.0e-09 | PTEN | Immune cell proportion |
| Liver enzyme levels (alanine transaminase) | PTEN - MED6P1 | 2.0e-11 | PTEN/MED6P1 | Hepatic function |
| Ambidextrousness | PTEN | 2.0e-08 | PTEN | Neurologic trait |
| Birth weight | MED6P1 - RNLS | 2.0e-08 | MED6P1/RNLS | Developmental parameter |
| Psoriasis | MED6P1 - RNLS | 3.0e-08 | MED6P1/RNLS | Autoimmune skin disease |
| Type 2 diabetes (adjusted for BMI) | PTEN - MED6P1 | 5.0e-08 | PTEN/MED6P1 | Metabolic disease |
| Thyroid stimulating hormone levels | MED6P1 - RNLS | 2.0e-10 | MED6P1/RNLS | Thyroid function |
| Periodontitis (mean PAL) | PTEN - MED6P1 | 3.0e-06 | PTEN/MED6P1 | Periodontal disease |
Note: GWAS associations represent common variants of small effect size in population studies, distinct from the Mendelian diseases caused by damaging PTEN mutations. The strongest GWAS signals are in hematologic and metabolic traits. PTEN appears on chromosome 10 (chr10) in all GWAS associations listed.