This gene was identified as a tumor suppressor that is mutated in a large number of cancers at high frequency. The protein encoded by this gene is a phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase. It contains a tensin like domain as well as a catalytic domain similar to that of the dual specificity protein tyrosine phosphatases. Unlike most of the protein tyrosine phosphatases, this protein preferentially dephosphorylates phosphoinositide substrates. It negatively regulates intracellular levels of phosphatidylinositol-3,4,5-trisphosphate in cells and functions as a tumor suppressor by negatively regulating AKT/PKB signaling pathway. The use of a non-canonical (CUG) upstream initiation site produces a longer isoform that initiates translation with a leucine, and is thought to be preferentially associated with the mitochondrial inner membrane. This longer isoform may help regulate energy metabolism in the mitochondria. A pseudogene of this gene is found on chromosome 9. Alternative splicing and the use of multiple translation start codons results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2015]
Transcription factors with Perturb-seq knockdown data for PTEN. The Binding column indicates whether any binding evidence exists for this TF–gene pair (ChIP-seq or motif footprint peaks). The Mean coef is the average Perturb-seq regression coefficient across active gRNAs (positive = PTEN upregulated upon KD; negative = downregulated). The Outlier column indicates whether this gene is in the top or bottom 5% of all TF knockdown effects.
| TF | Mean coef | Binding | Outlier | TF→Gene link |
|---|
Open chromatin peaks (ATAC-seq) in the genomic neighbourhood of PTEN, linked by TSS proximity or chromatin conformation (Multiome / HiCAR). Each element overlaps at least one TF ChIP-seq binding site — the TFs column shows how many distinct TFs bind that element.
| Accessibility | Element | Dist. to TSS | Link type | TFs |
|---|---|---|---|---|
| chr10:87,658,548–87,660,459 | 203.7 kb | Distal (>10kb) Multiome | 507 | |
| chr10:87,734,828–87,735,531 | 128.4 kb | Distal (>10kb) Multiome | 289 | |
| chr10:87,817,687–87,819,379 | 45.4 kb | Distal (>10kb) Multiome | 867 | |
| chr10:87,860,244–87,860,476 | 3.1 kb | Proximal (<10kb) | 165 | |
| chr10:87,861,521–87,864,430 | 62 bp | At TSS Multiome | 1208 | |
| chr10:87,915,332–87,915,810 | 52.0 kb | Distal (>10kb) Multiome | 128 | |
| chr10:88,121,996–88,122,828 | 258.8 kb | Distal (>10kb) Multiome | 132 | |
| chr10:88,243,697–88,244,508 | 380.3 kb | Distal (>10kb) Multiome HiCAR | 165 | |
| chr10:88,371,648–88,372,566 | 508.6 kb | Distal (>10kb) Multiome HiCAR | 115 | |
| chr10:88,375,677–88,376,274 | 512.4 kb | Distal (>10kb) Multiome HiCAR | 61 | |
| chr10:88,582,470–88,583,714 | 719.5 kb | Distal (>10kb) Multiome HiCAR | 465 |
Genomic view of the PTEN locus showing ATAC-seq accessibility and RNA-seq expression across the ESC → DE time course, together with TF binding peaks and element-to-TSS loop connections.