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Kinase Fusion Gene:PTEN_WNK1 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: PTEN_WNK1 | KinaseFusionDB ID: KFG5112 | FusionGDB2.0 ID: KFG5112 | Hgene | Tgene | Gene symbol | PTEN | WNK1 | Gene ID | 5728 | 65125 | |
| Gene name | phosphatase and tensin homolog | WNK lysine deficient protein kinase 1 | ||||||||||
| Synonyms | 10q23del|BZS|CWS1|DEC|GLM2|MHAM|MMAC1|PTEN1|PTENbeta|TEP1 | HSAN2|HSN2|KDP|PPP1R167|PRKWNK1|PSK|p65 | ||||||||||
| Cytomap | 10q23.31 | 12p13.33 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTENMMAC1 phosphatase and tensin homolog deleted on chromosome 10PTEN variant PTEN-K267Rfs*9PTEN variant PTEN-L247*PTEN variant PTEN-R234Afs*11PTENepsilon | serine/threonine-protein kinase WNK1erythrocyte 65 kDa proteinprostate-derived sterile 20-like kinaseprotein kinase with no lysine 1protein phosphatase 1, regulatory subunit 167serine/threonine-protein kinase WNK1 1serine/threonine-protein kinase WN | ||||||||||
| Modification date | 20240416 | 20240403 | ||||||||||
| UniProtAcc | P60484 | Q9H4A3 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000371953, ENST00000472832, | ENST00000340908, ENST00000540360, ENST00000574564, ENST00000315939, ENST00000447667, ENST00000530271, ENST00000535572, ENST00000537687, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: PTEN [Title/Abstract] AND WNK1 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | PTEN(89685314)-WNK1(922808), # samples:2 | |||||||||||
| Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Hgene | PTEN | GO:0001933 | negative regulation of protein phosphorylation | 20123964 |
| Hgene | PTEN | GO:0006470 | protein dephosphorylation | 9256433 |
| Hgene | PTEN | GO:0007056 | spindle assembly involved in female meiosis | 31492966 |
| Hgene | PTEN | GO:0008285 | negative regulation of cell population proliferation | 19057511 |
| Hgene | PTEN | GO:0045736 | negative regulation of cyclin-dependent protein serine/threonine kinase activity | 21241890 |
| Hgene | PTEN | GO:0046856 | phosphatidylinositol dephosphorylation | 9811831 |
| Hgene | PTEN | GO:0050821 | protein stabilization | 20123964 |
| Hgene | PTEN | GO:0051898 | negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | 31492966 |
| Hgene | PTEN | GO:0060070 | canonical Wnt signaling pathway | 20123964 |
| Hgene | PTEN | GO:1902807 | negative regulation of cell cycle G1/S phase transition | 10918569 |
| Hgene | PTEN | GO:1904668 | positive regulation of ubiquitin protein ligase activity | 21241890 |
| Hgene | PTEN | GO:2000060 | positive regulation of ubiquitin-dependent protein catabolic process | 21241890 |
| Hgene | PTEN | GO:2000134 | negative regulation of G1/S transition of mitotic cell cycle | 21241890 |
| Tgene | WNK1 | GO:0006468 | protein phosphorylation | 10660600 |
| Tgene | WNK1 | GO:0006884 | cell volume homeostasis | 36318922 |
| Tgene | WNK1 | GO:0007165 | signal transduction | 16669787 |
| Tgene | WNK1 | GO:0010793 | regulation of mRNA export from nucleus | 29196535 |
| Tgene | WNK1 | GO:0031397 | negative regulation of protein ubiquitination | 33964204 |
| Tgene | WNK1 | GO:0035556 | intracellular signal transduction | 10660600 |
| Tgene | WNK1 | GO:0045050 | protein insertion into ER membrane by stop-transfer membrane-anchor sequence | 33964204 |
| Tgene | WNK1 | GO:0071474 | cellular hyperosmotic response | 15883153|17190791|34289367|36318922 |
| Tgene | WNK1 | GO:0140694 | non-membrane-bounded organelle assembly | 36318922 |
| Tgene | WNK1 | GO:1903490 | positive regulation of mitotic cytokinesis | 21220314 |
| Tgene | WNK1 | GO:1904595 | positive regulation of termination of RNA polymerase II transcription | 29196535 |
| Kinase Fusion gene breakpoints across PTEN (5'-gene) * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Kinase Fusion gene breakpoints across WNK1 (3'-gene) * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
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Kinase Fusion Gene Sample Information |
| Kinase Fusion gene information. |
| Kinase Fusion gene information from four resources (ChiTars 5.0, ChimerDB 4.0, COSMIC, and CCLE) * All genome coordinats were lifted-over on hg19. * Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser. |
| Source | Sample | Hgene | Hchr | Hbp | Tgene | Tchr | Tbp |
| ChimerDB4 | TCGA-A1-A0SP-01A | PTEN | chr10 | 89685314 | WNK1 | chr12 | 922808 |
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Kinase Fusion ORF Analysis |
| Kinase Fusion information from ORFfinder translation from full-length transcript sequence from KinaseFusionDB. |
| Henst | Tenst | Hgene | Hchr | Hbp | Tgene | Tchr | Tbp | Seq length (transcript) | Seq length (amino acids) |
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Kinase Fusion Amino Acid Sequences |
| For individual full-length fusion transcript sequence from KinaseFusionDB, we ran ORFfinder and chose the longest ORF among the all predicted ones. |
| >Henst_Tenst_Hgene_Hchr_Hbp_Tgene_Tchr_Tbp_length(fusion AA)_AAseq |
Multiple Sequence Alignment of All Fusion Protein Isoforms |
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Kinase Fusion Protein Functional Features |
| Four levels of functional features of fusion genes Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/:89685314/:922808) - FGviewer provides the online visualization of the retention search of the protein functional features across DNA, RNA, protein, and pathological levels. - How to search 1. Put your fusion gene symbol. 2. Press the tab key until there will be shown the breakpoint information filled. 4. Go down and press 'Search' tab twice. 4. Go down to have the hyperlink of the search result. 5. Click the hyperlink. 6. See the FGviewer result for your fusion gene. |
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| Main function of each fusion partner protein. (from UniProt) |
| Hgene | Tgene |
| PTEN | WNK1 |
| FUNCTION: Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins (PubMed:9187108, PubMed:9256433, PubMed:9616126). Also functions as a lipid phosphatase, removing the phosphate in the D3 position of the inositol ring of PtdIns(3,4,5)P3/phosphatidylinositol 3,4,5-trisphosphate, PtdIns(3,4)P2/phosphatidylinositol 3,4-diphosphate and PtdIns3P/phosphatidylinositol 3-phosphate with a preference for PtdIns(3,4,5)P3 (PubMed:9811831, PubMed:16824732, PubMed:26504226, PubMed:9593664). Furthermore, this enzyme can also act as a cytosolic inositol 3-phosphatase acting on Ins(1,3,4,5,6)P5/inositol 1,3,4,5,6 pentakisphosphate and possibly Ins(1,3,4,5)P4/1D-myo-inositol 1,3,4,5-tetrakisphosphate (PubMed:11418101, PubMed:15979280). Antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival (PubMed:31492966, PubMed:37279284). The unphosphorylated form cooperates with MAGI2 to suppress AKT1 activation (PubMed:11707428). In motile cells, suppresses the formation of lateral pseudopods and thereby promotes cell polarization and directed movement (PubMed:22279049). Dephosphorylates tyrosine-phosphorylated focal adhesion kinase and inhibits cell migration and integrin-mediated cell spreading and focal adhesion formation (PubMed:22279049). Required for growth factor-induced epithelial cell migration; growth factor stimulation induces PTEN phosphorylation which changes its binding preference from the p85 regulatory subunit of the PI3K kinase complex to DLC1 and results in translocation of the PTEN-DLC1 complex to the posterior of migrating cells to promote RHOA activation (PubMed:26166433). Meanwhile, TNS3 switches binding preference from DLC1 to p85 and the TNS3-p85 complex translocates to the leading edge of migrating cells to activate RAC1 activation (PubMed:26166433). Plays a role as a key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation (By similarity). Involved in the regulation of synaptic function in excitatory hippocampal synapses. Recruited to the postsynaptic membrane upon NMDA receptor activation, is required for the modulation of synaptic activity during plasticity. Enhancement of lipid phosphatase activity is able to drive depression of AMPA receptor-mediated synaptic responses, activity required for NMDA receptor-dependent long-term depression (LTD) (By similarity). May be a negative regulator of insulin signaling and glucose metabolism in adipose tissue. The nuclear monoubiquitinated form possesses greater apoptotic potential, whereas the cytoplasmic nonubiquitinated form induces less tumor suppressive ability (PubMed:10468583, PubMed:18716620). {ECO:0000250|UniProtKB:O08586, ECO:0000250|UniProtKB:O54857, ECO:0000269|PubMed:10468583, ECO:0000269|PubMed:11418101, ECO:0000269|PubMed:11707428, ECO:0000269|PubMed:15979280, ECO:0000269|PubMed:16824732, ECO:0000269|PubMed:18716620, ECO:0000269|PubMed:22279049, ECO:0000269|PubMed:26166433, ECO:0000269|PubMed:26504226, ECO:0000269|PubMed:31492966, ECO:0000269|PubMed:37279284, ECO:0000269|PubMed:9187108, ECO:0000269|PubMed:9256433, ECO:0000269|PubMed:9593664, ECO:0000269|PubMed:9616126, ECO:0000269|PubMed:9811831}.; FUNCTION: [Isoform alpha]: Functional kinase, like isoform 1 it antagonizes the PI3K-AKT/PKB signaling pathway. Plays a role in mitochondrial energetic metabolism by promoting COX activity and ATP production, via collaboration with isoform 1 in increasing protein levels of PINK1. {ECO:0000269|PubMed:23744781}. | FUNCTION: Serine/threonine-protein kinase component of the WNK1-SPAK/OSR1 kinase cascade, which acts as a key regulator of blood pressure and regulatory volume increase by promoting ion influx (PubMed:15883153, PubMed:17190791, PubMed:31656913, PubMed:34289367, PubMed:36318922). WNK1 mediates regulatory volume increase in response to hyperosmotic stress by acting as a molecular crowding sensor, which senses cell shrinkage and mediates formation of a membraneless compartment by undergoing liquid-liquid phase separation (PubMed:36318922). The membraneless compartment concentrates WNK1 with its substrates, OXSR1/OSR1 and STK39/SPAK, promoting WNK1-dependent phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK (PubMed:15883153, PubMed:16263722, PubMed:17190791, PubMed:19739668, PubMed:21321328, PubMed:22989884, PubMed:25477473, PubMed:34289367, PubMed:36318922). Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A5/KCC2 and SLC12A6/KCC3, regulating their activity (PubMed:16263722, PubMed:21321328). Phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion influx; simultaneously, phosphorylation of K-Cl cotransporters SLC12A5/KCC2 and SLC12A6/KCC3 inhibit their activity, blocking ion efflux (PubMed:19665974, PubMed:21321328). Also acts as a regulator of angiogenesis in endothelial cells via activation of OXSR1/OSR1 and STK39/SPAK: activation of OXSR1/OSR1 regulates chemotaxis and invasion, while STK39/SPAK regulates endothelial cell proliferation (PubMed:25362046). Also acts independently of the WNK1-SPAK/OSR1 kinase cascade by catalyzing phosphorylation of other substrates, such as SYT2, PCF11 and NEDD4L (PubMed:29196535). Mediates phosphorylation of SYT2, regulating SYT2 association with phospholipids and membrane-binding (By similarity). Regulates mRNA export in the nucleus by mediating phosphorylation of PCF11, thereby decreasing the association between PCF11 and POLR2A/RNA polymerase II and promoting mRNA export to the cytoplasm (PubMed:29196535). Acts as a negative regulator of autophagy (PubMed:27911840). Required for the abscission step during mitosis, independently of the WNK1-SPAK/OSR1 kinase cascade (PubMed:21220314). May also play a role in actin cytoskeletal reorganization (PubMed:10660600). Also acts as a scaffold protein independently of its protein kinase activity: negatively regulates cell membrane localization of various transporters and channels, such as SLC4A4, SLC26A6, SLC26A9, TRPV4 and CFTR (By similarity). Involved in the regulation of epithelial Na(+) channel (ENaC) by promoting activation of SGK1 in a kinase-independent manner: probably acts as a scaffold protein that promotes the recruitment of SGK1 to the mTORC2 complex in response to chloride, leading to mTORC2-dependent phosphorylation and activation of SGK1 (PubMed:36373794). Acts as an assembly factor for the ER membrane protein complex independently of its protein kinase activity: associates with EMC2 in the cytoplasm via its amphipathic alpha-helix, and prevents EMC2 ubiquitination and subsequent degradation, thereby promoting EMC2 stabilization (PubMed:33964204). {ECO:0000250|UniProtKB:P83741, ECO:0000250|UniProtKB:Q9JIH7, ECO:0000269|PubMed:10660600, ECO:0000269|PubMed:15883153, ECO:0000269|PubMed:16263722, ECO:0000269|PubMed:17190791, ECO:0000269|PubMed:19665974, ECO:0000269|PubMed:19739668, ECO:0000269|PubMed:21220314, ECO:0000269|PubMed:21321328, ECO:0000269|PubMed:22989884, ECO:0000269|PubMed:25362046, ECO:0000269|PubMed:25477473, ECO:0000269|PubMed:27911840, ECO:0000269|PubMed:29196535, ECO:0000269|PubMed:31656913, ECO:0000269|PubMed:33964204, ECO:0000269|PubMed:34289367, ECO:0000269|PubMed:36318922, ECO:0000269|PubMed:36373794}.; FUNCTION: [Isoform 3]: Kinase-defective isoform specifically expressed in kidney, which acts as a dominant-negative regulator of the longer isoform 1 (PubMed:14645531). Does not directly inhibit WNK4 and has no direct effect on sodium and chloride ion transport (By similarity). Down-regulates sodium-chloride cotransporter activity indirectly by inhibiting isoform 1, it associates with isoform 1 and attenuates its kinase activity (By similarity). In kidney, may play an important role regulating sodium and potassium balance (By similarity). {ECO:0000250|UniProtKB:Q9JIH7, ECO:0000269|PubMed:14645531}. |
| Retention analysis result of each fusion partner protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained domain in the 5'-partner of fusion protein (protein functional feature from UniProt). |
| Partner | Hgeneene | Hbp | Tgeneene | Tbp | ENST | BPexon | TotalExon | Protein feature loci | BPloci | TotalLen | Feature | Note |
| - Retained domain in the 3'-partner of fusion protein (protein functional feature from UniProt). |
| Partner | Hgeneene | Hbp | Tgeneene | Tbp | ENST | BPexon | TotalExon | Protein feature loci | BPloci | TotalLen | Feature | Note |
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Kinase-Substrate Information of PTEN_WNK1 |
| Phosphorylation target of the kinase (phosphosite, 03-17-2024) |
| Kinase | Kinase UniProt Acc | Kinase species | Substrate | Substrate UniProt Acc | Substrate phosphorylated residues | Substrate phosphorylated sites (+/-7AA) | Domain |
| WNK1 | Q9H4A3 | human | PCF11 | O94913 | S120 | KSLFKLRstWDEIFP | CID |
| WNK1 | Q9H4A3 | human | WNK1 | Q9H4A3 | S382 | kRAsFAKsVIGTPEF | Pkinase |
| WNK1 | Q9H4A3 | human | SLC12A6 | Q9UHW9 | T991 | SAYTYERtLMMEQRS | SLC12 |
| WNK1 | Q9H4A3 | human | OXSR1 | O95747 | S325 | VRRVPGssGRLHKtE | |
| WNK1 | Q9H4A3 | human | OXSR1 | O95747 | T185 | TRNKVRktFVGtPCW | Pkinase |
| WNK1 | Q9H4A3 | human | SLC12A6 | Q9UHW9 | T1048 | YQEKVHMtWTKDKYM | SLC12 |
| WNK1 | Q9H4A3 | human | STK39 | Q9UEW8 | T231 | tRNKVRktFVGtPCW | Pkinase |
| WNK1 | Q9H4A3 | human | PCF11 | O94913 | T121 | SLFKLRstWDEIFPL | CID |
| WNK1 | Q9H4A3 | human | STK39 | Q9UEW8 | S371 | VRRVPGssGHLHKTE |
| Biological Network Integration of This Kinase and Substrates (GeneMANIA website) |
| Enriched GO biological processes of the phosphorylation target genes of the kinase |
| Kinase | GOID | GO term | P.adjust |
| WNK1 | ID | Description | 0.00e+00 |
| WNK1 | GO:0006884 | cell volume homeostasis | 1.28e-08 |
| WNK1 | GO:0071470 | cellular response to osmotic stress | 3.30e-08 |
| WNK1 | GO:0071476 | cellular hypotonic response | 1.01e-07 |
| WNK1 | GO:0006970 | response to osmotic stress | 1.01e-07 |
| WNK1 | GO:0006971 | hypotonic response | 1.32e-07 |
| WNK1 | GO:0010820 | positive regulation of T cell chemotaxis | 1.75e-07 |
| WNK1 | GO:0010819 | regulation of T cell chemotaxis | 1.84e-07 |
| WNK1 | GO:0055064 | chloride ion homeostasis | 2.62e-07 |
| WNK1 | GO:0071474 | cellular hyperosmotic response | 2.62e-07 |
| WNK1 | GO:0140131 | positive regulation of lymphocyte chemotaxis | 2.62e-07 |
| WNK1 | GO:0055081 | monoatomic anion homeostasis | 2.78e-07 |
| WNK1 | GO:1901623 | regulation of lymphocyte chemotaxis | 4.80e-07 |
| WNK1 | GO:0006972 | hyperosmotic response | 4.80e-07 |
| WNK1 | GO:0010818 | T cell chemotaxis | 4.80e-07 |
| WNK1 | GO:0008361 | regulation of cell size | 7.97e-07 |
| WNK1 | GO:2000406 | positive regulation of T cell migration | 9.40e-07 |
| WNK1 | GO:2000403 | positive regulation of lymphocyte migration | 1.55e-06 |
| WNK1 | GO:2000404 | regulation of T cell migration | 2.35e-06 |
| WNK1 | GO:0048247 | lymphocyte chemotaxis | 4.98e-06 |
| WNK1 | GO:0062197 | cellular response to chemical stress | 4.98e-06 |
| WNK1 | GO:2000401 | regulation of lymphocyte migration | 5.33e-06 |
| WNK1 | GO:0071214 | cellular response to abiotic stimulus | 5.33e-06 |
| WNK1 | GO:0104004 | cellular response to environmental stimulus | 5.33e-06 |
| WNK1 | GO:0071677 | positive regulation of mononuclear cell migration | 5.70e-06 |
| WNK1 | GO:0072678 | T cell migration | 5.70e-06 |
| WNK1 | GO:0032535 | regulation of cellular component size | 7.11e-06 |
| WNK1 | GO:0070098 | chemokine-mediated signaling pathway | 1.03e-05 |
| WNK1 | GO:0002690 | positive regulation of leukocyte chemotaxis | 1.17e-05 |
| WNK1 | GO:1990868 | response to chemokine | 1.19e-05 |
| WNK1 | GO:1990869 | cellular response to chemokine | 1.19e-05 |
| WNK1 | GO:0018107 | peptidyl-threonine phosphorylation | 1.19e-05 |
| WNK1 | GO:0018210 | peptidyl-threonine modification | 1.54e-05 |
| WNK1 | GO:0030002 | intracellular monoatomic anion homeostasis | 1.92e-05 |
| WNK1 | GO:0030644 | intracellular chloride ion homeostasis | 1.92e-05 |
| WNK1 | GO:0072676 | lymphocyte migration | 2.01e-05 |
| WNK1 | GO:0071675 | regulation of mononuclear cell migration | 2.01e-05 |
| WNK1 | GO:0002688 | regulation of leukocyte chemotaxis | 2.01e-05 |
| WNK1 | GO:0030157 | pancreatic juice secretion | 2.10e-05 |
| WNK1 | GO:0070294 | renal sodium ion absorption | 2.83e-05 |
| WNK1 | GO:0050921 | positive regulation of chemotaxis | 2.83e-05 |
| WNK1 | GO:0002687 | positive regulation of leukocyte migration | 3.00e-05 |
| WNK1 | GO:0060457 | negative regulation of digestive system process | 3.14e-05 |
| WNK1 | GO:0003096 | renal sodium ion transport | 3.95e-05 |
| WNK1 | GO:0006369 | termination of RNA polymerase II transcription | 3.95e-05 |
| WNK1 | GO:0071674 | mononuclear cell migration | 7.34e-05 |
| WNK1 | GO:0071805 | potassium ion transmembrane transport | 8.27e-05 |
| WNK1 | GO:0002685 | regulation of leukocyte migration | 9.59e-05 |
| WNK1 | GO:0050920 | regulation of chemotaxis | 9.59e-05 |
| WNK1 | GO:1901017 | negative regulation of potassium ion transmembrane transporter activity | 9.59e-05 |
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Related Drugs to PTEN_WNK1 |
| Drugs used for this fusion-positive patient. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
| Hgene | Tgene | Drug | Source | PMID |
| Distribution of the number of studies mentioning PTEN-WNK1 and kinase inhibitors the PubMed Abstract (04-01-2024) |
| Fusion gene - drug pair 1 | Fusion gene - drug pair 2 | PMID | Publication date | DOI | Study title |
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Related Diseases to PTEN_WNK1 |
| Diseases that have this fusion gene. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
| Hgene | Tgene | Disease | Source | PMID |
| Related diseases from the literature mentioned this fusion gene and drug. (PubMed, 04-01-2024) |
| MeSH ID | MeSH term |
| Diseases associated with fusion partners. (DisGeNet 4.0) |
| Partner | Gene | Disease ID | Disease name | # pubmeds | Source |
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Clinical Trials of the Found Drugs/Small Molecules |
| Statistics of the Clinical Trials of the Found Kinase Inibitors from clinicaltrials.gov (06-17-2024) |
| Clinical Trials from clinicaltrials.gov (06-17-2024) |
| Fusion Gene | Kinase Inhibitor | NCT ID | Study Status | Phases | Disease | # Enrolment | Date |
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