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Kinase Fusion Gene:WNK3_TNFRSF10D |
Kinase Fusion Protein Summary |
Kinase Fusion gene summary |
Kinase Fusion partner gene information | Kinase Fusion gene name: WNK3_TNFRSF10D | KinaseFusionDB ID: KFG7173 | FusionGDB2.0 ID: KFG7173 | Hgene | Tgene | Gene symbol | WNK3 | TNFRSF10D | Gene ID | 65267 | 8793 | |
Gene name | WNK lysine deficient protein kinase 3 | TNF receptor superfamily member 10d | ||||||||||
Synonyms | MRXS2|PRKWNK3|PRS | CD264|DCR2|TRAIL-R4|TRAILR4|TRUNDD | ||||||||||
Cytomap | Xp11.22 | 8p21.3 | ||||||||||
Type of gene | protein-coding | protein-coding | ||||||||||
Description | serine/threonine-protein kinase WNK3Prieto X-linked mental retardation syndromeprotein kinase with no lysine 3 | tumor necrosis factor receptor superfamily member 10DTNF receptor-related receptor for TRAILTNF-related apoptosis-inducing ligand receptor 4TRAIL receptor 4TRAIL receptor with a truncated death domaindecoy receptor 2tumor necrosis factor receptor su | ||||||||||
Modification date | 20240305 | 20240411 | ||||||||||
UniProtAcc | Q9BYP7 | Q9UBN6 | ||||||||||
Ensembl transtripts involved in fusion gene | ENST ids | ENST00000354646, ENST00000375159, ENST00000375169, | ENST00000312584, | |||||||||
Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: WNK3 [Title/Abstract] AND TNFRSF10D [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | WNK3(54285549)-TNFRSF10D(22995183), # samples:1 |
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 | WNK3 | GO:0006884 | cell volume homeostasis | 36318922 |
Hgene | WNK3 | GO:0010765 | positive regulation of sodium ion transport | 16275913 |
Hgene | WNK3 | GO:0010800 | positive regulation of peptidyl-threonine phosphorylation | 16275913 |
Hgene | WNK3 | GO:0032414 | positive regulation of ion transmembrane transporter activity | 16275913 |
Hgene | WNK3 | GO:0046777 | protein autophosphorylation | 16275913 |
Hgene | WNK3 | GO:0071474 | cellular hyperosmotic response | 36318922 |
Hgene | WNK3 | GO:0140694 | non-membrane-bounded organelle assembly | 36318922 |
Hgene | WNK3 | GO:1903077 | negative regulation of protein localization to plasma membrane | 17673510 |
Hgene | WNK3 | GO:1903078 | positive regulation of protein localization to plasma membrane | 16275913 |
Hgene | WNK3 | GO:2000651 | positive regulation of sodium ion transmembrane transporter activity | 16275913 |
Kinase Fusion gene breakpoints across WNK3 (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 TNFRSF10D (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 |
ChiTaRS5.0 | AI821853 | WNK3 | chrX | 54285549 | TNFRSF10D | chr8 | 22995183 |
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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/:54285549/:22995183) - 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. |
Main function of each fusion partner protein. (from UniProt) |
Hgene | Tgene |
WNK3 | TNFRSF10D |
FUNCTION: Serine/threonine-protein kinase component of the WNK3-SPAK/OSR1 kinase cascade, which plays an important role in the regulation of electrolyte homeostasis and regulatory volume increase in response to hyperosmotic stress (PubMed:16275911, PubMed:16275913, PubMed:16501604, PubMed:22989884, PubMed:36318922). WNK3 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 WNK3 with its substrates, OXSR1/OSR1 and STK39/SPAK, promoting WNK3-dependent phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK (PubMed:22989884). Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A3/NCC, SLC12A4/KCC1, SLC12A5/KCC2 or SLC12A6/KCC3, regulating their activity (PubMed:16275911, PubMed:16275913). Phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion influx; simultaneously, phosphorylation of K-Cl cotransporters SLC12A4/KCC1, SLC12A5/KCC2 and SLC12A6/KCC3 inhibits its activity, blocking ion efflux (PubMed:16275911, PubMed:16275913, PubMed:16357011, PubMed:19470686, PubMed:21613606). Phosphorylates WNK4, possibly regulating the activity of SLC12A3/NCC (PubMed:17975670). May also phosphorylate NEDD4L (PubMed:20525693). Also acts as a scaffold protein independently of its protein kinase activity: negatively regulates cell membrane localization of various transporters and channels, such as KCNJ1 and SLC26A9 (PubMed:16357011, PubMed:17673510). Increases Ca(2+) influx mediated by TRPV5 and TRPV6 by enhancing their membrane expression level via a kinase-dependent pathway (PubMed:18768590). {ECO:0000269|PubMed:16275911, ECO:0000269|PubMed:16275913, ECO:0000269|PubMed:16357011, ECO:0000269|PubMed:16501604, ECO:0000269|PubMed:17673510, ECO:0000269|PubMed:17975670, ECO:0000269|PubMed:18768590, ECO:0000269|PubMed:19470686, ECO:0000269|PubMed:20525693, ECO:0000269|PubMed:21613606, ECO:0000269|PubMed:22989884, ECO:0000269|PubMed:36318922}. | FUNCTION: Receptor for the cytotoxic ligand TRAIL (PubMed:9430226). Contains a truncated death domain and hence is not capable of inducing apoptosis but protects against TRAIL-mediated apoptosis (PubMed:9537512). Reports are contradictory with regards to its ability to induce the NF-kappa-B pathway. According to PubMed:9382840, it cannot but according to PubMed:9430226, it can induce the NF-kappa-B pathway (PubMed:9382840, PubMed:9430226). {ECO:0000269|PubMed:9382840, ECO:0000269|PubMed:9430226, ECO:0000269|PubMed:9537512}. |
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 WNK3_TNFRSF10D |
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 |
WNK3 | Q9BYP7 | human | WNK1 | Q9H4A3 | S382 | kRAsFAKsVIGTPEF | Pkinase |
WNK3 | Q9BYP7 | human | SLC12A6 | Q9UHW9 | T991 | SAYTYERtLMMEQRS | SLC12 |
WNK3 | Q9BYP7 | human | SLC12A6 | Q9UHW9 | T1048 | YQEKVHMtWTKDKYM | SLC12 |
WNK3 | Q9BYP7 | human | SLC12A6 | Q9UHW9 | S96 | IEDLSQNsITGEHSQ |
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 |
WNK3 | ID | Description | 0.00e+00 |
WNK3 | GO:0055064 | chloride ion homeostasis | 1.14e-04 |
WNK3 | GO:0055081 | monoatomic anion homeostasis | 1.14e-04 |
WNK3 | GO:0055075 | potassium ion homeostasis | 1.61e-04 |
WNK3 | GO:0006884 | cell volume homeostasis | 1.61e-04 |
WNK3 | GO:0071470 | cellular response to osmotic stress | 2.88e-04 |
WNK3 | GO:0006970 | response to osmotic stress | 5.85e-04 |
WNK3 | GO:0008361 | regulation of cell size | 2.69e-03 |
WNK3 | GO:0062197 | cellular response to chemical stress | 6.03e-03 |
WNK3 | GO:0071214 | cellular response to abiotic stimulus | 6.03e-03 |
WNK3 | GO:0104004 | cellular response to environmental stimulus | 6.03e-03 |
WNK3 | GO:0032535 | regulation of cellular component size | 6.73e-03 |
WNK3 | GO:0030002 | intracellular monoatomic anion homeostasis | 1.02e-02 |
WNK3 | GO:0030644 | intracellular chloride ion homeostasis | 1.02e-02 |
WNK3 | GO:0030157 | pancreatic juice secretion | 1.02e-02 |
WNK3 | GO:0033632 | regulation of cell-cell adhesion mediated by integrin | 1.02e-02 |
WNK3 | GO:0034115 | negative regulation of heterotypic cell-cell adhesion | 1.02e-02 |
WNK3 | GO:0045050 | protein insertion into ER membrane by stop-transfer membrane-anchor sequence | 1.02e-02 |
WNK3 | GO:0070587 | regulation of cell-cell adhesion involved in gastrulation | 1.02e-02 |
WNK3 | GO:0071476 | cellular hypotonic response | 1.02e-02 |
WNK3 | GO:1902412 | regulation of mitotic cytokinesis | 1.02e-02 |
WNK3 | GO:0003084 | positive regulation of systemic arterial blood pressure | 1.02e-02 |
WNK3 | GO:0033629 | negative regulation of cell adhesion mediated by integrin | 1.02e-02 |
WNK3 | GO:0070586 | cell-cell adhesion involved in gastrulation | 1.02e-02 |
WNK3 | GO:0072488 | ammonium transmembrane transport | 1.02e-02 |
WNK3 | GO:0006971 | hypotonic response | 1.02e-02 |
WNK3 | GO:0046831 | regulation of RNA export from nucleus | 1.02e-02 |
WNK3 | GO:0060457 | negative regulation of digestive system process | 1.02e-02 |
WNK3 | GO:0071472 | cellular response to salt stress | 1.02e-02 |
WNK3 | GO:0010820 | positive regulation of T cell chemotaxis | 1.02e-02 |
WNK3 | GO:0006369 | termination of RNA polymerase II transcription | 1.02e-02 |
WNK3 | GO:0010819 | regulation of T cell chemotaxis | 1.02e-02 |
WNK3 | GO:0032239 | regulation of nucleobase-containing compound transport | 1.02e-02 |
WNK3 | GO:0033631 | cell-cell adhesion mediated by integrin | 1.05e-02 |
WNK3 | GO:0071474 | cellular hyperosmotic response | 1.17e-02 |
WNK3 | GO:0140131 | positive regulation of lymphocyte chemotaxis | 1.17e-02 |
WNK3 | GO:0009651 | response to salt stress | 1.29e-02 |
WNK3 | GO:0034114 | regulation of heterotypic cell-cell adhesion | 1.29e-02 |
WNK3 | GO:0034260 | negative regulation of GTPase activity | 1.29e-02 |
WNK3 | GO:1901623 | regulation of lymphocyte chemotaxis | 1.35e-02 |
WNK3 | GO:0006972 | hyperosmotic response | 1.35e-02 |
WNK3 | GO:0010818 | T cell chemotaxis | 1.35e-02 |
WNK3 | GO:1903077 | negative regulation of protein localization to plasma membrane | 1.36e-02 |
WNK3 | GO:0006353 | DNA-templated transcription termination | 1.39e-02 |
WNK3 | GO:1904376 | negative regulation of protein localization to cell periphery | 1.39e-02 |
WNK3 | GO:0045048 | protein insertion into ER membrane | 1.41e-02 |
WNK3 | GO:0045777 | positive regulation of blood pressure | 1.47e-02 |
WNK3 | GO:2000406 | positive regulation of T cell migration | 1.51e-02 |
WNK3 | GO:0043243 | positive regulation of protein-containing complex disassembly | 1.51e-02 |
WNK3 | GO:0044058 | regulation of digestive system process | 1.51e-02 |
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Related Drugs to WNK3_TNFRSF10D |
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 WNK3-TNFRSF10D 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 WNK3_TNFRSF10D |
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 |