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Kinase Fusion Gene:WNK4_MT1G |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: WNK4_MT1G | KinaseFusionDB ID: KFG7174 | FusionGDB2.0 ID: KFG7174 | Hgene | Tgene | Gene symbol | WNK4 | MT1G | Gene ID | 65266 | 4495 | |
| Gene name | WNK lysine deficient protein kinase 4 | metallothionein 1G | ||||||||||
| Synonyms | PHA2B|PRKWNK4 | MT1|MT1K | ||||||||||
| Cytomap | 17q21.2 | 16q13 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | serine/threonine-protein kinase WNK4protein kinase lysine-deficient 4protein kinase with no lysine 4 | metallothionein-1GMT-1GMT-1KMT-IGmetallothionein-1Kmetallothionein-IG | ||||||||||
| Modification date | 20240407 | 20240416 | ||||||||||
| UniProtAcc | Q96J92 | P13640 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000246914, ENST00000587705, | ENST00000379811, ENST00000444837, ENST00000568675, ENST00000569500, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: WNK4 [Title/Abstract] AND MT1G [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | WNK4(40939214)-MT1G(56701936), # samples:3 | |||||||||||
| 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 |
| Tgene | MT1G | GO:0045926 | negative regulation of growth | 18332874 |
| Tgene | MT1G | GO:0071294 | cellular response to zinc ion | 7559655 |
| Kinase Fusion gene breakpoints across WNK4 (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 MT1G (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 | DD229468 | WNK4 | chr17 | 40939214 | MT1G | chr16 | 56701936 |
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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/:40939214/:56701936) - 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 |
| WNK4 | MT1G |
| FUNCTION: Serine/threonine-protein kinase component of the WNK4-SPAK/OSR1 kinase cascade, which acts as a key regulator of ion transport in the distal nephron and blood pressure (By similarity). The WNK4-SPAK/OSR1 kinase cascade is composed of WNK4, which mediates phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK (PubMed:16832045). Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters, such as SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A3/NCC, SLC12A5/KCC2 or SLC12A6/KCC3, regulating their activity (PubMed:16832045, PubMed:22989884). Acts as a molecular switch that regulates the balance between renal salt reabsorption and K(+) secretion by modulating the activities of renal transporters and channels, including the Na-Cl cotransporter SLC12A3/NCC and the K(+) channel, KCNJ1/ROMK (By similarity). Regulates NaCl reabsorption in the distal nephron by activating the thiazide-sensitive Na-Cl cotransporter SLC12A3/NCC in distal convoluted tubule cells of kidney: activates SLC12A3/NCC in a OXSR1/OSR1- and STK39/SPAK-dependent process (By similarity). Also acts as a scaffold protein independently of its protein kinase activity: negatively regulates cell membrane localization of various transporters and channels (CFTR, KCNJ1/ROMK, SLC4A4, SLC26A9 and TRPV4) by clathrin-dependent endocytosis (By similarity). Also inhbits the activity of the epithelial Na(+) channel (ENaC) SCNN1A, SCNN1B, SCNN1D in a inase-independent mechanism (By similarity). May also phosphorylate NEDD4L (PubMed:20525693). {ECO:0000250|UniProtKB:Q80UE6, ECO:0000269|PubMed:16832045, ECO:0000269|PubMed:20525693, ECO:0000269|PubMed:22989884}. | FUNCTION: Metallothioneins have a high content of cysteine residues that bind various heavy metals; these proteins are transcriptionally regulated by both heavy metals and glucocorticoids. |
| 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 WNK4_MT1G |
| 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 |
| WNK4 | Q96J92 | human | CLDN7 | O95471 | S206 | RsYPksNsskEyV__ | |
| WNK4 | Q96J92 | human | SLC12A3 | P55017 | T50 | SHLtHSStFCMRtFG | AA_permease_N |
| WNK4 | Q96J92 | human | WNK4 | Q96J92 | S335 | kRAsFAKsVIGTPEF | Pkinase |
| WNK4 | Q96J92 | human | SLC12A3 | P55017 | T46 | SSHPSHLtHSStFCM | AA_permease_N |
| WNK4 | Q96J92 | human | SLC12A3 | P55017 | T55 | SStFCMRtFGYNtID | AA_permease_N |
| 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 |
| WNK4 | ID | Description | 0.00e+00 |
| WNK4 | GO:0070294 | renal sodium ion absorption | 9.81e-05 |
| WNK4 | GO:0003096 | renal sodium ion transport | 9.81e-05 |
| WNK4 | GO:0055064 | chloride ion homeostasis | 9.81e-05 |
| WNK4 | GO:0055081 | monoatomic anion homeostasis | 9.81e-05 |
| WNK4 | GO:0070293 | renal absorption | 1.85e-04 |
| WNK4 | GO:0002021 | response to dietary excess | 1.85e-04 |
| WNK4 | GO:0097009 | energy homeostasis | 8.00e-04 |
| WNK4 | GO:0006821 | chloride transport | 1.63e-03 |
| WNK4 | GO:0003014 | renal system process | 1.63e-03 |
| WNK4 | GO:0015698 | inorganic anion transport | 2.49e-03 |
| WNK4 | GO:0006820 | monoatomic anion transport | 2.49e-03 |
| WNK4 | GO:0035725 | sodium ion transmembrane transport | 2.50e-03 |
| WNK4 | GO:0071805 | potassium ion transmembrane transport | 3.35e-03 |
| WNK4 | GO:0006813 | potassium ion transport | 3.72e-03 |
| WNK4 | GO:0006814 | sodium ion transport | 3.72e-03 |
| WNK4 | GO:0097305 | response to alcohol | 3.72e-03 |
| WNK4 | GO:0030002 | intracellular monoatomic anion homeostasis | 9.80e-03 |
| WNK4 | GO:0030644 | intracellular chloride ion homeostasis | 9.80e-03 |
| WNK4 | GO:0030157 | pancreatic juice secretion | 1.02e-02 |
| WNK4 | GO:0072017 | distal tubule development | 1.06e-02 |
| WNK4 | GO:0031667 | response to nutrient levels | 1.07e-02 |
| WNK4 | GO:0060457 | negative regulation of digestive system process | 1.12e-02 |
| WNK4 | GO:0010766 | negative regulation of sodium ion transport | 1.32e-02 |
| WNK4 | GO:1904044 | response to aldosterone | 1.32e-02 |
| WNK4 | GO:0035930 | corticosteroid hormone secretion | 1.34e-02 |
| WNK4 | GO:0097623 | potassium ion export across plasma membrane | 1.36e-02 |
| WNK4 | GO:0016338 | calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules | 1.50e-02 |
| WNK4 | GO:0035929 | steroid hormone secretion | 1.70e-02 |
| WNK4 | GO:1903077 | negative regulation of protein localization to plasma membrane | 1.70e-02 |
| WNK4 | GO:1904376 | negative regulation of protein localization to cell periphery | 1.76e-02 |
| WNK4 | GO:0055075 | potassium ion homeostasis | 1.81e-02 |
| WNK4 | GO:0070528 | protein kinase C signaling | 1.81e-02 |
| WNK4 | GO:0006884 | cell volume homeostasis | 1.81e-02 |
| WNK4 | GO:0044058 | regulation of digestive system process | 1.81e-02 |
| WNK4 | GO:0051385 | response to mineralocorticoid | 1.81e-02 |
| WNK4 | GO:1905476 | negative regulation of protein localization to membrane | 1.81e-02 |
| WNK4 | GO:0032941 | secretion by tissue | 2.00e-02 |
| WNK4 | GO:0055078 | sodium ion homeostasis | 2.07e-02 |
| WNK4 | GO:1990573 | potassium ion import across plasma membrane | 2.07e-02 |
| WNK4 | GO:0140353 | lipid export from cell | 2.07e-02 |
| WNK4 | GO:0060986 | endocrine hormone secretion | 2.40e-02 |
| WNK4 | GO:0070830 | bicellular tight junction assembly | 2.88e-02 |
| WNK4 | GO:0120192 | tight junction assembly | 2.88e-02 |
| WNK4 | GO:0043297 | apical junction assembly | 2.88e-02 |
| WNK4 | GO:0072078 | nephron tubule morphogenesis | 2.88e-02 |
| WNK4 | GO:0072088 | nephron epithelium morphogenesis | 2.88e-02 |
| WNK4 | GO:0061333 | renal tubule morphogenesis | 2.88e-02 |
| WNK4 | GO:0072028 | nephron morphogenesis | 2.88e-02 |
| WNK4 | GO:0120193 | tight junction organization | 2.88e-02 |
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Related Drugs to WNK4_MT1G |
| 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 WNK4-MT1G 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 WNK4_MT1G |
| 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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