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Kinase Fusion Gene:AKR1B1_ITK |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: AKR1B1_ITK | KinaseFusionDB ID: KFG258 | FusionGDB2.0 ID: KFG258 | Hgene | Tgene | Gene symbol | AKR1B1 | ITK | Gene ID | 231 | 3702 | |
| Gene name | aldo-keto reductase family 1 member B | IL2 inducible T cell kinase | ||||||||||
| Synonyms | ADR|ALDR1|ALR2|AR | EMT|LPFS1|LYK|PSCTK2 | ||||||||||
| Cytomap | 7q33 | 5q33.3 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | aldo-keto reductase family 1 member B1Lii5-2 CTCL tumor antigenaldehyde reductase 1aldose reductaselow Km aldose reductase | tyrosine-protein kinase ITK/TSKIL-2-inducible T-cell kinaseT-cell-specific kinasehomolog of mouse T-cell itk/tskinterleukin-2-inducible T-cell kinasekinase EMTtyrosine-protein kinase LYK | ||||||||||
| Modification date | 20240411 | 20240305 | ||||||||||
| UniProtAcc | P15121 | Q08881 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000285930, ENST00000489022, | ENST00000422843, ENST00000519749, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: AKR1B1 [Title/Abstract] AND ITK [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | AKR1B1(134130004)-ITK(156679822), # 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 | AKR1B1 | GO:0071475 | cellular hyperosmotic salinity response | 8435445 |
| Kinase Fusion gene breakpoints across AKR1B1 (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 ITK (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 | AV705293 | AKR1B1 | chr7 | 134130004 | ITK | chr5 | 156679822 |
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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/:134130004/:156679822) - 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 |
| AKR1B1 | ITK |
| FUNCTION: Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols. Displays enzymatic activity towards endogenous metabolites such as aromatic and aliphatic aldehydes, ketones, monosacharides, bile acids and xenobiotics substrates. Key enzyme in the polyol pathway, catalyzes reduction of glucose to sorbitol during hyperglycemia (PubMed:1936586). Reduces steroids and their derivatives and prostaglandins. Displays low enzymatic activity toward all-trans-retinal, 9-cis-retinal, and 13-cis-retinal (PubMed:12732097, PubMed:19010934, PubMed:8343525). Catalyzes the reduction of diverse phospholipid aldehydes such as 1-palmitoyl-2-(5-oxovaleroyl)-sn -glycero-3-phosphoethanolamin (POVPC) and related phospholipid aldehydes that are generated from the oxydation of phosphotidylcholine and phosphatdyleethanolamides (PubMed:17381426). Plays a role in detoxifying dietary and lipid-derived unsaturated carbonyls, such as crotonaldehyde, 4-hydroxynonenal, trans-2-hexenal, trans-2,4-hexadienal and their glutathione-conjugates carbonyls (GS-carbonyls) (PubMed:21329684). {ECO:0000269|PubMed:12732097, ECO:0000269|PubMed:17381426, ECO:0000269|PubMed:19010934, ECO:0000269|PubMed:1936586, ECO:0000269|PubMed:21329684, ECO:0000269|PubMed:8343525}. | FUNCTION: Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. When antigen presenting cells (APC) activate T-cell receptor (TCR), a series of phosphorylation lead to the recruitment of ITK to the cell membrane, in the vicinity of the stimulated TCR receptor, where it is phosphorylated by LCK. Phosphorylation leads to ITK autophosphorylation and full activation. Once activated, phosphorylates PLCG1, leading to the activation of this lipase and subsequent cleavage of its substrates. In turn, the endoplasmic reticulum releases calcium in the cytoplasm and the nuclear activator of activated T-cells (NFAT) translocates into the nucleus to perform its transcriptional duty. Phosphorylates 2 essential adapter proteins: the linker for activation of T-cells/LAT protein and LCP2. Then, a large number of signaling molecules such as VAV1 are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation (PubMed:12186560, PubMed:12682224, PubMed:21725281). Required for TCR-mediated calcium response in gamma-delta T-cells, may also be involved in the modulation of the transcriptomic signature in the Vgamma2-positive subset of immature gamma-delta T-cells (By similarity). Phosphorylates TBX21 at 'Tyr-530' and mediates its interaction with GATA3 (By similarity). {ECO:0000250|UniProtKB:Q03526, ECO:0000269|PubMed:12186560, ECO:0000269|PubMed:12682224, ECO:0000269|PubMed:21725281}. |
| 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 AKR1B1_ITK |
| 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 |
| ITK | Q08881 | human | DEF6 | Q9H4E7 | Y222 | QDVLKQGyLWkRGHL | PH |
| ITK | Q08881 | human | BMX | P51813 | Y216 | SSTSLAQyDSNSKKI | |
| ITK | Q08881 | human | SIGLEC10 | Q96LC7 | Y597 | RHstILDyINVVPTA | |
| ITK | Q08881 | human | HAVCR2 | Q8TDQ0 | Y265 | IRSEENIyTIEENVy | |
| ITK | Q08881 | human | LCP2 | Q13094 | Y173 | FPNsNsMyIDRPPSG | |
| ITK | Q08881 | human | TEC | P42680 | Y206 | RLERGQEyLILEKND | SH3_1 |
| ITK | Q08881 | human | DEF6 | Q9H4E7 | Y210 | SMAIHEVyQELIQDV | |
| ITK | Q08881 | human | BTK | Q06187 | Y223 | LKKVVALyDyMPMNA | SH3_1 |
| ITK | Q08881 | human | ITK | Q08881 | Y180 | ETVVIALyDyQtNDP | SH3_1 |
| ITK | Q08881 | human | GRAP2 | O75791 | Y45 | ELGsQEGyVPkNFID | SH3_1 |
| ITK | Q08881 | human | PLCG1 | P19174 | Y783 | EGRNPGFyVEANPMP | |
| ITK | Q08881 | human | SIGLEC10 | Q96LC7 | Y667 | ESQEELHyATLNFPG |
| 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 |
| ITK | ID | Description | 0.00e+00 |
| ITK | GO:0050851 | antigen receptor-mediated signaling pathway | 1.29e-07 |
| ITK | GO:0002757 | immune response-activating signaling pathway | 1.37e-07 |
| ITK | GO:0002764 | immune response-regulating signaling pathway | 1.37e-07 |
| ITK | GO:0002429 | immune response-activating cell surface receptor signaling pathway | 4.52e-07 |
| ITK | GO:0050852 | T cell receptor signaling pathway | 4.92e-07 |
| ITK | GO:0002768 | immune response-regulating cell surface receptor signaling pathway | 4.99e-07 |
| ITK | GO:0050853 | B cell receptor signaling pathway | 3.15e-06 |
| ITK | GO:0038095 | Fc-epsilon receptor signaling pathway | 3.93e-03 |
| ITK | GO:0002274 | myeloid leukocyte activation | 1.07e-02 |
| ITK | GO:0002861 | regulation of inflammatory response to antigenic stimulus | 1.17e-02 |
| ITK | GO:0038093 | Fc receptor signaling pathway | 1.45e-02 |
| ITK | GO:0031348 | negative regulation of defense response | 1.86e-02 |
| ITK | GO:0045576 | mast cell activation | 1.87e-02 |
| ITK | GO:0002437 | inflammatory response to antigenic stimulus | 2.33e-02 |
| ITK | GO:0050672 | negative regulation of lymphocyte proliferation | 2.52e-02 |
| ITK | GO:0032945 | negative regulation of mononuclear cell proliferation | 2.52e-02 |
| ITK | GO:0070664 | negative regulation of leukocyte proliferation | 2.66e-02 |
| ITK | GO:0002275 | myeloid cell activation involved in immune response | 2.66e-02 |
| ITK | GO:0050727 | regulation of inflammatory response | 2.66e-02 |
| ITK | GO:0032760 | positive regulation of tumor necrosis factor production | 2.85e-02 |
| ITK | GO:1903557 | positive regulation of tumor necrosis factor superfamily cytokine production | 2.92e-02 |
| ITK | GO:0032102 | negative regulation of response to external stimulus | 3.28e-02 |
| ITK | GO:0001819 | positive regulation of cytokine production | 3.48e-02 |
| ITK | GO:0007498 | mesoderm development | 3.88e-02 |
| ITK | GO:0050671 | positive regulation of lymphocyte proliferation | 4.07e-02 |
| ITK | GO:0002753 | cytosolic pattern recognition receptor signaling pathway | 4.07e-02 |
| ITK | GO:0032946 | positive regulation of mononuclear cell proliferation | 4.07e-02 |
| ITK | GO:0046488 | phosphatidylinositol metabolic process | 4.30e-02 |
| ITK | GO:0070665 | positive regulation of leukocyte proliferation | 4.54e-02 |
| ITK | GO:0051250 | negative regulation of lymphocyte activation | 4.54e-02 |
| ITK | GO:0032635 | interleukin-6 production | 4.54e-02 |
| ITK | GO:0032675 | regulation of interleukin-6 production | 4.54e-02 |
| ITK | GO:0032640 | tumor necrosis factor production | 4.54e-02 |
| ITK | GO:0032680 | regulation of tumor necrosis factor production | 4.54e-02 |
| ITK | GO:0002706 | regulation of lymphocyte mediated immunity | 4.54e-02 |
| ITK | GO:0071706 | tumor necrosis factor superfamily cytokine production | 4.54e-02 |
| ITK | GO:1903555 | regulation of tumor necrosis factor superfamily cytokine production | 4.54e-02 |
| ITK | GO:0002822 | regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains | 4.54e-02 |
| ITK | GO:0002695 | negative regulation of leukocyte activation | 4.54e-02 |
| ITK | GO:0050728 | negative regulation of inflammatory response | 4.54e-02 |
| ITK | GO:0050777 | negative regulation of immune response | 4.54e-02 |
| ITK | GO:0002819 | regulation of adaptive immune response | 4.54e-02 |
| ITK | GO:0019722 | calcium-mediated signaling | 4.54e-02 |
| ITK | GO:0002291 | T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell | 4.54e-02 |
| ITK | GO:0002420 | natural killer cell mediated cytotoxicity directed against tumor cell target | 4.54e-02 |
| ITK | GO:0002855 | regulation of natural killer cell mediated immune response to tumor cell | 4.54e-02 |
| ITK | GO:0002883 | regulation of hypersensitivity | 4.54e-02 |
| ITK | GO:0032815 | negative regulation of natural killer cell activation | 4.54e-02 |
| ITK | GO:0050679 | positive regulation of epithelial cell proliferation | 4.54e-02 |
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Related Drugs to AKR1B1_ITK |
| 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 AKR1B1-ITK 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 AKR1B1_ITK |
| 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 |
| Tgene | ITK | C3552634 | LYMPHOPROLIFERATIVE SYNDROME 1 | 7 | CLINGEN;GENOMICS_ENGLAND;ORPHANET;UNIPROT |
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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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