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Kinase Fusion Gene:IL4I1_VRK3 |
Kinase Fusion Protein Summary |
Kinase Fusion gene summary |
Kinase Fusion partner gene information | Kinase Fusion gene name: IL4I1_VRK3 | KinaseFusionDB ID: KFG2860 | FusionGDB2.0 ID: KFG2860 | Hgene | Tgene | Gene symbol | IL4I1 | VRK3 | Gene ID | 259307 | 51231 | |
Gene name | interleukin 4 induced 1 | VRK serine/threonine kinase 3 | ||||||||||
Synonyms | FIG1|LAAO|LAO|hIL4I1 | - | ||||||||||
Cytomap | 19q13.33 | 19q13.33 | ||||||||||
Type of gene | protein-coding | protein-coding | ||||||||||
Description | L-amino-acid oxidaseFig-1 proteinIL4-induced protein 1interleukin four induced 1 | inactive serine/threonine-protein kinase VRK3serine/threonine-protein kinase VRK3serine/threonine-protein pseudokinase VRK3vaccinia related kinase 3 | ||||||||||
Modification date | 20240305 | 20240411 | ||||||||||
UniProtAcc | Q96RQ9 | Q8IV63 | ||||||||||
Ensembl transtripts involved in fusion gene | ENST ids | ENST00000391826, ENST00000595948, ENST00000341114, | ENST00000316763, ENST00000377011, ENST00000599538, ENST00000443401, ENST00000601341, ENST00000594948, ENST00000601912, ENST00000594092, ENST00000593919, ENST00000424804, | |||||||||
Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: IL4I1 [Title/Abstract] AND VRK3 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) |
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 | IL4I1 | GO:0002819 | regulation of adaptive immune response | 17356132 |
Hgene | IL4I1 | GO:0002841 | negative regulation of T cell mediated immune response to tumor cell | 32818467 |
Hgene | IL4I1 | GO:0006559 | L-phenylalanine catabolic process | 17356132|25767141 |
Hgene | IL4I1 | GO:0006569 | tryptophan catabolic process | 17356132|25767141 |
Hgene | IL4I1 | GO:0006572 | tyrosine catabolic process | 17356132 |
Hgene | IL4I1 | GO:0019440 | tryptophan catabolic process to indole-3-acetate | 32818467|32866000 |
Hgene | IL4I1 | GO:0045591 | positive regulation of regulatory T cell differentiation | 25778793 |
Hgene | IL4I1 | GO:0045944 | positive regulation of transcription by RNA polymerase II | 32818467 |
Hgene | IL4I1 | GO:0050868 | negative regulation of T cell activation | 28891065 |
Kinase Fusion gene breakpoints across IL4I1 (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 VRK3 (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 |
CCLE | TE 125.T | IL4I1 | chr19 | 50432583 | VRK3 | chr19 | 50496209 |
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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/:/:) - 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 |
IL4I1 | VRK3 |
FUNCTION: Secreted L-amino-acid oxidase that acts as a key immunoregulator (PubMed:17356132, PubMed:32818467, PubMed:32866000). Has preference for L-aromatic amino acids: converts phenylalanine (Phe), tyrosine (Tyr) and tryptophan (Trp) to phenylpyruvic acid (PP), hydroxyphenylpyruvic acid (HPP), and indole-3-pyruvic acid (I3P), respectively (PubMed:17356132, PubMed:32818467, PubMed:32866000). Also has weak L-arginine oxidase activity (PubMed:26673964). Acts as a negative regulator of anti-tumor immunity by mediating Trp degradation via an indole pyruvate pathway that activates the transcription factor AHR (PubMed:32818467, PubMed:32866000). IL4I1-mediated Trp catabolism generates I3P, giving rise to indole metabolites (indole-3-acetic acid (IAA) and indole-3-aldehyde (I3A)) and kynurenic acid, which act as ligands for AHR, a ligand-activated transcription factor that plays important roles in immunity and cancer (PubMed:32818467, PubMed:32866000). AHR activation by indoles following IL4I1-mediated Trp degradation enhances tumor progression by promoting cancer cell motility and suppressing adaptive immunity (PubMed:32818467). Also has an immunoregulatory function in some immune cells, probably by mediating Trp degradation and promoting downstream AHR activation: inhibits T-cell activation and proliferation, promotes the differentiation of naive CD4(+) T-cells into FOXP3(+) regulatory T-cells (Treg) and regulates the development and function of B-cells (PubMed:17356132, PubMed:25446972, PubMed:25778793, PubMed:28891065). Also regulates M2 macrophage polarization by inhibiting T-cell activation (By similarity). Also has antibacterial properties by inhibiting growth of Gram negative and Gram positive bacteria through the production of NH4(+) and H2O2 (PubMed:23355881). {ECO:0000250|UniProtKB:O09046, ECO:0000269|PubMed:17356132, ECO:0000269|PubMed:23355881, ECO:0000269|PubMed:25446972, ECO:0000269|PubMed:25778793, ECO:0000269|PubMed:26673964, ECO:0000269|PubMed:28891065, ECO:0000269|PubMed:32818467, ECO:0000269|PubMed:32866000}. | FUNCTION: Inactive kinase that suppresses ERK activity by promoting phosphatase activity of DUSP3 which specifically dephosphorylates and inactivates ERK in the nucleus. {ECO:0000250, ECO:0000269|PubMed:14645249, ECO:0000269|PubMed:19141289}. |
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 IL4I1_VRK3 |
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 |
VRK3 | Q8IV63 | human | BANF1 | O75531 | S4 | ____MttsQkHRDFV | BAF |
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 |
VRK3 | ID | Description | 0.00e+00 |
VRK3 | GO:0007084 | mitotic nuclear membrane reassembly | 7.81e-03 |
VRK3 | GO:0101024 | mitotic nuclear membrane organization | 7.81e-03 |
VRK3 | GO:0015074 | DNA integration | 7.81e-03 |
VRK3 | GO:0031468 | nuclear membrane reassembly | 1.15e-02 |
VRK3 | GO:0071763 | nuclear membrane organization | 1.15e-02 |
VRK3 | GO:0032480 | negative regulation of type I interferon production | 1.15e-02 |
VRK3 | GO:0006998 | nuclear envelope organization | 1.15e-02 |
VRK3 | GO:0045071 | negative regulation of viral genome replication | 1.15e-02 |
VRK3 | GO:0071709 | membrane assembly | 1.15e-02 |
VRK3 | GO:0044091 | membrane biogenesis | 1.15e-02 |
VRK3 | GO:0045069 | regulation of viral genome replication | 1.29e-02 |
VRK3 | GO:0045824 | negative regulation of innate immune response | 1.29e-02 |
VRK3 | GO:0048525 | negative regulation of viral process | 1.29e-02 |
VRK3 | GO:0032479 | regulation of type I interferon production | 1.42e-02 |
VRK3 | GO:0032606 | type I interferon production | 1.42e-02 |
VRK3 | GO:0019079 | viral genome replication | 1.42e-02 |
VRK3 | GO:1903900 | regulation of viral life cycle | 1.42e-02 |
VRK3 | GO:0006997 | nucleus organization | 1.42e-02 |
VRK3 | GO:0002832 | negative regulation of response to biotic stimulus | 1.42e-02 |
VRK3 | GO:0050792 | regulation of viral process | 1.51e-02 |
VRK3 | GO:0050777 | negative regulation of immune response | 1.76e-02 |
VRK3 | GO:0051348 | negative regulation of transferase activity | 1.84e-02 |
VRK3 | GO:0140014 | mitotic nuclear division | 2.15e-02 |
VRK3 | GO:0019058 | viral life cycle | 2.31e-02 |
VRK3 | GO:0031348 | negative regulation of defense response | 2.31e-02 |
VRK3 | GO:0001818 | negative regulation of cytokine production | 2.56e-02 |
VRK3 | GO:0006979 | response to oxidative stress | 2.56e-02 |
VRK3 | GO:0045088 | regulation of innate immune response | 2.56e-02 |
VRK3 | GO:0016032 | viral process | 2.56e-02 |
VRK3 | GO:0009615 | response to virus | 2.56e-02 |
VRK3 | GO:0000280 | nuclear division | 2.56e-02 |
VRK3 | GO:0043086 | negative regulation of catalytic activity | 2.59e-02 |
VRK3 | GO:0032102 | negative regulation of response to external stimulus | 2.59e-02 |
VRK3 | GO:0048285 | organelle fission | 2.59e-02 |
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Related Drugs to IL4I1_VRK3 |
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 IL4I1-VRK3 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 IL4I1_VRK3 |
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 |