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Center for Computational Systems Medicine
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Kinase Fusion Gene Summary

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Kinase Fusion Gene Sample Information

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Kinase Fusion ORF Analysis

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Kinase Fusion Amino Acid Sequences

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Multiple Sequence Alignment of All Fusion Protein Isoforms

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Kinase Fusion Protein Functional Features

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Kinase Fusion Protein Structures

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Comparison of Fusion Protein Isoforms

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Comparison of Fusion Protein Sequences/Structures with Known Sequences/Structures from PDB

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pLDDT Scores and Difference Analysis of pLDDT Scores Between the Active Sites (Best) and Non-Active Sites.

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Ramachandran Plot of Kinase Fusion Protein Structure

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Potential Active Site Information

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Virtual Screening Results

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Kinase-Substrate Information

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Related Drugs with This Kinase Fusion Protein

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Related Disease with This Kinase Fusion Protein

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Clinical Trials of the Found Drugs/Small Molecules

Kinase Fusion Gene:IL4I1_VRK3

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: IL4I1_VRK3
KinaseFusionDB ID: KFG2860
FusionGDB2.0 ID: KFG2860
HgeneTgene
Gene symbol

IL4I1

VRK3

Gene ID

259307

51231

Gene nameinterleukin 4 induced 1VRK serine/threonine kinase 3
SynonymsFIG1|LAAO|LAO|hIL4I1-
Cytomap

19q13.33

19q13.33

Type of geneprotein-codingprotein-coding
DescriptionL-amino-acid oxidaseFig-1 proteinIL4-induced protein 1interleukin four induced 1inactive serine/threonine-protein kinase VRK3serine/threonine-protein kinase VRK3serine/threonine-protein pseudokinase VRK3vaccinia related kinase 3
Modification date2024030520240411
UniProtAcc

Q96RQ9

Q8IV63

Ensembl transtripts involved in fusion geneENST idsENST00000391826, 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)
check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneIL4I1

GO:0002819

regulation of adaptive immune response

17356132

HgeneIL4I1

GO:0002841

negative regulation of T cell mediated immune response to tumor cell

32818467

HgeneIL4I1

GO:0006559

L-phenylalanine catabolic process

17356132|25767141

HgeneIL4I1

GO:0006569

tryptophan catabolic process

17356132|25767141

HgeneIL4I1

GO:0006572

tyrosine catabolic process

17356132

HgeneIL4I1

GO:0019440

tryptophan catabolic process to indole-3-acetate

32818467|32866000

HgeneIL4I1

GO:0045591

positive regulation of regulatory T cell differentiation

25778793

HgeneIL4I1

GO:0045944

positive regulation of transcription by RNA polymerase II

32818467

HgeneIL4I1

GO:0050868

negative regulation of T cell activation

28891065


check buttonKinase 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.

check buttonKinase 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

check buttonKinase Fusion gene information.
check button 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.
SourceSampleHgeneHchrHbpTgeneTchrTbp
CCLETE 125.TIL4I1chr19

50432583

VRK3chr19

50496209



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Kinase Fusion ORF Analysis


check buttonKinase Fusion information from ORFfinder translation from full-length transcript sequence from KinaseFusionDB.
HenstTenstHgeneHchrHbpTgeneTchrTbpSeq length
(transcript)
Seq length
(amino acids)

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Kinase Fusion Amino Acid Sequences


check button 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


check button 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.
FGviewer

check buttonMain function of each fusion partner protein. (from UniProt)
HgeneTgene
IL4I1

Q96RQ9

VRK3

Q8IV63

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}.

check buttonRetention 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

download page

* Minus value of BPloci means that the break pointn is located before the CDS.

check button - Retained domain in the 5'-partner of fusion protein (protein functional feature from UniProt).
PartnerHgeneeneHbpTgeneeneTbpENSTBPexonTotalExonProtein feature lociBPlociTotalLenFeatureNote


check button - Retained domain in the 3'-partner of fusion protein (protein functional feature from UniProt).
PartnerHgeneeneHbpTgeneeneTbpENSTBPexonTotalExonProtein feature lociBPlociTotalLenFeatureNote


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Kinase-Substrate Information of IL4I1_VRK3


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain
VRK3Q8IV63humanBANF1O75531S4____MttsQkHRDFVBAF


check button Biological Network Integration of This Kinase and Substrates
(GeneMANIA website)

check button Enriched GO biological processes of the phosphorylation target genes of the kinase
KinaseGOIDGO termP.adjust
VRK3IDDescription0.00e+00
VRK3GO:0007084mitotic nuclear membrane reassembly7.81e-03
VRK3GO:0101024mitotic nuclear membrane organization7.81e-03
VRK3GO:0015074DNA integration7.81e-03
VRK3GO:0031468nuclear membrane reassembly1.15e-02
VRK3GO:0071763nuclear membrane organization1.15e-02
VRK3GO:0032480negative regulation of type I interferon production1.15e-02
VRK3GO:0006998nuclear envelope organization1.15e-02
VRK3GO:0045071negative regulation of viral genome replication1.15e-02
VRK3GO:0071709membrane assembly1.15e-02
VRK3GO:0044091membrane biogenesis1.15e-02
VRK3GO:0045069regulation of viral genome replication1.29e-02
VRK3GO:0045824negative regulation of innate immune response1.29e-02
VRK3GO:0048525negative regulation of viral process1.29e-02
VRK3GO:0032479regulation of type I interferon production1.42e-02
VRK3GO:0032606type I interferon production1.42e-02
VRK3GO:0019079viral genome replication1.42e-02
VRK3GO:1903900regulation of viral life cycle1.42e-02
VRK3GO:0006997nucleus organization1.42e-02
VRK3GO:0002832negative regulation of response to biotic stimulus1.42e-02
VRK3GO:0050792regulation of viral process1.51e-02
VRK3GO:0050777negative regulation of immune response1.76e-02
VRK3GO:0051348negative regulation of transferase activity1.84e-02
VRK3GO:0140014mitotic nuclear division2.15e-02
VRK3GO:0019058viral life cycle2.31e-02
VRK3GO:0031348negative regulation of defense response2.31e-02
VRK3GO:0001818negative regulation of cytokine production2.56e-02
VRK3GO:0006979response to oxidative stress2.56e-02
VRK3GO:0045088regulation of innate immune response2.56e-02
VRK3GO:0016032viral process2.56e-02
VRK3GO:0009615response to virus2.56e-02
VRK3GO:0000280nuclear division2.56e-02
VRK3GO:0043086negative regulation of catalytic activity2.59e-02
VRK3GO:0032102negative regulation of response to external stimulus2.59e-02
VRK3GO:0048285organelle fission2.59e-02

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Related Drugs to IL4I1_VRK3


check button Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDrugSourcePMID

check button Distribution of the number of studies mentioning IL4I1-VRK3 and kinase inhibitors the PubMed Abstract (04-01-2024)

Fusion gene - drug pair 1Fusion gene - drug pair 2PMIDPublication dateDOIStudy title

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Related Diseases to IL4I1_VRK3


check button Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDiseaseSourcePMID

check button Related diseases from the literature mentioned this fusion gene and drug.
(PubMed, 04-01-2024)
MeSH IDMeSH term

check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource


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Clinical Trials of the Found Drugs/Small Molecules


check button Statistics of the Clinical Trials of the Found Kinase Inibitors from clinicaltrials.gov (06-17-2024)

check button Clinical Trials from clinicaltrials.gov (06-17-2024)

Fusion GeneKinase InhibitorNCT IDStudy StatusPhasesDisease# EnrolmentDate