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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:VRK1_ALOX5AP

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: VRK1_ALOX5AP
KinaseFusionDB ID: KFG7077
FusionGDB2.0 ID: KFG7077
HgeneTgene
Gene symbol

VRK1

ALOX5AP

Gene ID

7443

241

Gene nameVRK serine/threonine kinase 1arachidonate 5-lipoxygenase activating protein
SynonymsHMNR10|PCH1|PCH1AFLAP
Cytomap

14q32.2

13q12.3

Type of geneprotein-codingprotein-coding
Descriptionserine/threonine-protein kinase VRK1vaccinia related kinase 1vaccinia virus B1R-related kinase 1arachidonate 5-lipoxygenase-activating proteinMK-886-binding protein
Modification date2024041620240305
UniProtAcc

Q99986

P20292

Ensembl transtripts involved in fusion geneENST idsENST00000216639, ENST00000555067, 
ENST00000479597, ENST00000380490, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: VRK1 [Title/Abstract] AND ALOX5AP [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)VRK1(97329001)-ALOX5AP(31318411), # samples:1
check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneVRK1

GO:0006974

DNA damage response

33076429

HgeneVRK1

GO:0046777

protein autophosphorylation

21543316|22194607

HgeneVRK1

GO:0090166

Golgi disassembly

19103756

HgeneVRK1

GO:0120187

positive regulation of protein localization to chromatin

33076429

TgeneALOX5AP

GO:0019370

leukotriene biosynthetic process

2300173

TgeneALOX5AP

GO:0071277

cellular response to calcium ion

2300173


check buttonKinase Fusion gene breakpoints across VRK1 (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 ALOX5AP (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
ChiTaRS5.0AA077909VRK1chr14

97329001

ALOX5APchr13

31318411



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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/:97329001/:31318411)
- 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
VRK1

Q99986

ALOX5AP

P20292

FUNCTION: Serine/threonine kinase involved in cell cycle, nuclear condensation and transcription regulation (PubMed:14645249, PubMed:18617507, PubMed:19103756). Involved in Golgi disassembly during the cell cycle: following phosphorylation by PLK3 during mitosis, required to induce Golgi fragmentation (PubMed:19103756). Phosphorylates 'Thr-18' of p53/TP53 and may thereby prevent the interaction between p53/TP53 and MDM2 (PubMed:10951572). Phosphorylates KAT5 in response to DNA damage, promoting KAT5 association with chromatin and histone acetyltransferase activity (PubMed:33076429). Phosphorylates BANF1: disrupts its ability to bind DNA, reduces its binding to LEM domain-containing proteins and causes its relocalization from the nucleus to the cytoplasm (PubMed:16495336). Phosphorylates ATF2 which activates its transcriptional activity (PubMed:15105425). {ECO:0000269|PubMed:10951572, ECO:0000269|PubMed:14645249, ECO:0000269|PubMed:15105425, ECO:0000269|PubMed:16495336, ECO:0000269|PubMed:18617507, ECO:0000269|PubMed:19103756, ECO:0000269|PubMed:33076429}.FUNCTION: Required for leukotriene biosynthesis by ALOX5 (5-lipoxygenase). Anchors ALOX5 to the membrane. Binds arachidonic acid, and could play an essential role in the transfer of arachidonic acid to ALOX5. Binds to MK-886, a compound that blocks the biosynthesis of leukotrienes. {ECO:0000269|PubMed:2300173, ECO:0000269|PubMed:8440384}.

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 VRK1_ALOX5AP


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain
VRK1Q99986humanVRK1Q99986S376GVEDTEWsNtQtEEA
VRK1Q99986humanCOILP38432S184NEEAKRKsPKKKEKCCoilin_N
VRK1Q99986humanTP53P04637T18EPPLsQEtFsDLWkLP53_TAD
VRK1Q99986humanH3C1P68431T3_____ArtkQtArksHistone
VRK1Q99986humanH3C1P68431S10tkQtArkstGGkAPrHistone
VRK1Q99986humanATF2P15336T73ADQtPtPtRFLkNCE
VRK1Q99986humanBANF1O75531S4____MttsQkHRDFVBAF
VRK1Q99986humanBANF1O75531T3_____MttsQkHRDFBAF
VRK1Q99986humanVRK1Q99986T386QtEEAIQtRSRTRKR
VRK1Q99986humanJUNP05412S73VGLLkLAsPELERLIJun
VRK1Q99986humanATF2P15336S62FGPARNDsVIVADQt
VRK1Q99986humanH2AC17P0C0S8T120AVLLPkktEsHHkAkHistone_H2A_C
VRK1Q99986humanJUNP05412S63kNsDLLtsPDVGLLkJun
VRK1Q99986humanNR1I2O75469S350MQAISLFsPDRPGVLHormone_recep
VRK1Q99986humanBANF1O75531T2______MttsQkHRDBAF
VRK1Q99986humanKAT5Q92993T158VEVVsPAtPVPSETA
VRK1Q99986humanVRK1Q99986T355GLkAKTItKKRKKEI


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
VRK1IDDescription0.00e+00
VRK1GO:1901522positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus4.76e-03
VRK1GO:0006979response to oxidative stress4.76e-03
VRK1GO:0006978DNA damage respons3.85e-05
VRK1GO:0042772DNA damage respons4.30e-05
VRK1GO:1903008organelle disassembly4.76e-03
VRK1GO:0009267cellular response to starvation7.64e-03
VRK1GO:0042770signal transduction in response to DNA damage7.98e-03
VRK1GO:0043618regulation of transcription from RNA polymerase II promoter in response to stress8.43e-03
VRK1GO:0060218hematopoietic stem cell differentiation8.43e-03
VRK1GO:0042594response to starvation8.43e-03
VRK1GO:0045815transcription initiation-coupled chromatin remodeling8.43e-03
VRK1GO:0043620regulation of DNA-templated transcription in response to stress8.43e-03
VRK1GO:0040029epigenetic regulation of gene expression8.44e-03
VRK1GO:0071763nuclear membrane organization8.77e-03
VRK1GO:0031669cellular response to nutrient levels8.77e-03
VRK1GO:0035794positive regulation of mitochondrial membrane permeability8.77e-03
VRK1GO:0034599cellular response to oxidative stress8.77e-03
VRK1GO:1902108regulation of mitochondrial membrane permeability involved in apoptotic process8.77e-03
VRK1GO:0009299mRNA transcription8.77e-03
VRK1GO:0042149cellular response to glucose starvation8.77e-03
VRK1GO:1905710positive regulation of membrane permeability8.77e-03
VRK1GO:1902895positive regulation of miRNA transcription8.77e-03
VRK1GO:0006998nuclear envelope organization8.89e-03
VRK1GO:0031668cellular response to extracellular stimulus8.89e-03
VRK1GO:0046902regulation of mitochondrial membrane permeability1.07e-02
VRK1GO:0030217T cell differentiation1.07e-02
VRK1GO:2000630positive regulation of miRNA metabolic process1.10e-02
VRK1GO:0062197cellular response to chemical stress1.10e-02
VRK1GO:2000144positive regulation of DNA-templated transcription initiation1.16e-02
VRK1GO:1902893regulation of miRNA transcription1.19e-02
VRK1GO:0061614miRNA transcription1.19e-02
VRK1GO:0030330DNA damage respons6.51e-04
VRK1GO:0090559regulation of membrane permeability1.22e-02
VRK1GO:2000142regulation of DNA-templated transcription initiation1.34e-02
VRK1GO:0006970response to osmotic stress1.34e-02
VRK1GO:0044773mitotic DNA damage checkpoint signaling1.37e-02
VRK1GO:0006289nucleotide-excision repair1.40e-02
VRK1GO:2000628regulation of miRNA metabolic process1.40e-02
VRK1GO:0044774mitotic DNA integrity checkpoint signaling1.40e-02
VRK1GO:0140747regulation of ncRNA transcription1.53e-02
VRK1GO:0007178transmembrane receptor protein serine/threonine kinase signaling pathway1.58e-02
VRK1GO:0030098lymphocyte differentiation1.76e-02
VRK1GO:0016032viral process1.76e-02
VRK1GO:0010586miRNA metabolic process1.82e-02
VRK1GO:0008637apoptotic mitochondrial changes1.91e-02
VRK1GO:0090398cellular senescence1.91e-02
VRK1GO:0022037metencephalon development1.97e-02
VRK1GO:0042752regulation of circadian rhythm1.97e-02
VRK1GO:1903131mononuclear cell differentiation2.10e-02

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Related Drugs to VRK1_ALOX5AP


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 VRK1-ALOX5AP 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 VRK1_ALOX5AP


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