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Center for Computational Systems Medicine
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Fusion Gene Summary

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Fusion Gene ORF analysis

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Fusion Genomic Features

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Fusion Protein Features

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Fusion Gene Sequence

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Fusion Gene PPI analysis

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Related Drugs

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Related Diseases

Fusion gene:MAPK8-KIRREL2 (FusionGDB2 ID:51575)

Fusion Gene Summary for MAPK8-KIRREL2

check button Fusion gene summary
Fusion gene informationFusion gene name: MAPK8-KIRREL2
Fusion gene ID: 51575
HgeneTgene
Gene symbol

MAPK8

KIRREL2

Gene ID

5599

84063

Gene namemitogen-activated protein kinase 8kirre like nephrin family adhesion molecule 2
SynonymsJNK|JNK-46|JNK1|JNK1A2|JNK21B1/2|PRKM8|SAPK1|SAPK1cFILTRIN|NEPH3|NLG1
Cytomap

10q11.22

19q13.12

Type of geneprotein-codingprotein-coding
Descriptionmitogen-activated protein kinase 8JUN N-terminal kinaseMAP kinase 8c-Jun N-terminal kinase 1mitogen-activated protein kinase 8 isoform JNK1 alpha1mitogen-activated protein kinase 8 isoform JNK1 beta2stress-activated protein kinase 1stress-activatedkin of IRRE-like protein 2kin of IRRE like 2kin of irregular chiasm-like protein 2nephrin-like gene 1nephrin-like protein 3
Modification date2020032920200313
UniProtAcc

P45983

.
Ensembl transtripts involved in fusion geneENST00000360332, ENST00000374174, 
ENST00000374182, ENST00000374189, 
ENST00000395611, ENST00000459755, 
ENST00000262625, ENST00000347900, 
ENST00000360202, ENST00000592409, 
Fusion gene scores* DoF score5 X 4 X 5=1004 X 3 X 4=48
# samples 54
** MAII scorelog2(5/100*10)=-1
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(4/48*10)=-0.263034405833794
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: MAPK8 [Title/Abstract] AND KIRREL2 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointMAPK8(49534008)-KIRREL2(36355550), # samples:1
Anticipated loss of major functional domain due to fusion event.
* DoF score (Degree of Frequency) = # partners X # break points X # cancer types
** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10)

check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneMAPK8

GO:0006468

protein phosphorylation

21856198

HgeneMAPK8

GO:0007254

JNK cascade

8654373

HgeneMAPK8

GO:0007258

JUN phosphorylation

14967141|21095239

HgeneMAPK8

GO:0009411

response to UV

14967141

HgeneMAPK8

GO:0018105

peptidyl-serine phosphorylation

15850461|20027304|21095239

HgeneMAPK8

GO:0018107

peptidyl-threonine phosphorylation

21095239

HgeneMAPK8

GO:0032091

negative regulation of protein binding

21095239

HgeneMAPK8

GO:0032880

regulation of protein localization

20027304

HgeneMAPK8

GO:0034198

cellular response to amino acid starvation

11096076

HgeneMAPK8

GO:0043066

negative regulation of apoptotic process

14967141|21095239

HgeneMAPK8

GO:0051403

stress-activated MAPK cascade

11096076

HgeneMAPK8

GO:0071222

cellular response to lipopolysaccharide

23776175


check buttonFusion gene breakpoints across MAPK8 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

check buttonFusion gene breakpoints across KIRREL2 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

check button Fusion gene information from two resources (ChiTars 5.0 and ChimerDB 4.0)
* 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.
SourceDiseaseSampleHgeneHchrHbpHstrandTgeneTchrTbpTstrand
ChimerDB4BRCATCGA-A2-A0EV-01AMAPK8chr10

49534008

-KIRREL2chr19

36355550

+


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Fusion Gene ORF analysis for MAPK8-KIRREL2

check button Open reading frame (ORF) analsis of fusion genes based on Ensembl gene isoform structure.
* Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser.
ORFHenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrand
intron-3CDSENST00000360332ENST00000262625MAPK8chr10

49534008

-KIRREL2chr19

36355550

+
intron-3CDSENST00000360332ENST00000347900MAPK8chr10

49534008

-KIRREL2chr19

36355550

+
intron-3CDSENST00000360332ENST00000360202MAPK8chr10

49534008

-KIRREL2chr19

36355550

+
intron-3CDSENST00000360332ENST00000592409MAPK8chr10

49534008

-KIRREL2chr19

36355550

+
intron-3CDSENST00000374174ENST00000262625MAPK8chr10

49534008

-KIRREL2chr19

36355550

+
intron-3CDSENST00000374174ENST00000347900MAPK8chr10

49534008

-KIRREL2chr19

36355550

+
intron-3CDSENST00000374174ENST00000360202MAPK8chr10

49534008

-KIRREL2chr19

36355550

+
intron-3CDSENST00000374174ENST00000592409MAPK8chr10

49534008

-KIRREL2chr19

36355550

+
intron-3CDSENST00000374182ENST00000262625MAPK8chr10

49534008

-KIRREL2chr19

36355550

+
intron-3CDSENST00000374182ENST00000347900MAPK8chr10

49534008

-KIRREL2chr19

36355550

+
intron-3CDSENST00000374182ENST00000360202MAPK8chr10

49534008

-KIRREL2chr19

36355550

+
intron-3CDSENST00000374182ENST00000592409MAPK8chr10

49534008

-KIRREL2chr19

36355550

+
intron-3CDSENST00000374189ENST00000262625MAPK8chr10

49534008

-KIRREL2chr19

36355550

+
intron-3CDSENST00000374189ENST00000347900MAPK8chr10

49534008

-KIRREL2chr19

36355550

+
intron-3CDSENST00000374189ENST00000360202MAPK8chr10

49534008

-KIRREL2chr19

36355550

+
intron-3CDSENST00000374189ENST00000592409MAPK8chr10

49534008

-KIRREL2chr19

36355550

+
intron-3CDSENST00000395611ENST00000262625MAPK8chr10

49534008

-KIRREL2chr19

36355550

+
intron-3CDSENST00000395611ENST00000347900MAPK8chr10

49534008

-KIRREL2chr19

36355550

+
intron-3CDSENST00000395611ENST00000360202MAPK8chr10

49534008

-KIRREL2chr19

36355550

+
intron-3CDSENST00000395611ENST00000592409MAPK8chr10

49534008

-KIRREL2chr19

36355550

+
intron-3CDSENST00000459755ENST00000262625MAPK8chr10

49534008

-KIRREL2chr19

36355550

+
intron-3CDSENST00000459755ENST00000347900MAPK8chr10

49534008

-KIRREL2chr19

36355550

+
intron-3CDSENST00000459755ENST00000360202MAPK8chr10

49534008

-KIRREL2chr19

36355550

+
intron-3CDSENST00000459755ENST00000592409MAPK8chr10

49534008

-KIRREL2chr19

36355550

+

check buttonORFfinder result based on the fusion transcript sequence of in-frame fusion genes.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)		BP loci
(transcript)		Predicted start
(transcript)		Predicted stop
(transcript)		Seq length
(amino acids)

check buttonDeepORF prediction of the coding potential based on the fusion transcript sequence of in-frame fusion genes. DeepORF is a coding potential classifier based on convolutional neural network by comparing the real Ribo-seq data. If the no-coding score < 0.5 and coding score > 0.5, then the in-frame fusion transcript is predicted as being likely translated.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandNo-coding scoreCoding score

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Fusion Genomic Features for MAPK8-KIRREL2


check buttonFusionAI prediction of the potential fusion gene breakpoint based on the pre-mature RNA sequence context (+/- 5kb of individual partner genes, total 20kb length sequence). FusionAI is a fusion gene breakpoint classifier based on convolutional neural network by comparing the fusion positive and negative sequence context of ~ 20K fusion gene data. From here, we can have the relative potentency of the 20K genomic sequence how individual sequnce will be likely used as the gene fusion breakpoints.
HgeneHchrHbpHstrandTgeneTchrTbpTstrand1-pp (fusion gene breakpoint)

check buttonDistribution of 44 human genomic features loci across 20kb length fusion breakpoint regions. We integrated a total of 44 different types of human genomic feature loci information across five big categories including virus integration sites, repeats, structural variants, chromatin states, and gene expression regulation. More details are in help page.

check buttonDistribution of 44 human genomic features loci across 20kb length fusion breakpoint regions that are ovelapped with the top 1% feature importance score regions. More details are in help page.

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Fusion Protein Features for MAPK8-KIRREL2


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/:49534008/:36355550)
- 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
MAPK8

P45983

.
FUNCTION: Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity (PubMed:18307971). Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins (PubMed:21856198). Loss of this interaction abrogates the acetylation required for replication initiation. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1 (PubMed:21364637). In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Contributes to the survival of erythroid cells by phosphorylating the antagonist of cell death BAD upon EPO stimulation (PubMed:21095239). Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy (PubMed:18570871). Phosphorylates STMN2 and hence regulates microtubule dynamics, controlling neurite elongation in cortical neurons. In the developing brain, through its cytoplasmic activity on STMN2, negatively regulates the rate of exit from multipolar stage and of radial migration from the ventricular zone. Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH (PubMed:20027304, PubMed:17296730, PubMed:16581800). Phosphorylates the CLOCK-ARNTL/BMAL1 heterodimer and plays a role in the regulation of the circadian clock (PubMed:22441692). Phosphorylates the heat shock transcription factor HSF1, suppressing HSF1-induced transcriptional activity (PubMed:10747973). Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteosomal degradation (By similarity). Phosphorylates JUND and this phosphorylation is inhibited in the presence of MEN1 (PubMed:22327296). In neurons, phosphorylates SYT4 which captures neuronal dense core vesicles at synapses (By similarity). Phosphorylates EIF4ENIF1/4-ET in response to oxidative stress, promoting P-body assembly (PubMed:22966201). {ECO:0000250|UniProtKB:P49185, ECO:0000250|UniProtKB:Q91Y86, ECO:0000269|PubMed:10747973, ECO:0000269|PubMed:16581800, ECO:0000269|PubMed:17296730, ECO:0000269|PubMed:18307971, ECO:0000269|PubMed:18570871, ECO:0000269|PubMed:20027304, ECO:0000269|PubMed:21095239, ECO:0000269|PubMed:21364637, ECO:0000269|PubMed:21856198, ECO:0000269|PubMed:22327296, ECO:0000269|PubMed:22441692, ECO:0000269|PubMed:22966201}.; FUNCTION: JNK1 isoforms display different binding patterns: beta-1 preferentially binds to c-Jun, whereas alpha-1, alpha-2, and beta-2 have a similar low level of binding to both c-Jun or ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms.FUNCTION: Transcriptional activator which is required for calcium-dependent dendritic growth and branching in cortical neurons. Recruits CREB-binding protein (CREBBP) to nuclear bodies. Component of the CREST-BRG1 complex, a multiprotein complex that regulates promoter activation by orchestrating a calcium-dependent release of a repressor complex and a recruitment of an activator complex. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex. At the same time, there is increased recruitment of CREBBP to the promoter by a CREST-dependent mechanism, which leads to transcriptional activation. The CREST-BRG1 complex also binds to the NR2B promoter, and activity-dependent induction of NR2B expression involves a release of HDAC1 and recruitment of CREBBP (By similarity). {ECO:0000250}.

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.
- In-frame and retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

- In-frame and not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note


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Fusion Gene Sequence for MAPK8-KIRREL2


check button For in-frame fusion transcripts, we provide the fusion transcript sequences and fusion amino acid sequences. To have fusion amino acid sequence, we ran ORFfinder and chose the longest ORF among the all predicted ones.

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Fusion Gene PPI Analysis for MAPK8-KIRREL2


check button Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in

ChiPPI page.


check button Protein-protein interactors with each fusion partner protein in wild-type (BIOGRID-3.4.160)
HgeneHgene's interactorsTgeneTgene's interactors


check button - Retained PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenStill interaction with


check button - Lost PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


check button - Retained PPIs, but lost function due to frame-shift fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


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Related Drugs for MAPK8-KIRREL2


check button Drugs targeting genes involved in this fusion gene.
(DrugBank Version 5.1.8 2021-05-08)
PartnerGeneUniProtAccDrugBank IDDrug nameDrug activityDrug typeDrug status

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Related Diseases for MAPK8-KIRREL2


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