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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:MAP3K2-IWS1 (FusionGDB2 ID:51293)

Fusion Gene Summary for MAP3K2-IWS1

check button Fusion gene summary
Fusion gene informationFusion gene name: MAP3K2-IWS1
Fusion gene ID: 51293
HgeneTgene
Gene symbol

MAP3K2

IWS1

Gene ID

10746

55677

Gene namemitogen-activated protein kinase kinase kinase 2interacts with SUPT6H, CTD assembly factor 1
SynonymsMEKK2|MEKK2B-
Cytomap

2q14.3

2q14.3

Type of geneprotein-codingprotein-coding
Descriptionmitogen-activated protein kinase kinase kinase 2MAP/ERK kinase kinase 2MAPK/ERK kinase kinase 2MEK kinase 2MEKK 2protein IWS1 homologIWS1 homologIWS1, SUPT6H interacting proteinIWS1-like proteininteracts with Spt6
Modification date2020032920200313
UniProtAcc

Q9Y2U5

Q96ST2

Ensembl transtripts involved in fusion geneENST00000344908, ENST00000409947, 
ENST00000455721, ENST00000486662, 
ENST00000295321, 
Fusion gene scores* DoF score10 X 8 X 3=2403 X 4 X 2=24
# samples 94
** MAII scorelog2(9/240*10)=-1.41503749927884
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(4/24*10)=0.736965594166206
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Context

PubMed: MAP3K2 [Title/Abstract] AND IWS1 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointMAP3K2(128093446)-IWS1(128238751), # samples:2
Anticipated loss of major functional domain due to fusion event.MAP3K2-IWS1 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
MAP3K2-IWS1 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
MAP3K2-IWS1 seems lost the major protein functional domain in Hgene partner, which is a kinase due to the frame-shifted ORF.
MAP3K2-IWS1 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
* 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
HgeneMAP3K2

GO:0045893

positive regulation of transcription, DNA-templated

14515274


check buttonFusion gene breakpoints across MAP3K2 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure

check buttonFusion gene breakpoints across IWS1 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure

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-AC-A2BM-01AMAP3K2chr2

128093446

-IWS1chr2

128238751

-


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Fusion Gene ORF analysis for MAP3K2-IWS1

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
5CDS-intronENST00000344908ENST00000455721MAP3K2chr2

128093446

-IWS1chr2

128238751

-
5CDS-intronENST00000344908ENST00000486662MAP3K2chr2

128093446

-IWS1chr2

128238751

-
5CDS-intronENST00000409947ENST00000455721MAP3K2chr2

128093446

-IWS1chr2

128238751

-
5CDS-intronENST00000409947ENST00000486662MAP3K2chr2

128093446

-IWS1chr2

128238751

-
Frame-shiftENST00000344908ENST00000295321MAP3K2chr2

128093446

-IWS1chr2

128238751

-
In-frameENST00000409947ENST00000295321MAP3K2chr2

128093446

-IWS1chr2

128238751

-

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)
ENST00000409947MAP3K2chr2128093446-ENST00000295321IWS1chr2128238751-917547271678135

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
ENST00000409947ENST00000295321MAP3K2chr2128093446-IWS1chr2128238751-0.0082617350.99173826

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Fusion Genomic Features for MAP3K2-IWS1


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.
genomic feature

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 MAP3K2-IWS1


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/chr2:128093446/chr2:128238751)
- 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
MAP3K2

Q9Y2U5

IWS1

Q96ST2

FUNCTION: Component of a protein kinase signal transduction cascade. Regulates the JNK and ERK5 pathways by phosphorylating and activating MAP2K5 and MAP2K7 (By similarity). Plays a role in caveolae kiss-and-run dynamics. {ECO:0000250, ECO:0000269|PubMed:10713157, ECO:0000269|PubMed:16001074}.FUNCTION: Transcription factor which plays a key role in defining the composition of the RNA polymerase II (RNAPII) elongation complex and in modulating the production of mature mRNA transcripts. Acts as an assembly factor to recruit various factors to the RNAPII elongation complex and is recruited to the complex via binding to the transcription elongation factor SUPT6H bound to the C-terminal domain (CTD) of the RNAPII subunit RPB1 (POLR2A). The SUPT6H:IWS1:CTD complex recruits mRNA export factors (ALYREF/THOC4, EXOSC10) as well as histone modifying enzymes (such as SETD2) to ensure proper mRNA splicing, efficient mRNA export and elongation-coupled H3K36 methylation, a signature chromatin mark of active transcription. {ECO:0000269|PubMed:17184735, ECO:0000269|PubMed:17234882, ECO:0000269|PubMed:19141475}.

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
HgeneMAP3K2chr2:128093446chr2:128238751ENST00000344908-416357_61788620.0DomainProtein kinase
HgeneMAP3K2chr2:128093446chr2:128238751ENST00000344908-41643_12288620.0DomainPB1
HgeneMAP3K2chr2:128093446chr2:128238751ENST00000409947-517357_61788620.0DomainProtein kinase
HgeneMAP3K2chr2:128093446chr2:128238751ENST00000409947-51743_12288620.0DomainPB1
HgeneMAP3K2chr2:128093446chr2:128238751ENST00000344908-416362_37188620.0Nucleotide bindingATP
HgeneMAP3K2chr2:128093446chr2:128238751ENST00000409947-517362_37188620.0Nucleotide bindingATP
TgeneIWS1chr2:128093446chr2:128238751ENST00000295321121483_509776820.0Compositional biasNote=Glu-rich
TgeneIWS1chr2:128093446chr2:128238751ENST000002953211214614_692776820.0DomainTFIIS N-terminal
TgeneIWS1chr2:128093446chr2:128238751ENST000002953211214469_495776820.0MotifIntegrase domain-binding motif (IBM)
TgeneIWS1chr2:128093446chr2:128238751ENST000002953211214235_296776820.0RegionNote=3 X approximate tandem repeats
TgeneIWS1chr2:128093446chr2:128238751ENST000002953211214235_260776820.0RepeatNote=1
TgeneIWS1chr2:128093446chr2:128238751ENST000002953211214261_286776820.0RepeatNote=2
TgeneIWS1chr2:128093446chr2:128238751ENST000002953211214287_296776820.0RepeatNote=3%3B half-length


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Fusion Gene Sequence for MAP3K2-IWS1


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.
>51293_51293_1_MAP3K2-IWS1_MAP3K2_chr2_128093446_ENST00000409947_IWS1_chr2_128238751_ENST00000295321_length(transcript)=917nt_BP=547nt
TTTCTAAAGTCCCTCAGGAAAAAAATTCTGAAACTTGAGCCACAAATTAAGAGGCAGACGGCTTTTCTCCTTGCAAATGACCTGCCACAC
AGTCCGTCACTGCCTCTGCTAGCTCTGCTACCCTTGGGCCCTGTCCACAGCCCACGTGGGAGACCTTTTCACGGGATCTACTCGGATGTC
TGGGATCTGGCCACTACCGCAGGCTCGAGACAACCCAGGCCATAAAGAATGCTGATGGGAGAACCATTTTCCTAATTTTCAAATTGTTGA
GCTGTTTGCCATAATGGATGATCAGCAAGCTTTGAACTCAATCATGCAAGATTTGGCTGTCCTTCATAAGGCCAGTCGACCAGCATTATC
CTTGCAGGAAACCAGAAAAGCAAAATCTTCATCACCAAAAAAACAGAATGATGTCCGAGTCAAATTTGAACATAGAGGAGAAAAAAGAAT
CCTTCAGTTCCCCAGACCAGTTAAACTGGAAGATCTGAGATCTAAAGCTAAAATTGCCTTTGGACAGTCTATGGATCTACATTATACCAA
TAACGAGTTTCAGGCGACCTCCAAGAAGGGTATCAGTCGACTGGATAAACAGATGAGAAAGTTCACAGATATAAGGAAAAAAAGCAGATC
TGCACACGCAGTGAAAATCAGCATTGAGGGCAACAAAATGCCATTGTGACCTTGCCTGGAATGTGTCCCCATCTCTACTCTAAGAAATGC
GCAATGGACTCTTTGGAGAAAGAAGATATTTTAAAACATTTTTAGTGTGTCTGTAAATGGTTCAGCGTGTATCAGATGTTGTCATAGGAC
TCACATTTCTCTCAGTTATATTTAAAACCGTTGTGTACTTTGTACAAAGGAATACTAGTCATACTTCTATAAACTTTACACAATAAAATT

>51293_51293_1_MAP3K2-IWS1_MAP3K2_chr2_128093446_ENST00000409947_IWS1_chr2_128238751_ENST00000295321_length(amino acids)=135AA_BP=92
MFAIMDDQQALNSIMQDLAVLHKASRPALSLQETRKAKSSSPKKQNDVRVKFEHRGEKRILQFPRPVKLEDLRSKAKIAFGQSMDLHYTN

--------------------------------------------------------------

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Fusion Gene PPI Analysis for MAP3K2-IWS1


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
TgeneIWS1chr2:128093446chr2:128238751ENST000002953211214523_819776.0820.0SUPT6H and ALYREF


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 MAP3K2-IWS1


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 MAP3K2-IWS1


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