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Center for Computational Systems Medicine
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Fusion Gene and Fusion Protein Summary

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Fusion Amino Acid Sequences (multiple BPs and multiple gene isoforms)

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Fusion Protein Breakpoint Sequences - (for the Screening of the FusionNeoAntigens)

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Potential FusionNeoAntigens in HLA I - (netMHCpan v4.1 + deepHLApan v1.1)

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Potential FusionNeoAntigens in HLA II - (netMHCIIpan v4.1)

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Fusion Breakpoint 14 AA Peptide Structure - (RoseTTAFold)

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D - (Glide)

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Vaccine Design for the FusionNeoAntigens (RNA/protein sequences)

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Potential target of CAR-T therapy development

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Information on the samples that have these potential fusion neoantigens

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Fusion Protein Targeting Drugs - (Manual Curation)

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Fusion Protein Related diseases - (Manual Curation)

Fusion Protein:MAP3K3-DDX42

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: MAP3K3-DDX42
FusionPDB ID: 51305
FusionGDB2.0 ID: 51305
HgeneTgene
Gene symbol

MAP3K3

DDX42

Gene ID

4215

11325

Gene namemitogen-activated protein kinase kinase kinase 3DEAD-box helicase 42
SynonymsMAPKKK3|MEKK3DDX42P|RHELP|RNAHP|SF3B8|SF3b125
Cytomap

17q23.3

17q23.3

Type of geneprotein-codingprotein-coding
Descriptionmitogen-activated protein kinase kinase kinase 3MAP/ERK kinase kinase 3MAPK/ERK kinase kinase 3MEK kinase 3MEKK 3ATP-dependent RNA helicase DDX42DEAD (Asp-Glu-Ala-Asp) box helicase 42DEAD (Asp-Glu-Ala-Asp) box polypeptide 42SF3b DEAD box proteinsplicing factor 3B-associated 125 kDa proteinsplicing factor 3b, subunit 8
Modification date2020031320200313
UniProtAcc

Q99759

Main function of 5'-partner protein: FUNCTION: Component of a protein kinase signal transduction cascade. Mediates activation of the NF-kappa-B, AP1 and DDIT3 transcriptional regulators. {ECO:0000269|PubMed:12912994, ECO:0000269|PubMed:14661019, ECO:0000269|PubMed:14743216, ECO:0000269|PubMed:9006902}.

Q86XP3

Main function of 5'-partner protein: FUNCTION: ATP-dependent RNA helicase. Binds to partially double-stranded RNAs (dsRNAs) in order to unwind RNA secondary structures. Unwinding is promoted in the presence of single-strand binding proteins. Mediates also RNA duplex formation thereby displacing the single-strand RNA binding protein. ATP and ADP modulate its activity: ATP binding and hydrolysis by DDX42 triggers RNA strand separation, whereas the ADP-bound form of the protein triggers annealing of complementary RNA strands. Involved in the survival of cells by interacting with TP53BP2 and thereby counteracting the apoptosis-stimulating activity of TP53BP2. Relocalizes TP53BP2 to the cytoplasm. {ECO:0000269|PubMed:16397294, ECO:0000269|PubMed:19377511}.
Ensembl transtripts involved in fusion geneENST idsENST00000361357, ENST00000361733, 
ENST00000577395, ENST00000579585, 
ENST00000584573, ENST00000577784, 
ENST00000582985, ENST00000578681, 
ENST00000583590, ENST00000359353, 
ENST00000389924, ENST00000457800, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score10 X 10 X 8=80015 X 18 X 10=2700
# samples 1318
** MAII scorelog2(13/800*10)=-2.62148837674627
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(18/2700*10)=-3.90689059560852
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: MAP3K3 [Title/Abstract] AND DDX42 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: MAP3K3 [Title/Abstract] AND DDX42 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MAP3K3(61735267)-DDX42(61886920), # samples:1
MAP3K3(61729953)-DDX42(61895627), # samples:1
Anticipated loss of major functional domain due to fusion event.MAP3K3-DDX42 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF.
MAP3K3-DDX42 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF.
MAP3K3-DDX42 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF.
MAP3K3-DDX42 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF.
MAP3K3-DDX42 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
MAP3K3-DDX42 seems lost the major protein functional domain in Hgene partner, which is a kinase due to the frame-shifted ORF.
MAP3K3-DDX42 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
HgeneMAP3K3

GO:0035556

intracellular signal transduction

15001576

HgeneMAP3K3

GO:0046777

protein autophosphorylation

15001576

TgeneDDX42

GO:0008104

protein localization

19377511



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/chr17:61735267/chr17:61886920)
- 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 buttonRetention analysis results 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, are available here.

check buttonFusion gene breakpoints across MAP3K3 (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 DDX42 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure


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Fusion Amino Acid Sequences


check buttonFusion information from ORFfinder translation from full-length transcript sequence from FusionPDB.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)		BP loci
(transcript)		Predicted start
(transcript)		Predicted stop
(transcript)		Seq length
(amino acids)
ENST00000579585MAP3K3chr1761735267+ENST00000578681DDX42chr1761886920+3124540662204712
ENST00000579585MAP3K3chr1761735267+ENST00000583590DDX42chr1761886920+3124540662204712
ENST00000579585MAP3K3chr1761735267+ENST00000359353DDX42chr1761886920+2205540662204712
ENST00000579585MAP3K3chr1761735267+ENST00000389924DDX42chr1761886920+3123540662204712
ENST00000579585MAP3K3chr1761735267+ENST00000457800DDX42chr1761886920+3123540662204712
ENST00000584573MAP3K3chr1761735267+ENST00000578681DDX42chr1761886920+33938093352473712
ENST00000584573MAP3K3chr1761735267+ENST00000583590DDX42chr1761886920+33938093352473712
ENST00000584573MAP3K3chr1761735267+ENST00000359353DDX42chr1761886920+24748093352473713
ENST00000584573MAP3K3chr1761735267+ENST00000389924DDX42chr1761886920+33928093352473712
ENST00000584573MAP3K3chr1761735267+ENST00000457800DDX42chr1761886920+33928093352473712
ENST00000361733MAP3K3chr1761735267+ENST00000578681DDX42chr1761886920+32857013202365681
ENST00000361733MAP3K3chr1761735267+ENST00000583590DDX42chr1761886920+32857013202365681
ENST00000361733MAP3K3chr1761735267+ENST00000359353DDX42chr1761886920+23667013202365682
ENST00000361733MAP3K3chr1761735267+ENST00000389924DDX42chr1761886920+32847013202365681
ENST00000361733MAP3K3chr1761735267+ENST00000457800DDX42chr1761886920+32847013202365681
ENST00000361357MAP3K3chr1761735267+ENST00000578681DDX42chr1761886920+33767923182456712
ENST00000361357MAP3K3chr1761735267+ENST00000583590DDX42chr1761886920+33767923182456712
ENST00000361357MAP3K3chr1761735267+ENST00000359353DDX42chr1761886920+24577923182456712
ENST00000361357MAP3K3chr1761735267+ENST00000389924DDX42chr1761886920+33757923182456712
ENST00000361357MAP3K3chr1761735267+ENST00000457800DDX42chr1761886920+33757923182456712
ENST00000577395MAP3K3chr1761735267+ENST00000578681DDX42chr1761886920+3015431502095681
ENST00000577395MAP3K3chr1761735267+ENST00000583590DDX42chr1761886920+3015431502095681
ENST00000577395MAP3K3chr1761735267+ENST00000359353DDX42chr1761886920+2096431502095682
ENST00000577395MAP3K3chr1761735267+ENST00000389924DDX42chr1761886920+3014431502095681
ENST00000577395MAP3K3chr1761735267+ENST00000457800DDX42chr1761886920+3014431502095681
ENST00000579585MAP3K3chr1761729953+ENST00000359353DDX42chr1761895627+5203896634191
ENST00000579585MAP3K3chr1761729953+ENST00000389924DDX42chr1761895627+14383896634191
ENST00000579585MAP3K3chr1761729953+ENST00000457800DDX42chr1761895627+14383896634191
ENST00000584573MAP3K3chr1761729953+ENST00000359353DDX42chr1761895627+7896583620121
ENST00000584573MAP3K3chr1761729953+ENST00000389924DDX42chr1761895627+17076583620121
ENST00000584573MAP3K3chr1761729953+ENST00000457800DDX42chr1761895627+17076583620121
ENST00000361733MAP3K3chr1761729953+ENST00000359353DDX42chr1761895627+6815503470116
ENST00000361733MAP3K3chr1761729953+ENST00000389924DDX42chr1761895627+15995503470116
ENST00000361733MAP3K3chr1761729953+ENST00000457800DDX42chr1761895627+15995503470116
ENST00000361357MAP3K3chr1761729953+ENST00000359353DDX42chr1761895627+7726413451115
ENST00000361357MAP3K3chr1761729953+ENST00000389924DDX42chr1761895627+16906413451115
ENST00000361357MAP3K3chr1761729953+ENST00000457800DDX42chr1761895627+16906413451115
ENST00000577395MAP3K3chr1761729953+ENST00000359353DDX42chr1761895627+41128040616480
ENST00000577395MAP3K3chr1761729953+ENST00000389924DDX42chr1761895627+1329280831108885
ENST00000577395MAP3K3chr1761729953+ENST00000457800DDX42chr1761895627+1329280831108885

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
ENST00000579585ENST00000578681MAP3K3chr1761735267+DDX42chr1761886920+0.0011558390.99884415
ENST00000579585ENST00000583590MAP3K3chr1761735267+DDX42chr1761886920+0.0011558390.99884415
ENST00000579585ENST00000359353MAP3K3chr1761735267+DDX42chr1761886920+0.0033625530.99663746
ENST00000579585ENST00000389924MAP3K3chr1761735267+DDX42chr1761886920+0.0011494280.9988506
ENST00000579585ENST00000457800MAP3K3chr1761735267+DDX42chr1761886920+0.0011494280.9988506
ENST00000584573ENST00000578681MAP3K3chr1761735267+DDX42chr1761886920+0.0014167690.9985832
ENST00000584573ENST00000583590MAP3K3chr1761735267+DDX42chr1761886920+0.0014167690.9985832
ENST00000584573ENST00000359353MAP3K3chr1761735267+DDX42chr1761886920+0.0038100940.99618983
ENST00000584573ENST00000389924MAP3K3chr1761735267+DDX42chr1761886920+0.001408670.99859136
ENST00000584573ENST00000457800MAP3K3chr1761735267+DDX42chr1761886920+0.001408670.99859136
ENST00000361733ENST00000578681MAP3K3chr1761735267+DDX42chr1761886920+0.0012598770.99874014
ENST00000361733ENST00000583590MAP3K3chr1761735267+DDX42chr1761886920+0.0012598770.99874014
ENST00000361733ENST00000359353MAP3K3chr1761735267+DDX42chr1761886920+0.0034588740.9965411
ENST00000361733ENST00000389924MAP3K3chr1761735267+DDX42chr1761886920+0.0012525970.99874735
ENST00000361733ENST00000457800MAP3K3chr1761735267+DDX42chr1761886920+0.0012525970.99874735
ENST00000361357ENST00000578681MAP3K3chr1761735267+DDX42chr1761886920+0.0014778070.9985222
ENST00000361357ENST00000583590MAP3K3chr1761735267+DDX42chr1761886920+0.0014778070.9985222
ENST00000361357ENST00000359353MAP3K3chr1761735267+DDX42chr1761886920+0.0039044620.9960956
ENST00000361357ENST00000389924MAP3K3chr1761735267+DDX42chr1761886920+0.0014693720.9985306
ENST00000361357ENST00000457800MAP3K3chr1761735267+DDX42chr1761886920+0.0014693720.9985306
ENST00000577395ENST00000578681MAP3K3chr1761735267+DDX42chr1761886920+0.001009390.9989906
ENST00000577395ENST00000583590MAP3K3chr1761735267+DDX42chr1761886920+0.001009390.9989906
ENST00000577395ENST00000359353MAP3K3chr1761735267+DDX42chr1761886920+0.0028670210.997133
ENST00000577395ENST00000389924MAP3K3chr1761735267+DDX42chr1761886920+0.00100350.99899656
ENST00000577395ENST00000457800MAP3K3chr1761735267+DDX42chr1761886920+0.00100350.99899656
ENST00000579585ENST00000359353MAP3K3chr1761729953+DDX42chr1761895627+0.085748030.9142519
ENST00000579585ENST00000389924MAP3K3chr1761729953+DDX42chr1761895627+0.0852910650.9147089
ENST00000579585ENST00000457800MAP3K3chr1761729953+DDX42chr1761895627+0.0852910650.9147089
ENST00000584573ENST00000359353MAP3K3chr1761729953+DDX42chr1761895627+0.1100951950.88990486
ENST00000584573ENST00000389924MAP3K3chr1761729953+DDX42chr1761895627+0.08116120.9188388
ENST00000584573ENST00000457800MAP3K3chr1761729953+DDX42chr1761895627+0.08116120.9188388
ENST00000361733ENST00000359353MAP3K3chr1761729953+DDX42chr1761895627+0.143026580.85697347
ENST00000361733ENST00000389924MAP3K3chr1761729953+DDX42chr1761895627+0.600008960.39999107
ENST00000361733ENST00000457800MAP3K3chr1761729953+DDX42chr1761895627+0.600008960.39999107
ENST00000361357ENST00000359353MAP3K3chr1761729953+DDX42chr1761895627+0.1070929840.892907
ENST00000361357ENST00000389924MAP3K3chr1761729953+DDX42chr1761895627+0.122682660.8773173
ENST00000361357ENST00000457800MAP3K3chr1761729953+DDX42chr1761895627+0.122682660.8773173
ENST00000577395ENST00000359353MAP3K3chr1761729953+DDX42chr1761895627+0.096965530.9030345
ENST00000577395ENST00000389924MAP3K3chr1761729953+DDX42chr1761895627+0.649361850.3506382
ENST00000577395ENST00000457800MAP3K3chr1761729953+DDX42chr1761895627+0.649361850.3506382

check button Predicted full-length fusion amino acid sequences. For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among all the predicted ones.

Get the fusion protein sequences from here.

Fusion protein sequence information is available in the fasta format.
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

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Fusion Protein Breakpoint Sequences for MAP3K3-DDX42

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide

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Potential FusionNeoAntigen Information of MAP3K3-DDX42 in HLA I

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.

check button Potential FusionNeoAntigen Information
* We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5)
Fusion geneHchrHbpTgeneTchrTbpHLA IFusionNeoAntigen peptideBinding scoreImmunogenic scoreNeoantigen start (at BP 13)Neoantigen end (at BP 13)

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Potential FusionNeoAntigen Information of MAP3K3-DDX42 in HLA II

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.

check button Potential FusionNeoAntigen Information
* We used NetMHCIIpan v4.1 (%rank<0.5).
Fusion geneHchrHbpTgeneTchrTbpHLA IIFusionNeoAntigen peptideNeoantigen start (at BP 13)Neoantigen end (at BP 13)

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Fusion breakpoint peptide structures of MAP3K3-DDX42

check button3D structures of the fusion breakpoint peptide of 14AA sequence that have potential fusion neoantigens
* The minimum length of the amino acid sequence in RoseTTAFold is 14AA. Here, we predicted the 14AA fusion protein breakpoint sequence not the fusion neoantigen peptide, which is shorter than 14 AA.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of MAP3K3-DDX42

check buttonVirtual screening between 25 HLAs (from PDB) and FusionNeoAntigens
* We used Glide to predict the interaction between HLAs and neoantigens.
HLA allelePDB IDFile nameBPseqDocking scoreGlide score

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Vaccine Design for the FusionNeoAntigens of MAP3K3-DDX42

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptide sequenceFusionNeoAntigen RNA sequence

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence

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Information of the samples that have these potential fusion neoantigens of MAP3K3-DDX42

check button These samples were reported as having these fusion breakpoints. For individual breakpoints, we checked the open reading frames considering multiple gene isoforms and chose the in-frame fusion genes only. Then, we made fusion protein sequences and predicted the fusion neoantigens. These fusion-positive samples may have these potential fusion neoantigens.
Cancer typeFusion geneHchrHbpHenstTchrTbpTenstSample

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Potential target of CAR-T therapy development for MAP3K3-DDX42

check button Predicted 3D structure. We used RoseTTAFold.

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, to provide the retention of the transmembrane domain, we only show the protein feature retention information of those transmembrane features


* Minus value of BPloci means that the break point is located before the CDS.
- In-frame and retained 'Transmembrane'.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

check button Subcellular localization prediction of the transmembrane domain retained fusion proteins
* We used DeepLoc 1.0. The order of the X-axis of the barplot is as follows: Entry_ID, Localization, Type, Nucleus, Cytoplasm, Extracellular, Mitochondrion, Cell_membrane, Endoplasmic_reticulum, Plastid, Golgi.apparatus, Lysosome.Vacuole, Peroxisome. Y-axis is the output score of DeepLoc. Clicking the image will open a new tab with a large image.
HgeneHchrHbpHenstTgeneTchrTbpTenstDeepLoc result

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Related Drugs to MAP3K3-DDX42

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

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Related Diseases to MAP3K3-DDX42

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

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