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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:TGM4-NF2 (FusionGDB2 ID:90529)

Fusion Gene Summary for TGM4-NF2

check button Fusion gene summary
Fusion gene informationFusion gene name: TGM4-NF2
Fusion gene ID: 90529
HgeneTgene
Gene symbol

TGM4

NF2

Gene ID

7047

4771

Gene nametransglutaminase 4neurofibromin 2
SynonymsTGP|hTGPACN|BANF|SCH
Cytomap

3p21.31

22q12.2

Type of geneprotein-codingprotein-coding
Descriptionprotein-glutamine gamma-glutamyltransferase 4TG(P)TGase PTGase-4fibrinoligaseprostate transglutaminaseprostate-specific transglutaminasetransglutaminase 4 (prostate)transglutaminase Pmerlinmoesin-ezrin-radixin likemoesin-ezrin-radixin-like proteinmoesin-ezrin-radizin-like proteinneurofibromin 2 (bilateral acoustic neuroma)schwannomerlinschwannomin
Modification date2020031320200322
UniProtAcc.

P35240

Ensembl transtripts involved in fusion geneENST00000296125, ENST00000471637, 
ENST00000334961, ENST00000338641, 
ENST00000347330, ENST00000353887, 
ENST00000361166, ENST00000361452, 
ENST00000361676, ENST00000397789, 
ENST00000403435, ENST00000403999, 
ENST00000413209, 
Fusion gene scores* DoF score3 X 2 X 2=1215 X 13 X 7=1365
# samples 317
** MAII scorelog2(3/12*10)=1.32192809488736
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0		log2(17/1365*10)=-3.00529429966951
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: TGM4 [Title/Abstract] AND NF2 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointTGM4(44956093)-NF2(30012730), # 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
TgeneNF2

GO:0008285

negative regulation of cell proliferation

12444102|20178741

TgeneNF2

GO:0022408

negative regulation of cell-cell adhesion

17210637

TgeneNF2

GO:0042532

negative regulation of tyrosine phosphorylation of STAT protein

12444102

TgeneNF2

GO:0046426

negative regulation of JAK-STAT cascade

12444102


check buttonFusion gene breakpoints across TGM4 (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 NF2 (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
ChiTaRS5.0N/AAA420653TGM4chr3

44956093

+NF2chr22

30012730

+


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Fusion Gene ORF analysis for TGM4-NF2

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
3UTR-intronENST00000296125ENST00000334961TGM4chr3

44956093

+NF2chr22

30012730

+
3UTR-intronENST00000296125ENST00000338641TGM4chr3

44956093

+NF2chr22

30012730

+
3UTR-intronENST00000296125ENST00000347330TGM4chr3

44956093

+NF2chr22

30012730

+
3UTR-intronENST00000296125ENST00000353887TGM4chr3

44956093

+NF2chr22

30012730

+
3UTR-intronENST00000296125ENST00000361166TGM4chr3

44956093

+NF2chr22

30012730

+
3UTR-intronENST00000296125ENST00000361452TGM4chr3

44956093

+NF2chr22

30012730

+
3UTR-intronENST00000296125ENST00000361676TGM4chr3

44956093

+NF2chr22

30012730

+
3UTR-intronENST00000296125ENST00000397789TGM4chr3

44956093

+NF2chr22

30012730

+
3UTR-intronENST00000296125ENST00000403435TGM4chr3

44956093

+NF2chr22

30012730

+
3UTR-intronENST00000296125ENST00000403999TGM4chr3

44956093

+NF2chr22

30012730

+
3UTR-intronENST00000296125ENST00000413209TGM4chr3

44956093

+NF2chr22

30012730

+
intron-intronENST00000471637ENST00000334961TGM4chr3

44956093

+NF2chr22

30012730

+
intron-intronENST00000471637ENST00000338641TGM4chr3

44956093

+NF2chr22

30012730

+
intron-intronENST00000471637ENST00000347330TGM4chr3

44956093

+NF2chr22

30012730

+
intron-intronENST00000471637ENST00000353887TGM4chr3

44956093

+NF2chr22

30012730

+
intron-intronENST00000471637ENST00000361166TGM4chr3

44956093

+NF2chr22

30012730

+
intron-intronENST00000471637ENST00000361452TGM4chr3

44956093

+NF2chr22

30012730

+
intron-intronENST00000471637ENST00000361676TGM4chr3

44956093

+NF2chr22

30012730

+
intron-intronENST00000471637ENST00000397789TGM4chr3

44956093

+NF2chr22

30012730

+
intron-intronENST00000471637ENST00000403435TGM4chr3

44956093

+NF2chr22

30012730

+
intron-intronENST00000471637ENST00000403999TGM4chr3

44956093

+NF2chr22

30012730

+
intron-intronENST00000471637ENST00000413209TGM4chr3

44956093

+NF2chr22

30012730

+

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 TGM4-NF2


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 TGM4-NF2


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/:44956093/:30012730)
- 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
.NF2

P35240

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}.FUNCTION: Probable regulator of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway, a signaling pathway that plays a pivotal role in tumor suppression by restricting proliferation and promoting apoptosis. Along with WWC1 can synergistically induce the phosphorylation of LATS1 and LATS2 and can probably function in the regulation of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway. May act as a membrane stabilizing protein. May inhibit PI3 kinase by binding to AGAP2 and impairing its stimulating activity. Suppresses cell proliferation and tumorigenesis by inhibiting the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein ligase complex. {ECO:0000269|PubMed:20159598, ECO:0000269|PubMed:20178741, ECO:0000269|PubMed:21167305}.

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 TGM4-NF2


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 TGM4-NF2


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 TGM4-NF2


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 TGM4-NF2


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