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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:NONO-TFE3 (FusionGDB2 ID:59614)

Fusion Gene Summary for NONO-TFE3

check button Fusion gene summary
Fusion gene informationFusion gene name: NONO-TFE3
Fusion gene ID: 59614
HgeneTgene
Gene symbol

NONO

TFE3

Gene ID

4841

7030

Gene namenon-POU domain containing octamer bindingtranscription factor binding to IGHM enhancer 3
SynonymsMRXS34|NMT55|NRB54|P54|P54NRB|PPP1R114RCCP2|RCCX1|TFEA|bHLHe33
Cytomap

Xq13.1

Xp11.23

Type of geneprotein-codingprotein-coding
Descriptionnon-POU domain-containing octamer-binding protein54 kDa nuclear RNA- and DNA-binding protein55 kDa nuclear proteinDNA-binding p52/p100 complex, 52 kDa subunitnon-POU domain-containing octamer (ATGCAAAT) binding proteinp54(nrb)protein phosphatase 1, transcription factor E3class E basic helix-loop-helix protein 33transcription factor E family, member Atranscription factor for IgH enhancertranscription factor for immunoglobulin heavy-chain enhancer 3
Modification date2020031320200327
UniProtAcc

Q15233

P19532

Ensembl transtripts involved in fusion geneENST00000490044, ENST00000276079, 
ENST00000373841, ENST00000373856, 
ENST00000535149, 
ENST00000315869, 
ENST00000487451, 
Fusion gene scores* DoF score8 X 8 X 2=12814 X 15 X 6=1260
# samples 815
** MAII scorelog2(8/128*10)=-0.678071905112638
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(15/1260*10)=-3.0703893278914
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: NONO [Title/Abstract] AND TFE3 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint
Anticipated loss of major functional domain due to fusion event.NONO-TFE3 seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF.
NONO-TFE3 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
NONO-TFE3 seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF.
NONO-TFE3 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
NONO-TFE3 seems lost the major protein functional domain in Tgene partner, which is a transcription factor 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
HgeneNONO

GO:0002218

activation of innate immune response

28712728

HgeneNONO

GO:1903377

negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway

15790595


check buttonFusion gene breakpoints across NONO (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 TFE3 (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
ChimerKB3..NONOchrX

70517311

+TFE3chrX

48891766

-
ChimerKB3..NONOchrX

70518358

+TFE3chrX

48891766

-


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Fusion Gene ORF analysis for NONO-TFE3

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-3CDSENST00000490044ENST00000315869NONOchrX

70517311

+TFE3chrX

48891766

-
3UTR-3CDSENST00000490044ENST00000315869NONOchrX

70518358

+TFE3chrX

48891766

-
3UTR-5UTRENST00000490044ENST00000487451NONOchrX

70517311

+TFE3chrX

48891766

-
3UTR-5UTRENST00000490044ENST00000487451NONOchrX

70518358

+TFE3chrX

48891766

-
5CDS-5UTRENST00000276079ENST00000487451NONOchrX

70517311

+TFE3chrX

48891766

-
5CDS-5UTRENST00000276079ENST00000487451NONOchrX

70518358

+TFE3chrX

48891766

-
5CDS-5UTRENST00000373841ENST00000487451NONOchrX

70517311

+TFE3chrX

48891766

-
5CDS-5UTRENST00000373841ENST00000487451NONOchrX

70518358

+TFE3chrX

48891766

-
5CDS-5UTRENST00000373856ENST00000487451NONOchrX

70517311

+TFE3chrX

48891766

-
5CDS-5UTRENST00000373856ENST00000487451NONOchrX

70518358

+TFE3chrX

48891766

-
5CDS-5UTRENST00000535149ENST00000487451NONOchrX

70517311

+TFE3chrX

48891766

-
5CDS-5UTRENST00000535149ENST00000487451NONOchrX

70518358

+TFE3chrX

48891766

-
Frame-shiftENST00000276079ENST00000315869NONOchrX

70517311

+TFE3chrX

48891766

-
Frame-shiftENST00000276079ENST00000315869NONOchrX

70518358

+TFE3chrX

48891766

-
Frame-shiftENST00000373841ENST00000315869NONOchrX

70517311

+TFE3chrX

48891766

-
Frame-shiftENST00000373841ENST00000315869NONOchrX

70518358

+TFE3chrX

48891766

-
Frame-shiftENST00000373856ENST00000315869NONOchrX

70517311

+TFE3chrX

48891766

-
Frame-shiftENST00000373856ENST00000315869NONOchrX

70518358

+TFE3chrX

48891766

-
Frame-shiftENST00000535149ENST00000315869NONOchrX

70517311

+TFE3chrX

48891766

-
Frame-shiftENST00000535149ENST00000315869NONOchrX

70518358

+TFE3chrX

48891766

-

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 NONO-TFE3


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 NONO-TFE3


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/:/:)
- 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
NONO

Q15233

TFE3

P19532

FUNCTION: DNA- and RNA binding protein, involved in several nuclear processes. Binds the conventional octamer sequence in double-stranded DNA. Also binds single-stranded DNA and RNA at a site independent of the duplex site. Involved in pre-mRNA splicing, probably as a heterodimer with SFPQ. Interacts with U5 snRNA, probably by binding to a purine-rich sequence located on the 3' side of U5 snRNA stem 1b. Together with PSPC1, required for the formation of nuclear paraspeckles. The SFPQ-NONO heteromer associated with MATR3 may play a role in nuclear retention of defective RNAs. The SFPQ-NONO heteromer may be involved in DNA unwinding by modulating the function of topoisomerase I/TOP1. The SFPQ-NONO heteromer may be involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination and may stabilize paired DNA ends. In vitro, the complex strongly stimulates DNA end joining, binds directly to the DNA substrates and cooperates with the Ku70/G22P1-Ku80/XRCC5 (Ku) dimer to establish a functional preligation complex. NONO is involved in transcriptional regulation. The SFPQ-NONO-NR5A1 complex binds to the CYP17 promoter and regulates basal and cAMP-dependent transcriptional activity. NONO binds to an enhancer element in long terminal repeats of endogenous intracisternal A particles (IAPs) and activates transcription. Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-ARNTL/BMAL1 heterodimer. Important for the functional organization of GABAergic synapses. Plays a specific and important role in the regulation of synaptic RNAs and GPHN/gephyrin scaffold structure, through the regulation of GABRA2 transcript. Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). {ECO:0000250|UniProtKB:Q99K48, ECO:0000269|PubMed:10858305, ECO:0000269|PubMed:11525732, ECO:0000269|PubMed:11897684, ECO:0000269|PubMed:15590677, ECO:0000269|PubMed:22416126, ECO:0000269|PubMed:26571461, ECO:0000269|PubMed:28712728}.FUNCTION: Transcription factor that acts as a master regulator of lysosomal biogenesis and immune response (PubMed:2338243, PubMed:29146937, PubMed:30733432, PubMed:31672913). Specifically recognizes and binds E-box sequences (5'-CANNTG-3'); efficient DNA-binding requires dimerization with itself or with another MiT/TFE family member such as TFEB or MITF (By similarity). Involved in the cellular response to amino acid availability by acting downstream of MTOR: in the presence of nutrients, TFE3 phosphorylation by MTOR promotes its cytosolic retention and subsequent inactivation (PubMed:31672913). Upon starvation or lysosomal stress, inhibition of MTOR induces TFE3 dephosphorylation, resulting in nuclear localization and transcription factor activity (PubMed:31672913). In association with TFEB, activates the expression of CD40L in T-cells, thereby playing a role in T-cell-dependent antibody responses in activated CD4(+) T-cells and thymus-dependent humoral immunity (By similarity). Specifically recognizes the MUE3 box, a subset of E-boxes, present in the immunoglobulin enhancer (PubMed:2338243). It also binds very well to a USF/MLTF site (PubMed:2338243). May regulate lysosomal positioning in response to nutrient deprivation by promoting the expression of PIP4P1 (PubMed:29146937). Acts as a positive regulator of browning of adipose tissue by promoting expression of target genes; mTOR-dependent phosphorylation promotes cytoplasmic retention of TFE3 and inhibits browning of adipose tissue (By similarity). Maintains the pluripotent state of embryonic stem cells by promoting the expression of genes such as ESRRB; mTOR-dependent nuclear exclusion promotes exit from pluripotency (By similarity). Required to maintain the naive pluripotent state of hematopoietic stem cell; mTOR-dependent cytoplasmic retention of TFE3 promotes the exit of hematopoietic stem cell from pluripotency (PubMed:30733432). {ECO:0000250|UniProtKB:Q64092, ECO:0000269|PubMed:2338243, ECO:0000269|PubMed:29146937, ECO:0000269|PubMed:30733432, ECO:0000269|PubMed:31672913}.

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 NONO-TFE3


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 NONO-TFE3


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 NONO-TFE3


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 NONO-TFE3


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