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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:NR4A3-EWSR1 (FusionGDB2 ID:60180)

Fusion Gene Summary for NR4A3-EWSR1

check button Fusion gene summary
Fusion gene informationFusion gene name: NR4A3-EWSR1
Fusion gene ID: 60180
HgeneTgene
Gene symbol

NR4A3

EWSR1

Gene ID

8013

2130

Gene namenuclear receptor subfamily 4 group A member 3EWS RNA binding protein 1
SynonymsCHN|CSMF|MINOR|NOR1|TECEWS|EWS-FLI1|bK984G1.4
Cytomap

9q31.1

22q12.2

Type of geneprotein-codingprotein-coding
Descriptionnuclear receptor subfamily 4 group A member 3chondrosarcoma, extraskeletal myxoid, fused to EWSmitogen-induced nuclear orphan receptorneuron-derived orphan receptor 1nuclear hormone receptor NOR-1translocated in extraskeletal chondrosarcomaRNA-binding protein EWSEWS RNA-binding protein variant 6Ewing sarcoma breakpoint region 1Ewings sarcoma EWS-Fli1 (type 1) oncogene
Modification date2020031320200329
UniProtAcc

Q92570

Q01844

Ensembl transtripts involved in fusion geneENST00000330847, ENST00000338488, 
ENST00000395097, 		ENST00000331029, 
ENST00000332035, ENST00000333395, 
ENST00000414183, ENST00000332050, 
ENST00000397938, ENST00000406548, 
Fusion gene scores* DoF score5 X 5 X 3=7517 X 58 X 10=9860
# samples 448
** MAII scorelog2(4/75*10)=-0.906890595608519
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(48/9860*10)=-4.36048133565676
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: NR4A3 [Title/Abstract] AND EWSR1 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointEWSR1(29688159)-NR4A3(102589010), # samples:2
Anticipated loss of major functional domain due to fusion event.EWSR1-NR4A3 seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF.
EWSR1-NR4A3 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
EWSR1-NR4A3 seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF.
EWSR1-NR4A3 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
EWSR1-NR4A3 seems lost the major protein functional domain in Tgene partner, which is a transcription factor due to the frame-shifted ORF.
EWSR1-NR4A3 seems lost the major protein functional domain in Tgene partner, which is a tumor suppressor due to the frame-shifted ORF.
NR4A3-EWSR1 seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF.
NR4A3-EWSR1 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
NR4A3-EWSR1 seems lost the major protein functional domain in Hgene partner, which is a transcription factor due to the frame-shifted ORF.
NR4A3-EWSR1 seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted ORF.
NR4A3-EWSR1 seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF.
NR4A3-EWSR1 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
HgeneNR4A3

GO:0010828

positive regulation of glucose transmembrane transport

24022864

HgeneNR4A3

GO:0045944

positive regulation of transcription by RNA polymerase II

20558821

HgeneNR4A3

GO:0048008

platelet-derived growth factor receptor signaling pathway

23554459

HgeneNR4A3

GO:0048660

regulation of smooth muscle cell proliferation

25852083


check buttonFusion gene breakpoints across NR4A3 (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 EWSR1 (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..NR4A3chr9

102588114

+EWSR1chr22

29692358

+
ChimerKB3..NR4A3chr9

102591275

+EWSR1chr22

29688476

+


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Fusion Gene ORF analysis for NR4A3-EWSR1

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-intronENST00000330847ENST00000331029NR4A3chr9

102591275

+EWSR1chr22

29688476

+
5CDS-intronENST00000330847ENST00000332035NR4A3chr9

102591275

+EWSR1chr22

29688476

+
5CDS-intronENST00000330847ENST00000333395NR4A3chr9

102591275

+EWSR1chr22

29688476

+
5CDS-intronENST00000330847ENST00000414183NR4A3chr9

102591275

+EWSR1chr22

29688476

+
5CDS-intronENST00000338488ENST00000331029NR4A3chr9

102591275

+EWSR1chr22

29688476

+
5CDS-intronENST00000338488ENST00000332035NR4A3chr9

102591275

+EWSR1chr22

29688476

+
5CDS-intronENST00000338488ENST00000333395NR4A3chr9

102591275

+EWSR1chr22

29688476

+
5CDS-intronENST00000338488ENST00000414183NR4A3chr9

102591275

+EWSR1chr22

29688476

+
5CDS-intronENST00000395097ENST00000331029NR4A3chr9

102591275

+EWSR1chr22

29688476

+
5CDS-intronENST00000395097ENST00000332035NR4A3chr9

102591275

+EWSR1chr22

29688476

+
5CDS-intronENST00000395097ENST00000333395NR4A3chr9

102591275

+EWSR1chr22

29688476

+
5CDS-intronENST00000395097ENST00000414183NR4A3chr9

102591275

+EWSR1chr22

29688476

+
5UTR-intronENST00000338488ENST00000331029NR4A3chr9

102588114

+EWSR1chr22

29692358

+
5UTR-intronENST00000338488ENST00000332035NR4A3chr9

102588114

+EWSR1chr22

29692358

+
5UTR-intronENST00000338488ENST00000332050NR4A3chr9

102588114

+EWSR1chr22

29692358

+
5UTR-intronENST00000338488ENST00000333395NR4A3chr9

102588114

+EWSR1chr22

29692358

+
5UTR-intronENST00000338488ENST00000397938NR4A3chr9

102588114

+EWSR1chr22

29692358

+
5UTR-intronENST00000338488ENST00000406548NR4A3chr9

102588114

+EWSR1chr22

29692358

+
5UTR-intronENST00000338488ENST00000414183NR4A3chr9

102588114

+EWSR1chr22

29692358

+
5UTR-intronENST00000395097ENST00000331029NR4A3chr9

102588114

+EWSR1chr22

29692358

+
5UTR-intronENST00000395097ENST00000332035NR4A3chr9

102588114

+EWSR1chr22

29692358

+
5UTR-intronENST00000395097ENST00000332050NR4A3chr9

102588114

+EWSR1chr22

29692358

+
5UTR-intronENST00000395097ENST00000333395NR4A3chr9

102588114

+EWSR1chr22

29692358

+
5UTR-intronENST00000395097ENST00000397938NR4A3chr9

102588114

+EWSR1chr22

29692358

+
5UTR-intronENST00000395097ENST00000406548NR4A3chr9

102588114

+EWSR1chr22

29692358

+
5UTR-intronENST00000395097ENST00000414183NR4A3chr9

102588114

+EWSR1chr22

29692358

+
Frame-shiftENST00000330847ENST00000332050NR4A3chr9

102591275

+EWSR1chr22

29688476

+
Frame-shiftENST00000330847ENST00000397938NR4A3chr9

102591275

+EWSR1chr22

29688476

+
Frame-shiftENST00000330847ENST00000406548NR4A3chr9

102591275

+EWSR1chr22

29688476

+
Frame-shiftENST00000338488ENST00000332050NR4A3chr9

102591275

+EWSR1chr22

29688476

+
Frame-shiftENST00000338488ENST00000397938NR4A3chr9

102591275

+EWSR1chr22

29688476

+
Frame-shiftENST00000338488ENST00000406548NR4A3chr9

102591275

+EWSR1chr22

29688476

+
Frame-shiftENST00000395097ENST00000332050NR4A3chr9

102591275

+EWSR1chr22

29688476

+
Frame-shiftENST00000395097ENST00000397938NR4A3chr9

102591275

+EWSR1chr22

29688476

+
Frame-shiftENST00000395097ENST00000406548NR4A3chr9

102591275

+EWSR1chr22

29688476

+
intron-intronENST00000330847ENST00000331029NR4A3chr9

102588114

+EWSR1chr22

29692358

+
intron-intronENST00000330847ENST00000332035NR4A3chr9

102588114

+EWSR1chr22

29692358

+
intron-intronENST00000330847ENST00000332050NR4A3chr9

102588114

+EWSR1chr22

29692358

+
intron-intronENST00000330847ENST00000333395NR4A3chr9

102588114

+EWSR1chr22

29692358

+
intron-intronENST00000330847ENST00000397938NR4A3chr9

102588114

+EWSR1chr22

29692358

+
intron-intronENST00000330847ENST00000406548NR4A3chr9

102588114

+EWSR1chr22

29692358

+
intron-intronENST00000330847ENST00000414183NR4A3chr9

102588114

+EWSR1chr22

29692358

+

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 NR4A3-EWSR1


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 NR4A3-EWSR1


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/:29688159/:102589010)
- 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
NR4A3

Q92570

EWSR1

Q01844

FUNCTION: Transcriptional activator that binds to regulatory elements in promoter regions in a cell- and response element (target)-specific manner. Induces gene expression by binding as monomers to the NR4A1 response element (NBRE) 5'-AAAAGGTCA-3' site and as homodimers to the Nur response element (NurRE) site in the promoter of their regulated target genes (By similarity). Plays a role in the regulation of proliferation, survival and differentiation of many different cell types and also in metabolism and inflammation. Mediates proliferation of vascular smooth muscle, myeloid progenitor cell and type B pancreatic cells; promotes mitogen-induced vascular smooth muscle cell proliferation through transactivation of SKP2 promoter by binding a NBRE site (By similarity). Upon PDGF stimulation, stimulates vascular smooth muscle cell proliferation by regulating CCND1 and CCND2 expression. In islets, induces type B pancreatic cell proliferation through up-regulation of genes that activate cell cycle, as well as genes that cause degradation of the CDKN1A (By similarity). Negatively regulates myeloid progenitor cell proliferation by repressing RUNX1 in a NBRE site-independent manner. During inner ear, plays a role as a key mediator of the proliferative growth phase of semicircular canal development (By similarity). Mediates also survival of neuron and smooth muscle cells; mediates CREB-induced neuronal survival, and during hippocampus development, plays a critical role in pyramidal cell survival and axonal guidance. Is required for S phase entry of the cell cycle and survival of smooth muscle cells by inducing CCND1, resulting in RB1 phosphorylation. Binds to NBRE motif in CCND1 promoter, resulting in the activation of the promoter and CCND1 transcription (By similarity). Plays also a role in inflammation; upon TNF stimulation, mediates monocyte adhesion by inducing the expression of VCAM1 and ICAM1 by binding to the NBRE consensus site (By similarity) (PubMed:20558821). In mast cells activated by Fc-epsilon receptor cross-linking, promotes the synthesis and release of cytokines but impairs events leading to degranulation (By similarity). Plays also a role in metabolism; by modulating feeding behavior; and by playing a role in energy balance by inhibiting the glucocorticoid-induced orexigenic neuropeptides AGRP expression, at least in part by forming a complex with activated NR3C1 on the AGRP- glucocorticoid response element (GRE), and thus weakening the DNA binding activity of NR3C1. Upon catecholamines stimulation, regulates gene expression that controls oxidative metabolism in skeletal muscle (By similarity). Plays a role in glucose transport by regulating translocation of the SLC2A4 glucose transporter to the cell surface (PubMed:24022864). Finally, during gastrulation plays a crucial role in the formation of anterior mesoderm by controlling cell migration. Inhibits adipogenesis (By similarity). Also participates in cardiac hypertrophy by activating PARP1 (By similarity). {ECO:0000250|UniProtKB:P51179, ECO:0000250|UniProtKB:Q9QZB6, ECO:0000269|PubMed:20558821, ECO:0000269|PubMed:24022864}.FUNCTION: Might normally function as a transcriptional repressor. EWS-fusion-proteins (EFPS) may play a role in the tumorigenic process. They may disturb gene expression by mimicking, or interfering with the normal function of CTD-POLII within the transcription initiation complex. They may also contribute to an aberrant activation of the fusion protein target genes.

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 NR4A3-EWSR1


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 NR4A3-EWSR1


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 NR4A3-EWSR1


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 NR4A3-EWSR1


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