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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:DDIT3-ATF2 (FusionGDB2 ID:21818)

Fusion Gene Summary for DDIT3-ATF2

check button Fusion gene summary
Fusion gene informationFusion gene name: DDIT3-ATF2
Fusion gene ID: 21818
HgeneTgene
Gene symbol

DDIT3

ATF2

Gene ID

1649

2668

Gene nameDNA damage inducible transcript 3glial cell derived neurotrophic factor
SynonymsAltDDIT3|C/EBPzeta|CEBPZ|CHOP|CHOP-10|CHOP10|GADD153ATF|ATF1|ATF2|HFB1-GDNF|HSCR3
Cytomap

12q13.3

5p13.2

Type of geneprotein-codingprotein-coding
DescriptionDNA damage-inducible transcript 3 proteinC/EBP zetaCCAAT/enhancer-binding protein homologous proteinalternative DDIT3 proteinc/EBP-homologous protein 10growth arrest and DNA damage-inducible protein GADD153glial cell line-derived neurotrophic factorastrocyte-derived trophic factor
Modification date2020031320200314
UniProtAcc

P35638

P15336

Ensembl transtripts involved in fusion geneENST00000346473, ENST00000547303, 
ENST00000551116, ENST00000552740, 
ENST00000264110, ENST00000345739, 
ENST00000392543, ENST00000392544, 
ENST00000409437, ENST00000409499, 
ENST00000409635, ENST00000409833, 
ENST00000413123, ENST00000426833, 
ENST00000487334, ENST00000538946, 
Fusion gene scores* DoF score5 X 11 X 4=2201 X 1 X 1=1
# samples 111
** MAII scorelog2(11/220*10)=-1
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(1/1*10)=3.32192809488736
Context

PubMed: DDIT3 [Title/Abstract] AND ATF2 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointDDIT3(57914201)-ATF2(175986270), # 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
HgeneDDIT3

GO:0000122

negative regulation of transcription by RNA polymerase II

18940792

HgeneDDIT3

GO:0006986

response to unfolded protein

18940792

HgeneDDIT3

GO:0007050

cell cycle arrest

22496745

HgeneDDIT3

GO:0032792

negative regulation of CREB transcription factor activity

8622660

HgeneDDIT3

GO:0034976

response to endoplasmic reticulum stress

18940792|19061639|20829347

HgeneDDIT3

GO:0042789

mRNA transcription by RNA polymerase II

14667815

HgeneDDIT3

GO:0043161

proteasome-mediated ubiquitin-dependent protein catabolic process

17872950

HgeneDDIT3

GO:0043433

negative regulation of DNA-binding transcription factor activity

16434966

HgeneDDIT3

GO:0045454

cell redox homeostasis

14667815

HgeneDDIT3

GO:0045892

negative regulation of transcription, DNA-templated

18940792

HgeneDDIT3

GO:0045893

positive regulation of transcription, DNA-templated

15322075|15775988

HgeneDDIT3

GO:0045944

positive regulation of transcription by RNA polymerase II

22065586

HgeneDDIT3

GO:0070059

intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress

18940792|20829347

HgeneDDIT3

GO:1903026

negative regulation of RNA polymerase II regulatory region sequence-specific DNA binding

8622660

HgeneDDIT3

GO:1990440

positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress

15322075|24939851

HgeneDDIT3

GO:2000016

negative regulation of determination of dorsal identity

16434966

TgeneATF2

GO:0001755

neural crest cell migration

15242795

TgeneATF2

GO:0008284

positive regulation of cell proliferation

22897442

TgeneATF2

GO:0031175

neuron projection development

15242795

TgeneATF2

GO:0032770

positive regulation of monooxygenase activity

12358785

TgeneATF2

GO:0043524

negative regulation of neuron apoptotic process

8493557

TgeneATF2

GO:0045944

positive regulation of transcription by RNA polymerase II

12358785

TgeneATF2

GO:0048255

mRNA stabilization

12358785

TgeneATF2

GO:0051584

regulation of dopamine uptake involved in synaptic transmission

8493557

TgeneATF2

GO:0072107

positive regulation of ureteric bud formation

8657307

TgeneATF2

GO:0090190

positive regulation of branching involved in ureteric bud morphogenesis

8657307|17229286

TgeneATF2

GO:2001240

negative regulation of extrinsic apoptotic signaling pathway in absence of ligand

10921886


check buttonFusion gene breakpoints across DDIT3 (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 ATF2 (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/ABU662818DDIT3chr12

57914201

-ATF2chr2

175986270

-


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Fusion Gene ORF analysis for DDIT3-ATF2

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
5UTR-intronENST00000346473ENST00000264110DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000346473ENST00000345739DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000346473ENST00000392543DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000346473ENST00000392544DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000346473ENST00000409437DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000346473ENST00000409499DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000346473ENST00000409635DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000346473ENST00000409833DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000346473ENST00000413123DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000346473ENST00000426833DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000346473ENST00000487334DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000346473ENST00000538946DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000547303ENST00000264110DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000547303ENST00000345739DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000547303ENST00000392543DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000547303ENST00000392544DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000547303ENST00000409437DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000547303ENST00000409499DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000547303ENST00000409635DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000547303ENST00000409833DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000547303ENST00000413123DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000547303ENST00000426833DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000547303ENST00000487334DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000547303ENST00000538946DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000551116ENST00000264110DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000551116ENST00000345739DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000551116ENST00000392543DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000551116ENST00000392544DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000551116ENST00000409437DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000551116ENST00000409499DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000551116ENST00000409635DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000551116ENST00000409833DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000551116ENST00000413123DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000551116ENST00000426833DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000551116ENST00000487334DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000551116ENST00000538946DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000552740ENST00000264110DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000552740ENST00000345739DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000552740ENST00000392543DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000552740ENST00000392544DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000552740ENST00000409437DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000552740ENST00000409499DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000552740ENST00000409635DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000552740ENST00000409833DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000552740ENST00000413123DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000552740ENST00000426833DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000552740ENST00000487334DDIT3chr12

57914201

-ATF2chr2

175986270

-
5UTR-intronENST00000552740ENST00000538946DDIT3chr12

57914201

-ATF2chr2

175986270

-

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 DDIT3-ATF2


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 DDIT3-ATF2


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/:57914201/:175986270)
- 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
DDIT3

P35638

ATF2

P15336

FUNCTION: Multifunctional transcription factor in endoplasmic reticulum (ER) stress response (PubMed:15322075, PubMed:15775988, PubMed:19672300). Plays an essential role in the response to a wide variety of cell stresses and induces cell cycle arrest and apoptosis in response to ER stress (PubMed:15322075, PubMed:15775988). Plays a dual role both as an inhibitor of CCAAT/enhancer-binding protein (C/EBP) function and as an activator of other genes (By similarity). Acts as a dominant-negative regulator of C/EBP-induced transcription: dimerizes with members of the C/EBP family, impairs their association with C/EBP binding sites in the promoter regions, and inhibits the expression of C/EBP regulated genes (By similarity). Positively regulates the transcription of TRIB3, IL6, IL8, IL23, TNFRSF10B/DR5, PPP1R15A/GADD34, BBC3/PUMA, BCL2L11/BIM and ERO1L (PubMed:15775988, PubMed:17709599, PubMed:22761832, PubMed:20876114). Negatively regulates; expression of BCL2 and MYOD1, ATF4-dependent transcriptional activation of asparagine synthetase (ASNS), CEBPA-dependent transcriptional activation of hepcidin (HAMP) and CEBPB-mediated expression of peroxisome proliferator-activated receptor gamma (PPARG) (PubMed:18940792, PubMed:19672300, PubMed:20829347). Together with ATF4, mediates ER-mediated cell death by promoting expression of genes involved in cellular amino acid metabolic processes, mRNA translation and the unfolded protein response (UPR) in response to ER stress (By similarity). Inhibits the canonical Wnt signaling pathway by binding to TCF7L2/TCF4, impairing its DNA-binding properties and repressing its transcriptional activity (PubMed:16434966). Plays a regulatory role in the inflammatory response through the induction of caspase-11 (CASP4/CASP11) which induces the activation of caspase-1 (CASP1) and both these caspases increase the activation of pro-IL1B to mature IL1B which is involved in the inflammatory response (By similarity). Acts as a major regulator of postnatal neovascularization through regulation of endothelial nitric oxide synthase (NOS3)-related signaling (By similarity). {ECO:0000250|UniProtKB:P35639, ECO:0000269|PubMed:15322075, ECO:0000269|PubMed:15775988, ECO:0000269|PubMed:16434966, ECO:0000269|PubMed:17709599, ECO:0000269|PubMed:18940792, ECO:0000269|PubMed:19672300, ECO:0000269|PubMed:20829347, ECO:0000269|PubMed:20876114, ECO:0000269|PubMed:22761832}.FUNCTION: Transcriptional activator which regulates the transcription of various genes, including those involved in anti-apoptosis, cell growth, and DNA damage response. Dependent on its binding partner, binds to CRE (cAMP response element) consensus sequences (5'-TGACGTCA-3') or to AP-1 (activator protein 1) consensus sequences (5'-TGACTCA-3'). In the nucleus, contributes to global transcription and the DNA damage response, in addition to specific transcriptional activities that are related to cell development, proliferation and death. In the cytoplasm, interacts with and perturbs HK1- and VDAC1-containing complexes at the mitochondrial outer membrane, thereby impairing mitochondrial membrane potential, inducing mitochondrial leakage and promoting cell death. The phosphorylated form (mediated by ATM) plays a role in the DNA damage response and is involved in the ionizing radiation (IR)-induced S phase checkpoint control and in the recruitment of the MRN complex into the IR-induced foci (IRIF). Exhibits histone acetyltransferase (HAT) activity which specifically acetylates histones H2B and H4 in vitro (PubMed:10821277). In concert with CUL3 and RBX1, promotes the degradation of KAT5 thereby attenuating its ability to acetylate and activate ATM. Can elicit oncogenic or tumor suppressor activities depending on the tissue or cell type. {ECO:0000269|PubMed:10821277, ECO:0000269|PubMed:15916964, ECO:0000269|PubMed:18397884, ECO:0000269|PubMed:22304920}.

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 DDIT3-ATF2


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 DDIT3-ATF2


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 DDIT3-ATF2


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 DDIT3-ATF2


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