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	Fusion Gene Summary
	Fusion Gene ORF analysis
	Fusion Genomic Features
	Fusion Protein Features
	Fusion Gene Sequence
	Fusion Gene PPI analysis
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Fusion gene:TLE2-AES (FusionGDB2 ID:91110)

Fusion Gene Summary for TLE2-AES

Fusion gene summary

Fusion gene information	Fusion gene name: TLE2-AES
	Fusion gene ID: 91110
		Hgene	Tgene
	Gene symbol	TLE2	AES
	Gene ID	7089	166
	Gene name	TLE family member 2, transcriptional corepressor	TLE family member 5, transcriptional modulator
	Synonyms	ESG\|ESG2\|GRG2	AES\|AES-1\|AES-2\|ESP1\|GRG\|GRG5\|Grg-5
	Cytomap	19p13.3	19p13.3
	Type of gene	protein-coding	protein-coding
	Description	transducin-like enhancer protein 2enhancer of split groucho-like protein 2transducin like enhancer of split 2transducin-like enhancer of split 2 (E(sp1) homolog, Drosophila)transducin-like enhancer of split 2, homolog of Drosophila E(sp1)	TLE family member 5amino-terminal enhancer of splitgp130-associated protein GAMgroucho-related protein 5
	Modification date	20200313	20200327
	UniProtAcc	.	.
	Ensembl transtripts involved in fusion gene	ENST00000262953, ENST00000426948, ENST00000590536, ENST00000591529, ENST00000443826, ENST00000455444, ENST00000447365, ENST00000586422, ENST00000587217,	ENST00000586839, ENST00000592330, ENST00000221561, ENST00000327141,
Fusion gene scores	* DoF score	2 X 3 X 2=12	10 X 12 X 6=720
	# samples	3	13
	** MAII score	log2(3/12*10)=1.32192809488736 effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs). DoF>8 and MAII>0	log2(13/720*10)=-2.46948528330122 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context	PubMed: TLE2 [Title/Abstract] AND AES [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint	TLE2(3028703)-AES(3057739), # samples:1
Anticipated loss of major functional domain due to fusion event.	TLE2-AES seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF. TLE2-AES seems lost the major protein functional domain in Hgene 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)

Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez

Partner	Gene	GO ID	GO term	PubMed ID
Hgene	TLE2	GO:0045892	negative regulation of transcription, DNA-templated	19460168
Hgene	TLE2	GO:0090090	negative regulation of canonical Wnt signaling pathway	19460168
Tgene	AES	GO:0032091	negative regulation of protein binding	15489227
Tgene	AES	GO:0045892	negative regulation of transcription, DNA-templated	19460168
Tgene	AES	GO:0070555	response to interleukin-1	15489227
Tgene	AES	GO:0090090	negative regulation of canonical Wnt signaling pathway	19460168

Fusion gene breakpoints across TLE2 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

Fusion gene breakpoints across AES (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

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.

Source	Disease	Sample	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand
ChimerDB4	LUAD	TCGA-91-7771-01A	TLE2	chr19	3028703	-	AES	chr19	3057739	-

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Fusion Gene ORF analysis for TLE2-AES

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.

ORF	Henst	Tenst	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand
5CDS-5UTR	ENST00000262953	ENST00000586839	TLE2	chr19	3028703	-	AES	chr19	3057739	-
5CDS-5UTR	ENST00000262953	ENST00000592330	TLE2	chr19	3028703	-	AES	chr19	3057739	-
5CDS-5UTR	ENST00000426948	ENST00000586839	TLE2	chr19	3028703	-	AES	chr19	3057739	-
5CDS-5UTR	ENST00000426948	ENST00000592330	TLE2	chr19	3028703	-	AES	chr19	3057739	-
5CDS-5UTR	ENST00000590536	ENST00000586839	TLE2	chr19	3028703	-	AES	chr19	3057739	-
5CDS-5UTR	ENST00000590536	ENST00000592330	TLE2	chr19	3028703	-	AES	chr19	3057739	-
5CDS-5UTR	ENST00000591529	ENST00000586839	TLE2	chr19	3028703	-	AES	chr19	3057739	-
5CDS-5UTR	ENST00000591529	ENST00000592330	TLE2	chr19	3028703	-	AES	chr19	3057739	-
5UTR-3CDS	ENST00000443826	ENST00000221561	TLE2	chr19	3028703	-	AES	chr19	3057739	-
5UTR-3CDS	ENST00000443826	ENST00000327141	TLE2	chr19	3028703	-	AES	chr19	3057739	-
5UTR-3CDS	ENST00000455444	ENST00000221561	TLE2	chr19	3028703	-	AES	chr19	3057739	-
5UTR-3CDS	ENST00000455444	ENST00000327141	TLE2	chr19	3028703	-	AES	chr19	3057739	-
5UTR-5UTR	ENST00000443826	ENST00000586839	TLE2	chr19	3028703	-	AES	chr19	3057739	-
5UTR-5UTR	ENST00000443826	ENST00000592330	TLE2	chr19	3028703	-	AES	chr19	3057739	-
5UTR-5UTR	ENST00000455444	ENST00000586839	TLE2	chr19	3028703	-	AES	chr19	3057739	-
5UTR-5UTR	ENST00000455444	ENST00000592330	TLE2	chr19	3028703	-	AES	chr19	3057739	-
Frame-shift	ENST00000591529	ENST00000221561	TLE2	chr19	3028703	-	AES	chr19	3057739	-
Frame-shift	ENST00000591529	ENST00000327141	TLE2	chr19	3028703	-	AES	chr19	3057739	-
In-frame	ENST00000262953	ENST00000221561	TLE2	chr19	3028703	-	AES	chr19	3057739	-
In-frame	ENST00000262953	ENST00000327141	TLE2	chr19	3028703	-	AES	chr19	3057739	-
In-frame	ENST00000426948	ENST00000221561	TLE2	chr19	3028703	-	AES	chr19	3057739	-
In-frame	ENST00000426948	ENST00000327141	TLE2	chr19	3028703	-	AES	chr19	3057739	-
In-frame	ENST00000590536	ENST00000221561	TLE2	chr19	3028703	-	AES	chr19	3057739	-
In-frame	ENST00000590536	ENST00000327141	TLE2	chr19	3028703	-	AES	chr19	3057739	-
intron-3CDS	ENST00000447365	ENST00000221561	TLE2	chr19	3028703	-	AES	chr19	3057739	-
intron-3CDS	ENST00000447365	ENST00000327141	TLE2	chr19	3028703	-	AES	chr19	3057739	-
intron-3CDS	ENST00000586422	ENST00000221561	TLE2	chr19	3028703	-	AES	chr19	3057739	-
intron-3CDS	ENST00000586422	ENST00000327141	TLE2	chr19	3028703	-	AES	chr19	3057739	-
intron-3CDS	ENST00000587217	ENST00000221561	TLE2	chr19	3028703	-	AES	chr19	3057739	-
intron-3CDS	ENST00000587217	ENST00000327141	TLE2	chr19	3028703	-	AES	chr19	3057739	-
intron-5UTR	ENST00000447365	ENST00000586839	TLE2	chr19	3028703	-	AES	chr19	3057739	-
intron-5UTR	ENST00000447365	ENST00000592330	TLE2	chr19	3028703	-	AES	chr19	3057739	-
intron-5UTR	ENST00000586422	ENST00000586839	TLE2	chr19	3028703	-	AES	chr19	3057739	-
intron-5UTR	ENST00000586422	ENST00000592330	TLE2	chr19	3028703	-	AES	chr19	3057739	-
intron-5UTR	ENST00000587217	ENST00000586839	TLE2	chr19	3028703	-	AES	chr19	3057739	-
intron-5UTR	ENST00000587217	ENST00000592330	TLE2	chr19	3028703	-	AES	chr19	3057739	-

ORFfinder result based on the fusion transcript sequence of in-frame fusion genes.

Henst

Tenst

Hgene

Hchr

Hbp

Hstrand

Tgene

Tchr

Tbp

Tstrand

Seq length
(transcript)

BP loci
(transcript)

Predicted start
(transcript)

Predicted stop
(transcript)

Seq length
(amino acids)

DeepORF 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.

Henst

Tenst

Hgene

Hchr

Hbp

Hstrand

Tgene

Tchr

Tbp

Tstrand

No-coding score

Coding score

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Fusion Genomic Features for TLE2-AES

FusionAI 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.

Hgene

Hchr

Hbp

Hstrand

Tgene

Tchr

Tbp

Tstrand

1-p

p (fusion gene breakpoint)

Distribution 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.

Distribution 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 TLE2-AES

Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr19:3028703/chr19:3057739)
- 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.

Main function of each fusion partner protein. (from UniProt)

Hgene	Tgene
.	.
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: 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}.

Retention 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.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Protein feature

Protein feature note

Tgene

AES

chr19:3028703

chr19:3057739

ENST00000221561

132_165

108

265.0

Compositional bias

Note=Gly/Pro-rich (GP domain)

Tgene

AES

chr19:3028703

chr19:3057739

ENST00000327141

132_165

198.0

Compositional bias

Note=Gly/Pro-rich (GP domain)

Tgene

AES

chr19:3028703

chr19:3057739

ENST00000221561

166_197

108

265.0

Region

Note=CCN domain

Tgene

AES

chr19:3028703

chr19:3057739

ENST00000327141

166_197

198.0

Region

Note=CCN domain

- In-frame and not-retained protein feature among the 13 regional features.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Protein feature

Protein feature note

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000262953

214_217

744.0

Motif

Nuclear localization signal

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000426948

214_217

707.0

Motif

Nuclear localization signal

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000443826

214_217

622.0

Motif

Nuclear localization signal

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000455444

214_217

622.0

Motif

Nuclear localization signal

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000591529

214_217

707.0

Motif

Nuclear localization signal

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000262953

128_191

744.0

Region

GP domain

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000262953

192_254

744.0

Region

CcN domain

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000262953

1_127

744.0

Region

Q domain

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000262953

255_423

744.0

Region

SP domain

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000426948

128_191

707.0

Region

GP domain

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000426948

192_254

707.0

Region

CcN domain

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000426948

1_127

707.0

Region

Q domain

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000426948

255_423

707.0

Region

SP domain

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000443826

128_191

622.0

Region

GP domain

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000443826

192_254

622.0

Region

CcN domain

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000443826

1_127

622.0

Region

Q domain

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000443826

255_423

622.0

Region

SP domain

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000455444

128_191

622.0

Region

GP domain

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000455444

192_254

622.0

Region

CcN domain

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000455444

1_127

622.0

Region

Q domain

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000455444

255_423

622.0

Region

SP domain

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000591529

128_191

707.0

Region

GP domain

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000591529

192_254

707.0

Region

CcN domain

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000591529

1_127

707.0

Region

Q domain

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000591529

255_423

707.0

Region

SP domain

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000262953

455_493

744.0

Repeat

Note=WD 1

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000262953

501_540

744.0

Repeat

Note=WD 2

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000262953

545_584

744.0

Repeat

Note=WD 3

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000262953

587_626

744.0

Repeat

Note=WD 4

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000262953

669_708

744.0

Repeat

Note=WD 5

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000262953

710_742

744.0

Repeat

Note=WD 6

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000426948

455_493

707.0

Repeat

Note=WD 1

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000426948

501_540

707.0

Repeat

Note=WD 2

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000426948

545_584

707.0

Repeat

Note=WD 3

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000426948

587_626

707.0

Repeat

Note=WD 4

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000426948

669_708

707.0

Repeat

Note=WD 5

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000426948

710_742

707.0

Repeat

Note=WD 6

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000443826

455_493

622.0

Repeat

Note=WD 1

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000443826

501_540

622.0

Repeat

Note=WD 2

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000443826

545_584

622.0

Repeat

Note=WD 3

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000443826

587_626

622.0

Repeat

Note=WD 4

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000443826

669_708

622.0

Repeat

Note=WD 5

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000443826

710_742

622.0

Repeat

Note=WD 6

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000455444

455_493

622.0

Repeat

Note=WD 1

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000455444

501_540

622.0

Repeat

Note=WD 2

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000455444

545_584

622.0

Repeat

Note=WD 3

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000455444

587_626

622.0

Repeat

Note=WD 4

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000455444

669_708

622.0

Repeat

Note=WD 5

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000455444

710_742

622.0

Repeat

Note=WD 6

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000591529

455_493

707.0

Repeat

Note=WD 1

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000591529

501_540

707.0

Repeat

Note=WD 2

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000591529

545_584

707.0

Repeat

Note=WD 3

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000591529

587_626

707.0

Repeat

Note=WD 4

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000591529

669_708

707.0

Repeat

Note=WD 5

Hgene

TLE2

chr19:3028703

chr19:3057739

ENST00000591529

710_742

707.0

Repeat

Note=WD 6

Tgene

AES

chr19:3028703

chr19:3057739

ENST00000221561

1_131

108

265.0

Compositional bias

Note=Gln-rich (Q domain)

Tgene

AES

chr19:3028703

chr19:3057739

ENST00000327141

1_131

198.0

Compositional bias

Note=Gln-rich (Q domain)

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Fusion Gene Sequence for TLE2-AES

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 TLE2-AES

Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in
ChiPPI page.

Protein-protein interactors with each fusion partner protein in wild-type (BIOGRID-3.4.160)

Hgene

Hgene's interactors

Tgene

Tgene's interactors

- Retained PPIs in in-frame fusion.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Still interaction with

- Lost PPIs in in-frame fusion.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Interaction lost with

- Retained PPIs, but lost function due to frame-shift fusion.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Interaction lost with

Top

Related Drugs for TLE2-AES

Drugs targeting genes involved in this fusion gene.
(DrugBank Version 5.1.8 2021-05-08)

Partner

Gene

UniProtAcc

DrugBank ID

Drug name

Drug activity

Drug type

Drug status

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Related Diseases for TLE2-AES

Diseases associated with fusion partners.
(DisGeNet 4.0)

Partner

Gene

Disease ID

Disease name

# pubmeds

Source