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	Fusion Gene Summary
	Fusion Gene ORF analysis
	Fusion Genomic Features
	Fusion Protein Features
	Fusion Gene Sequence
	Fusion Gene PPI analysis
	Related Drugs
	Related Diseases

Fusion gene:WWTR1-ESRRG (FusionGDB2 ID:98876)

Fusion Gene Summary for WWTR1-ESRRG

Fusion gene summary

Fusion gene information	Fusion gene name: WWTR1-ESRRG
	Fusion gene ID: 98876
		Hgene	Tgene
	Gene symbol	WWTR1	ESRRG
	Gene ID	25937	2104
	Gene name	WW domain containing transcription regulator 1	estrogen related receptor gamma
	Synonyms	TAZ	ERR-gamma\|ERR3\|ERRg\|ERRgamma\|NR3B3
	Cytomap	3q25.1	1q41
	Type of gene	protein-coding	protein-coding
	Description	WW domain-containing transcription regulator protein 1transcriptional co-activator with PDZ-binding motif	estrogen-related receptor gammaERR gamma-2estrogen receptor-related protein 3nuclear receptor subfamily 3 group B member 3
	Modification date	20200313	20200313
	UniProtAcc	.	P62508
	Ensembl transtripts involved in fusion gene	ENST00000465804, ENST00000360632, ENST00000467467, ENST00000474080,	ENST00000361525, ENST00000366940, ENST00000361395, ENST00000366938, ENST00000359162, ENST00000493603, ENST00000463665, ENST00000487276, ENST00000493748, ENST00000471371, ENST00000391890, ENST00000366937, ENST00000408911, ENST00000360012,
Fusion gene scores	* DoF score	12 X 10 X 6=720	7 X 6 X 4=168
	# samples	12	7
	** MAII score	log2(12/720*10)=-2.58496250072116 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(7/168*10)=-1.26303440583379 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context	PubMed: WWTR1 [Title/Abstract] AND ESRRG [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint	WWTR1(149290651)-ESRRG(216741440), # samples:1
Anticipated loss of major functional domain due to fusion event.	WWTR1-ESRRG seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF. WWTR1-ESRRG seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF. WWTR1-ESRRG seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF. WWTR1-ESRRG seems lost the major protein functional domain in Tgene partner, which is a transcription factor due to the frame-shifted ORF. WWTR1-ESRRG seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target 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	WWTR1	GO:0008284	positive regulation of cell proliferation	18227151
Hgene	WWTR1	GO:0010718	positive regulation of epithelial to mesenchymal transition	18227151
Hgene	WWTR1	GO:0017145	stem cell division	18568018
Hgene	WWTR1	GO:0035329	hippo signaling	18227151\|20412773
Hgene	WWTR1	GO:0060390	regulation of SMAD protein signal transduction	18568018
Tgene	ESRRG	GO:0006355	regulation of transcription, DNA-templated	23836911

Fusion gene breakpoints across WWTR1 (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 ESRRG (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	SKCM	TCGA-WE-AAA4-06A	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-

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Fusion Gene ORF analysis for WWTR1-ESRRG

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
Frame-shift	ENST00000465804	ENST00000361525	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
Frame-shift	ENST00000465804	ENST00000366940	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
Frame-shift	ENST00000465804	ENST00000361395	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
Frame-shift	ENST00000465804	ENST00000366938	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
Frame-shift	ENST00000465804	ENST00000359162	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
Frame-shift	ENST00000465804	ENST00000493603	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
Frame-shift	ENST00000465804	ENST00000463665	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
Frame-shift	ENST00000465804	ENST00000487276	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
Frame-shift	ENST00000465804	ENST00000493748	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
5CDS-intron	ENST00000465804	ENST00000471371	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
5CDS-intron	ENST00000465804	ENST00000391890	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
5CDS-intron	ENST00000465804	ENST00000366937	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
5CDS-intron	ENST00000465804	ENST00000408911	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
5CDS-intron	ENST00000465804	ENST00000360012	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
Frame-shift	ENST00000360632	ENST00000361525	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
Frame-shift	ENST00000360632	ENST00000366940	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
Frame-shift	ENST00000360632	ENST00000361395	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
Frame-shift	ENST00000360632	ENST00000366938	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
Frame-shift	ENST00000360632	ENST00000359162	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
Frame-shift	ENST00000360632	ENST00000493603	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
Frame-shift	ENST00000360632	ENST00000463665	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
Frame-shift	ENST00000360632	ENST00000487276	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
Frame-shift	ENST00000360632	ENST00000493748	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
5CDS-intron	ENST00000360632	ENST00000471371	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
5CDS-intron	ENST00000360632	ENST00000391890	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
5CDS-intron	ENST00000360632	ENST00000366937	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
5CDS-intron	ENST00000360632	ENST00000408911	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
5CDS-intron	ENST00000360632	ENST00000360012	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
Frame-shift	ENST00000467467	ENST00000361525	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
Frame-shift	ENST00000467467	ENST00000366940	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
Frame-shift	ENST00000467467	ENST00000361395	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
Frame-shift	ENST00000467467	ENST00000366938	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
Frame-shift	ENST00000467467	ENST00000359162	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
Frame-shift	ENST00000467467	ENST00000493603	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
Frame-shift	ENST00000467467	ENST00000463665	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
Frame-shift	ENST00000467467	ENST00000487276	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
Frame-shift	ENST00000467467	ENST00000493748	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
5CDS-intron	ENST00000467467	ENST00000471371	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
5CDS-intron	ENST00000467467	ENST00000391890	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
5CDS-intron	ENST00000467467	ENST00000366937	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
5CDS-intron	ENST00000467467	ENST00000408911	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
5CDS-intron	ENST00000467467	ENST00000360012	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
intron-3CDS	ENST00000474080	ENST00000361525	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
intron-3CDS	ENST00000474080	ENST00000366940	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
intron-3CDS	ENST00000474080	ENST00000361395	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
intron-3CDS	ENST00000474080	ENST00000366938	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
intron-3CDS	ENST00000474080	ENST00000359162	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
intron-3CDS	ENST00000474080	ENST00000493603	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
intron-3CDS	ENST00000474080	ENST00000463665	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
intron-3CDS	ENST00000474080	ENST00000487276	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
intron-3CDS	ENST00000474080	ENST00000493748	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
intron-intron	ENST00000474080	ENST00000471371	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
intron-intron	ENST00000474080	ENST00000391890	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
intron-intron	ENST00000474080	ENST00000366937	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
intron-intron	ENST00000474080	ENST00000408911	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-
intron-intron	ENST00000474080	ENST00000360012	WWTR1	chr3	149290651	-	ESRRG	chr1	216741440	-

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 WWTR1-ESRRG

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 WWTR1-ESRRG

Go to
FGviewer for the breakpoints of :-:
.
- FGviewer provides the online visualization of the retention search of the protein functional features across DNA, RNA, protein, and pathological levels.

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

Hgene	Tgene
.	ESRRG P62508
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.	FUNCTION: Orphan receptor that acts as transcription activator in the absence of bound ligand. Binds specifically to an estrogen response element and activates reporter genes controlled by estrogen response elements (By similarity). Induces the expression of PERM1 in the skeletal muscle. {ECO:0000250, ECO:0000269\|PubMed:11864604, ECO:0000269\|PubMed:18063693, ECO:0000269\|PubMed:19067653, ECO:0000269\|PubMed:23836911}.

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

- 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

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Fusion Gene Sequence for WWTR1-ESRRG

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 WWTR1-ESRRG

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

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Related Drugs for WWTR1-ESRRG

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
Tgene	ESRRG	P62508	DB00675	Tamoxifen		Small molecule	Approved
Tgene	ESRRG	P62508	DB00675	Tamoxifen		Small molecule	Approved
Tgene	ESRRG	P62508	DB00675	Tamoxifen		Small molecule	Approved
Tgene	ESRRG	P62508	DB00675	Tamoxifen		Small molecule	Approved
Tgene	ESRRG	P62508	DB00675	Tamoxifen		Small molecule	Approved
Tgene	ESRRG	P62508	DB02659	Cholic Acid		Small molecule	Approved
Tgene	ESRRG	P62508	DB02659	Cholic Acid		Small molecule	Approved
Tgene	ESRRG	P62508	DB02659	Cholic Acid		Small molecule	Approved
Tgene	ESRRG	P62508	DB02659	Cholic Acid		Small molecule	Approved
Tgene	ESRRG	P62508	DB02659	Cholic Acid		Small molecule	Approved
Tgene	ESRRG	P62508	DB00255	Diethylstilbestrol	Agonist	Small molecule	Approved\|Investigational
Tgene	ESRRG	P62508	DB00255	Diethylstilbestrol	Agonist	Small molecule	Approved\|Investigational
Tgene	ESRRG	P62508	DB00255	Diethylstilbestrol	Agonist	Small molecule	Approved\|Investigational
Tgene	ESRRG	P62508	DB00255	Diethylstilbestrol	Agonist	Small molecule	Approved\|Investigational
Tgene	ESRRG	P62508	DB00255	Diethylstilbestrol	Agonist	Small molecule	Approved\|Investigational
Tgene	ESRRG	P62508	DB13952	Estradiol acetate	Ligand	Small molecule	Approved\|Investigational\|Vet_approved
Tgene	ESRRG	P62508	DB13952	Estradiol acetate	Ligand	Small molecule	Approved\|Investigational\|Vet_approved
Tgene	ESRRG	P62508	DB13952	Estradiol acetate	Ligand	Small molecule	Approved\|Investigational\|Vet_approved
Tgene	ESRRG	P62508	DB13952	Estradiol acetate	Ligand	Small molecule	Approved\|Investigational\|Vet_approved
Tgene	ESRRG	P62508	DB13952	Estradiol acetate	Ligand	Small molecule	Approved\|Investigational\|Vet_approved
Tgene	ESRRG	P62508	DB13953	Estradiol benzoate	Ligand	Small molecule	Approved\|Investigational\|Vet_approved
Tgene	ESRRG	P62508	DB13953	Estradiol benzoate	Ligand	Small molecule	Approved\|Investigational\|Vet_approved
Tgene	ESRRG	P62508	DB13953	Estradiol benzoate	Ligand	Small molecule	Approved\|Investigational\|Vet_approved
Tgene	ESRRG	P62508	DB13953	Estradiol benzoate	Ligand	Small molecule	Approved\|Investigational\|Vet_approved
Tgene	ESRRG	P62508	DB13953	Estradiol benzoate	Ligand	Small molecule	Approved\|Investigational\|Vet_approved
Tgene	ESRRG	P62508	DB13954	Estradiol cypionate	Ligand	Small molecule	Approved\|Investigational\|Vet_approved
Tgene	ESRRG	P62508	DB13954	Estradiol cypionate	Ligand	Small molecule	Approved\|Investigational\|Vet_approved
Tgene	ESRRG	P62508	DB13954	Estradiol cypionate	Ligand	Small molecule	Approved\|Investigational\|Vet_approved
Tgene	ESRRG	P62508	DB13954	Estradiol cypionate	Ligand	Small molecule	Approved\|Investigational\|Vet_approved
Tgene	ESRRG	P62508	DB13954	Estradiol cypionate	Ligand	Small molecule	Approved\|Investigational\|Vet_approved
Tgene	ESRRG	P62508	DB13955	Estradiol dienanthate	Ligand	Small molecule	Approved\|Investigational\|Vet_approved
Tgene	ESRRG	P62508	DB13955	Estradiol dienanthate	Ligand	Small molecule	Approved\|Investigational\|Vet_approved
Tgene	ESRRG	P62508	DB13955	Estradiol dienanthate	Ligand	Small molecule	Approved\|Investigational\|Vet_approved
Tgene	ESRRG	P62508	DB13955	Estradiol dienanthate	Ligand	Small molecule	Approved\|Investigational\|Vet_approved
Tgene	ESRRG	P62508	DB13955	Estradiol dienanthate	Ligand	Small molecule	Approved\|Investigational\|Vet_approved
Tgene	ESRRG	P62508	DB13956	Estradiol valerate	Ligand	Small molecule	Approved\|Investigational\|Vet_approved
Tgene	ESRRG	P62508	DB13956	Estradiol valerate	Ligand	Small molecule	Approved\|Investigational\|Vet_approved
Tgene	ESRRG	P62508	DB13956	Estradiol valerate	Ligand	Small molecule	Approved\|Investigational\|Vet_approved
Tgene	ESRRG	P62508	DB13956	Estradiol valerate	Ligand	Small molecule	Approved\|Investigational\|Vet_approved
Tgene	ESRRG	P62508	DB13956	Estradiol valerate	Ligand	Small molecule	Approved\|Investigational\|Vet_approved
Tgene	ESRRG	P62508	DB00197	Troglitazone	Inverse agonist	Small molecule	Approved\|Investigational\|Withdrawn
Tgene	ESRRG	P62508	DB00197	Troglitazone	Inverse agonist	Small molecule	Approved\|Investigational\|Withdrawn
Tgene	ESRRG	P62508	DB00197	Troglitazone	Inverse agonist	Small molecule	Approved\|Investigational\|Withdrawn
Tgene	ESRRG	P62508	DB00197	Troglitazone	Inverse agonist	Small molecule	Approved\|Investigational\|Withdrawn
Tgene	ESRRG	P62508	DB00197	Troglitazone	Inverse agonist	Small molecule	Approved\|Investigational\|Withdrawn

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Related Diseases for WWTR1-ESRRG

Diseases associated with fusion partners.
(DisGeNet 4.0)

Partner	Gene	Disease ID	Disease name	# pubmeds	Source
Hgene	WWTR1	C0026846	Muscular Atrophy	1	CTD_human
Hgene	WWTR1	C0206655	Alveolar rhabdomyosarcoma	1	CTD_human
Hgene	WWTR1	C0206732	Epithelioid hemangioendothelioma	1	ORPHANET
Hgene	WWTR1	C0270948	Neurogenic Muscular Atrophy	1	CTD_human