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Center for Computational Systems Medicine
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Fusion Gene and Fusion Protein Summary

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Fusion Amino Acid Sequences (multiple BPs and multiple gene isoforms)

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Fusion Protein Breakpoint Sequences - (for the Screening of the FusionNeoAntigens)

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Potential FusionNeoAntigens in HLA I - (netMHCpan v4.1 + deepHLApan v1.1)

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Potential FusionNeoAntigens in HLA II - (netMHCIIpan v4.1)

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Fusion Breakpoint 14 AA Peptide Structure - (RoseTTAFold)

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D - (Glide)

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Vaccine Design for the FusionNeoAntigens (RNA/protein sequences)

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Potential target of CAR-T therapy development

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Information on the samples that have these potential fusion neoantigens

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Fusion Protein Targeting Drugs - (Manual Curation)

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Fusion Protein Related diseases - (Manual Curation)

Fusion Protein:ECE1-WNT4

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ECE1-WNT4
FusionPDB ID: 24864
FusionGDB2.0 ID: 24864
HgeneTgene
Gene symbol

ECE1

WNT4

Gene ID

1889

54361

Gene nameendothelin converting enzyme 1Wnt family member 4
SynonymsECESERKAL|WNT-4
Cytomap

1p36.12

1p36.12

Type of geneprotein-codingprotein-coding
Descriptionendothelin-converting enzyme 1ECE-1protein Wnt-4wingless-type MMTV integration site family, member 4
Modification date2020031320200313
UniProtAcc

P42892

Main function of 5'-partner protein: FUNCTION: Converts big endothelin-1 to endothelin-1. {ECO:0000269|PubMed:9396733}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000264205, ENST00000357071, 
ENST00000374893, ENST00000415912, 
ENST00000436918, ENST00000528294, 
ENST00000290167, ENST00000542383, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score16 X 15 X 9=21604 X 4 X 4=64
# samples 187
** MAII scorelog2(18/2160*10)=-3.58496250072116
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(7/64*10)=0.129283016944966
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: ECE1 [Title/Abstract] AND WNT4 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ECE1 [Title/Abstract] AND WNT4 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ECE1(21599192)-WNT4(22448069), # samples:3
Anticipated loss of major functional domain due to fusion event.ECE1-WNT4 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF.
ECE1-WNT4 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame 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
HgeneECE1

GO:0010814

substance P catabolic process

18039931

HgeneECE1

GO:0010815

bradykinin catabolic process

18039931

HgeneECE1

GO:0010816

calcitonin catabolic process

18039931

HgeneECE1

GO:0016485

protein processing

7805846

HgeneECE1

GO:0016486

peptide hormone processing

7864876

HgeneECE1

GO:0034959

endothelin maturation

7805846

HgeneECE1

GO:0042447

hormone catabolic process

7864876

TgeneWNT4

GO:0010629

negative regulation of gene expression

15317892

TgeneWNT4

GO:0010894

negative regulation of steroid biosynthetic process

15317892|18182450

TgeneWNT4

GO:0030501

positive regulation of bone mineralization

17720811

TgeneWNT4

GO:0032349

positive regulation of aldosterone biosynthetic process

16981135

TgeneWNT4

GO:0032967

positive regulation of collagen biosynthetic process

17720811

TgeneWNT4

GO:0038030

non-canonical Wnt signaling pathway via MAPK cascade

17720811

TgeneWNT4

GO:0045669

positive regulation of osteoblast differentiation

17720811

TgeneWNT4

GO:0045893

positive regulation of transcription, DNA-templated

16959810|16981135|18182450

TgeneWNT4

GO:0060070

canonical Wnt signaling pathway

15317892|16959810|18182450

TgeneWNT4

GO:0061184

positive regulation of dermatome development

10654605

TgeneWNT4

GO:2000066

positive regulation of cortisol biosynthetic process

16981135

TgeneWNT4

GO:2000180

negative regulation of androgen biosynthetic process

16959810



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/chr1:21599192/chr1:22448069)
- 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 buttonRetention analysis results 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, are available here.

check buttonFusion gene breakpoints across ECE1 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure

check buttonFusion gene breakpoints across WNT4 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure


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Fusion Amino Acid Sequences


check buttonFusion information from ORFfinder translation from full-length transcript sequence from FusionPDB.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)
BP loci
(transcript)
Predicted start
(transcript)
Predicted stop
(transcript)
Seq length
(amino acids)
ENST00000415912ECE1chr121599192-ENST00000290167WNT4chr122448069-40595711261313395
ENST00000415912ECE1chr121599192-ENST00000542383WNT4chr122448069-13365711261313395
ENST00000357071ECE1chr121599192-ENST00000290167WNT4chr122448069-4060572461314422
ENST00000357071ECE1chr121599192-ENST00000542383WNT4chr122448069-1337572461314422
ENST00000374893ECE1chr121599192-ENST00000290167WNT4chr122448069-4056568631310415
ENST00000374893ECE1chr121599192-ENST00000542383WNT4chr122448069-1333568631310415
ENST00000436918ECE1chr121599192-ENST00000290167WNT4chr122448069-4031543381285415
ENST00000436918ECE1chr121599192-ENST00000542383WNT4chr122448069-1308543381285415
ENST00000264205ECE1chr121599192-ENST00000290167WNT4chr122448069-4031543591285408
ENST00000264205ECE1chr121599192-ENST00000542383WNT4chr122448069-1308543591285408
ENST00000415912ECE1chr121599191-ENST00000290167WNT4chr122448069-40595711261313395
ENST00000415912ECE1chr121599191-ENST00000542383WNT4chr122448069-13365711261313395
ENST00000357071ECE1chr121599191-ENST00000290167WNT4chr122448069-4060572461314422
ENST00000357071ECE1chr121599191-ENST00000542383WNT4chr122448069-1337572461314422
ENST00000374893ECE1chr121599191-ENST00000290167WNT4chr122448069-4056568631310415
ENST00000374893ECE1chr121599191-ENST00000542383WNT4chr122448069-1333568631310415
ENST00000436918ECE1chr121599191-ENST00000290167WNT4chr122448069-4031543381285415
ENST00000436918ECE1chr121599191-ENST00000542383WNT4chr122448069-1308543381285415
ENST00000264205ECE1chr121599191-ENST00000290167WNT4chr122448069-4031543591285408
ENST00000264205ECE1chr121599191-ENST00000542383WNT4chr122448069-1308543591285408
ENST00000415912ECE1chr121599191-ENST00000290167WNT4chr122448068-40595711261313395
ENST00000415912ECE1chr121599191-ENST00000542383WNT4chr122448068-13365711261313395
ENST00000357071ECE1chr121599191-ENST00000290167WNT4chr122448068-4060572461314422
ENST00000357071ECE1chr121599191-ENST00000542383WNT4chr122448068-1337572461314422
ENST00000374893ECE1chr121599191-ENST00000290167WNT4chr122448068-4056568631310415
ENST00000374893ECE1chr121599191-ENST00000542383WNT4chr122448068-1333568631310415
ENST00000436918ECE1chr121599191-ENST00000290167WNT4chr122448068-4031543381285415
ENST00000436918ECE1chr121599191-ENST00000542383WNT4chr122448068-1308543381285415
ENST00000264205ECE1chr121599191-ENST00000290167WNT4chr122448068-4031543591285408
ENST00000264205ECE1chr121599191-ENST00000542383WNT4chr122448068-1308543591285408

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
ENST00000415912ENST00000290167ECE1chr121599192-WNT4chr122448069-0.086190730.91380924
ENST00000415912ENST00000542383ECE1chr121599192-WNT4chr122448069-0.094002910.9059971
ENST00000357071ENST00000290167ECE1chr121599192-WNT4chr122448069-0.152670230.8473298
ENST00000357071ENST00000542383ECE1chr121599192-WNT4chr122448069-0.112736630.8872633
ENST00000374893ENST00000290167ECE1chr121599192-WNT4chr122448069-0.066130360.9338696
ENST00000374893ENST00000542383ECE1chr121599192-WNT4chr122448069-0.074910360.9250896
ENST00000436918ENST00000290167ECE1chr121599192-WNT4chr122448069-0.067220.93277997
ENST00000436918ENST00000542383ECE1chr121599192-WNT4chr122448069-0.074584640.92541534
ENST00000264205ENST00000290167ECE1chr121599192-WNT4chr122448069-0.033121050.96687895
ENST00000264205ENST00000542383ECE1chr121599192-WNT4chr122448069-0.049015240.9509848
ENST00000415912ENST00000290167ECE1chr121599191-WNT4chr122448069-0.086190730.91380924
ENST00000415912ENST00000542383ECE1chr121599191-WNT4chr122448069-0.094002910.9059971
ENST00000357071ENST00000290167ECE1chr121599191-WNT4chr122448069-0.152670230.8473298
ENST00000357071ENST00000542383ECE1chr121599191-WNT4chr122448069-0.112736630.8872633
ENST00000374893ENST00000290167ECE1chr121599191-WNT4chr122448069-0.066130360.9338696
ENST00000374893ENST00000542383ECE1chr121599191-WNT4chr122448069-0.074910360.9250896
ENST00000436918ENST00000290167ECE1chr121599191-WNT4chr122448069-0.067220.93277997
ENST00000436918ENST00000542383ECE1chr121599191-WNT4chr122448069-0.074584640.92541534
ENST00000264205ENST00000290167ECE1chr121599191-WNT4chr122448069-0.033121050.96687895
ENST00000264205ENST00000542383ECE1chr121599191-WNT4chr122448069-0.049015240.9509848
ENST00000415912ENST00000290167ECE1chr121599191-WNT4chr122448068-0.086190730.91380924
ENST00000415912ENST00000542383ECE1chr121599191-WNT4chr122448068-0.094002910.9059971
ENST00000357071ENST00000290167ECE1chr121599191-WNT4chr122448068-0.152670230.8473298
ENST00000357071ENST00000542383ECE1chr121599191-WNT4chr122448068-0.112736630.8872633
ENST00000374893ENST00000290167ECE1chr121599191-WNT4chr122448068-0.066130360.9338696
ENST00000374893ENST00000542383ECE1chr121599191-WNT4chr122448068-0.074910360.9250896
ENST00000436918ENST00000290167ECE1chr121599191-WNT4chr122448068-0.067220.93277997
ENST00000436918ENST00000542383ECE1chr121599191-WNT4chr122448068-0.074584640.92541534
ENST00000264205ENST00000290167ECE1chr121599191-WNT4chr122448068-0.033121050.96687895
ENST00000264205ENST00000542383ECE1chr121599191-WNT4chr122448068-0.049015240.9509848

check button Predicted full-length fusion amino acid sequences. For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among all the predicted ones.

Get the fusion protein sequences from here.

Fusion protein sequence information is available in the fasta format.
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

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Fusion Protein Breakpoint Sequences for ECE1-WNT4

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ECE1chr121599191WNT4chr122448068543161LWEHNQAIIKHLLGTREAAFVYAISS
ECE1chr121599191WNT4chr122448068543168LWEHNQAIIKHLLGTREAAFVYAISS
ECE1chr121599191WNT4chr122448068568168LWEHNQAIIKHLLGTREAAFVYAISS
ECE1chr121599191WNT4chr122448068571148LWEHNQAIIKHLLGTREAAFVYAISS
ECE1chr121599191WNT4chr122448068572175LWEHNQAIIKHLLGTREAAFVYAISS
ECE1chr121599191WNT4chr122448069543161LWEHNQAIIKHLLGTREAAFVYAISS
ECE1chr121599191WNT4chr122448069543168LWEHNQAIIKHLLGTREAAFVYAISS
ECE1chr121599191WNT4chr122448069568168LWEHNQAIIKHLLGTREAAFVYAISS
ECE1chr121599191WNT4chr122448069571148LWEHNQAIIKHLLGTREAAFVYAISS
ECE1chr121599191WNT4chr122448069572175LWEHNQAIIKHLLGTREAAFVYAISS
ECE1chr121599192WNT4chr122448069543161LWEHNQAIIKHLLGTREAAFVYAISS
ECE1chr121599192WNT4chr122448069543168LWEHNQAIIKHLLGTREAAFVYAISS
ECE1chr121599192WNT4chr122448069568168LWEHNQAIIKHLLGTREAAFVYAISS
ECE1chr121599192WNT4chr122448069571148LWEHNQAIIKHLLGTREAAFVYAISS
ECE1chr121599192WNT4chr122448069572175LWEHNQAIIKHLLGTREAAFVYAISS

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Potential FusionNeoAntigen Information of ECE1-WNT4 in HLA I

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.
ECE1-WNT4_21599191_22448068.msa

check button Potential FusionNeoAntigen Information
* We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5)
Fusion geneHchrHbpTgeneTchrTbpHLA IFusionNeoAntigen peptideBinding scoreImmunogenic scoreNeoantigen start (at BP 13)Neoantigen end (at BP 13)
ECE1-WNT4chr121599191chr122448068543HLA-B39:06KHLLGTREA0.97860.9084918
ECE1-WNT4chr121599191chr122448068543HLA-A31:02IIKHLLGTR0.90830.5339716
ECE1-WNT4chr121599191chr122448068543HLA-A31:06AIIKHLLGTR0.97120.6522616
ECE1-WNT4chr121599191chr122448068543HLA-A74:11AIIKHLLGTR0.96530.7779616
ECE1-WNT4chr121599191chr122448068543HLA-A74:09AIIKHLLGTR0.96530.7779616
ECE1-WNT4chr121599191chr122448068543HLA-A74:03AIIKHLLGTR0.96530.7779616
ECE1-WNT4chr121599191chr122448068543HLA-A31:01IIKHLLGTR0.94410.5132716
ECE1-WNT4chr121599191chr122448068543HLA-A31:01AIIKHLLGTR0.97310.7155616
ECE1-WNT4chr121599191chr122448068543HLA-A74:01AIIKHLLGTR0.96530.7779616

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Potential FusionNeoAntigen Information of ECE1-WNT4 in HLA II

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.

check button Potential FusionNeoAntigen Information
* We used NetMHCIIpan v4.1 (%rank<0.5).
Fusion geneHchrHbpTgeneTchrTbpHLA IIFusionNeoAntigen peptideNeoantigen start (at BP 13)Neoantigen end (at BP 13)

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Fusion breakpoint peptide structures of ECE1-WNT4

check button3D structures of the fusion breakpoint peptide of 14AA sequence that have potential fusion neoantigens
* The minimum length of the amino acid sequence in RoseTTAFold is 14AA. Here, we predicted the 14AA fusion protein breakpoint sequence not the fusion neoantigen peptide, which is shorter than 14 AA.
File nameBPseqHgeneTgeneHchrHbpTchrTbpAAlen
283AIIKHLLGTREAAFECE1WNT4chr121599191chr122448068543

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ECE1-WNT4

check buttonVirtual screening between 25 HLAs (from PDB) and FusionNeoAntigens
* We used Glide to predict the interaction between HLAs and neoantigens.
HLA allelePDB IDFile nameBPseqDocking scoreGlide score
HLA-B14:023BVN283AIIKHLLGTREAAF-8.46672-8.58012
HLA-B14:023BVN283AIIKHLLGTREAAF-4.13749-5.17279
HLA-B52:013W39283AIIKHLLGTREAAF-7.85514-7.96854
HLA-B52:013W39283AIIKHLLGTREAAF-2.01447-3.04977
HLA-A11:014UQ2283AIIKHLLGTREAAF-9.68879-9.80219
HLA-A24:025HGA283AIIKHLLGTREAAF-8.7721-8.8855
HLA-A24:025HGA283AIIKHLLGTREAAF-5.53899-6.57429
HLA-B44:053DX8283AIIKHLLGTREAAF-7.04417-7.15757
HLA-B44:053DX8283AIIKHLLGTREAAF-3.2143-4.2496

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Vaccine Design for the FusionNeoAntigens of ECE1-WNT4

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptide sequenceFusionNeoAntigen RNA sequence
ECE1-WNT4chr121599191chr122448068616AIIKHLLGTRCAATCATCAAGCACCTCCTCGGGACTCGGG
ECE1-WNT4chr121599191chr122448068716IIKHLLGTRTCATCAAGCACCTCCTCGGGACTCGGG
ECE1-WNT4chr121599191chr122448068918KHLLGTREAAGCACCTCCTCGGGACTCGGGAGGCGG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence

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Information of the samples that have these potential fusion neoantigens of ECE1-WNT4

check button These samples were reported as having these fusion breakpoints. For individual breakpoints, we checked the open reading frames considering multiple gene isoforms and chose the in-frame fusion genes only. Then, we made fusion protein sequences and predicted the fusion neoantigens. These fusion-positive samples may have these potential fusion neoantigens.
Cancer typeFusion geneHchrHbpHenstTchrTbpTenstSample
UCECECE1-WNT4chr121599191ENST00000264205chr122448068ENST00000290167TCGA-AJ-A3BF-01A

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Potential target of CAR-T therapy development for ECE1-WNT4

check button Predicted 3D structure. We used RoseTTAFold.

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, to provide the retention of the transmembrane domain, we only show the protein feature retention information of those transmembrane features


* Minus value of BPloci means that the break point is located before the CDS.
- In-frame and retained 'Transmembrane'.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneECE1chr1:21599191chr1:22448068ENST00000264205-31869_89161768.0TransmembraneHelical%3B Signal-anchor for type II membrane protein
HgeneECE1chr1:21599191chr1:22448068ENST00000357071-21769_89152759.0TransmembraneHelical%3B Signal-anchor for type II membrane protein
HgeneECE1chr1:21599191chr1:22448068ENST00000374893-41969_89164771.0TransmembraneHelical%3B Signal-anchor for type II membrane protein
HgeneECE1chr1:21599191chr1:22448068ENST00000415912-41969_89148755.0TransmembraneHelical%3B Signal-anchor for type II membrane protein
HgeneECE1chr1:21599191chr1:22448069ENST00000264205-31869_89161768.0TransmembraneHelical%3B Signal-anchor for type II membrane protein
HgeneECE1chr1:21599191chr1:22448069ENST00000357071-21769_89152759.0TransmembraneHelical%3B Signal-anchor for type II membrane protein
HgeneECE1chr1:21599191chr1:22448069ENST00000374893-41969_89164771.0TransmembraneHelical%3B Signal-anchor for type II membrane protein
HgeneECE1chr1:21599191chr1:22448069ENST00000415912-41969_89148755.0TransmembraneHelical%3B Signal-anchor for type II membrane protein
HgeneECE1chr1:21599192chr1:22448069ENST00000264205-31869_89161768.0TransmembraneHelical%3B Signal-anchor for type II membrane protein
HgeneECE1chr1:21599192chr1:22448069ENST00000357071-21769_89152759.0TransmembraneHelical%3B Signal-anchor for type II membrane protein
HgeneECE1chr1:21599192chr1:22448069ENST00000374893-41969_89164771.0TransmembraneHelical%3B Signal-anchor for type II membrane protein
HgeneECE1chr1:21599192chr1:22448069ENST00000415912-41969_89148755.0TransmembraneHelical%3B Signal-anchor for type II membrane protein

check button Subcellular localization prediction of the transmembrane domain retained fusion proteins
* We used DeepLoc 1.0. The order of the X-axis of the barplot is as follows: Entry_ID, Localization, Type, Nucleus, Cytoplasm, Extracellular, Mitochondrion, Cell_membrane, Endoplasmic_reticulum, Plastid, Golgi.apparatus, Lysosome.Vacuole, Peroxisome. Y-axis is the output score of DeepLoc. Clicking the image will open a new tab with a large image.
HgeneHchrHbpHenstTgeneTchrTbpTenstDeepLoc result

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Related Drugs to ECE1-WNT4

check button Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDrugSourcePMID

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Related Diseases to ECE1-WNT4

check button Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDiseaseSourcePMID

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