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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:EDNRB-COL4A1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: EDNRB-COL4A1
FusionPDB ID: 24990
FusionGDB2.0 ID: 24990
HgeneTgene
Gene symbol

EDNRB

COL4A1

Gene ID

1910

1282

Gene nameendothelin receptor type Bcollagen type IV alpha 1 chain
SynonymsABCDS|ET-B|ET-BR|ETB|ETB1|ETBR|ETRB|HSCR|HSCR2|WS4ABSVD|BSVD1|PADMAL|RATOR
Cytomap

13q22.3

13q34

Type of geneprotein-codingprotein-coding
Descriptionendothelin receptor type BHirschsprung disease 2endothelin receptor non-selective typeendothelin receptor subtype B1collagen alpha-1(IV) chainCOL4A1 NC1 domainarrestencollagen IV, alpha-1 polypeptidecollagen of basement membrane, alpha-1 chain
Modification date2020031520200313
UniProtAcc

P24530

Main function of 5'-partner protein: FUNCTION: Non-specific receptor for endothelin 1, 2, and 3. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. {ECO:0000269|PubMed:7536888}.

P02462

Main function of 5'-partner protein: FUNCTION: Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen. {ECO:0000250|UniProtKB:P02463}.; FUNCTION: Arresten, comprising the C-terminal NC1 domain, inhibits angiogenesis and tumor formation. The C-terminal half is found to possess the anti-angiogenic activity. Specifically inhibits endothelial cell proliferation, migration and tube formation. {ECO:0000269|PubMed:10811134, ECO:0000269|PubMed:18775695}.
Ensembl transtripts involved in fusion geneENST idsENST00000334286, ENST00000377211, 
ENST00000446573, ENST00000475537, 
ENST00000467182, ENST00000375820, 
ENST00000543140, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score4 X 4 X 3=4814 X 14 X 7=1372
# samples 416
** MAII scorelog2(4/48*10)=-0.263034405833794
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(16/1372*10)=-3.10013667128545
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: EDNRB [Title/Abstract] AND COL4A1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: EDNRB [Title/Abstract] AND COL4A1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)EDNRB(78492226)-COL4A1(110895081), # samples:1
Anticipated loss of major functional domain due to fusion event.EDNRB-COL4A1 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.
EDNRB-COL4A1 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
HgeneEDNRB

GO:0086100

endothelin receptor signaling pathway

1713452



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/chr13:78492226/chr13:110895081)
- 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 EDNRB (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 COL4A1 (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)
ENST00000446573EDNRBchr1378492226-ENST00000375820COL4A1chr13110895081-705974121056661818
ENST00000446573EDNRBchr1378492226-ENST00000543140COL4A1chr13110895081-31007412102216668
ENST00000377211EDNRBchr1378492226-ENST00000375820COL4A1chr13110895081-722490615358311892
ENST00000377211EDNRBchr1378492226-ENST00000543140COL4A1chr13110895081-32659061532381742
ENST00000334286EDNRBchr1378492226-ENST00000375820COL4A1chr13110895081-703872018956451818
ENST00000334286EDNRBchr1378492226-ENST00000543140COL4A1chr13110895081-30797201892195668

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
ENST00000446573ENST00000375820EDNRBchr1378492226-COL4A1chr13110895081-0.0010044920.9989955
ENST00000446573ENST00000543140EDNRBchr1378492226-COL4A1chr13110895081-0.0029104680.99708956
ENST00000377211ENST00000375820EDNRBchr1378492226-COL4A1chr13110895081-0.0010275210.99897254
ENST00000377211ENST00000543140EDNRBchr1378492226-COL4A1chr13110895081-0.0137259540.98627406
ENST00000334286ENST00000375820EDNRBchr1378492226-COL4A1chr13110895081-0.0009703640.99902964
ENST00000334286ENST00000543140EDNRBchr1378492226-COL4A1chr13110895081-0.0028456660.99715436

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 EDNRB-COL4A1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide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Potential FusionNeoAntigen Information of EDNRB-COL4A1 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.
EDNRB-COL4A1_78492226_110895081.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)
EDNRB-COL4A1chr1378492226chr13110895081720HLA-B07:05GPKGSVGGMGL0.99990.5544415
EDNRB-COL4A1chr1378492226chr13110895081720HLA-B81:01GPKGSVGGMGL0.91590.7841415
EDNRB-COL4A1chr1378492226chr13110895081720HLA-B07:12GPKGSVGGMGL0.99920.5887415
EDNRB-COL4A1chr1378492226chr13110895081720HLA-B42:01GPKGSVGGMGL0.9710.8766415

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Potential FusionNeoAntigen Information of EDNRB-COL4A1 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 EDNRB-COL4A1

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
4264KGSVGGMGLPGTPGEDNRBCOL4A1chr1378492226chr13110895081720

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of EDNRB-COL4A1

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-B14:023BVN4264KGSVGGMGLPGTPG-5.30778-5.42118
HLA-B14:023BVN4264KGSVGGMGLPGTPG-4.13357-5.16887
HLA-B52:013W394264KGSVGGMGLPGTPG-7.05194-7.16534
HLA-B52:013W394264KGSVGGMGLPGTPG-4.86134-5.89664
HLA-A24:025HGA4264KGSVGGMGLPGTPG-8.91386-9.02726
HLA-A24:025HGA4264KGSVGGMGLPGTPG-5.20057-6.23587
HLA-B44:053DX84264KGSVGGMGLPGTPG-5.2293-5.3427
HLA-B44:053DX84264KGSVGGMGLPGTPG-4.04567-5.08097

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Vaccine Design for the FusionNeoAntigens of EDNRB-COL4A1

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
EDNRB-COL4A1chr1378492226chr13110895081415GPKGSVGGMGLATTGACATCCCTATCAATGTCTACAAGGGTGGC

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 EDNRB-COL4A1

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
KIRCEDNRB-COL4A1chr1378492226ENST00000334286chr13110895081ENST00000375820TCGA-A3-A8OW-01A

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Potential target of CAR-T therapy development for EDNRB-COL4A1

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
HgeneEDNRBchr13:78492226chr13:110895081ENST00000334286-17102_126161443.0TransmembraneHelical%3B Name%3D1
HgeneEDNRBchr13:78492226chr13:110895081ENST00000334286-17138_163161443.0TransmembraneHelical%3B Name%3D2
HgeneEDNRBchr13:78492226chr13:110895081ENST00000377211-28102_126251533.0TransmembraneHelical%3B Name%3D1
HgeneEDNRBchr13:78492226chr13:110895081ENST00000377211-28138_163251533.0TransmembraneHelical%3B Name%3D2
HgeneEDNRBchr13:78492226chr13:110895081ENST00000377211-28176_197251533.0TransmembraneHelical%3B Name%3D3
HgeneEDNRBchr13:78492226chr13:110895081ENST00000377211-28219_243251533.0TransmembraneHelical%3B Name%3D4
HgeneEDNRBchr13:78492226chr13:110895081ENST00000446573-17102_126161437.0TransmembraneHelical%3B Name%3D1
HgeneEDNRBchr13:78492226chr13:110895081ENST00000446573-17138_163161437.0TransmembraneHelical%3B Name%3D2

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 EDNRB-COL4A1

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 EDNRB-COL4A1

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