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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:CDH1-TRADD

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CDH1-TRADD
FusionPDB ID: 15043
FusionGDB2.0 ID: 15043
HgeneTgene
Gene symbol

CDH1

TRADD

Gene ID

51343

8717

Gene namefizzy and cell division cycle 20 related 1TNFRSF1A associated via death domain
SynonymsCDC20C|CDH1|FZR|FZR2|HCDH|HCDH1Hs.89862
Cytomap

19p13.3

16q22.1

Type of geneprotein-codingprotein-coding
Descriptionfizzy-related protein homologCDC20 homolog 1CDC20-like 1bCDC20-like protein 1cdh1/Hct1 homologfizzy/cell division cycle 20 related 1tumor necrosis factor receptor type 1-associated DEATH domain proteinTNFR1-associated death domain proteintumor necrosis factor receptor type 1 associated death domain proteintumor necrosis factor receptor-1-associated protein
Modification date2020031320200313
UniProtAcc

Q9H159

Main function of 5'-partner protein: FUNCTION: Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types.
.
Ensembl transtripts involved in fusion geneENST idsENST00000261769, ENST00000422392, 
ENST00000562836, 
ENST00000486556, 
ENST00000566104, ENST00000345057, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score21 X 16 X 8=26881 X 1 X 1=1
# samples 291
** MAII scorelog2(29/2688*10)=-3.21240833276383
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(1/1*10)=3.32192809488736
Fusion gene context

PubMed: CDH1 [Title/Abstract] AND TRADD [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CDH1 [Title/Abstract] AND TRADD [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CDH1(68772314)-TRADD(67189557), # samples:1
Anticipated loss of major functional domain due to fusion event.CDH1-TRADD 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.
CDH1-TRADD 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.
CDH1-TRADD 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.
CDH1-TRADD 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
HgeneCDH1

GO:0031145

anaphase-promoting complex-dependent catabolic process

18662541|21596315

HgeneCDH1

GO:0072425

signal transduction involved in G2 DNA damage checkpoint

18662541

HgeneCDH1

GO:1904668

positive regulation of ubiquitin protein ligase activity

11459826



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/chr16:68772314/chr16:67189557)
- 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 CDH1 (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 TRADD (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)
ENST00000261769CDH1chr1668772314+ENST00000345057TRADDchr1667189557-1611354411141366
ENST00000422392CDH1chr1668772314+ENST00000345057TRADDchr1667189557-1484227641014316

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
ENST00000261769ENST00000345057CDH1chr1668772314+TRADDchr1667189557-0.0249305610.9750694
ENST00000422392ENST00000345057CDH1chr1668772314+TRADDchr1667189557-0.026360330.9736397

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 CDH1-TRADD

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CDH1chr1668772314TRADDchr166718955722754PRRHLERGRVLGRESGGSPDVLQMLK
CDH1chr1668772314TRADDchr1667189557354104PRRHLERGRVLGRESGGSPDVLQMLK

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Potential FusionNeoAntigen Information of CDH1-TRADD 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.
CDH1-TRADD_68772314_67189557.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)
CDH1-TRADDchr1668772314chr1667189557354HLA-B45:01RESGGSPDV0.95240.82591221
CDH1-TRADDchr1668772314chr1667189557354HLA-B50:02RESGGSPDV0.94510.6721221
CDH1-TRADDchr1668772314chr1667189557354HLA-B40:01RESGGSPDV0.90420.61681221
CDH1-TRADDchr1668772314chr1667189557354HLA-B41:01RESGGSPDV0.38160.7181221
CDH1-TRADDchr1668772314chr1667189557354HLA-B39:13RESGGSPDV0.07490.79571221
CDH1-TRADDchr1668772314chr1667189557354HLA-B50:01RESGGSPDV0.070.89551221
CDH1-TRADDchr1668772314chr1667189557354HLA-B48:01RESGGSPDVL0.96750.59431222
CDH1-TRADDchr1668772314chr1667189557354HLA-B47:01RESGGSPDVL0.79320.60791222
CDH1-TRADDchr1668772314chr1667189557354HLA-B39:13RESGGSPDVL0.76740.89241222
CDH1-TRADDchr1668772314chr1667189557354HLA-B41:01RESGGSPDVL0.54050.80831222
CDH1-TRADDchr1668772314chr1667189557354HLA-B40:06RESGGSPDV0.99240.73951221
CDH1-TRADDchr1668772314chr1667189557354HLA-B39:08RESGGSPDV0.22470.7421221
CDH1-TRADDchr1668772314chr1667189557354HLA-B48:03RESGGSPDVL0.97250.50681222
CDH1-TRADDchr1668772314chr1667189557354HLA-B39:08RESGGSPDVL0.95180.89321222
CDH1-TRADDchr1668772314chr1667189557354HLA-B40:04RESGGSPDV0.97610.83321221
CDH1-TRADDchr1668772314chr1667189557354HLA-B40:36RESGGSPDV0.91840.61221221
CDH1-TRADDchr1668772314chr1667189557354HLA-B40:49RESGGSPDV0.83950.61751221
CDH1-TRADDchr1668772314chr1667189557354HLA-B41:03RESGGSPDV0.48470.58351221
CDH1-TRADDchr1668772314chr1667189557354HLA-B50:05RESGGSPDV0.070.89551221
CDH1-TRADDchr1668772314chr1667189557354HLA-B50:04RESGGSPDV0.070.89551221
CDH1-TRADDchr1668772314chr1667189557354HLA-B40:04RESGGSPDVL0.98320.67571222
CDH1-TRADDchr1668772314chr1667189557354HLA-B40:12RESGGSPDVL0.97250.50681222
CDH1-TRADDchr1668772314chr1667189557354HLA-B39:02RESGGSPDVL0.82040.89141222
CDH1-TRADDchr1668772314chr1667189557354HLA-B41:03RESGGSPDVL0.63630.59831222

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Potential FusionNeoAntigen Information of CDH1-TRADD 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 CDH1-TRADD

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
7901RGRVLGRESGGSPDCDH1TRADDchr1668772314chr1667189557354

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CDH1-TRADD

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-B14:023BVN7901RGRVLGRESGGSPD-7.47685-7.66885
HLA-B14:023BVN7901RGRVLGRESGGSPD-4.29364-5.05464
HLA-B52:013W397901RGRVLGRESGGSPD-6.01069-6.20269
HLA-B52:013W397901RGRVLGRESGGSPD-4.45369-5.21469
HLA-B18:014JQV7901RGRVLGRESGGSPD-7.98337-8.17537
HLA-A11:014UQ27901RGRVLGRESGGSPD-7.99589-8.18789
HLA-A11:014UQ27901RGRVLGRESGGSPD-4.70281-5.46381
HLA-A24:025HGA7901RGRVLGRESGGSPD-7.22917-7.99017
HLA-A24:025HGA7901RGRVLGRESGGSPD-6.12023-6.31223
HLA-B27:056PYJ7901RGRVLGRESGGSPD-6.28372-6.47572
HLA-B27:056PYJ7901RGRVLGRESGGSPD-4.56493-5.32593
HLA-B44:053DX87901RGRVLGRESGGSPD-4.78356-4.97556
HLA-B44:053DX87901RGRVLGRESGGSPD-4.33664-5.09764
HLA-A02:016TDR7901RGRVLGRESGGSPD-3.11044-3.30244

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Vaccine Design for the FusionNeoAntigens of CDH1-TRADD

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
CDH1-TRADDchr1668772314chr16671895571221RESGGSPDVGAGAGAGCGGCGGGAGCCCGGACGTGC
CDH1-TRADDchr1668772314chr16671895571222RESGGSPDVLGAGAGAGCGGCGGGAGCCCGGACGTGCTGC

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 CDH1-TRADD

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
THCACDH1-TRADDchr1668772314ENST00000261769chr1667189557ENST00000345057TCGA-EM-A3FR-01A

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Potential target of CAR-T therapy development for CDH1-TRADD

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

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 CDH1-TRADD

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 CDH1-TRADD

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