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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:VPS13B-CDH17

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: VPS13B-CDH17
FusionPDB ID: 98266
FusionGDB2.0 ID: 98266
HgeneTgene
Gene symbol

VPS13B

CDH17

Gene ID

157680

1015

Gene namevacuolar protein sorting 13 homolog Bcadherin 17
SynonymsCHS1|COH1CDH16|HPT-1|HPT1
Cytomap

8q22.2

8q22.1

Type of geneprotein-codingprotein-coding
Descriptionvacuolar protein sorting-associated protein 13Bcadherin-17HPT-1 cadherinLI cadherincadherin 17, LI cadherin (liver-intestine)cadherin-16human intestinal peptide-associated transporter HPT-1human peptide transporter 1intestinal peptide-associated transporter HPT-1liver-intestine cadherin
Modification date2020031320200313
UniProtAcc.

Q12864

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. LI-cadherin may have a role in the morphological organization of liver and intestine. Involved in intestinal peptide transport. {ECO:0000269|PubMed:8153632}.
Ensembl transtripts involved in fusion geneENST idsENST00000355155, ENST00000357162, 
ENST00000358544, ENST00000395996, 
ENST00000441350, ENST00000521932, 
ENST00000027335, ENST00000441892, 
ENST00000450165, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score43 X 36 X 17=263166 X 6 X 3=108
# samples 506
** MAII scorelog2(50/26316*10)=-5.71786831273266
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(6/108*10)=-0.84799690655495
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: VPS13B [Title/Abstract] AND CDH17 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: VPS13B [Title/Abstract] AND CDH17 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)VPS13B(100050794)-CDH17(95189949), # samples:2
Anticipated loss of major functional domain due to fusion event.VPS13B-CDH17 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.
VPS13B-CDH17 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.
VPS13B-CDH17 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.
VPS13B-CDH17 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


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/chr8:100050794/chr8:95189949)
- 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 VPS13B (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 CDH17 (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)
ENST00000395996VPS13Bchr8100050794+ENST00000027335CDH17chr895189949-38204021112750879
ENST00000395996VPS13Bchr8100050794+ENST00000441892CDH17chr895189949-23634021111994627
ENST00000395996VPS13Bchr8100050794+ENST00000450165CDH17chr895189949-27514021112750879
ENST00000358544VPS13Bchr8100050794+ENST00000027335CDH17chr895189949-38204021112750879
ENST00000358544VPS13Bchr8100050794+ENST00000441892CDH17chr895189949-23634021111994627
ENST00000358544VPS13Bchr8100050794+ENST00000450165CDH17chr895189949-27514021112750879
ENST00000357162VPS13Bchr8100050794+ENST00000027335CDH17chr895189949-38204021112750879
ENST00000357162VPS13Bchr8100050794+ENST00000441892CDH17chr895189949-23634021111994627
ENST00000357162VPS13Bchr8100050794+ENST00000450165CDH17chr895189949-27514021112750879
ENST00000355155VPS13Bchr8100050794+ENST00000027335CDH17chr895189949-38204021112750879
ENST00000355155VPS13Bchr8100050794+ENST00000441892CDH17chr895189949-23634021111994627
ENST00000355155VPS13Bchr8100050794+ENST00000450165CDH17chr895189949-27514021112750879
ENST00000441350VPS13Bchr8100050794+ENST00000027335CDH17chr895189949-38123941032742879
ENST00000441350VPS13Bchr8100050794+ENST00000441892CDH17chr895189949-23553941031986627
ENST00000441350VPS13Bchr8100050794+ENST00000450165CDH17chr895189949-27433941032742880

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
ENST00000395996ENST00000027335VPS13Bchr8100050794+CDH17chr895189949-0.0003859190.99961406
ENST00000395996ENST00000441892VPS13Bchr8100050794+CDH17chr895189949-0.0006946050.99930537
ENST00000395996ENST00000450165VPS13Bchr8100050794+CDH17chr895189949-0.0005079530.99949205
ENST00000358544ENST00000027335VPS13Bchr8100050794+CDH17chr895189949-0.0003859190.99961406
ENST00000358544ENST00000441892VPS13Bchr8100050794+CDH17chr895189949-0.0006946050.99930537
ENST00000358544ENST00000450165VPS13Bchr8100050794+CDH17chr895189949-0.0005079530.99949205
ENST00000357162ENST00000027335VPS13Bchr8100050794+CDH17chr895189949-0.0003859190.99961406
ENST00000357162ENST00000441892VPS13Bchr8100050794+CDH17chr895189949-0.0006946050.99930537
ENST00000357162ENST00000450165VPS13Bchr8100050794+CDH17chr895189949-0.0005079530.99949205
ENST00000355155ENST00000027335VPS13Bchr8100050794+CDH17chr895189949-0.0003859190.99961406
ENST00000355155ENST00000441892VPS13Bchr8100050794+CDH17chr895189949-0.0006946050.99930537
ENST00000355155ENST00000450165VPS13Bchr8100050794+CDH17chr895189949-0.0005079530.99949205
ENST00000441350ENST00000027335VPS13Bchr8100050794+CDH17chr895189949-0.0003950880.9996049
ENST00000441350ENST00000441892VPS13Bchr8100050794+CDH17chr895189949-0.0007220050.999278
ENST00000441350ENST00000450165VPS13Bchr8100050794+CDH17chr895189949-0.0005249870.99947506

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 VPS13B-CDH17

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
VPS13Bchr8100050794CDH17chr89518994939488SEPVVITINTMECILKLKDGIQFKAN
VPS13Bchr8100050794CDH17chr89518994940288SEPVVITINTMECILKLKDGIQFKAN

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Potential FusionNeoAntigen Information of VPS13B-CDH17 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.
VPS13B-CDH17_100050794_95189949.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)
VPS13B-CDH17chr8100050794chr895189949402HLA-C15:06NTMECILKL0.99930.9051817
VPS13B-CDH17chr8100050794chr895189949402HLA-C03:07NTMECILKL0.99830.9599817
VPS13B-CDH17chr8100050794chr895189949402HLA-C04:06NTMECILKL0.99430.7911817
VPS13B-CDH17chr8100050794chr895189949402HLA-C12:04NTMECILKL0.87180.9933817
VPS13B-CDH17chr8100050794chr895189949402HLA-C06:03NTMECILKL0.86250.9939817
VPS13B-CDH17chr8100050794chr895189949402HLA-C02:06NTMECILKL0.38910.9535817
VPS13B-CDH17chr8100050794chr895189949402HLA-C15:05NTMECILKL0.99910.8894817
VPS13B-CDH17chr8100050794chr895189949402HLA-C15:02NTMECILKL0.9990.8744817
VPS13B-CDH17chr8100050794chr895189949402HLA-A69:01NTMECILKL0.99440.5181817
VPS13B-CDH17chr8100050794chr895189949402HLA-C16:02NTMECILKL0.95720.981817
VPS13B-CDH17chr8100050794chr895189949402HLA-C17:01NTMECILKL0.41330.8049817

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Potential FusionNeoAntigen Information of VPS13B-CDH17 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 VPS13B-CDH17

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
9411TINTMECILKLKDGVPS13BCDH17chr8100050794chr895189949402

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of VPS13B-CDH17

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-B14:023BVN9411TINTMECILKLKDG-7.15543-7.26883
HLA-B14:023BVN9411TINTMECILKLKDG-4.77435-5.80965
HLA-B52:013W399411TINTMECILKLKDG-6.80875-6.92215
HLA-B52:013W399411TINTMECILKLKDG-4.20386-5.23916
HLA-A11:014UQ29411TINTMECILKLKDG-7.5194-8.5547
HLA-A11:014UQ29411TINTMECILKLKDG-6.9601-7.0735
HLA-A24:025HGA9411TINTMECILKLKDG-7.52403-7.63743
HLA-A24:025HGA9411TINTMECILKLKDG-5.82433-6.85963
HLA-B27:056PYJ9411TINTMECILKLKDG-3.28285-4.31815
HLA-B44:053DX89411TINTMECILKLKDG-5.91172-6.94702
HLA-B44:053DX89411TINTMECILKLKDG-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of VPS13B-CDH17

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
VPS13B-CDH17chr8100050794chr895189949817NTMECILKLAAGGATGGGATACAGTTTAAGGCCAAT

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 VPS13B-CDH17

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
SKCMVPS13B-CDH17chr8100050794ENST00000355155chr895189949ENST00000027335TCGA-FR-A7U9-06A

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Potential target of CAR-T therapy development for VPS13B-CDH17

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
TgeneCDH17chr8:100050794chr8:95189949ENST00000027335218788_8080833.0TransmembraneHelical
TgeneCDH17chr8:100050794chr8:95189949ENST00000450165218788_8080833.0TransmembraneHelical

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 VPS13B-CDH17

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 VPS13B-CDH17

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