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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:FAT3-DPP3

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: FAT3-DPP3
FusionPDB ID: 29474
FusionGDB2.0 ID: 29474
HgeneTgene
Gene symbol

FAT3

DPP3

Gene ID

120114

10072

Gene nameFAT atypical cadherin 3dipeptidyl peptidase 3
SynonymsCDHF15|CDHR10|hFat3DPPIII
Cytomap

11q14.3

11q13.2

Type of geneprotein-codingprotein-coding
Descriptionprotocadherin Fat 3FAT tumor suppressor homolog 3cadherin family member 15cadherin-related family member 10dipeptidyl peptidase 3DPP IIIdipeptidyl aminopeptidase IIIdipeptidyl arylamidase IIIdipeptidyl peptidase IIIenkephalinase B
Modification date2020031320200313
UniProtAcc

Q8TDW7

Main function of 5'-partner protein: FUNCTION: May play a role in the interactions between neurites derived from specific subsets of neurons during development. {ECO:0000250}.

Q9NY33

Main function of 5'-partner protein: FUNCTION: Cleaves and degrades bioactive peptides, including angiotensin, Leu-enkephalin and Met-enkephalin (PubMed:3233187, PubMed:1515063). Also cleaves Arg-Arg-beta-naphthylamide (in vitro) (PubMed:9425109, PubMed:3233187, PubMed:11209758). {ECO:0000269|PubMed:11209758, ECO:0000269|PubMed:1515063, ECO:0000269|PubMed:3233187, ECO:0000269|PubMed:9425109}.
Ensembl transtripts involved in fusion geneENST idsENST00000298047, ENST00000409404, 
ENST00000525166, ENST00000541502, 
ENST00000489716, ENST00000533797, 
ENST00000533799, ENST00000360510, 
ENST00000453114, ENST00000530165, 
ENST00000532677, ENST00000541961, 
ENST00000531863, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score10 X 9 X 3=27010 X 9 X 4=360
# samples 1010
** MAII scorelog2(10/270*10)=-1.43295940727611
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(10/360*10)=-1.84799690655495
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: FAT3 [Title/Abstract] AND DPP3 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: FAT3 [Title/Abstract] AND DPP3 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)FAT3(92088570)-DPP3(66276550), # samples:3
Anticipated loss of major functional domain due to fusion event.FAT3-DPP3 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.
FAT3-DPP3 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.
FAT3-DPP3 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.
FAT3-DPP3 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.
FAT3-DPP3 seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF.
FAT3-DPP3 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
FAT3-DPP3 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
FAT3-DPP3 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)

check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
TgeneDPP3

GO:0006508

proteolysis

9425109|10387075



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/chr11:92088570/chr11:66276550)
- 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 FAT3 (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 DPP3 (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)
ENST00000541502FAT3chr1192088570+ENST00000531863DPP3chr1166276550+378133091734811154
ENST00000409404FAT3chr1192088570+ENST00000531863DPP3chr1166276550+378133091734811154
ENST00000298047FAT3chr1192088570+ENST00000531863DPP3chr1166276550+378133091734811154
ENST00000525166FAT3chr1192088570+ENST00000531863DPP3chr1166276550+333628642230361004
ENST00000541502FAT3chr1192088570+ENST00000531863DPP3chr1166276549+378133091734811154
ENST00000409404FAT3chr1192088570+ENST00000531863DPP3chr1166276549+378133091734811154
ENST00000298047FAT3chr1192088570+ENST00000531863DPP3chr1166276549+378133091734811154
ENST00000525166FAT3chr1192088570+ENST00000531863DPP3chr1166276549+333628642230361004

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
ENST00000541502ENST00000531863FAT3chr1192088570+DPP3chr1166276550+0.0001401090.9998599
ENST00000409404ENST00000531863FAT3chr1192088570+DPP3chr1166276550+0.0001401090.9998599
ENST00000298047ENST00000531863FAT3chr1192088570+DPP3chr1166276550+0.0001401090.9998599
ENST00000525166ENST00000531863FAT3chr1192088570+DPP3chr1166276550+0.000126340.99987364
ENST00000541502ENST00000531863FAT3chr1192088570+DPP3chr1166276549+0.0001401090.9998599
ENST00000409404ENST00000531863FAT3chr1192088570+DPP3chr1166276549+0.0001401090.9998599
ENST00000298047ENST00000531863FAT3chr1192088570+DPP3chr1166276549+0.0001401090.9998599
ENST00000525166ENST00000531863FAT3chr1192088570+DPP3chr1166276549+0.000126340.99987364

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 FAT3-DPP3

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
FAT3chr1192088570DPP3chr11662765492864947GSGLGRFSIDDESGSDVQLLEYEASA
FAT3chr1192088570DPP3chr116627654933091097GSGLGRFSIDDESGSDVQLLEYEASA
FAT3chr1192088570DPP3chr11662765502864947GSGLGRFSIDDESGSDVQLLEYEASA
FAT3chr1192088570DPP3chr116627655033091097GSGLGRFSIDDESGSDVQLLEYEASA

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Potential FusionNeoAntigen Information of FAT3-DPP3 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.
FAT3-DPP3_92088570_66276549.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)
FAT3-DPP3chr1192088570chr11662765493309HLA-B18:01DESGSDVQL0.8490.771019
FAT3-DPP3chr1192088570chr11662765493309HLA-B40:01IDDESGSDVQL0.94660.5332819
FAT3-DPP3chr1192088570chr11662765493309HLA-B39:08IDDESGSDVQL0.99660.7295819
FAT3-DPP3chr1192088570chr11662765493309HLA-B40:04DESGSDVQL0.92870.69841019
FAT3-DPP3chr1192088570chr11662765493309HLA-B18:04DESGSDVQL0.9180.77561019
FAT3-DPP3chr1192088570chr11662765493309HLA-B18:07DESGSDVQL0.89680.70051019
FAT3-DPP3chr1192088570chr11662765493309HLA-B18:05DESGSDVQL0.8490.771019
FAT3-DPP3chr1192088570chr11662765493309HLA-B18:08DESGSDVQL0.84620.88771019
FAT3-DPP3chr1192088570chr11662765493309HLA-B18:03DESGSDVQL0.81340.75671019
FAT3-DPP3chr1192088570chr11662765493309HLA-B18:06DESGSDVQL0.80490.81661019
FAT3-DPP3chr1192088570chr11662765493309HLA-B18:11DESGSDVQL0.42530.72371019
FAT3-DPP3chr1192088570chr11662765493309HLA-B39:11DESGSDVQL0.36180.73791019
FAT3-DPP3chr1192088570chr11662765493309HLA-B41:03DESGSDVQL0.25570.64021019
FAT3-DPP3chr1192088570chr11662765493309HLA-B39:31DESGSDVQL0.23510.89291019
FAT3-DPP3chr1192088570chr11662765493309HLA-B40:49IDDESGSDVQL0.95080.552819
FAT3-DPP3chr1192088570chr11662765493309HLA-B40:36IDDESGSDVQL0.95040.5061819

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Potential FusionNeoAntigen Information of FAT3-DPP3 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 FAT3-DPP3

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
2567FSIDDESGSDVQLLFAT3DPP3chr1192088570chr11662765493309

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of FAT3-DPP3

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-B14:023BVN2567FSIDDESGSDVQLL-7.9962-8.1096
HLA-B14:023BVN2567FSIDDESGSDVQLL-5.70842-6.74372
HLA-B52:013W392567FSIDDESGSDVQLL-6.83737-6.95077
HLA-B52:013W392567FSIDDESGSDVQLL-4.4836-5.5189
HLA-A11:014UQ22567FSIDDESGSDVQLL-10.0067-10.1201
HLA-A11:014UQ22567FSIDDESGSDVQLL-9.03915-10.0745
HLA-A24:025HGA2567FSIDDESGSDVQLL-6.56204-6.67544
HLA-A24:025HGA2567FSIDDESGSDVQLL-5.42271-6.45801
HLA-B44:053DX82567FSIDDESGSDVQLL-7.85648-8.89178
HLA-B44:053DX82567FSIDDESGSDVQLL-5.3978-5.5112
HLA-A02:016TDR2567FSIDDESGSDVQLL-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of FAT3-DPP3

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
FAT3-DPP3chr1192088570chr11662765491019DESGSDVQLACGAGAGTGGCTCAGACGTGCAGCTTC
FAT3-DPP3chr1192088570chr1166276549819IDDESGSDVQLTAGACGACGAGAGTGGCTCAGACGTGCAGCTTC

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 FAT3-DPP3

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
LUADFAT3-DPP3chr1192088570ENST00000298047chr1166276549ENST00000531863TCGA-97-A4M3

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Potential target of CAR-T therapy development for FAT3-DPP3

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 FAT3-DPP3

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 FAT3-DPP3

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