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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:DPP3-KDM2A

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: DPP3-KDM2A
FusionPDB ID: 24013
FusionGDB2.0 ID: 24013
HgeneTgene
Gene symbol

DPP3

KDM2A

Gene ID

10072

22992

Gene namedipeptidyl peptidase 3lysine demethylase 2A
SynonymsDPPIIICXXC8|FBL11|FBL7|FBXL11|JHDM1A|LILINA
Cytomap

11q13.2

11q13.2

Type of geneprotein-codingprotein-coding
Descriptiondipeptidyl peptidase 3DPP IIIdipeptidyl aminopeptidase IIIdipeptidyl arylamidase IIIdipeptidyl peptidase IIIenkephalinase Blysine-specific demethylase 2ACXXC-type zinc finger protein 8F-box and leucine-rich repeat protein 11F-box/LRR-repeat protein 11[Histone-H3]-lysine-36 demethylase 1AjmjC domain-containing histone demethylation protein 1Ajumonji C domain-containing h
Modification date2020031320200320
UniProtAcc

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}.

Q9Y2K7

Main function of 5'-partner protein: FUNCTION: Histone demethylase that specifically demethylates 'Lys-36' of histone H3, thereby playing a central role in histone code. Preferentially demethylates dimethylated H3 'Lys-36' residue while it has weak or no activity for mono- and tri-methylated H3 'Lys-36'. May also recognize and bind to some phosphorylated proteins and promote their ubiquitination and degradation. Required to maintain the heterochromatic state. Associates with centromeres and represses transcription of small non-coding RNAs that are encoded by the clusters of satellite repeats at the centromere. Required to sustain centromeric integrity and genomic stability, particularly during mitosis. Regulates circadian gene expression by repressing the transcriptional activator activity of CLOCK-ARNTL/BMAL1 heterodimer and RORA in a catalytically-independent manner (PubMed:26037310). {ECO:0000269|PubMed:16362057, ECO:0000269|PubMed:19001877, ECO:0000269|PubMed:26037310, ECO:0000269|PubMed:28262558}.
Ensembl transtripts involved in fusion geneENST idsENST00000360510, ENST00000453114, 
ENST00000530165, ENST00000531863, 
ENST00000532677, ENST00000541961, 
ENST00000533799, 
ENST00000526258, 
ENST00000308783, ENST00000530342, 
ENST00000398645, ENST00000529006, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score8 X 8 X 6=38428 X 27 X 8=6048
# samples 1032
** MAII scorelog2(10/384*10)=-1.94110631094643
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(32/6048*10)=-4.24031432933371
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: DPP3 [Title/Abstract] AND KDM2A [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: DPP3 [Title/Abstract] AND KDM2A [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)DPP3(66264948)-KDM2A(66995508), # samples:2
Anticipated loss of major functional domain due to fusion event.DPP3-KDM2A 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.
DPP3-KDM2A 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.
DPP3-KDM2A 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.
DPP3-KDM2A 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
HgeneDPP3

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/chr11:66264948/chr11:66995508)
- 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 DPP3 (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 KDM2A (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)
ENST00000531863DPP3chr1166264948+ENST00000398645KDM2Achr1166995508+7029233940137301109
ENST00000531863DPP3chr1166264948+ENST00000529006KDM2Achr1166995508+7903233940148701489
ENST00000532677DPP3chr1166264948+ENST00000398645KDM2Achr1166995508+7026233640137271108
ENST00000532677DPP3chr1166264948+ENST00000529006KDM2Achr1166995508+7900233640148671488
ENST00000453114DPP3chr1166264948+ENST00000398645KDM2Achr1166995508+66301940533311108
ENST00000453114DPP3chr1166264948+ENST00000529006KDM2Achr1166995508+75041940544711488
ENST00000360510DPP3chr1166264948+ENST00000398645KDM2Achr1166995508+66331943533341109
ENST00000360510DPP3chr1166264948+ENST00000529006KDM2Achr1166995508+75071943544741489
ENST00000541961DPP3chr1166264948+ENST00000398645KDM2Achr1166995508+662419345633251089
ENST00000541961DPP3chr1166264948+ENST00000529006KDM2Achr1166995508+749819345644651469
ENST00000530165DPP3chr1166264948+ENST00000398645KDM2Achr1166995508+651118213332121059
ENST00000530165DPP3chr1166264948+ENST00000529006KDM2Achr1166995508+738518213343521439

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
ENST00000531863ENST00000398645DPP3chr1166264948+KDM2Achr1166995508+0.0010298790.99897015
ENST00000531863ENST00000529006DPP3chr1166264948+KDM2Achr1166995508+0.0013062110.99869376
ENST00000532677ENST00000398645DPP3chr1166264948+KDM2Achr1166995508+0.0010108120.99898916
ENST00000532677ENST00000529006DPP3chr1166264948+KDM2Achr1166995508+0.0012939210.9987061
ENST00000453114ENST00000398645DPP3chr1166264948+KDM2Achr1166995508+0.0007112460.9992887
ENST00000453114ENST00000529006DPP3chr1166264948+KDM2Achr1166995508+0.0008803480.9991197
ENST00000360510ENST00000398645DPP3chr1166264948+KDM2Achr1166995508+0.0007275580.9992724
ENST00000360510ENST00000529006DPP3chr1166264948+KDM2Achr1166995508+0.0008916720.99910825
ENST00000541961ENST00000398645DPP3chr1166264948+KDM2Achr1166995508+0.0007308180.9992692
ENST00000541961ENST00000529006DPP3chr1166264948+KDM2Achr1166995508+0.0009188720.99908113
ENST00000530165ENST00000398645DPP3chr1166264948+KDM2Achr1166995508+0.0007731440.9992268
ENST00000530165ENST00000529006DPP3chr1166264948+KDM2Achr1166995508+0.0009345660.99906546

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 DPP3-KDM2A

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 DPP3-KDM2A 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.

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)

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Potential FusionNeoAntigen Information of DPP3-KDM2A 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 DPP3-KDM2A

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.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of DPP3-KDM2A

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

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Vaccine Design for the FusionNeoAntigens of DPP3-KDM2A

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

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 DPP3-KDM2A

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

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Potential target of CAR-T therapy development for DPP3-KDM2A

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 DPP3-KDM2A

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 DPP3-KDM2A

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