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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:NPM2-CDC16

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NPM2-CDC16
FusionPDB ID: 59994
FusionGDB2.0 ID: 59994
HgeneTgene
Gene symbol

NPM2

CDC16

Gene ID

10361

8881

Gene namenucleophosmin/nucleoplasmin 2cell division cycle 16
Synonyms-ANAPC6|APC6|CDC16Hs|CUT9
Cytomap

8p21.3

13q34

Type of geneprotein-codingprotein-coding
Descriptionnucleoplasmin-2cell division cycle protein 16 homologanaphase-promoting complex, subunit 6cell division cycle 16 homologcyclosome subunit 6
Modification date2020031320200313
UniProtAcc

Q86SE8

Main function of 5'-partner protein: FUNCTION: Core histones chaperone involved in chromatin reprogramming, specially during fertilization and early embryonic development. Probably involved in sperm DNA decondensation during fertilization. {ECO:0000269|PubMed:21863821}.

Q13042

Main function of 5'-partner protein: FUNCTION: Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains. {ECO:0000269|PubMed:18485873}.
Ensembl transtripts involved in fusion geneENST idsENST00000289820, ENST00000381530, 
ENST00000397940, ENST00000518119, 
ENST00000521157, ENST00000520180, 
ENST00000461716, ENST00000252457, 
ENST00000252458, ENST00000356221, 
ENST00000360383, ENST00000375308, 
ENST00000375310, ENST00000375312, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score1 X 1 X 1=16 X 8 X 6=288
# samples 19
** MAII scorelog2(1/1*10)=3.32192809488736log2(9/288*10)=-1.67807190511264
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: NPM2 [Title/Abstract] AND CDC16 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: NPM2 [Title/Abstract] AND CDC16 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NPM2(21892055)-CDC16(115028352), # samples:1
Anticipated loss of major functional domain due to fusion event.NPM2-CDC16 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.
NPM2-CDC16 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.
NPM2-CDC16 seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF.
NPM2-CDC16 seems lost the major protein functional domain in Tgene partner, which is a essential gene 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
HgeneNPM2

GO:0006338

chromatin remodeling

12714744

TgeneCDC16

GO:0070979

protein K11-linked ubiquitination

18485873



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/chr8:21892055/chr13:115028352)
- 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 NPM2 (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 CDC16 (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)
ENST00000521157NPM2chr821892055+ENST00000375312CDC16chr13115028352+194312245501710386
ENST00000521157NPM2chr821892055+ENST00000360383CDC16chr13115028352+186112245501710386
ENST00000521157NPM2chr821892055+ENST00000356221CDC16chr13115028352+194312245501710386
ENST00000521157NPM2chr821892055+ENST00000375310CDC16chr13115028352+186112245501710386
ENST00000521157NPM2chr821892055+ENST00000375308CDC16chr13115028352+186112245501710386
ENST00000521157NPM2chr821892055+ENST00000252457CDC16chr13115028352+186112245501710386
ENST00000521157NPM2chr821892055+ENST00000252458CDC16chr13115028352+199112245501710386
ENST00000397940NPM2chr821892055+ENST00000375312CDC16chr13115028352+230015819072067386
ENST00000397940NPM2chr821892055+ENST00000360383CDC16chr13115028352+221815819072067386
ENST00000397940NPM2chr821892055+ENST00000356221CDC16chr13115028352+230015819072067386
ENST00000397940NPM2chr821892055+ENST00000375310CDC16chr13115028352+221815819072067386
ENST00000397940NPM2chr821892055+ENST00000375308CDC16chr13115028352+221815819072067386
ENST00000397940NPM2chr821892055+ENST00000252457CDC16chr13115028352+221815819072067386
ENST00000397940NPM2chr821892055+ENST00000252458CDC16chr13115028352+234815819072067386
ENST00000518119NPM2chr821892055+ENST00000375312CDC16chr13115028352+16158962731382369
ENST00000518119NPM2chr821892055+ENST00000360383CDC16chr13115028352+15338962731382369
ENST00000518119NPM2chr821892055+ENST00000356221CDC16chr13115028352+16158962731382369
ENST00000518119NPM2chr821892055+ENST00000375310CDC16chr13115028352+15338962731382369
ENST00000518119NPM2chr821892055+ENST00000375308CDC16chr13115028352+15338962731382369
ENST00000518119NPM2chr821892055+ENST00000252457CDC16chr13115028352+15338962731382369
ENST00000518119NPM2chr821892055+ENST00000252458CDC16chr13115028352+16638962731382369
ENST00000289820NPM2chr821892055+ENST00000375312CDC16chr13115028352+15258062071292361
ENST00000289820NPM2chr821892055+ENST00000360383CDC16chr13115028352+14438062071292361
ENST00000289820NPM2chr821892055+ENST00000356221CDC16chr13115028352+15258062071292361
ENST00000289820NPM2chr821892055+ENST00000375310CDC16chr13115028352+14438062071292361
ENST00000289820NPM2chr821892055+ENST00000375308CDC16chr13115028352+14438062071292361
ENST00000289820NPM2chr821892055+ENST00000252457CDC16chr13115028352+14438062071292361
ENST00000289820NPM2chr821892055+ENST00000252458CDC16chr13115028352+15738062071292361

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
ENST00000521157ENST00000375312NPM2chr821892055+CDC16chr13115028352+0.0024019330.9975981
ENST00000521157ENST00000360383NPM2chr821892055+CDC16chr13115028352+0.00300560.9969944
ENST00000521157ENST00000356221NPM2chr821892055+CDC16chr13115028352+0.0024019330.9975981
ENST00000521157ENST00000375310NPM2chr821892055+CDC16chr13115028352+0.00300560.9969944
ENST00000521157ENST00000375308NPM2chr821892055+CDC16chr13115028352+0.00300560.9969944
ENST00000521157ENST00000252457NPM2chr821892055+CDC16chr13115028352+0.00300560.9969944
ENST00000521157ENST00000252458NPM2chr821892055+CDC16chr13115028352+0.0021198010.9978802
ENST00000397940ENST00000375312NPM2chr821892055+CDC16chr13115028352+0.0026522130.9973477
ENST00000397940ENST00000360383NPM2chr821892055+CDC16chr13115028352+0.0031235670.9968765
ENST00000397940ENST00000356221NPM2chr821892055+CDC16chr13115028352+0.0026522130.9973477
ENST00000397940ENST00000375310NPM2chr821892055+CDC16chr13115028352+0.0031235670.9968765
ENST00000397940ENST00000375308NPM2chr821892055+CDC16chr13115028352+0.0031235670.9968765
ENST00000397940ENST00000252457NPM2chr821892055+CDC16chr13115028352+0.0031235670.9968765
ENST00000397940ENST00000252458NPM2chr821892055+CDC16chr13115028352+0.0023966990.99760336
ENST00000518119ENST00000375312NPM2chr821892055+CDC16chr13115028352+0.0010631540.99893683
ENST00000518119ENST00000360383NPM2chr821892055+CDC16chr13115028352+0.0013482040.9986518
ENST00000518119ENST00000356221NPM2chr821892055+CDC16chr13115028352+0.0010631540.99893683
ENST00000518119ENST00000375310NPM2chr821892055+CDC16chr13115028352+0.0013482040.9986518
ENST00000518119ENST00000375308NPM2chr821892055+CDC16chr13115028352+0.0013482040.9986518
ENST00000518119ENST00000252457NPM2chr821892055+CDC16chr13115028352+0.0013482040.9986518
ENST00000518119ENST00000252458NPM2chr821892055+CDC16chr13115028352+0.0009242640.9990758
ENST00000289820ENST00000375312NPM2chr821892055+CDC16chr13115028352+0.0014077810.9985922
ENST00000289820ENST00000360383NPM2chr821892055+CDC16chr13115028352+0.0019878550.99801207
ENST00000289820ENST00000356221NPM2chr821892055+CDC16chr13115028352+0.0014077810.9985922
ENST00000289820ENST00000375310NPM2chr821892055+CDC16chr13115028352+0.0019878550.99801207
ENST00000289820ENST00000375308NPM2chr821892055+CDC16chr13115028352+0.0019878550.99801207
ENST00000289820ENST00000252457NPM2chr821892055+CDC16chr13115028352+0.0019878550.99801207
ENST00000289820ENST00000252458NPM2chr821892055+CDC16chr13115028352+0.001139680.99886036

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 NPM2-CDC16

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
NPM2chr821892055CDC16chr131150283521224164SGQERYEASDLTWEEEEEEEGEEEEE
NPM2chr821892055CDC16chr131150283521581164SGQERYEASDLTWEEEEEEEGEEEEE
NPM2chr821892055CDC16chr13115028352806139SGQERYEASDLTWEEEEEEEGEEEEE
NPM2chr821892055CDC16chr13115028352896147SGQERYEASDLTWEEEEEEEGEEEEE

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Potential FusionNeoAntigen Information of NPM2-CDC16 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 NPM2-CDC16 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 NPM2-CDC16

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 NPM2-CDC16

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 NPM2-CDC16

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 NPM2-CDC16

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 NPM2-CDC16

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 NPM2-CDC16

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 NPM2-CDC16

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