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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:NQO1-JAG1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NQO1-JAG1
FusionPDB ID: 60056
FusionGDB2.0 ID: 60056
HgeneTgene
Gene symbol

NQO1

JAG1

Gene ID

1728

182

Gene nameNAD(P)H quinone dehydrogenase 1jagged canonical Notch ligand 1
SynonymsDHQU|DIA4|DTD|NMOR1|NMORI|QR1AGS|AGS1|AHD|AWS|CD339|DCHE|HJ1|JAGL1
Cytomap

16q22.1

20p12.2

Type of geneprotein-codingprotein-coding
DescriptionNAD(P)H dehydrogenase [quinone] 1DT-diaphoraseNAD(P)H dehydrogenase, quinone 1NAD(P)H:Quinone acceptor oxidoreductase type 1NAD(P)H:menadione oxidoreductase 1NAD(P)H:quinone oxidoreductase 1NAD(P)H:quinone oxireductaseazoreductasediaphorase (NADH/protein jagged-1
Modification date2020032920200313
UniProtAcc

P15559

Main function of 5'-partner protein: FUNCTION: The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinons involved in detoxification pathways as well as in biosynthetic processes such as the vitamin K-dependent gamma-carboxylation of glutamate residues in prothrombin synthesis.

P78504

Main function of 5'-partner protein: FUNCTION: Ligand for multiple Notch receptors and involved in the mediation of Notch signaling (PubMed:18660822, PubMed:20437614). May be involved in cell-fate decisions during hematopoiesis (PubMed:9462510). Seems to be involved in early and late stages of mammalian cardiovascular development. Inhibits myoblast differentiation (By similarity). Enhances fibroblast growth factor-induced angiogenesis (in vitro). {ECO:0000250, ECO:0000269|PubMed:18660822, ECO:0000269|PubMed:20437614, ECO:0000269|PubMed:9462510}.
Ensembl transtripts involved in fusion geneENST idsENST00000320623, ENST00000379046, 
ENST00000379047, ENST00000439109, 
ENST00000561500, ENST00000564043, 
ENST00000488480, ENST00000254958, 
ENST00000423891, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score12 X 11 X 5=6608 X 9 X 4=288
# samples 138
** MAII scorelog2(13/660*10)=-2.34395440121736
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(8/288*10)=-1.84799690655495
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: NQO1 [Title/Abstract] AND JAG1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: NQO1 [Title/Abstract] AND JAG1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NQO1(69760336)-JAG1(10621892), # samples:1
Anticipated loss of major functional domain due to fusion event.NQO1-JAG1 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.
NQO1-JAG1 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
TgeneJAG1

GO:0001953

negative regulation of cell-matrix adhesion

11549580

TgeneJAG1

GO:0022408

negative regulation of cell-cell adhesion

11549580

TgeneJAG1

GO:0030336

negative regulation of cell migration

11549580



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/chr16:69760336/chr20:10621892)
- 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 NQO1 (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 JAG1 (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)
ENST00000561500NQO1chr1669760336-ENST00000254958JAG1chr2010621892-262974104814236
ENST00000561500NQO1chr1669760336-ENST00000423891JAG1chr2010621892-105074104814236
ENST00000379047NQO1chr1669760336-ENST00000254958JAG1chr2010621892-279123692976294
ENST00000379047NQO1chr1669760336-ENST00000423891JAG1chr2010621892-121223692976294
ENST00000320623NQO1chr1669760336-ENST00000254958JAG1chr2010621892-30745193751259294
ENST00000320623NQO1chr1669760336-ENST00000423891JAG1chr2010621892-14955193751259294
ENST00000379046NQO1chr1669760336-ENST00000254958JAG1chr2010621892-27071528892294
ENST00000379046NQO1chr1669760336-ENST00000423891JAG1chr2010621892-11281528892294
ENST00000439109NQO1chr1669760336-ENST00000254958JAG1chr2010621892-2683128158868236
ENST00000439109NQO1chr1669760336-ENST00000423891JAG1chr2010621892-1104128158868236

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
ENST00000561500ENST00000254958NQO1chr1669760336-JAG1chr2010621892-0.149489480.8505105
ENST00000561500ENST00000423891NQO1chr1669760336-JAG1chr2010621892-0.0709539060.9290461
ENST00000379047ENST00000254958NQO1chr1669760336-JAG1chr2010621892-0.0006962120.9993038
ENST00000379047ENST00000423891NQO1chr1669760336-JAG1chr2010621892-0.0052968170.9947031
ENST00000320623ENST00000254958NQO1chr1669760336-JAG1chr2010621892-0.0009868050.9990132
ENST00000320623ENST00000423891NQO1chr1669760336-JAG1chr2010621892-0.0109581660.98904186
ENST00000379046ENST00000254958NQO1chr1669760336-JAG1chr2010621892-0.0007001050.9992999
ENST00000379046ENST00000423891NQO1chr1669760336-JAG1chr2010621892-0.0050867170.9949132
ENST00000439109ENST00000254958NQO1chr1669760336-JAG1chr2010621892-0.062632840.9373672
ENST00000439109ENST00000423891NQO1chr1669760336-JAG1chr2010621892-0.0555908160.9444092

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 NQO1-JAG1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
NQO1chr1669760336JAG1chr201062189215248SQSAPRTAPEPWSGLTTEHICSELRN
NQO1chr1669760336JAG1chr201062189223648SQSAPRTAPEPWSGLTTEHICSELRN
NQO1chr1669760336JAG1chr201062189251948SQSAPRTAPEPWSGLTTEHICSELRN

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Potential FusionNeoAntigen Information of NQO1-JAG1 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.
NQO1-JAG1_69760336_10621892.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)
NQO1-JAG1chr1669760336chr2010621892519HLA-B15:17RTAPEPWSGL0.99410.9582515
NQO1-JAG1chr1669760336chr2010621892519HLA-B15:16RTAPEPWSGL0.99260.9481515
NQO1-JAG1chr1669760336chr2010621892519HLA-B58:01RTAPEPWSGL0.99090.9683515
NQO1-JAG1chr1669760336chr2010621892519HLA-B57:03RTAPEPWSGL0.97930.9948515
NQO1-JAG1chr1669760336chr2010621892519HLA-A30:08RTAPEPWSGL0.95760.8742515
NQO1-JAG1chr1669760336chr2010621892519HLA-A32:13RTAPEPWSGL0.89520.9482515
NQO1-JAG1chr1669760336chr2010621892519HLA-B51:01EPWSGLTTEHI0.96670.5771920
NQO1-JAG1chr1669760336chr2010621892519HLA-B07:12APEPWSGL0.9970.5699715
NQO1-JAG1chr1669760336chr2010621892519HLA-C03:07TAPEPWSGL0.99850.9873615
NQO1-JAG1chr1669760336chr2010621892519HLA-C03:19TAPEPWSGL0.99810.9947615
NQO1-JAG1chr1669760336chr2010621892519HLA-C03:08TAPEPWSGL0.99810.9457615
NQO1-JAG1chr1669760336chr2010621892519HLA-C04:06TAPEPWSGL0.98480.9728615
NQO1-JAG1chr1669760336chr2010621892519HLA-C01:30TAPEPWSGL0.95840.9687615
NQO1-JAG1chr1669760336chr2010621892519HLA-C01:17TAPEPWSGL0.95740.9727615
NQO1-JAG1chr1669760336chr2010621892519HLA-C08:13TAPEPWSGL0.90290.9904615
NQO1-JAG1chr1669760336chr2010621892519HLA-C08:04TAPEPWSGL0.90290.9904615
NQO1-JAG1chr1669760336chr2010621892519HLA-C08:03TAPEPWSGL0.7780.9966615
NQO1-JAG1chr1669760336chr2010621892519HLA-C02:06TAPEPWSGL0.66790.9839615
NQO1-JAG1chr1669760336chr2010621892519HLA-C07:13TAPEPWSGL0.49220.9605615
NQO1-JAG1chr1669760336chr2010621892519HLA-C07:29TAPEPWSGL0.36910.9571615
NQO1-JAG1chr1669760336chr2010621892519HLA-C15:06RTAPEPWSGL0.99920.93515
NQO1-JAG1chr1669760336chr2010621892519HLA-C01:30RTAPEPWSGL0.9520.9708515
NQO1-JAG1chr1669760336chr2010621892519HLA-C01:17RTAPEPWSGL0.92270.9688515
NQO1-JAG1chr1669760336chr2010621892519HLA-C03:04TAPEPWSGL0.99840.9936615
NQO1-JAG1chr1669760336chr2010621892519HLA-C03:03TAPEPWSGL0.99840.9936615
NQO1-JAG1chr1669760336chr2010621892519HLA-C03:05TAPEPWSGL0.9970.9496615
NQO1-JAG1chr1669760336chr2010621892519HLA-C03:17TAPEPWSGL0.99680.9766615
NQO1-JAG1chr1669760336chr2010621892519HLA-C03:06TAPEPWSGL0.96660.9946615
NQO1-JAG1chr1669760336chr2010621892519HLA-C01:02TAPEPWSGL0.9470.9726615
NQO1-JAG1chr1669760336chr2010621892519HLA-C01:03TAPEPWSGL0.94520.9639615
NQO1-JAG1chr1669760336chr2010621892519HLA-A68:02TAPEPWSGL0.88530.8067615
NQO1-JAG1chr1669760336chr2010621892519HLA-C08:01TAPEPWSGL0.7780.9966615
NQO1-JAG1chr1669760336chr2010621892519HLA-A69:01TAPEPWSGL0.77570.8249615
NQO1-JAG1chr1669760336chr2010621892519HLA-B07:13TAPEPWSGL0.76740.8682615
NQO1-JAG1chr1669760336chr2010621892519HLA-C17:01TAPEPWSGL0.28470.9867615
NQO1-JAG1chr1669760336chr2010621892519HLA-B57:04RTAPEPWSGL0.99650.8221515
NQO1-JAG1chr1669760336chr2010621892519HLA-B57:02RTAPEPWSGL0.99210.9735515
NQO1-JAG1chr1669760336chr2010621892519HLA-C01:03RTAPEPWSGL0.97850.9717515
NQO1-JAG1chr1669760336chr2010621892519HLA-A32:01RTAPEPWSGL0.96470.9825515
NQO1-JAG1chr1669760336chr2010621892519HLA-C01:02RTAPEPWSGL0.93340.9693515
NQO1-JAG1chr1669760336chr2010621892519HLA-B51:09EPWSGLTTEHI0.94730.5128920

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Potential FusionNeoAntigen Information of NQO1-JAG1 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 NQO1-JAG1

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
9238TAPEPWSGLTTEHINQO1JAG1chr1669760336chr2010621892519

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of NQO1-JAG1

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-B14:023BVN9238TAPEPWSGLTTEHI-4.90311-5.01651
HLA-B14:023BVN9238TAPEPWSGLTTEHI-1.98102-3.01632
HLA-B52:013W399238TAPEPWSGLTTEHI-5.89733-6.01073
HLA-B52:013W399238TAPEPWSGLTTEHI-4.93657-5.97187
HLA-A24:025HGA9238TAPEPWSGLTTEHI-6.32379-6.43719
HLA-A24:025HGA9238TAPEPWSGLTTEHI-5.44633-6.48163
HLA-B44:053DX89238TAPEPWSGLTTEHI-5.19893-5.31233
HLA-B44:053DX89238TAPEPWSGLTTEHI-4.49659-5.53189

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Vaccine Design for the FusionNeoAntigens of NQO1-JAG1

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
NQO1-JAG1chr1669760336chr2010621892515RTAPEPWSGLCGGACTGCACCAGAGCCATGGTCGGGTCTT
NQO1-JAG1chr1669760336chr2010621892615TAPEPWSGLACTGCACCAGAGCCATGGTCGGGTCTT
NQO1-JAG1chr1669760336chr2010621892715APEPWSGLGCACCAGAGCCATGGTCGGGTCTT
NQO1-JAG1chr1669760336chr2010621892920EPWSGLTTEHIGAGCCATGGTCGGGTCTTACTACGGAGCACATT

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 NQO1-JAG1

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
LUADNQO1-JAG1chr1669760336ENST00000320623chr2010621892ENST00000254958TCGA-55-6987-01A

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Potential target of CAR-T therapy development for NQO1-JAG1

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
TgeneJAG1chr16:69760336chr20:10621892ENST0000025495822261068_109301219.0TransmembraneHelical

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 NQO1-JAG1

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 NQO1-JAG1

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