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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:REL-MVP

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: REL-MVP
FusionPDB ID: 73448
FusionGDB2.0 ID: 73448
HgeneTgene
Gene symbol

REL

MVP

Gene ID

5966

9961

Gene nameREL proto-oncogene, NF-kB subunitmajor vault protein
SynonymsC-RelLRP|VAULT1
Cytomap

2p16.1

16p11.2

Type of geneprotein-codingprotein-coding
Descriptionproto-oncogene c-Reloncogene REL, avian reticuloendotheliosisv-rel avian reticuloendotheliosis viral oncogene homologmajor vault proteinlung resistance-related proteintesticular secretory protein Li 30
Modification date2020032720200313
UniProtAcc

RELL2

Main function of 5'-partner protein: 303

Q14764

Main function of 5'-partner protein: FUNCTION: Required for normal vault structure. Vaults are multi-subunit structures that may act as scaffolds for proteins involved in signal transduction. Vaults may also play a role in nucleo-cytoplasmic transport. Down-regulates IFNG-mediated STAT1 signaling and subsequent activation of JAK. Down-regulates SRC activity and signaling through MAP kinases. {ECO:0000269|PubMed:15133037, ECO:0000269|PubMed:16418217, ECO:0000269|PubMed:16441665}.
Ensembl transtripts involved in fusion geneENST idsENST00000295025, ENST00000394479, 
ENST00000395353, ENST00000452209, 
ENST00000566554, ENST00000357402, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score5 X 6 X 4=12014 X 16 X 6=1344
# samples 716
** MAII scorelog2(7/120*10)=-0.777607578663552
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(16/1344*10)=-3.0703893278914
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: REL [Title/Abstract] AND MVP [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: REL [Title/Abstract] AND MVP [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)REL(61144152)-MVP(29847025), # samples:3
Anticipated loss of major functional domain due to fusion event.REL-MVP 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.
REL-MVP 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
HgeneREL

GO:0010629

negative regulation of gene expression

22065573

HgeneREL

GO:0032688

negative regulation of interferon-beta production

22065573

HgeneREL

GO:0045944

positive regulation of transcription by RNA polymerase II

1406630

TgeneMVP

GO:0023057

negative regulation of signaling

16441665

TgeneMVP

GO:0031953

negative regulation of protein autophosphorylation

16441665

TgeneMVP

GO:0038127

ERBB signaling pathway

15133037

TgeneMVP

GO:0061099

negative regulation of protein tyrosine kinase activity

16441665



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/chr2:61144152/chr16:29847025)
- 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 REL (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 MVP (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)
ENST00000295025RELchr261144152+ENST00000357402MVPchr1629847025+30058552542959901
ENST00000394479RELchr261144152+ENST00000357402MVPchr1629847025+28707201192824901
ENST00000295025RELchr261144152+ENST00000357402MVPchr1629847024+30058552542959901
ENST00000394479RELchr261144152+ENST00000357402MVPchr1629847024+28707201192824901

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
ENST00000295025ENST00000357402RELchr261144152+MVPchr1629847025+0.0047200310.99528
ENST00000394479ENST00000357402RELchr261144152+MVPchr1629847025+0.0044115470.9955884
ENST00000295025ENST00000357402RELchr261144152+MVPchr1629847024+0.0047200310.99528
ENST00000394479ENST00000357402RELchr261144152+MVPchr1629847024+0.0044115470.9955884

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 REL-MVP

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
RELchr261144152MVPchr1629847024720201LPPVVSNPIYDNREEWLVTTVGAYLP
RELchr261144152MVPchr1629847024855201LPPVVSNPIYDNREEWLVTTVGAYLP
RELchr261144152MVPchr1629847025720201LPPVVSNPIYDNREEWLVTTVGAYLP
RELchr261144152MVPchr1629847025855201LPPVVSNPIYDNREEWLVTTVGAYLP

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Potential FusionNeoAntigen Information of REL-MVP 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.
REL-MVP_61144152_29847024.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)
REL-MVPchr261144152chr1629847024855HLA-B45:01REEWLVTTV0.99850.95871221
REL-MVPchr261144152chr1629847024855HLA-B50:02REEWLVTTV0.99630.82131221
REL-MVPchr261144152chr1629847024855HLA-B40:01REEWLVTTV0.9960.70281221
REL-MVPchr261144152chr1629847024855HLA-B13:02REEWLVTTV0.98650.98291221
REL-MVPchr261144152chr1629847024855HLA-B39:06NREEWLVTT0.98520.82271120
REL-MVPchr261144152chr1629847024855HLA-B13:01REEWLVTTV0.97790.99751221
REL-MVPchr261144152chr1629847024855HLA-B47:01REEWLVTTV0.87860.78021221
REL-MVPchr261144152chr1629847024855HLA-B41:01REEWLVTTV0.56250.96111221
REL-MVPchr261144152chr1629847024855HLA-B39:13REEWLVTTV0.43980.9931221
REL-MVPchr261144152chr1629847024855HLA-B40:05REEWLVTTV0.39460.65731221
REL-MVPchr261144152chr1629847024855HLA-B50:01REEWLVTTV0.36990.97681221
REL-MVPchr261144152chr1629847024855HLA-C04:10IYDNREEW0.99950.6341816
REL-MVPchr261144152chr1629847024855HLA-C04:07IYDNREEW0.99950.6424816
REL-MVPchr261144152chr1629847024855HLA-B40:06REEWLVTTV0.99970.80781221
REL-MVPchr261144152chr1629847024855HLA-C04:10IYDNREEWL0.99740.7446817
REL-MVPchr261144152chr1629847024855HLA-C04:07IYDNREEWL0.99710.7402817
REL-MVPchr261144152chr1629847024855HLA-B48:03REEWLVTTV0.99340.74451221
REL-MVPchr261144152chr1629847024855HLA-B44:10REEWLVTTV0.98010.84041221
REL-MVPchr261144152chr1629847024855HLA-B73:01NREEWLVTT0.88870.86391120
REL-MVPchr261144152chr1629847024855HLA-B40:03REEWLVTTV0.85380.71961221
REL-MVPchr261144152chr1629847024855HLA-C07:80IYDNREEWL0.84160.9504817
REL-MVPchr261144152chr1629847024855HLA-C07:67IYDNREEWL0.84160.9504817
REL-MVPchr261144152chr1629847024855HLA-C07:29IYDNREEWL0.83570.9648817
REL-MVPchr261144152chr1629847024855HLA-C07:13IYDNREEWL0.78890.9285817
REL-MVPchr261144152chr1629847024855HLA-C04:14IYDNREEWL0.69130.7512817
REL-MVPchr261144152chr1629847024855HLA-B39:08REEWLVTTV0.53170.96561221
REL-MVPchr261144152chr1629847024855HLA-B73:01NREEWLVTTV0.96570.88251121
REL-MVPchr261144152chr1629847024855HLA-C04:01IYDNREEW0.99950.6424816
REL-MVPchr261144152chr1629847024855HLA-C18:01IYDNREEW0.99930.6581816
REL-MVPchr261144152chr1629847024855HLA-B40:04REEWLVTTV0.9980.93991221
REL-MVPchr261144152chr1629847024855HLA-C04:03IYDNREEWL0.99790.7652817
REL-MVPchr261144152chr1629847024855HLA-C04:01IYDNREEWL0.99710.7402817
REL-MVPchr261144152chr1629847024855HLA-B40:36REEWLVTTV0.99620.7091221
REL-MVPchr261144152chr1629847024855HLA-C18:01IYDNREEWL0.99610.7404817
REL-MVPchr261144152chr1629847024855HLA-B40:49REEWLVTTV0.99380.71031221
REL-MVPchr261144152chr1629847024855HLA-B40:12REEWLVTTV0.99340.74451221
REL-MVPchr261144152chr1629847024855HLA-B15:13PIYDNREEW0.95830.6934716
REL-MVPchr261144152chr1629847024855HLA-C04:04IYDNREEWL0.86440.7968817
REL-MVPchr261144152chr1629847024855HLA-C07:02IYDNREEWL0.84160.9504817
REL-MVPchr261144152chr1629847024855HLA-C06:06IYDNREEWL0.82090.9917817
REL-MVPchr261144152chr1629847024855HLA-C07:04IYDNREEWL0.80210.9489817
REL-MVPchr261144152chr1629847024855HLA-B41:03REEWLVTTV0.62650.87631221
REL-MVPchr261144152chr1629847024855HLA-B39:02REEWLVTTV0.44060.99291221
REL-MVPchr261144152chr1629847024855HLA-B50:05REEWLVTTV0.36990.97681221
REL-MVPchr261144152chr1629847024855HLA-B50:04REEWLVTTV0.36990.97681221
REL-MVPchr261144152chr1629847024855HLA-B15:13NPIYDNREEW0.96960.5984616
REL-MVPchr261144152chr1629847024855HLA-A25:01NPIYDNREEW0.41330.9268616

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Potential FusionNeoAntigen Information of REL-MVP 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.
REL-MVP_61144152_29847024.msa

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)
REL-MVPchr261144152chr1629847024855DRB3-0201LPPVVSNPIYDNREE015
REL-MVPchr261144152chr1629847024855DRB3-0204LPPVVSNPIYDNREE015
REL-MVPchr261144152chr1629847024855DRB3-0204PPVVSNPIYDNREEW116
REL-MVPchr261144152chr1629847024855DRB3-0214LPPVVSNPIYDNREE015
REL-MVPchr261144152chr1629847024855DRB3-0224LPPVVSNPIYDNREE015

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Fusion breakpoint peptide structures of REL-MVP

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
6314NPIYDNREEWLVTTRELMVPchr261144152chr1629847024855

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of REL-MVP

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-B14:023BVN6314NPIYDNREEWLVTT-7.9962-8.1096
HLA-B14:023BVN6314NPIYDNREEWLVTT-5.70842-6.74372
HLA-B52:013W396314NPIYDNREEWLVTT-6.83737-6.95077
HLA-B52:013W396314NPIYDNREEWLVTT-4.4836-5.5189
HLA-A11:014UQ26314NPIYDNREEWLVTT-10.0067-10.1201
HLA-A11:014UQ26314NPIYDNREEWLVTT-9.03915-10.0745
HLA-A24:025HGA6314NPIYDNREEWLVTT-6.56204-6.67544
HLA-A24:025HGA6314NPIYDNREEWLVTT-5.42271-6.45801
HLA-B44:053DX86314NPIYDNREEWLVTT-7.85648-8.89178
HLA-B44:053DX86314NPIYDNREEWLVTT-5.3978-5.5112
HLA-A02:016TDR6314NPIYDNREEWLVTT-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of REL-MVP

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
REL-MVPchr261144152chr16298470241120NREEWLVTTACAACCGGGAAGAATGGCTGGTCACCA
REL-MVPchr261144152chr16298470241121NREEWLVTTVACAACCGGGAAGAATGGCTGGTCACCACAG
REL-MVPchr261144152chr16298470241221REEWLVTTVACCGGGAAGAATGGCTGGTCACCACAG
REL-MVPchr261144152chr1629847024616NPIYDNREEWCGAACCCAATTTATGACAACCGGGAAGAAT
REL-MVPchr261144152chr1629847024716PIYDNREEWACCCAATTTATGACAACCGGGAAGAAT
REL-MVPchr261144152chr1629847024816IYDNREEWCAATTTATGACAACCGGGAAGAAT
REL-MVPchr261144152chr1629847024817IYDNREEWLCAATTTATGACAACCGGGAAGAATGGC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
REL-MVPchr261144152chr1629847024015LPPVVSNPIYDNREECTCTTCCTCCTGTTGTCTCGAACCCAATTTATGACAACCGGGAAG
REL-MVPchr261144152chr1629847024116PPVVSNPIYDNREEWTTCCTCCTGTTGTCTCGAACCCAATTTATGACAACCGGGAAGAAT

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Information of the samples that have these potential fusion neoantigens of REL-MVP

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
LUADREL-MVPchr261144152ENST00000295025chr1629847024ENST00000357402TCGA-49-6743

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Potential target of CAR-T therapy development for REL-MVP

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 REL-MVP

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 REL-MVP

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