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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:MTUS1-PDCD4

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: MTUS1-PDCD4
FusionPDB ID: 55938
FusionGDB2.0 ID: 55938
HgeneTgene
Gene symbol

MTUS1

PDCD4

Gene ID

57509

27250

Gene namemicrotubule associated scaffold protein 1programmed cell death 4
SynonymsATBP|ATIP|ATIP3|ICIS|MP44|MTSG1H731
Cytomap

8p22

10q25.2

Type of geneprotein-codingprotein-coding
Descriptionmicrotubule-associated tumor suppressor 1AT2 receptor-binding proteinAT2 receptor-interacting proteinAT2R binding proteinangiotensin-II type 2 receptor-interacting proteinerythroid differentiation-relatedmicrotubule associated tumor suppressor 1mitprogrammed cell death protein 4neoplastic transformation inhibitor proteinnuclear antigen H731programmed cell death 4 (neoplastic transformation inhibitor)protein 197/15a
Modification date2020031320200329
UniProtAcc

Q9ULD2

Main function of 5'-partner protein: FUNCTION: Cooperates with AGTR2 to inhibit ERK2 activation and cell proliferation. May be required for AGTR2 cell surface expression. Together with PTPN6, induces UBE2V2 expression upon angiotensin-II stimulation. Isoform 1 inhibits breast cancer cell proliferation, delays the progression of mitosis by prolonging metaphase and reduces tumor growth. {ECO:0000269|PubMed:12692079, ECO:0000269|PubMed:19794912}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000262102, ENST00000297488, 
ENST00000381861, ENST00000381869, 
ENST00000400046, ENST00000519263, 
ENST00000544260, ENST00000518713, 
ENST00000381862, 
ENST00000481353, 
ENST00000280154, ENST00000393104, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score12 X 13 X 5=7805 X 6 X 5=150
# samples 156
** MAII scorelog2(15/780*10)=-2.37851162325373
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(6/150*10)=-1.32192809488736
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: MTUS1 [Title/Abstract] AND PDCD4 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: MTUS1 [Title/Abstract] AND PDCD4 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MTUS1(17532695)-PDCD4(112640991), # samples:1
Anticipated loss of major functional domain due to fusion event.MTUS1-PDCD4 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.
MTUS1-PDCD4 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.
MTUS1-PDCD4 seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted ORF.
MTUS1-PDCD4 seems lost the major protein functional domain in Tgene partner, which is a tumor suppressor 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
TgenePDCD4

GO:0007569

cell aging

12054647

TgenePDCD4

GO:0030509

BMP signaling pathway

18548003

TgenePDCD4

GO:0045892

negative regulation of transcription, DNA-templated

16357133

TgenePDCD4

GO:1905064

negative regulation of vascular smooth muscle cell differentiation

18548003



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/chr8:17532695/chr10:112640991)
- 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 MTUS1 (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 PDCD4 (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)
ENST00000544260MTUS1chr817532695-ENST00000280154PDCD4chr10112640991+38966112351977580
ENST00000544260MTUS1chr817532695-ENST00000393104PDCD4chr10112640991+38956112351977580
ENST00000381861MTUS1chr817532695-ENST00000280154PDCD4chr10112640991+42519663202332670
ENST00000381861MTUS1chr817532695-ENST00000393104PDCD4chr10112640991+42509663202332670
ENST00000519263MTUS1chr817532695-ENST00000280154PDCD4chr10112640991+6202291717442831369
ENST00000519263MTUS1chr817532695-ENST00000393104PDCD4chr10112640991+6201291717442831369
ENST00000400046MTUS1chr817532695-ENST00000280154PDCD4chr10112640991+340612101487495
ENST00000400046MTUS1chr817532695-ENST00000393104PDCD4chr10112640991+340512101487495
ENST00000297488MTUS1chr817532695-ENST00000280154PDCD4chr10112640991+39816962932062589
ENST00000297488MTUS1chr817532695-ENST00000393104PDCD4chr10112640991+39806962932062589

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
ENST00000544260ENST00000280154MTUS1chr817532695-PDCD4chr10112640991+0.0001915390.9998085
ENST00000544260ENST00000393104MTUS1chr817532695-PDCD4chr10112640991+0.0001918580.99980813
ENST00000381861ENST00000280154MTUS1chr817532695-PDCD4chr10112640991+0.0001774650.99982256
ENST00000381861ENST00000393104MTUS1chr817532695-PDCD4chr10112640991+0.0001780950.99982196
ENST00000519263ENST00000280154MTUS1chr817532695-PDCD4chr10112640991+8.39E-050.9999161
ENST00000519263ENST00000393104MTUS1chr817532695-PDCD4chr10112640991+8.40E-050.99991596
ENST00000400046ENST00000280154MTUS1chr817532695-PDCD4chr10112640991+5.06E-050.99994934
ENST00000400046ENST00000393104MTUS1chr817532695-PDCD4chr10112640991+5.07E-050.99994934
ENST00000297488ENST00000280154MTUS1chr817532695-PDCD4chr10112640991+0.0002855890.99971443
ENST00000297488ENST00000393104MTUS1chr817532695-PDCD4chr10112640991+0.0002858830.9997141

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 MTUS1-PDCD4

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
MTUS1chr817532695PDCD4chr1011264099112140TLSQELVNLRGELDPDNLSDSLFSGD
MTUS1chr817532695PDCD4chr101126409912917914TLSQELVNLRGELDPDNLSDSLFSGD
MTUS1chr817532695PDCD4chr10112640991611125TLSQELVNLRGELDPDNLSDSLFSGD
MTUS1chr817532695PDCD4chr10112640991696134TLSQELVNLRGELDPDNLSDSLFSGD
MTUS1chr817532695PDCD4chr10112640991966215TLSQELVNLRGELDPDNLSDSLFSGD

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Potential FusionNeoAntigen Information of MTUS1-PDCD4 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.
MTUS1-PDCD4_17532695_112640991.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)
MTUS1-PDCD4chr817532695chr10112640991696HLA-B35:03LDPDNLSDSL0.74520.65151222
MTUS1-PDCD4chr817532695chr10112640991696HLA-B35:04LDPDNLSDSL0.66180.70031222
MTUS1-PDCD4chr817532695chr10112640991696HLA-B35:02LDPDNLSDSL0.66180.70031222
MTUS1-PDCD4chr817532695chr10112640991696HLA-B35:12LDPDNLSDSL0.66180.70031222
MTUS1-PDCD4chr817532695chr10112640991696HLA-B39:10LDPDNLSDSL0.60490.64431222
MTUS1-PDCD4chr817532695chr10112640991696HLA-B40:04GELDPDNL0.99970.63821018
MTUS1-PDCD4chr817532695chr10112640991696HLA-B35:09LDPDNLSDSL0.66180.70031222

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Potential FusionNeoAntigen Information of MTUS1-PDCD4 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.
MTUS1-PDCD4_17532695_112640991.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)
MTUS1-PDCD4chr817532695chr10112640991696DRB1-1002SQELVNLRGELDPDN217

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Fusion breakpoint peptide structures of MTUS1-PDCD4

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
10143VNLRGELDPDNLSDMTUS1PDCD4chr817532695chr10112640991696

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of MTUS1-PDCD4

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-B14:023BVN10143VNLRGELDPDNLSD-6.80686-6.92026
HLA-B14:023BVN10143VNLRGELDPDNLSD-5.01234-6.04764
HLA-B52:013W3910143VNLRGELDPDNLSD-6.71251-6.82591
HLA-B52:013W3910143VNLRGELDPDNLSD-4.13165-5.16695
HLA-A11:014UQ210143VNLRGELDPDNLSD-4.31699-4.43039
HLA-A11:014UQ210143VNLRGELDPDNLSD-4.19959-5.23489
HLA-A24:025HGA10143VNLRGELDPDNLSD-7.74913-7.86253
HLA-A24:025HGA10143VNLRGELDPDNLSD-5.75888-6.79418
HLA-B27:036PZ510143VNLRGELDPDNLSD1000110000
HLA-B44:053DX810143VNLRGELDPDNLSD-4.89721-5.01061
HLA-B44:053DX810143VNLRGELDPDNLSD-3.74482-4.78012
HLA-B35:011A1N10143VNLRGELDPDNLSD-8.42572-8.53912
HLA-B35:011A1N10143VNLRGELDPDNLSD-6.4428-7.4781
HLA-A02:016TDR10143VNLRGELDPDNLSD-5.01451-6.04981

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Vaccine Design for the FusionNeoAntigens of MTUS1-PDCD4

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
MTUS1-PDCD4chr817532695chr101126409911018GELDPDNLGAGAGCTAGATCCTGATAACTTAA
MTUS1-PDCD4chr817532695chr101126409911222LDPDNLSDSLTAGATCCTGATAACTTAAGTGACTCTCTCT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
MTUS1-PDCD4chr817532695chr10112640991217SQELVNLRGELDPDNCTCAAGAACTTGTTAACCTCCGGGGAGAGCTAGATCCTGATAACT

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Information of the samples that have these potential fusion neoantigens of MTUS1-PDCD4

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
KIRCMTUS1-PDCD4chr817532695ENST00000297488chr10112640991ENST00000280154TCGA-A3-3362-01A

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Potential target of CAR-T therapy development for MTUS1-PDCD4

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 MTUS1-PDCD4

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 MTUS1-PDCD4

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