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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:PIAS1-DTNBP1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PIAS1-DTNBP1
FusionPDB ID: 65095
FusionGDB2.0 ID: 65095
HgeneTgene
Gene symbol

PIAS1

DTNBP1

Gene ID

8554

84062

Gene nameprotein inhibitor of activated STAT 1dystrobrevin binding protein 1
SynonymsDDXBP1|GBP|GU/RH-II|ZMIZ3BLOC1S8|DBND|HPS7|My031|SDY
Cytomap

15q23

6p22.3

Type of geneprotein-codingprotein-coding
DescriptionE3 SUMO-protein ligase PIAS1AR interacting proteinDEAD/H (Asp-Glu-Ala-Asp/His) box binding protein 1DEAD/H box-binding protein 1E3 SUMO-protein transferase PIAS1RNA helicase II-binding proteingu-binding proteinprotein inhibitor of activated STAT prdysbindinBLOC-1 subunit 8Hermansky-Pudlak syndrome 7 proteinbiogenesis of lysosomal organelles complex-1, subunit 8biogenesis of lysosome-related organelles complex 1 subunit 8dysbindin-1
Modification date2020031320200313
UniProtAcc.

Q96EV8

Main function of 5'-partner protein: FUNCTION: Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes. In concert with the AP-3 complex, the BLOC-1 complex is required to target membrane protein cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals. The BLOC-1 complex, in association with SNARE proteins, is also proposed to be involved in neurite extension. Associates with the BLOC-2 complex to facilitate the transport of TYRP1 independent of AP-3 function. Plays a role in synaptic vesicle trafficking and in neurotransmitter release. Plays a role in the regulation of cell surface exposure of DRD2. May play a role in actin cytoskeleton reorganization and neurite outgrowth. May modulate MAPK8 phosphorylation. Appears to promote neuronal transmission and viability through regulating the expression of SNAP25 and SYN1, modulating PI3-kinase-Akt signaling and influencing glutamatergic release. Regulates the expression of SYN1 through binding to its promoter. Modulates prefrontal cortical activity via the dopamine/D2 pathway. {ECO:0000269|PubMed:15345706, ECO:0000269|PubMed:16837549, ECO:0000269|PubMed:17182842, ECO:0000269|PubMed:17989303, ECO:0000269|PubMed:19094965, ECO:0000269|PubMed:20180862, ECO:0000269|PubMed:20921223}.
Ensembl transtripts involved in fusion geneENST idsENST00000249636, ENST00000545237, 
ENST00000567417, 
ENST00000338950, 
ENST00000344537, ENST00000355917, 
ENST00000462989, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score13 X 12 X 7=109215 X 8 X 9=1080
# samples 1517
** MAII scorelog2(15/1092*10)=-2.86393845042397
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(17/1080*10)=-2.66742466091313
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: PIAS1 [Title/Abstract] AND DTNBP1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PIAS1 [Title/Abstract] AND DTNBP1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PIAS1(68379088)-DTNBP1(15533626), # samples:1
Anticipated loss of major functional domain due to fusion event.PIAS1-DTNBP1 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.
PIAS1-DTNBP1 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.
PIAS1-DTNBP1 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.
PIAS1-DTNBP1 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
HgenePIAS1

GO:0016925

protein sumoylation

18579533

HgenePIAS1

GO:0033235

positive regulation of protein sumoylation

17696781|21965678

TgeneDTNBP1

GO:0031175

neuron projection development

16980328



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/chr15:68379088/chr6:15533626)
- 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 PIAS1 (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 DTNBP1 (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)
ENST00000249636PIAS1chr1568379088+ENST00000344537DTNBP1chr615533626-13366171481161337
ENST00000249636PIAS1chr1568379088+ENST00000355917DTNBP1chr615533626-13276171481161337
ENST00000249636PIAS1chr1568379088+ENST00000338950DTNBP1chr615533626-18806171481017289
ENST00000249636PIAS1chr1568379088+ENST00000462989DTNBP1chr615533626-13306171481161337
ENST00000545237PIAS1chr1568379088+ENST00000344537DTNBP1chr615533626-193512167411760339
ENST00000545237PIAS1chr1568379088+ENST00000355917DTNBP1chr615533626-192612167411760339
ENST00000545237PIAS1chr1568379088+ENST00000338950DTNBP1chr615533626-247912167411616291
ENST00000545237PIAS1chr1568379088+ENST00000462989DTNBP1chr615533626-192912167411760339

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
ENST00000249636ENST00000344537PIAS1chr1568379088+DTNBP1chr615533626-0.0054561510.9945438
ENST00000249636ENST00000355917PIAS1chr1568379088+DTNBP1chr615533626-0.0053796540.9946203
ENST00000249636ENST00000338950PIAS1chr1568379088+DTNBP1chr615533626-0.0050510660.99494886
ENST00000249636ENST00000462989PIAS1chr1568379088+DTNBP1chr615533626-0.0053442870.9946557
ENST00000545237ENST00000344537PIAS1chr1568379088+DTNBP1chr615533626-0.0034785050.9965215
ENST00000545237ENST00000355917PIAS1chr1568379088+DTNBP1chr615533626-0.0034687830.9965312
ENST00000545237ENST00000338950PIAS1chr1568379088+DTNBP1chr615533626-0.0057464040.9942536
ENST00000545237ENST00000462989PIAS1chr1568379088+DTNBP1chr615533626-0.0033700750.9966299

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 PIAS1-DTNBP1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
PIAS1chr1568379088DTNBP1chr6155336261216156PFYDLLDELIKPTSLAELDAEHAQKV
PIAS1chr1568379088DTNBP1chr615533626617154PFYDLLDELIKPTSLAELDAEHAQKV

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Potential FusionNeoAntigen Information of PIAS1-DTNBP1 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.
PIAS1-DTNBP1_68379088_15533626.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)
PIAS1-DTNBP1chr1568379088chr615533626617HLA-B45:01DELIKPTSLA0.94540.9051616
PIAS1-DTNBP1chr1568379088chr615533626617HLA-B50:02DELIKPTSLA0.87730.5672616
PIAS1-DTNBP1chr1568379088chr615533626617HLA-B39:10KPTSLAEL0.76470.88041018
PIAS1-DTNBP1chr1568379088chr615533626617HLA-B39:09IKPTSLAEL0.98120.625918
PIAS1-DTNBP1chr1568379088chr615533626617HLA-C07:13IKPTSLAEL0.83610.8873918
PIAS1-DTNBP1chr1568379088chr615533626617HLA-C07:29IKPTSLAEL0.7490.91918
PIAS1-DTNBP1chr1568379088chr615533626617HLA-C01:17LIKPTSLAEL0.97150.9585818
PIAS1-DTNBP1chr1568379088chr615533626617HLA-B67:01KPTSLAEL0.75360.69541018
PIAS1-DTNBP1chr1568379088chr615533626617HLA-A68:02ELIKPTSLA0.96360.6422716
PIAS1-DTNBP1chr1568379088chr615533626617HLA-A69:01ELIKPTSLA0.89260.6421716
PIAS1-DTNBP1chr1568379088chr615533626617HLA-C01:02LIKPTSLAEL0.96770.9569818

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Potential FusionNeoAntigen Information of PIAS1-DTNBP1 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.
PIAS1-DTNBP1_68379088_15533626.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)
PIAS1-DTNBP1chr1568379088chr615533626617DRB1-0101PTSLAELDAEHAQKV1126
PIAS1-DTNBP1chr1568379088chr615533626617DRB1-0101KPTSLAELDAEHAQK1025
PIAS1-DTNBP1chr1568379088chr615533626617DRB1-0102PTSLAELDAEHAQKV1126
PIAS1-DTNBP1chr1568379088chr615533626617DRB1-0102KPTSLAELDAEHAQK1025
PIAS1-DTNBP1chr1568379088chr615533626617DRB1-0102IKPTSLAELDAEHAQ924
PIAS1-DTNBP1chr1568379088chr615533626617DRB1-0105PTSLAELDAEHAQKV1126
PIAS1-DTNBP1chr1568379088chr615533626617DRB1-0105KPTSLAELDAEHAQK1025
PIAS1-DTNBP1chr1568379088chr615533626617DRB1-0107PTSLAELDAEHAQKV1126
PIAS1-DTNBP1chr1568379088chr615533626617DRB1-0107KPTSLAELDAEHAQK1025
PIAS1-DTNBP1chr1568379088chr615533626617DRB1-0109PTSLAELDAEHAQKV1126
PIAS1-DTNBP1chr1568379088chr615533626617DRB1-0111PTSLAELDAEHAQKV1126
PIAS1-DTNBP1chr1568379088chr615533626617DRB1-0111KPTSLAELDAEHAQK1025
PIAS1-DTNBP1chr1568379088chr615533626617DRB1-0117PTSLAELDAEHAQKV1126
PIAS1-DTNBP1chr1568379088chr615533626617DRB1-0119PTSLAELDAEHAQKV1126
PIAS1-DTNBP1chr1568379088chr615533626617DRB1-0119KPTSLAELDAEHAQK1025
PIAS1-DTNBP1chr1568379088chr615533626617DRB1-0121PTSLAELDAEHAQKV1126
PIAS1-DTNBP1chr1568379088chr615533626617DRB1-0121KPTSLAELDAEHAQK1025
PIAS1-DTNBP1chr1568379088chr615533626617DRB1-0123PTSLAELDAEHAQKV1126
PIAS1-DTNBP1chr1568379088chr615533626617DRB1-0123KPTSLAELDAEHAQK1025
PIAS1-DTNBP1chr1568379088chr615533626617DRB1-0125PTSLAELDAEHAQKV1126
PIAS1-DTNBP1chr1568379088chr615533626617DRB1-0125KPTSLAELDAEHAQK1025
PIAS1-DTNBP1chr1568379088chr615533626617DRB1-0127PTSLAELDAEHAQKV1126
PIAS1-DTNBP1chr1568379088chr615533626617DRB1-0127KPTSLAELDAEHAQK1025
PIAS1-DTNBP1chr1568379088chr615533626617DRB1-0129PTSLAELDAEHAQKV1126
PIAS1-DTNBP1chr1568379088chr615533626617DRB1-0131PTSLAELDAEHAQKV1126
PIAS1-DTNBP1chr1568379088chr615533626617DRB1-0131KPTSLAELDAEHAQK1025
PIAS1-DTNBP1chr1568379088chr615533626617DRB1-1001PTSLAELDAEHAQKV1126
PIAS1-DTNBP1chr1568379088chr615533626617DRB1-1001KPTSLAELDAEHAQK1025
PIAS1-DTNBP1chr1568379088chr615533626617DRB1-1002PTSLAELDAEHAQKV1126
PIAS1-DTNBP1chr1568379088chr615533626617DRB1-1002KPTSLAELDAEHAQK1025
PIAS1-DTNBP1chr1568379088chr615533626617DRB1-1002IKPTSLAELDAEHAQ924
PIAS1-DTNBP1chr1568379088chr615533626617DRB1-1003PTSLAELDAEHAQKV1126
PIAS1-DTNBP1chr1568379088chr615533626617DRB1-1003KPTSLAELDAEHAQK1025

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Fusion breakpoint peptide structures of PIAS1-DTNBP1

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
1071DELIKPTSLAELDAPIAS1DTNBP1chr1568379088chr615533626617

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PIAS1-DTNBP1

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-B14:023BVN1071DELIKPTSLAELDA-7.9962-8.1096
HLA-B14:023BVN1071DELIKPTSLAELDA-5.70842-6.74372
HLA-B52:013W391071DELIKPTSLAELDA-6.83737-6.95077
HLA-B52:013W391071DELIKPTSLAELDA-4.4836-5.5189
HLA-A11:014UQ21071DELIKPTSLAELDA-10.0067-10.1201
HLA-A11:014UQ21071DELIKPTSLAELDA-9.03915-10.0745
HLA-A24:025HGA1071DELIKPTSLAELDA-6.56204-6.67544
HLA-A24:025HGA1071DELIKPTSLAELDA-5.42271-6.45801
HLA-B44:053DX81071DELIKPTSLAELDA-7.85648-8.89178
HLA-B44:053DX81071DELIKPTSLAELDA-5.3978-5.5112
HLA-A02:016TDR1071DELIKPTSLAELDA-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of PIAS1-DTNBP1

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
PIAS1-DTNBP1chr1568379088chr6155336261018KPTSLAELCCAGTCTAGCTGAACTAGATGCAG
PIAS1-DTNBP1chr1568379088chr615533626616DELIKPTSLATGATAAAACCCACCAGTCTAGCTGAACTAG
PIAS1-DTNBP1chr1568379088chr615533626716ELIKPTSLATAAAACCCACCAGTCTAGCTGAACTAG
PIAS1-DTNBP1chr1568379088chr615533626818LIKPTSLAELAACCCACCAGTCTAGCTGAACTAGATGCAG
PIAS1-DTNBP1chr1568379088chr615533626918IKPTSLAELCCACCAGTCTAGCTGAACTAGATGCAG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
PIAS1-DTNBP1chr1568379088chr6155336261025KPTSLAELDAEHAQKCCAGTCTAGCTGAACTAGATGCAGAGCACGCCCAGAAGGTCCTGG
PIAS1-DTNBP1chr1568379088chr6155336261126PTSLAELDAEHAQKVGTCTAGCTGAACTAGATGCAGAGCACGCCCAGAAGGTCCTGGAAA
PIAS1-DTNBP1chr1568379088chr615533626924IKPTSLAELDAEHAQCCACCAGTCTAGCTGAACTAGATGCAGAGCACGCCCAGAAGGTCC

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Information of the samples that have these potential fusion neoantigens of PIAS1-DTNBP1

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
STADPIAS1-DTNBP1chr1568379088ENST00000249636chr615533626ENST00000338950TCGA-BR-6453

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Potential target of CAR-T therapy development for PIAS1-DTNBP1

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 PIAS1-DTNBP1

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 PIAS1-DTNBP1

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