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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:TBCK-PAPSS1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TBCK-PAPSS1
FusionPDB ID: 89496
FusionGDB2.0 ID: 89496
HgeneTgene
Gene symbol

TBCK

PAPSS1

Gene ID

93627

9061

Gene nameTBC1 domain containing kinase3'-phosphoadenosine 5'-phosphosulfate synthase 1
SynonymsHSPC302|IHPRF3|TBCKLATPSK1|PAPSS|SK1
Cytomap

4q24

4q25

Type of geneprotein-codingprotein-coding
DescriptionTBC domain-containing protein kinase-like proteinbifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 13-prime-phosphoadenosine 5-prime-phosphosulfate synthase 1PAPS synthase 1PAPSS 1SK 1adenylyl-sulfate kinasesulfate adenylyltransferasesulfurylase kinase 1
Modification date2020031320200313
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000273980, ENST00000361687, 
ENST00000394706, ENST00000394708, 
ENST00000432496, ENST00000514689, 
ENST00000511304, ENST00000265174, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score7 X 5 X 6=21010 X 9 X 6=540
# samples 710
** MAII scorelog2(7/210*10)=-1.58496250072116
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(10/540*10)=-2.43295940727611
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: TBCK [Title/Abstract] AND PAPSS1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: TBCK [Title/Abstract] AND PAPSS1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PAPSS1(108552786)-TBCK(106967837), # samples:1
TBCK(107092252)-PAPSS1(108553016), # samples:1
Anticipated loss of major functional domain due to fusion event.TBCK-PAPSS1 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.
TBCK-PAPSS1 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.
TBCK-PAPSS1 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.
TBCK-PAPSS1 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.
PAPSS1-TBCK seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
PAPSS1-TBCK seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
PAPSS1-TBCK seems lost the major protein functional domain in Tgene partner, which is a kinase due to the frame-shifted ORF.
TBCK-PAPSS1 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
TBCK-PAPSS1 seems lost the major protein functional domain in Hgene partner, which is a kinase due to the frame-shifted ORF.
TBCK-PAPSS1 seems lost the major protein functional domain in Tgene partner, which is a cell metabolism 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
TgenePAPSS1

GO:0000103

sulfate assimilation

14747722

TgenePAPSS1

GO:0050428

3'-phosphoadenosine 5'-phosphosulfate biosynthetic process

14747722|23207770



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/chr4:108552786/chr4:106967837)
- 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 TBCK (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 PAPSS1 (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)
ENST00000273980TBCKchr4107092252-ENST00000265174PAPSS1chr4108553016-363526834483051867

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
ENST00000273980ENST00000265174TBCKchr4107092252-PAPSS1chr4108553016-0.0002567670.9997433

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 TBCK-PAPSS1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
TBCKchr4107092252PAPSS1chr41085530162683745FSAECPDPPKTDLVQWHCRARMVAGA

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Potential FusionNeoAntigen Information of TBCK-PAPSS1 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.
TBCK-PAPSS1_107092252_108553016.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)
TBCK-PAPSS1chr4107092252chr41085530162683HLA-B53:01PPKTDLVQW0.69090.7124716
TBCK-PAPSS1chr4107092252chr41085530162683HLA-B53:01DPPKTDLVQW0.79060.7308616
TBCK-PAPSS1chr4107092252chr41085530162683HLA-B53:02PPKTDLVQW0.68290.7229716
TBCK-PAPSS1chr4107092252chr41085530162683HLA-B53:02DPPKTDLVQW0.79850.7779616

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Potential FusionNeoAntigen Information of TBCK-PAPSS1 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 TBCK-PAPSS1

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
1317DPPKTDLVQWHCRATBCKPAPSS1chr4107092252chr41085530162683

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of TBCK-PAPSS1

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-B14:023BVN1317DPPKTDLVQWHCRA-7.15543-7.26883
HLA-B14:023BVN1317DPPKTDLVQWHCRA-4.77435-5.80965
HLA-B52:013W391317DPPKTDLVQWHCRA-6.80875-6.92215
HLA-B52:013W391317DPPKTDLVQWHCRA-4.20386-5.23916
HLA-A11:014UQ21317DPPKTDLVQWHCRA-7.5194-8.5547
HLA-A11:014UQ21317DPPKTDLVQWHCRA-6.9601-7.0735
HLA-A24:025HGA1317DPPKTDLVQWHCRA-7.52403-7.63743
HLA-A24:025HGA1317DPPKTDLVQWHCRA-5.82433-6.85963
HLA-B27:056PYJ1317DPPKTDLVQWHCRA-3.28285-4.31815
HLA-B44:053DX81317DPPKTDLVQWHCRA-5.91172-6.94702
HLA-B44:053DX81317DPPKTDLVQWHCRA-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of TBCK-PAPSS1

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
TBCK-PAPSS1chr4107092252chr4108553016616DPPKTDLVQWGATCCTCCAAAGACAGATCTGGTCCAGTGG
TBCK-PAPSS1chr4107092252chr4108553016716PPKTDLVQWCCTCCAAAGACAGATCTGGTCCAGTGG

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 TBCK-PAPSS1

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
LUSCTBCK-PAPSS1chr4107092252ENST00000273980chr4108553016ENST00000265174TCGA-21-5783-01A

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Potential target of CAR-T therapy development for TBCK-PAPSS1

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 TBCK-PAPSS1

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 TBCK-PAPSS1

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