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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:CTSB-UBAP2L

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CTSB-UBAP2L
FusionPDB ID: 20480
FusionGDB2.0 ID: 20480
HgeneTgene
Gene symbol

CTSB

UBAP2L

Gene ID

1508

9898

Gene namecathepsin Bubiquitin associated protein 2 like
SynonymsAPPS|CPSB|RECEUPNICE-4|NICE4
Cytomap

8p23.1

1q21.3

Type of geneprotein-codingprotein-coding
Descriptioncathepsin BAPP secretaseamyloid precursor protein secretasecathepsin B1cysteine proteaseepididymis secretory sperm binding proteinubiquitin-associated protein 2-likeprotein NICE-4
Modification date2020031320200313
UniProtAcc

P07858

Main function of 5'-partner protein: FUNCTION: Thiol protease which is believed to participate in intracellular degradation and turnover of proteins (PubMed:12220505). Cleaves matrix extracellular phosphoglycoprotein MEPE (PubMed:12220505). Involved in the solubilization of cross-linked TG/thyroglobulin in the thyroid follicle lumen (By similarity). Has also been implicated in tumor invasion and metastasis (PubMed:3972105). {ECO:0000250|UniProtKB:P10605, ECO:0000269|PubMed:12220505, ECO:0000269|PubMed:3972105}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000345125, ENST00000353047, 
ENST00000415599, ENST00000434271, 
ENST00000453527, ENST00000530640, 
ENST00000531089, ENST00000533455, 
ENST00000534510, ENST00000525076, 
ENST00000484819, ENST00000271877, 
ENST00000343815, ENST00000361546, 
ENST00000428931, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score24 X 19 X 10=456017 X 15 X 7=1785
# samples 2518
** MAII scorelog2(25/4560*10)=-4.18903382439002
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(18/1785*10)=-3.30985526258679
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: CTSB [Title/Abstract] AND UBAP2L [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CTSB [Title/Abstract] AND UBAP2L [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CTSB(11710837)-UBAP2L(154234067), # samples:1
Anticipated loss of major functional domain due to fusion event.CTSB-UBAP2L 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.
CTSB-UBAP2L 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.
CTSB-UBAP2L seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
CTSB-UBAP2L seems lost the major protein functional domain in Tgene partner, which is a essential 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
HgeneCTSB

GO:0006508

proteolysis

7890620|8811434

HgeneCTSB

GO:0030574

collagen catabolic process

22952693

HgeneCTSB

GO:0051603

proteolysis involved in cellular protein catabolic process

22952693



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/chr8:11710837/chr1:154234067)
- 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 CTSB (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 UBAP2L (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)
ENST00000434271CTSBchr811710837-ENST00000343815UBAP2Lchr1154234067+873364817401138
ENST00000434271CTSBchr811710837-ENST00000428931UBAP2Lchr1154234067+1389364238831197
ENST00000434271CTSBchr811710837-ENST00000271877UBAP2Lchr1154234067+862364238771177
ENST00000434271CTSBchr811710837-ENST00000361546UBAP2Lchr1154234067+1390364238831197
ENST00000530640CTSBchr811710837-ENST00000343815UBAP2Lchr1154234067+772263716300138
ENST00000530640CTSBchr811710837-ENST00000428931UBAP2Lchr1154234067+1288263137730197
ENST00000530640CTSBchr811710837-ENST00000271877UBAP2Lchr1154234067+761263137670177
ENST00000530640CTSBchr811710837-ENST00000361546UBAP2Lchr1154234067+1289263137730197
ENST00000415599CTSBchr811710837-ENST00000343815UBAP2Lchr1154234067+707198651235138
ENST00000415599CTSBchr811710837-ENST00000428931UBAP2Lchr1154234067+122319872665197
ENST00000415599CTSBchr811710837-ENST00000271877UBAP2Lchr1154234067+69619872605177
ENST00000415599CTSBchr811710837-ENST00000361546UBAP2Lchr1154234067+122419872665197
ENST00000533455CTSBchr811710837-ENST00000343815UBAP2Lchr1154234067+854345798382138
ENST00000533455CTSBchr811710837-ENST00000428931UBAP2Lchr1154234067+1370345219812197
ENST00000533455CTSBchr811710837-ENST00000271877UBAP2Lchr1154234067+843345219752177
ENST00000533455CTSBchr811710837-ENST00000361546UBAP2Lchr1154234067+1371345219812197

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
ENST00000434271ENST00000343815CTSBchr811710837-UBAP2Lchr1154234067+0.522969960.47703004
ENST00000434271ENST00000428931CTSBchr811710837-UBAP2Lchr1154234067+0.0156503020.98434967
ENST00000434271ENST00000271877CTSBchr811710837-UBAP2Lchr1154234067+0.0083250490.99167496
ENST00000434271ENST00000361546CTSBchr811710837-UBAP2Lchr1154234067+0.0154904660.9845095
ENST00000530640ENST00000343815CTSBchr811710837-UBAP2Lchr1154234067+0.393612920.606387
ENST00000530640ENST00000428931CTSBchr811710837-UBAP2Lchr1154234067+0.0100027610.98999727
ENST00000530640ENST00000271877CTSBchr811710837-UBAP2Lchr1154234067+0.0028366540.99716336
ENST00000530640ENST00000361546CTSBchr811710837-UBAP2Lchr1154234067+0.0098852540.9901148
ENST00000415599ENST00000343815CTSBchr811710837-UBAP2Lchr1154234067+0.572641730.4273583
ENST00000415599ENST00000428931CTSBchr811710837-UBAP2Lchr1154234067+0.0103093020.98969066
ENST00000415599ENST00000271877CTSBchr811710837-UBAP2Lchr1154234067+0.0030787160.9969213
ENST00000415599ENST00000361546CTSBchr811710837-UBAP2Lchr1154234067+0.0102422820.98975766
ENST00000533455ENST00000343815CTSBchr811710837-UBAP2Lchr1154234067+0.44363930.5563607
ENST00000533455ENST00000428931CTSBchr811710837-UBAP2Lchr1154234067+0.0131854450.9868146
ENST00000533455ENST00000271877CTSBchr811710837-UBAP2Lchr1154234067+0.0047068870.9952931
ENST00000533455ENST00000361546CTSBchr811710837-UBAP2Lchr1154234067+0.0130554650.9869445

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 CTSB-UBAP2L

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CTSBchr811710837UBAP2Lchr115423406719842LVNYVNKRNTTWQVAPTSSKQHGVNV
CTSBchr811710837UBAP2Lchr115423406726342LVNYVNKRNTTWQVAPTSSKQHGVNV
CTSBchr811710837UBAP2Lchr115423406734542LVNYVNKRNTTWQVAPTSSKQHGVNV
CTSBchr811710837UBAP2Lchr115423406736442LVNYVNKRNTTWQVAPTSSKQHGVNV

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Potential FusionNeoAntigen Information of CTSB-UBAP2L 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.
CTSB-UBAP2L_11710837_154234067.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)
CTSB-UBAP2Lchr811710837chr1154234067198HLA-B27:14KRNTTWQVA0.99820.5066615
CTSB-UBAP2Lchr811710837chr1154234067198HLA-B73:01KRNTTWQVA0.98660.9092615
CTSB-UBAP2Lchr811710837chr1154234067198HLA-B73:01NKRNTTWQVA0.91620.9474515

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Potential FusionNeoAntigen Information of CTSB-UBAP2L 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.
CTSB-UBAP2L_11710837_154234067.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)
CTSB-UBAP2Lchr811710837chr1154234067198DRB5-0101NTTWQVAPTSSKQHG823
CTSB-UBAP2Lchr811710837chr1154234067198DRB5-0101RNTTWQVAPTSSKQH722
CTSB-UBAP2Lchr811710837chr1154234067198DRB5-0104NTTWQVAPTSSKQHG823
CTSB-UBAP2Lchr811710837chr1154234067198DRB5-0104RNTTWQVAPTSSKQH722
CTSB-UBAP2Lchr811710837chr1154234067198DRB5-0105NTTWQVAPTSSKQHG823
CTSB-UBAP2Lchr811710837chr1154234067198DRB5-0105RNTTWQVAPTSSKQH722
CTSB-UBAP2Lchr811710837chr1154234067198DRB5-0111NTTWQVAPTSSKQHG823
CTSB-UBAP2Lchr811710837chr1154234067198DRB5-0112NTTWQVAPTSSKQHG823
CTSB-UBAP2Lchr811710837chr1154234067198DRB5-0112RNTTWQVAPTSSKQH722
CTSB-UBAP2Lchr811710837chr1154234067198DRB5-0112KRNTTWQVAPTSSKQ621
CTSB-UBAP2Lchr811710837chr1154234067198DRB5-0112TTWQVAPTSSKQHGV924
CTSB-UBAP2Lchr811710837chr1154234067198DRB5-0113NTTWQVAPTSSKQHG823
CTSB-UBAP2Lchr811710837chr1154234067198DRB5-0113RNTTWQVAPTSSKQH722
CTSB-UBAP2Lchr811710837chr1154234067198DRB5-0114NTTWQVAPTSSKQHG823
CTSB-UBAP2Lchr811710837chr1154234067198DRB5-0114RNTTWQVAPTSSKQH722

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Fusion breakpoint peptide structures of CTSB-UBAP2L

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
4570KRNTTWQVAPTSSKCTSBUBAP2Lchr811710837chr1154234067198

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CTSB-UBAP2L

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-B14:023BVN4570KRNTTWQVAPTSSK-7.15543-7.26883
HLA-B14:023BVN4570KRNTTWQVAPTSSK-4.77435-5.80965
HLA-B52:013W394570KRNTTWQVAPTSSK-6.80875-6.92215
HLA-B52:013W394570KRNTTWQVAPTSSK-4.20386-5.23916
HLA-A11:014UQ24570KRNTTWQVAPTSSK-7.5194-8.5547
HLA-A11:014UQ24570KRNTTWQVAPTSSK-6.9601-7.0735
HLA-A24:025HGA4570KRNTTWQVAPTSSK-7.52403-7.63743
HLA-A24:025HGA4570KRNTTWQVAPTSSK-5.82433-6.85963
HLA-B27:056PYJ4570KRNTTWQVAPTSSK-3.28285-4.31815
HLA-B44:053DX84570KRNTTWQVAPTSSK-5.91172-6.94702
HLA-B44:053DX84570KRNTTWQVAPTSSK-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of CTSB-UBAP2L

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
CTSB-UBAP2Lchr811710837chr1154234067515NKRNTTWQVAAACAAACGGAATACCACGTGGCAGGTGGCT
CTSB-UBAP2Lchr811710837chr1154234067615KRNTTWQVAAAACGGAATACCACGTGGCAGGTGGCT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
CTSB-UBAP2Lchr811710837chr1154234067621KRNTTWQVAPTSSKQAAACGGAATACCACGTGGCAGGTGGCTCCTACCTCTTCCAAGCAG
CTSB-UBAP2Lchr811710837chr1154234067722RNTTWQVAPTSSKQHCGGAATACCACGTGGCAGGTGGCTCCTACCTCTTCCAAGCAGCAT
CTSB-UBAP2Lchr811710837chr1154234067823NTTWQVAPTSSKQHGAATACCACGTGGCAGGTGGCTCCTACCTCTTCCAAGCAGCATGGT
CTSB-UBAP2Lchr811710837chr1154234067924TTWQVAPTSSKQHGVACCACGTGGCAGGTGGCTCCTACCTCTTCCAAGCAGCATGGTGTG

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Information of the samples that have these potential fusion neoantigens of CTSB-UBAP2L

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
OVCTSB-UBAP2Lchr811710837ENST00000415599chr1154234067ENST00000271877TCGA-61-2008

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Potential target of CAR-T therapy development for CTSB-UBAP2L

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 CTSB-UBAP2L

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 CTSB-UBAP2L

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