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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:CTSZ-ZHX3

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CTSZ-ZHX3
FusionPDB ID: 20548
FusionGDB2.0 ID: 20548
HgeneTgene
Gene symbol

CTSZ

ZHX3

Gene ID

1522

23051

Gene namecathepsin Zzinc fingers and homeoboxes 3
SynonymsCTSXTIX1
Cytomap

20q13.32

20q12

Type of geneprotein-codingprotein-coding
Descriptioncathepsin Zcarboxypeptidase LBcathepsin B2cathepsin IVcathepsin Pcathepsin Xcathepsin Ycathepsin Z1cysteine-type carboxypeptidaselysosomal carboxypeptidase Bpreprocathepsin Pzinc fingers and homeoboxes protein 3triple homeobox 1triple homeobox protein 1zinc finger and homeodomain protein 3
Modification date2020031320200313
UniProtAcc

Q9UBR2

Main function of 5'-partner protein: FUNCTION: Exhibits carboxy-monopeptidase as well as carboxy-dipeptidase activity (PubMed:10504234). Capable of producing kinin potentiating peptides (By similarity). {ECO:0000250|UniProtKB:Q9R1T3, ECO:0000269|PubMed:10504234}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000217131, ENST00000561291, 
ENST00000309060, ENST00000432768, 
ENST00000540170, ENST00000544979, 
ENST00000557816, ENST00000558993, 
ENST00000559234, ENST00000560361, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score9 X 9 X 3=2435 X 4 X 4=80
# samples 95
** MAII scorelog2(9/243*10)=-1.43295940727611
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(5/80*10)=-0.678071905112638
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: CTSZ [Title/Abstract] AND ZHX3 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CTSZ [Title/Abstract] AND ZHX3 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CTSZ(57571694)-ZHX3(39813841), # samples:2
Anticipated loss of major functional domain due to fusion event.CTSZ-ZHX3 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.
CTSZ-ZHX3 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.
CTSZ-ZHX3 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
CTSZ-ZHX3 seems lost the major protein functional domain in Tgene partner, which is a transcription factor 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
HgeneCTSZ

GO:0032091

negative regulation of protein binding

19433310

TgeneZHX3

GO:0045892

negative regulation of transcription, DNA-templated

12659632



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/chr20:57571694/chr20:39813841)
- 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 CTSZ (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 ZHX3 (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)
ENST00000217131CTSZchr2057571694-ENST00000309060ZHX3chr2039813841-7674920681195375
ENST00000217131CTSZchr2057571694-ENST00000558993ZHX3chr2039813841-1301920681195375
ENST00000217131CTSZchr2057571694-ENST00000544979ZHX3chr2039813841-1295920681195375
ENST00000217131CTSZchr2057571694-ENST00000432768ZHX3chr2039813841-1206920681195375
ENST00000217131CTSZchr2057572658-ENST00000540170ZHX3chr2039813841-683975715725236
ENST00000217131CTSZchr2057572658-ENST00000559234ZHX3chr2039813841-384475715725236
ENST00000217131CTSZchr2057572658-ENST00000557816ZHX3chr2039813841-113875715725236
ENST00000217131CTSZchr2057572658-ENST00000560361ZHX3chr2039813841-113275715725236

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
ENST00000217131ENST00000309060CTSZchr2057571694-ZHX3chr2039813841-0.0030017740.9969982
ENST00000217131ENST00000558993CTSZchr2057571694-ZHX3chr2039813841-0.0194826310.9805173
ENST00000217131ENST00000544979CTSZchr2057571694-ZHX3chr2039813841-0.0201056150.97989434
ENST00000217131ENST00000432768CTSZchr2057571694-ZHX3chr2039813841-0.0262372340.97376275
ENST00000217131ENST00000540170CTSZchr2057572658-ZHX3chr2039813841-0.0046232010.9953768
ENST00000217131ENST00000559234CTSZchr2057572658-ZHX3chr2039813841-0.0037898050.9962102
ENST00000217131ENST00000557816CTSZchr2057572658-ZHX3chr2039813841-0.0136428720.9863571
ENST00000217131ENST00000560361CTSZchr2057572658-ZHX3chr2039813841-0.013808390.98619163

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 CTSZ-ZHX3

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CTSZchr2057571694ZHX3chr2039813841920284EYWIVRNSWGEPWKQTEFDLINVKDW

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Potential FusionNeoAntigen Information of CTSZ-ZHX3 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.
CTSZ-ZHX3_57571694_39813841.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)
CTSZ-ZHX3chr2057571694chr2039813841920HLA-B35:08EPWKQTEF0.96180.65581018
CTSZ-ZHX3chr2057571694chr2039813841920HLA-B35:01EPWKQTEF0.90690.74851018
CTSZ-ZHX3chr2057571694chr2039813841920HLA-B40:01GEPWKQTEF0.94940.5262918
CTSZ-ZHX3chr2057571694chr2039813841920HLA-B41:02GEPWKQTEF0.36460.5075918
CTSZ-ZHX3chr2057571694chr2039813841920HLA-A24:17SWGEPWKQTEF0.99810.6225718
CTSZ-ZHX3chr2057571694chr2039813841920HLA-A24:10SWGEPWKQTEF0.99740.6281718
CTSZ-ZHX3chr2057571694chr2039813841920HLA-A24:23SWGEPWKQTEF0.98950.6086718
CTSZ-ZHX3chr2057571694chr2039813841920HLA-A24:20SWGEPWKQTEF0.98710.7237718
CTSZ-ZHX3chr2057571694chr2039813841920HLA-A24:25SWGEPWKQTEF0.98480.724718
CTSZ-ZHX3chr2057571694chr2039813841920HLA-A24:15SWGEPWKQTEF0.98360.7351718
CTSZ-ZHX3chr2057571694chr2039813841920HLA-A24:31SWGEPWKQTEF0.98170.6987718
CTSZ-ZHX3chr2057571694chr2039813841920HLA-B42:02EPWKQTEF0.89040.64761018
CTSZ-ZHX3chr2057571694chr2039813841920HLA-B44:09GEPWKQTEF0.97850.5654918
CTSZ-ZHX3chr2057571694chr2039813841920HLA-B44:10GEPWKQTEF0.65430.6364918
CTSZ-ZHX3chr2057571694chr2039813841920HLA-A24:02SWGEPWKQTEF0.98710.7237718
CTSZ-ZHX3chr2057571694chr2039813841920HLA-B35:23EPWKQTEF0.90910.76741018
CTSZ-ZHX3chr2057571694chr2039813841920HLA-B35:77EPWKQTEF0.90690.74851018
CTSZ-ZHX3chr2057571694chr2039813841920HLA-B35:24EPWKQTEF0.86360.80421018
CTSZ-ZHX3chr2057571694chr2039813841920HLA-B35:30EPWKQTEF0.85120.66661018
CTSZ-ZHX3chr2057571694chr2039813841920HLA-B35:17EPWKQTEF0.85120.66661018
CTSZ-ZHX3chr2057571694chr2039813841920HLA-B18:07EPWKQTEF0.67170.79641018
CTSZ-ZHX3chr2057571694chr2039813841920HLA-B15:53GEPWKQTEF0.60710.8569918
CTSZ-ZHX3chr2057571694chr2039813841920HLA-B18:08GEPWKQTEF0.43820.9014918
CTSZ-ZHX3chr2057571694chr2039813841920HLA-B41:03GEPWKQTEF0.27140.7461918
CTSZ-ZHX3chr2057571694chr2039813841920HLA-A24:03SWGEPWKQTEF0.98950.6086718

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Potential FusionNeoAntigen Information of CTSZ-ZHX3 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 CTSZ-ZHX3

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
6405NSWGEPWKQTEFDLCTSZZHX3chr2057571694chr2039813841920

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CTSZ-ZHX3

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-B14:023BVN6405NSWGEPWKQTEFDL-7.9962-8.1096
HLA-B14:023BVN6405NSWGEPWKQTEFDL-5.70842-6.74372
HLA-B52:013W396405NSWGEPWKQTEFDL-6.83737-6.95077
HLA-B52:013W396405NSWGEPWKQTEFDL-4.4836-5.5189
HLA-A11:014UQ26405NSWGEPWKQTEFDL-10.0067-10.1201
HLA-A11:014UQ26405NSWGEPWKQTEFDL-9.03915-10.0745
HLA-A24:025HGA6405NSWGEPWKQTEFDL-6.56204-6.67544
HLA-A24:025HGA6405NSWGEPWKQTEFDL-5.42271-6.45801
HLA-B44:053DX86405NSWGEPWKQTEFDL-7.85648-8.89178
HLA-B44:053DX86405NSWGEPWKQTEFDL-5.3978-5.5112
HLA-A02:016TDR6405NSWGEPWKQTEFDL-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of CTSZ-ZHX3

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
CTSZ-ZHX3chr2057571694chr20398138411018EPWKQTEFGAACCATGGAAACAGACTGAATTT
CTSZ-ZHX3chr2057571694chr2039813841718SWGEPWKQTEFTCATGGGGTGAACCATGGAAACAGACTGAATTT
CTSZ-ZHX3chr2057571694chr2039813841918GEPWKQTEFGGTGAACCATGGAAACAGACTGAATTT

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 CTSZ-ZHX3

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
BRCACTSZ-ZHX3chr2057571694ENST00000217131chr2039813841ENST00000309060TCGA-BH-A0GY-01A

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Potential target of CAR-T therapy development for CTSZ-ZHX3

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 CTSZ-ZHX3

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 CTSZ-ZHX3

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