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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:CASZ1-IPO13

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CASZ1-IPO13
FusionPDB ID: 13287
FusionGDB2.0 ID: 13287
HgeneTgene
Gene symbol

CASZ1

IPO13

Gene ID

54897

9670

Gene namecastor zinc finger 1importin 13
SynonymsCAS11|CST|SRG|ZNF693|dJ734G22.1IMP13|KAP13|LGL2|RANBP13
Cytomap

1p36.22

1p34.1

Type of geneprotein-codingprotein-coding
Descriptionzinc finger protein castor homolog 1castor homolog 1, zinc fingercastor-related proteinsurvival-relatedzinc finger protein 693importin-13Ran binding protein 13karyopherin 13late gestation lung 2ran-binding protein 13
Modification date2020031320200327
UniProtAcc

Q86V15

Main function of 5'-partner protein: FUNCTION: Transcriptional activator (PubMed:23639441, PubMed:27693370). Involved in vascular assembly and morphogenesis through direct transcriptional regulation of EGFL7 (PubMed:23639441). {ECO:0000269|PubMed:23639441, ECO:0000269|PubMed:27693370}.

O94829

Main function of 5'-partner protein: FUNCTION: Functions in nuclear protein import as nuclear transport receptor. Serves as receptor for nuclear localization signals (NLS) in cargo substrates. Is thought to mediate docking of the importin/substrate complex to the nuclear pore complex (NPC) through binding to nucleoporin and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to the importin, the importin/substrate complex dissociates and importin is re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus (By similarity). Mediates the nuclear import of UBC9, the RBM8A/MAGOH complex, PAX6 and probably other members of the paired homeobox family. Also mediates nuclear export of eIF-1A, and the cytoplasmic release of eIF-1A is triggered by the loading of import substrates onto IPO13. {ECO:0000250, ECO:0000269|PubMed:11447110, ECO:0000269|PubMed:15143176}.
Ensembl transtripts involved in fusion geneENST idsENST00000377022, ENST00000344008, 
ENST00000478728, 
ENST00000372339, 
ENST00000492152, ENST00000372343, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score23 X 19 X 12=52444 X 4 X 3=48
# samples 304
** MAII scorelog2(30/5244*10)=-4.12763327972587
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(4/48*10)=-0.263034405833794
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: CASZ1 [Title/Abstract] AND IPO13 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CASZ1 [Title/Abstract] AND IPO13 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CASZ1(10704973)-IPO13(44423648), # samples:1
Anticipated loss of major functional domain due to fusion event.CASZ1-IPO13 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.
CASZ1-IPO13 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.
CASZ1-IPO13 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.
CASZ1-IPO13 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
HgeneCASZ1

GO:0045893

positive regulation of transcription, DNA-templated

27693370

TgeneIPO13

GO:0006606

protein import into nucleus

15964792



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/chr1:10704973/chr1:44423648)
- 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 CASZ1 (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 IPO13 (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)
ENST00000377022CASZ1chr110704973-ENST00000372343IPO13chr144423648+5878418628555371750

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
ENST00000377022ENST00000372343CASZ1chr110704973-IPO13chr144423648+0.0082326350.99176735

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 CASZ1-IPO13

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CASZ1chr110704973IPO13chr14442364841861300FKYFTKREECGRLGALSEWLADHPVM

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Potential FusionNeoAntigen Information of CASZ1-IPO13 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.
CASZ1-IPO13_10704973_44423648.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)
CASZ1-IPO13chr110704973chr1444236484186HLA-B27:02GRLGALSEW0.99910.72141019
CASZ1-IPO13chr110704973chr1444236484186HLA-B27:05GRLGALSEW0.99870.89791019
CASZ1-IPO13chr110704973chr1444236484186HLA-B27:04GRLGALSEW0.99820.89281019
CASZ1-IPO13chr110704973chr1444236484186HLA-B27:07GRLGALSEW0.9870.91391019
CASZ1-IPO13chr110704973chr1444236484186HLA-B45:01REECGRLGA0.98360.8708615
CASZ1-IPO13chr110704973chr1444236484186HLA-B50:02REECGRLGA0.93220.7651615
CASZ1-IPO13chr110704973chr1444236484186HLA-B41:01REECGRLGA0.33350.8384615
CASZ1-IPO13chr110704973chr1444236484186HLA-B50:01REECGRLGA0.07010.9428615
CASZ1-IPO13chr110704973chr1444236484186HLA-B27:02GRLGALSEWL0.99950.6191020
CASZ1-IPO13chr110704973chr1444236484186HLA-B27:04GRLGALSEWL0.99950.86521020
CASZ1-IPO13chr110704973chr1444236484186HLA-B27:05GRLGALSEWL0.99950.831020
CASZ1-IPO13chr110704973chr1444236484186HLA-B27:07GRLGALSEWL0.9990.88681020
CASZ1-IPO13chr110704973chr1444236484186HLA-B40:06REECGRLGA0.99670.7563615
CASZ1-IPO13chr110704973chr1444236484186HLA-B27:03GRLGALSEW0.99120.90311019
CASZ1-IPO13chr110704973chr1444236484186HLA-C07:95GRLGALSEW0.95520.84211019
CASZ1-IPO13chr110704973chr1444236484186HLA-B27:03GRLGALSEWL0.99130.84661020
CASZ1-IPO13chr110704973chr1444236484186HLA-B27:08GRLGALSEW0.99850.85171019
CASZ1-IPO13chr110704973chr1444236484186HLA-B27:10GRLGALSEW0.99840.94261019
CASZ1-IPO13chr110704973chr1444236484186HLA-B27:06GRLGALSEW0.99750.93551019
CASZ1-IPO13chr110704973chr1444236484186HLA-B27:09GRLGALSEW0.97580.87661019
CASZ1-IPO13chr110704973chr1444236484186HLA-C07:01GRLGALSEW0.96520.82351019
CASZ1-IPO13chr110704973chr1444236484186HLA-B18:03EECGRLGAL0.62960.7074716
CASZ1-IPO13chr110704973chr1444236484186HLA-C07:22GRLGALSEW0.48310.82651019
CASZ1-IPO13chr110704973chr1444236484186HLA-B50:05REECGRLGA0.07010.9428615
CASZ1-IPO13chr110704973chr1444236484186HLA-B50:04REECGRLGA0.07010.9428615
CASZ1-IPO13chr110704973chr1444236484186HLA-B27:08GRLGALSEWL0.99950.77931020
CASZ1-IPO13chr110704973chr1444236484186HLA-B27:10GRLGALSEWL0.99950.91861020
CASZ1-IPO13chr110704973chr1444236484186HLA-B27:06GRLGALSEWL0.99910.91171020
CASZ1-IPO13chr110704973chr1444236484186HLA-B27:09GRLGALSEWL0.99830.79911020

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Potential FusionNeoAntigen Information of CASZ1-IPO13 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 CASZ1-IPO13

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
7767REECGRLGALSEWLCASZ1IPO13chr110704973chr1444236484186

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CASZ1-IPO13

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-B14:023BVN7767REECGRLGALSEWL-7.15543-7.26883
HLA-B14:023BVN7767REECGRLGALSEWL-4.77435-5.80965
HLA-B52:013W397767REECGRLGALSEWL-6.80875-6.92215
HLA-B52:013W397767REECGRLGALSEWL-4.20386-5.23916
HLA-A11:014UQ27767REECGRLGALSEWL-7.5194-8.5547
HLA-A11:014UQ27767REECGRLGALSEWL-6.9601-7.0735
HLA-A24:025HGA7767REECGRLGALSEWL-7.52403-7.63743
HLA-A24:025HGA7767REECGRLGALSEWL-5.82433-6.85963
HLA-B27:056PYJ7767REECGRLGALSEWL-3.28285-4.31815
HLA-B44:053DX87767REECGRLGALSEWL-5.91172-6.94702
HLA-B44:053DX87767REECGRLGALSEWL-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of CASZ1-IPO13

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
CASZ1-IPO13chr110704973chr1444236481019GRLGALSEWGCAGGCTAGGAGCTCTGTCTGAATGGC
CASZ1-IPO13chr110704973chr1444236481020GRLGALSEWLGCAGGCTAGGAGCTCTGTCTGAATGGCTGG
CASZ1-IPO13chr110704973chr144423648615REECGRLGAGCGAGGAGTGTGGCAGGCTAGGAGCTC
CASZ1-IPO13chr110704973chr144423648716EECGRLGALAGGAGTGTGGCAGGCTAGGAGCTCTGT

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 CASZ1-IPO13

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
ESCACASZ1-IPO13chr110704973ENST00000377022chr144423648ENST00000372343TCGA-Q9-A6FU

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Potential target of CAR-T therapy development for CASZ1-IPO13

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 CASZ1-IPO13

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 CASZ1-IPO13

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