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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:XYLT1-ABR

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: XYLT1-ABR
FusionPDB ID: 99851
FusionGDB2.0 ID: 99851
HgeneTgene
Gene symbol

XYLT1

ABR

Gene ID

64131

29

Gene namexylosyltransferase 1ABR activator of RhoGEF and GTPase
SynonymsDBQD2|PXYLT1|XT-I|XT1|XTI|XYLTI|xylT-IMDB
Cytomap

16p12.3

17p13.3

Type of geneprotein-codingprotein-coding
Descriptionxylosyltransferase 1beta-D-xylosyltransferase 1peptide O-xylosyltransferase 1xylosyltransferase Ixylosyltransferase iotaactive breakpoint cluster region-related proteinABR, RhoGEF and GTPase activating proteinactive BCR-related
Modification date2020031320200313
UniProtAcc.

Q15018

Main function of 5'-partner protein: FUNCTION: Component of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked polyubiquitin, leaving the last ubiquitin chain attached to its substrates (PubMed:19214193, PubMed:20032457, PubMed:20656690, PubMed:24075985). May act as a central scaffold protein that assembles the various components of the BRISC complex and retains them in the cytoplasm (PubMed:20656690). Plays a role in regulating the onset of apoptosis via its role in modulating 'Lys-63'-linked ubiquitination of target proteins (By similarity). Required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating NUMA1 (PubMed:26195665). Plays a role in interferon signaling via its role in the deubiquitination of the interferon receptor IFNAR1; deubiquitination increases IFNAR1 activities by enhancing its stability and cell surface expression (PubMed:24075985, PubMed:26344097). Down-regulates the response to bacterial lipopolysaccharide (LPS) via its role in IFNAR1 deubiquitination (PubMed:24075985). Required for normal induction of p53/TP53 in response to DNA damage (PubMed:25283148). Independent of the BRISC complex, promotes interaction between USP7 and p53/TP53, and thereby promotes deubiquitination of p53/TP53, preventing its degradation and resulting in increased p53/TP53-mediated transcription regulation and p53/TP53-dependent apoptosis in response to DNA damage (PubMed:25283148). {ECO:0000250|UniProtKB:Q3TCJ1, ECO:0000269|PubMed:19214193, ECO:0000269|PubMed:20032457, ECO:0000269|PubMed:20656690, ECO:0000269|PubMed:24075985, ECO:0000269|PubMed:25283148}.
Ensembl transtripts involved in fusion geneENST idsENST00000261381, ENST00000568226, 
ENST00000544583, ENST00000574437, 
ENST00000291107, ENST00000536794, 
ENST00000543210, ENST00000572441, 
ENST00000573895, ENST00000302538, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score10 X 8 X 4=32017 X 14 X 9=2142
# samples 1021
** MAII scorelog2(10/320*10)=-1.67807190511264
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(21/2142*10)=-3.35049724708413
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: XYLT1 [Title/Abstract] AND ABR [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: XYLT1 [Title/Abstract] AND ABR [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)XYLT1(17352845)-ABR(1028702), # samples:1
Anticipated loss of major functional domain due to fusion event.XYLT1-ABR 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.
XYLT1-ABR 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.
XYLT1-ABR 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.
XYLT1-ABR 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
HgeneXYLT1

GO:0030166

proteoglycan biosynthetic process

11087729

TgeneABR

GO:0090630

activation of GTPase activity

7479768



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/chr16:17352845/chr17:1028702)
- 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 XYLT1 (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 ABR (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)
ENST00000261381XYLT1chr1617352845-ENST00000302538ABRchr171028702-60799981335161167

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
ENST00000261381ENST00000302538XYLT1chr1617352845-ABRchr171028702-0.001951660.9980483

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 XYLT1-ABR

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
XYLT1chr1617352845ABRchr17102870299887VGGGEQPPPAPAPRRERRDLPAEPAA

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Potential FusionNeoAntigen Information of XYLT1-ABR 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.
XYLT1-ABR_17352845_1028702.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)
XYLT1-ABRchr1617352845chr171028702998HLA-B07:02APRRERRDL0.99860.57791120
XYLT1-ABRchr1617352845chr171028702998HLA-B07:02APAPRRERRDL0.99980.6859920
XYLT1-ABRchr1617352845chr171028702998HLA-B07:12APRRERRDL0.87020.71971120
XYLT1-ABRchr1617352845chr171028702998HLA-B07:04APRRERRDL0.76530.51691120
XYLT1-ABRchr1617352845chr171028702998HLA-B07:12APAPRRERRDL0.99960.7788920
XYLT1-ABRchr1617352845chr171028702998HLA-B07:04APAPRRERRDL0.99180.637920
XYLT1-ABRchr1617352845chr171028702998HLA-B07:22APRRERRDL0.99860.57791120
XYLT1-ABRchr1617352845chr171028702998HLA-B07:09APRRERRDL0.99840.56711120
XYLT1-ABRchr1617352845chr171028702998HLA-B07:22APAPRRERRDL0.99980.6859920

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Potential FusionNeoAntigen Information of XYLT1-ABR 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 XYLT1-ABR

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
6874PPPAPAPRRERRDLXYLT1ABRchr1617352845chr171028702998

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of XYLT1-ABR

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-B14:023BVN6874PPPAPAPRRERRDL-7.9962-8.1096
HLA-B14:023BVN6874PPPAPAPRRERRDL-5.70842-6.74372
HLA-B52:013W396874PPPAPAPRRERRDL-6.83737-6.95077
HLA-B52:013W396874PPPAPAPRRERRDL-4.4836-5.5189
HLA-A11:014UQ26874PPPAPAPRRERRDL-10.0067-10.1201
HLA-A11:014UQ26874PPPAPAPRRERRDL-9.03915-10.0745
HLA-A24:025HGA6874PPPAPAPRRERRDL-6.56204-6.67544
HLA-A24:025HGA6874PPPAPAPRRERRDL-5.42271-6.45801
HLA-B44:053DX86874PPPAPAPRRERRDL-7.85648-8.89178
HLA-B44:053DX86874PPPAPAPRRERRDL-5.3978-5.5112
HLA-A02:016TDR6874PPPAPAPRRERRDL-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of XYLT1-ABR

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
XYLT1-ABRchr1617352845chr1710287021120APRRERRDLTCGAGGACTTCAGCTACGGGACGGACG
XYLT1-ABRchr1617352845chr171028702920APAPRRERRDLGCCCCCTCGAGGACTTCAGCTACGGGACGGACG

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 XYLT1-ABR

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
SARCXYLT1-ABRchr1617352845ENST00000261381chr171028702ENST00000302538TCGA-IE-A4EJ-01A

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Potential target of CAR-T therapy development for XYLT1-ABR

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
HgeneXYLT1chr16:17352845chr17:1028702ENST00000261381-31218_38304960.0TransmembraneHelical%3B Signal-anchor for type II membrane protein

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 XYLT1-ABR

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 XYLT1-ABR

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