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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:SPINT2-TYROBP

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: SPINT2-TYROBP
FusionPDB ID: 85854
FusionGDB2.0 ID: 85854
HgeneTgene
Gene symbol

SPINT2

TYROBP

Gene ID

10653

7305

Gene nameserine peptidase inhibitor, Kunitz type 2transmembrane immune signaling adaptor TYROBP
SynonymsDIAR3|HAI-2|HAI2|Kop|PBDAP12|KARAP|PLOSL|PLOSL1
Cytomap

19q13.2

19q13.12

Type of geneprotein-codingprotein-coding
Descriptionkunitz-type protease inhibitor 2hepatocyte growth factor activator inhibitor type 2serine protease inhibitor, Kunitz type, 2testicular tissue protein Li 183TYRO protein tyrosine kinase-binding proteinDNAX adaptor protein 12DNAX-activation protein 12KAR-associated proteinTYRO protein tyrosine kinase binding proteinkiller-activating receptor-associated proteinpolycystic lipomembranous osteodysplasia with
Modification date2020031520200329
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000301244, ENST00000454580, 
ENST00000587090, 
ENST00000262629, 
ENST00000424586, ENST00000544690, 
ENST00000585901, ENST00000589517, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score16 X 8 X 9=11525 X 6 X 4=120
# samples 217
** MAII scorelog2(21/1152*10)=-2.45567948377619
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(7/120*10)=-0.777607578663552
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: SPINT2 [Title/Abstract] AND TYROBP [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: SPINT2 [Title/Abstract] AND TYROBP [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)SPINT2(38755638)-TYROBP(36398482), # samples:2
Anticipated loss of major functional domain due to fusion event.SPINT2-TYROBP 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.
SPINT2-TYROBP 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
HgeneSPINT2

GO:0022408

negative regulation of cell-cell adhesion

19592578

HgeneSPINT2

GO:2000146

negative regulation of cell motility

19592578

TgeneTYROBP

GO:0002274

myeloid leukocyte activation

10604985

TgeneTYROBP

GO:0050821

protein stabilization

25957402



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/chr19:38755638/chr19:36398482)
- 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 SPINT2 (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 TYROBP (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)
ENST00000301244SPINT2chr1938755638+ENST00000424586TYROBPchr1936398482-9545418300277
ENST00000301244SPINT2chr1938755638+ENST00000585901TYROBPchr1936398482-1048541411881156
ENST00000301244SPINT2chr1938755638+ENST00000544690TYROBPchr1936398482-9555418330278
ENST00000301244SPINT2chr1938755638+ENST00000262629TYROBPchr1936398482-9485418330278
ENST00000301244SPINT2chr1938755638+ENST00000589517TYROBPchr1936398482-7955417670256
ENST00000454580SPINT2chr1938755638+ENST00000424586TYROBPchr1936398482-8364237122237
ENST00000454580SPINT2chr1938755638+ENST00000585901TYROBPchr1936398482-930423293763156
ENST00000454580SPINT2chr1938755638+ENST00000544690TYROBPchr1936398482-8374237152238
ENST00000454580SPINT2chr1938755638+ENST00000262629TYROBPchr1936398482-8304237152238
ENST00000454580SPINT2chr1938755638+ENST00000589517TYROBPchr1936398482-6774236492216

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
ENST00000301244ENST00000424586SPINT2chr1938755638+TYROBPchr1936398482-0.114161730.8858382
ENST00000301244ENST00000585901SPINT2chr1938755638+TYROBPchr1936398482-0.208315850.7916842
ENST00000301244ENST00000544690SPINT2chr1938755638+TYROBPchr1936398482-0.093468380.9065317
ENST00000301244ENST00000262629SPINT2chr1938755638+TYROBPchr1936398482-0.0953334640.90466654
ENST00000301244ENST00000589517SPINT2chr1938755638+TYROBPchr1936398482-0.0816135260.91838646
ENST00000454580ENST00000424586SPINT2chr1938755638+TYROBPchr1936398482-0.061796540.9382034
ENST00000454580ENST00000585901SPINT2chr1938755638+TYROBPchr1936398482-0.153067450.8469326
ENST00000454580ENST00000544690SPINT2chr1938755638+TYROBPchr1936398482-0.0588516670.9411484
ENST00000454580ENST00000262629SPINT2chr1938755638+TYROBPchr1936398482-0.06407960.9359204
ENST00000454580ENST00000589517SPINT2chr1938755638+TYROBPchr1936398482-0.04309090.9569091

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 SPINT2-TYROBP

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
SPINT2chr1938755638TYROBPchr193639848242343SGVLAADRERSIHDCSCSTVSPGVLA
SPINT2chr1938755638TYROBPchr193639848254143SGVLAADRERSIHDCSCSTVSPGVLA

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Potential FusionNeoAntigen Information of SPINT2-TYROBP 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.
SPINT2-TYROBP_38755638_36398482.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)
SPINT2-TYROBPchr1938755638chr1936398482541HLA-B39:11IHDCSCSTV0.58980.64841120

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Potential FusionNeoAntigen Information of SPINT2-TYROBP 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 SPINT2-TYROBP

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
1366DRERSIHDCSCSTVSPINT2TYROBPchr1938755638chr1936398482541

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of SPINT2-TYROBP

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-B14:023BVN1366DRERSIHDCSCSTV-7.15543-7.26883
HLA-B14:023BVN1366DRERSIHDCSCSTV-4.77435-5.80965
HLA-B52:013W391366DRERSIHDCSCSTV-6.80875-6.92215
HLA-B52:013W391366DRERSIHDCSCSTV-4.20386-5.23916
HLA-A11:014UQ21366DRERSIHDCSCSTV-7.5194-8.5547
HLA-A11:014UQ21366DRERSIHDCSCSTV-6.9601-7.0735
HLA-A24:025HGA1366DRERSIHDCSCSTV-7.52403-7.63743
HLA-A24:025HGA1366DRERSIHDCSCSTV-5.82433-6.85963
HLA-B27:056PYJ1366DRERSIHDCSCSTV-3.28285-4.31815
HLA-B44:053DX81366DRERSIHDCSCSTV-5.91172-6.94702
HLA-B44:053DX81366DRERSIHDCSCSTV-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of SPINT2-TYROBP

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
SPINT2-TYROBPchr1938755638chr19363984821120IHDCSCSTVTCCACGATTGCAGTTGCTCTACGGTGA

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 SPINT2-TYROBP

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
OVSPINT2-TYROBPchr1938755638ENST00000301244chr1936398482ENST00000585901TCGA-57-1994-01A

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Potential target of CAR-T therapy development for SPINT2-TYROBP

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
TgeneTYROBPchr19:38755638chr19:36398482ENST000002626291541_610114.0TransmembraneHelical
TgeneTYROBPchr19:38755638chr19:36398482ENST000005446900441_610103.0TransmembraneHelical
TgeneTYROBPchr19:38755638chr19:36398482ENST000005895171541_610113.0TransmembraneHelical

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 SPINT2-TYROBP

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 SPINT2-TYROBP

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