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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:EXOC6B-CASP10

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: EXOC6B-CASP10
FusionPDB ID: 27933
FusionGDB2.0 ID: 27933
HgeneTgene
Gene symbol

EXOC6B

CASP10

Gene ID

23233

843

Gene nameexocyst complex component 6Bcaspase 10
SynonymsSEC15B|SEC15L2|SEMDJL3ALPS2|FLICE2|MCH4
Cytomap

2p13.2

2q33.1

Type of geneprotein-codingprotein-coding
Descriptionexocyst complex component 6BSEC15 homolog BSEC15-like protein 2exocyst complex component Sec15Bcaspase-10CASP-10FADD-like ICE2FAS-associated death domain protein interleukin-1B-converting enzyme 2ICE-like apoptotic protease 4apoptotic protease MCH-4caspase 10 apoptosis-related cysteine peptidasecaspase 10, apoptosis-related cysteine protease
Modification date2020031320200313
UniProtAcc

Q9Y2D4

Main function of 5'-partner protein: FUNCTION: Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane.

Q92851

Main function of 5'-partner protein: FUNCTION: Involved in the activation cascade of caspases responsible for apoptosis execution. Recruited to both Fas- and TNFR-1 receptors in a FADD dependent manner. May participate in the granzyme B apoptotic pathways. Cleaves and activates caspase-3, -4, -6, -7, -8, and -9. Hydrolyzes the small- molecule substrates, Tyr-Val-Ala-Asp-|-AMC and Asp-Glu-Val-Asp-|-AMC. {ECO:0000269|PubMed:11717445}.; FUNCTION: Isoform 7 can enhance NF-kappaB activity but promotes only slight apoptosis. {ECO:0000269|PubMed:17822854}.; FUNCTION: Isoform C is proteolytically inactive. {ECO:0000269|PubMed:11717445}.
Ensembl transtripts involved in fusion geneENST idsENST00000272427, ENST00000490919, 
ENST00000410104, 
ENST00000492363, 
ENST00000313728, ENST00000346817, 
ENST00000374650, ENST00000448480, 
ENST00000272879, ENST00000286186, 
ENST00000360132, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score11 X 10 X 10=11005 X 3 X 3=45
# samples 154
** MAII scorelog2(15/1100*10)=-2.87446911791614
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(4/45*10)=-0.169925001442312
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: EXOC6B [Title/Abstract] AND CASP10 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: EXOC6B [Title/Abstract] AND CASP10 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)EXOC6B(72562076)-CASP10(202072798), # samples:1
Anticipated loss of major functional domain due to fusion event.EXOC6B-CASP10 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.
EXOC6B-CASP10 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.
EXOC6B-CASP10 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.
EXOC6B-CASP10 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.
EXOC6B-CASP10 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
EXOC6B-CASP10 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target 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


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/chr2:72562076/chr2:202072798)
- 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 EXOC6B (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 CASP10 (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)
ENST00000272427EXOC6Bchr272562076-ENST00000286186CASP10chr2202072798+700723271430821022
ENST00000272427EXOC6Bchr272562076-ENST00000272879CASP10chr2202072798+340323271430791021

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
ENST00000272427ENST00000286186EXOC6Bchr272562076-CASP10chr2202072798+0.0001892820.99981076
ENST00000272427ENST00000272879EXOC6Bchr272562076-CASP10chr2202072798+0.0003911850.9996088

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 EXOC6B-CASP10

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
EXOC6Bchr272562076CASP10chr22020727982327771EDTLQLAFIDLRQRAAVYRMNRNHRG

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Potential FusionNeoAntigen Information of EXOC6B-CASP10 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.
EXOC6B-CASP10_72562076_202072798.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)
EXOC6B-CASP10chr272562076chr22020727982327HLA-B08:09DLRQRAAV0.99970.5984917
EXOC6B-CASP10chr272562076chr22020727982327HLA-B15:01RQRAAVYRM0.9980.77041120
EXOC6B-CASP10chr272562076chr22020727982327HLA-B08:09FIDLRQRAA0.96380.6901716
EXOC6B-CASP10chr272562076chr22020727982327HLA-A30:08RQRAAVYRM0.96320.51021120
EXOC6B-CASP10chr272562076chr22020727982327HLA-B15:02DLRQRAAVY0.92290.8907918
EXOC6B-CASP10chr272562076chr22020727982327HLA-B15:25RQRAAVYRM0.75640.89431120
EXOC6B-CASP10chr272562076chr22020727982327HLA-B15:03RQRAAVYRM0.74170.75641120
EXOC6B-CASP10chr272562076chr22020727982327HLA-B13:02RQRAAVYRM0.59080.62081120
EXOC6B-CASP10chr272562076chr22020727982327HLA-B13:01RQRAAVYRM0.50120.92851120
EXOC6B-CASP10chr272562076chr22020727982327HLA-B15:07RQRAAVYRM0.96260.5821120
EXOC6B-CASP10chr272562076chr22020727982327HLA-B15:04RQRAAVYRM0.95540.82491120
EXOC6B-CASP10chr272562076chr22020727982327HLA-B15:21DLRQRAAVY0.92290.8567918
EXOC6B-CASP10chr272562076chr22020727982327HLA-B15:05RQRAAVYRM0.34240.74671120
EXOC6B-CASP10chr272562076chr22020727982327HLA-B15:135RQRAAVYRM0.99820.77111120
EXOC6B-CASP10chr272562076chr22020727982327HLA-B15:125RQRAAVYRM0.9980.77041120
EXOC6B-CASP10chr272562076chr22020727982327HLA-B15:33RQRAAVYRM0.9980.77041120
EXOC6B-CASP10chr272562076chr22020727982327HLA-B15:27RQRAAVYRM0.9980.81341120
EXOC6B-CASP10chr272562076chr22020727982327HLA-B15:34RQRAAVYRM0.9980.77041120
EXOC6B-CASP10chr272562076chr22020727982327HLA-B15:24RQRAAVYRM0.99720.84461120
EXOC6B-CASP10chr272562076chr22020727982327HLA-B15:50RQRAAVYRM0.9970.69641120
EXOC6B-CASP10chr272562076chr22020727982327HLA-A32:01RQRAAVYRM0.9750.79651120
EXOC6B-CASP10chr272562076chr22020727982327HLA-B15:12RQRAAVYRM0.970.76291120
EXOC6B-CASP10chr272562076chr22020727982327HLA-A30:01RQRAAVYRM0.96360.69381120
EXOC6B-CASP10chr272562076chr22020727982327HLA-B15:53RQRAAVYRM0.95330.76891120
EXOC6B-CASP10chr272562076chr22020727982327HLA-B15:35RQRAAVYRM0.91710.78061120
EXOC6B-CASP10chr272562076chr22020727982327HLA-B15:68RQRAAVYRM0.90770.50931120
EXOC6B-CASP10chr272562076chr22020727982327HLA-B15:73RQRAAVYRM0.89080.68361120
EXOC6B-CASP10chr272562076chr22020727982327HLA-B15:11DLRQRAAVY0.87820.7439918
EXOC6B-CASP10chr272562076chr22020727982327HLA-B15:08DLRQRAAVY0.86420.7395918
EXOC6B-CASP10chr272562076chr22020727982327HLA-B15:54RQRAAVYRM0.85220.74381120
EXOC6B-CASP10chr272562076chr22020727982327HLA-B15:12DLRQRAAVY0.81860.676918
EXOC6B-CASP10chr272562076chr22020727982327HLA-B18:04DLRQRAAVY0.78670.7288918
EXOC6B-CASP10chr272562076chr22020727982327HLA-B15:30RQRAAVYRM0.77310.80191120
EXOC6B-CASP10chr272562076chr22020727982327HLA-B15:39RQRAAVYRM0.7590.80021120
EXOC6B-CASP10chr272562076chr22020727982327HLA-B18:07DLRQRAAVY0.50110.6744918
EXOC6B-CASP10chr272562076chr22020727982327HLA-B48:02RQRAAVYRM0.40920.82221120
EXOC6B-CASP10chr272562076chr22020727982327HLA-B15:20RQRAAVYRM0.3260.82891120
EXOC6B-CASP10chr272562076chr22020727982327HLA-B35:28RQRAAVYRM0.3220.84721120

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Potential FusionNeoAntigen Information of EXOC6B-CASP10 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.
EXOC6B-CASP10_72562076_202072798.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)
EXOC6B-CASP10chr272562076chr22020727982327DRB1-1121RQRAAVYRMNRNHRG1126
EXOC6B-CASP10chr272562076chr22020727982327DRB1-1136RQRAAVYRMNRNHRG1126
EXOC6B-CASP10chr272562076chr22020727982327DRB1-1315RQRAAVYRMNRNHRG1126
EXOC6B-CASP10chr272562076chr22020727982327DRB1-1320RQRAAVYRMNRNHRG1126
EXOC6B-CASP10chr272562076chr22020727982327DRB1-1327RQRAAVYRMNRNHRG1126
EXOC6B-CASP10chr272562076chr22020727982327DRB1-1357RQRAAVYRMNRNHRG1126
EXOC6B-CASP10chr272562076chr22020727982327DRB1-1361RQRAAVYRMNRNHRG1126
EXOC6B-CASP10chr272562076chr22020727982327DRB1-1371RQRAAVYRMNRNHRG1126
EXOC6B-CASP10chr272562076chr22020727982327DRB1-1378RQRAAVYRMNRNHRG1126
EXOC6B-CASP10chr272562076chr22020727982327DRB3-0205RQRAAVYRMNRNHRG1126
EXOC6B-CASP10chr272562076chr22020727982327DRB3-0217RQRAAVYRMNRNHRG1126

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Fusion breakpoint peptide structures of EXOC6B-CASP10

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
192AFIDLRQRAAVYRMEXOC6BCASP10chr272562076chr22020727982327

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of EXOC6B-CASP10

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-B14:023BVN192AFIDLRQRAAVYRM-7.15543-7.26883
HLA-B14:023BVN192AFIDLRQRAAVYRM-4.77435-5.80965
HLA-B52:013W39192AFIDLRQRAAVYRM-6.80875-6.92215
HLA-B52:013W39192AFIDLRQRAAVYRM-4.20386-5.23916
HLA-A11:014UQ2192AFIDLRQRAAVYRM-7.5194-8.5547
HLA-A11:014UQ2192AFIDLRQRAAVYRM-6.9601-7.0735
HLA-A24:025HGA192AFIDLRQRAAVYRM-7.52403-7.63743
HLA-A24:025HGA192AFIDLRQRAAVYRM-5.82433-6.85963
HLA-B27:056PYJ192AFIDLRQRAAVYRM-3.28285-4.31815
HLA-B44:053DX8192AFIDLRQRAAVYRM-5.91172-6.94702
HLA-B44:053DX8192AFIDLRQRAAVYRM-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of EXOC6B-CASP10

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
EXOC6B-CASP10chr272562076chr22020727981120RQRAAVYRMAGACAAAGGGCAGCTGTGTACAGGATG
EXOC6B-CASP10chr272562076chr2202072798716FIDLRQRAATTCATCGACTTGAGACAAAGGGCAGCT
EXOC6B-CASP10chr272562076chr2202072798917DLRQRAAVGACTTGAGACAAAGGGCAGCTGTG
EXOC6B-CASP10chr272562076chr2202072798918DLRQRAAVYGACTTGAGACAAAGGGCAGCTGTGTAC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
EXOC6B-CASP10chr272562076chr22020727981126RQRAAVYRMNRNHRGAGACAAAGGGCAGCTGTGTACAGGATGAATCGGAACCACAGAGGC

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Information of the samples that have these potential fusion neoantigens of EXOC6B-CASP10

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
SKCMEXOC6B-CASP10chr272562076ENST00000272427chr2202072798ENST00000272879TCGA-FS-A1ZJ-06A

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Potential target of CAR-T therapy development for EXOC6B-CASP10

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 EXOC6B-CASP10

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 EXOC6B-CASP10

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