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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:CASP8-VMP1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CASP8-VMP1
FusionPDB ID: 13251
FusionGDB2.0 ID: 13251
HgeneTgene
Gene symbol

CASP8

VMP1

Gene ID

841

81671

Gene namecaspase 8vacuole membrane protein 1
SynonymsALPS2B|CAP4|Casp-8|FLICE|MACH|MCH5EPG3|TANGO5|TMEM49
Cytomap

2q33.1

17q23.1

Type of geneprotein-codingprotein-coding
Descriptioncaspase-8FADD-homologous ICE/CED-3-like proteaseFADD-like ICEICE-like apoptotic protease 5MACH-alpha-1/2/3 proteinMACH-beta-1/2/3/4 proteinMORT1-associated ced-3 homologapoptotic cysteine proteaseapoptotic protease Mch-5caspase 8, apoptosis-relatvacuole membrane protein 1ectopic P-granules autophagy protein 3 homologtransmembrane protein 49transport and golgi organization 5 homolog
Modification date2020032220200327
UniProtAcc

Q9UKL3

Main function of 5'-partner protein: FUNCTION: Participates in TNF-alpha-induced blockade of glucocorticoid receptor (GR) transactivation at the nuclear receptor coactivator level, upstream and independently of NF-kappa-B. Suppresses both NCOA2- and NCOA3-induced enhancement of GR transactivation. Involved in TNF-alpha-induced activation of NF-kappa-B via a TRAF2-dependent pathway. Acts as a downstream mediator for CASP8-induced activation of NF-kappa-B. Required for the activation of CASP8 in FAS-mediated apoptosis. Required for histone gene transcription and progression through S phase. {ECO:0000269|PubMed:12477726, ECO:0000269|PubMed:15698540, ECO:0000269|PubMed:17003125, ECO:0000269|PubMed:17245429}.		.
Ensembl transtripts involved in fusion geneENST idsENST00000392259, ENST00000392266, 
ENST00000264274, ENST00000264275, 
ENST00000323492, ENST00000358485, 
ENST00000432109, ENST00000392258, 
ENST00000490682, 		ENST00000262291, 
ENST00000536180, ENST00000537567, 
ENST00000539763, ENST00000545362, 
ENST00000588617, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score10 X 7 X 10=70042 X 34 X 19=27132
# samples 12151
** MAII scorelog2(12/700*10)=-2.54432051622381
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(151/27132*10)=-4.16737494326024
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: CASP8 [Title/Abstract] AND VMP1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CASP8 [Title/Abstract] AND VMP1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CASP8(202150040)-VMP1(57915656), # samples:3
Anticipated loss of major functional domain due to fusion event.CASP8-VMP1 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.
CASP8-VMP1 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.
CASP8-VMP1 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.
CASP8-VMP1 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.
CASP8-VMP1 seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF.
CASP8-VMP1 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
CASP8-VMP1 seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted ORF.
CASP8-VMP1 seems lost the major protein functional domain in Tgene partner, which is a essential gene 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
HgeneCASP8

GO:0006508

proteolysis

12888622

HgeneCASP8

GO:0036462

TRAIL-activated apoptotic signaling pathway

21785459

HgeneCASP8

GO:0045862

positive regulation of proteolysis

18387192

HgeneCASP8

GO:0097191

extrinsic apoptotic signaling pathway

21785459

HgeneCASP8

GO:0097202

activation of cysteine-type endopeptidase activity

18387192



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/chr2:202150040/chr17:57915656)
- 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 CASP8 (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 VMP1 (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)
ENST00000264274CASP8chr2202150040+ENST00000262291VMP1chr1757915656+271512872201533437
ENST00000264274CASP8chr2202150040+ENST00000537567VMP1chr1757915656+179412872201533437
ENST00000264274CASP8chr2202150040+ENST00000539763VMP1chr1757915656+175412872201533437
ENST00000264274CASP8chr2202150040+ENST00000536180VMP1chr1757915656+162612872201533437
ENST00000264274CASP8chr2202150040+ENST00000545362VMP1chr1757915656+178612872201533437
ENST00000432109CASP8chr2202150040+ENST00000262291VMP1chr1757915656+292114931681739523
ENST00000432109CASP8chr2202150040+ENST00000537567VMP1chr1757915656+200014931681739523
ENST00000432109CASP8chr2202150040+ENST00000539763VMP1chr1757915656+196014931681739523
ENST00000432109CASP8chr2202150040+ENST00000536180VMP1chr1757915656+183214931681739523
ENST00000432109CASP8chr2202150040+ENST00000545362VMP1chr1757915656+199214931681739523
ENST00000264275CASP8chr2202150040+ENST00000262291VMP1chr1757915656+306316352651881538
ENST00000264275CASP8chr2202150040+ENST00000537567VMP1chr1757915656+214216352651881538
ENST00000264275CASP8chr2202150040+ENST00000539763VMP1chr1757915656+210216352651881538
ENST00000264275CASP8chr2202150040+ENST00000536180VMP1chr1757915656+197416352651881538
ENST00000264275CASP8chr2202150040+ENST00000545362VMP1chr1757915656+213416352651881538
ENST00000358485CASP8chr2202150040+ENST00000262291VMP1chr1757915656+31051677941923609
ENST00000358485CASP8chr2202150040+ENST00000537567VMP1chr1757915656+21841677941923609
ENST00000358485CASP8chr2202150040+ENST00000539763VMP1chr1757915656+21441677941923609
ENST00000358485CASP8chr2202150040+ENST00000536180VMP1chr1757915656+20161677941923609
ENST00000358485CASP8chr2202150040+ENST00000545362VMP1chr1757915656+21761677941923609
ENST00000323492CASP8chr2202150040+ENST00000262291VMP1chr1757915656+282713991251645506
ENST00000323492CASP8chr2202150040+ENST00000537567VMP1chr1757915656+190613991251645506
ENST00000323492CASP8chr2202150040+ENST00000539763VMP1chr1757915656+186613991251645506
ENST00000323492CASP8chr2202150040+ENST00000536180VMP1chr1757915656+173813991251645506
ENST00000323492CASP8chr2202150040+ENST00000545362VMP1chr1757915656+189813991251645506
ENST00000323492CASP8chr2202151224+ENST00000262291VMP1chr1757915656+403526071251402425
ENST00000323492CASP8chr2202151224+ENST00000537567VMP1chr1757915656+311426071251402425
ENST00000323492CASP8chr2202151224+ENST00000539763VMP1chr1757915656+307426071251402425
ENST00000323492CASP8chr2202151224+ENST00000536180VMP1chr1757915656+294626071251402425
ENST00000323492CASP8chr2202151224+ENST00000545362VMP1chr1757915656+310626071251402425

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
ENST00000264274ENST00000262291CASP8chr2202150040+VMP1chr1757915656+0.0004765770.9995234
ENST00000264274ENST00000537567CASP8chr2202150040+VMP1chr1757915656+0.0021390650.99786097
ENST00000264274ENST00000539763CASP8chr2202150040+VMP1chr1757915656+0.0022243860.9977756
ENST00000264274ENST00000536180CASP8chr2202150040+VMP1chr1757915656+0.0029233590.99707663
ENST00000264274ENST00000545362CASP8chr2202150040+VMP1chr1757915656+0.0021640.99783605
ENST00000432109ENST00000262291CASP8chr2202150040+VMP1chr1757915656+0.0003922810.99960774
ENST00000432109ENST00000537567CASP8chr2202150040+VMP1chr1757915656+0.0020596490.99794036
ENST00000432109ENST00000539763CASP8chr2202150040+VMP1chr1757915656+0.0021519020.99784815
ENST00000432109ENST00000536180CASP8chr2202150040+VMP1chr1757915656+0.0026534360.9973465
ENST00000432109ENST00000545362CASP8chr2202150040+VMP1chr1757915656+0.0020872550.9979127
ENST00000264275ENST00000262291CASP8chr2202150040+VMP1chr1757915656+0.0006519050.9993481
ENST00000264275ENST00000537567CASP8chr2202150040+VMP1chr1757915656+0.0031966450.9968034
ENST00000264275ENST00000539763CASP8chr2202150040+VMP1chr1757915656+0.0032763850.9967236
ENST00000264275ENST00000536180CASP8chr2202150040+VMP1chr1757915656+0.0037756450.9962244
ENST00000264275ENST00000545362CASP8chr2202150040+VMP1chr1757915656+0.0032097170.99679023
ENST00000358485ENST00000262291CASP8chr2202150040+VMP1chr1757915656+0.0004034210.99959654
ENST00000358485ENST00000537567CASP8chr2202150040+VMP1chr1757915656+0.001588720.9984113
ENST00000358485ENST00000539763CASP8chr2202150040+VMP1chr1757915656+0.001579350.9984206
ENST00000358485ENST00000536180CASP8chr2202150040+VMP1chr1757915656+0.0019318870.99806815
ENST00000358485ENST00000545362CASP8chr2202150040+VMP1chr1757915656+0.001591790.99840826
ENST00000323492ENST00000262291CASP8chr2202150040+VMP1chr1757915656+0.0003158820.9996841
ENST00000323492ENST00000537567CASP8chr2202150040+VMP1chr1757915656+0.0013680740.9986319
ENST00000323492ENST00000539763CASP8chr2202150040+VMP1chr1757915656+0.0013857270.9986143
ENST00000323492ENST00000536180CASP8chr2202150040+VMP1chr1757915656+0.0017586090.9982414
ENST00000323492ENST00000545362CASP8chr2202150040+VMP1chr1757915656+0.001379750.9986203
ENST00000323492ENST00000262291CASP8chr2202151224+VMP1chr1757915656+0.0002286330.9997714
ENST00000323492ENST00000537567CASP8chr2202151224+VMP1chr1757915656+0.0004601430.99953985
ENST00000323492ENST00000539763CASP8chr2202151224+VMP1chr1757915656+0.0004641710.9995358
ENST00000323492ENST00000536180CASP8chr2202151224+VMP1chr1757915656+0.0004843260.99951565
ENST00000323492ENST00000545362CASP8chr2202151224+VMP1chr1757915656+0.0004609520.999539

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 CASP8-VMP1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CASP8chr2202150040VMP1chr17579156561287356QSLCQSLRERCPRAVPGIGPSLQKPF
CASP8chr2202150040VMP1chr17579156561399425QSLCQSLRERCPRAVPGIGPSLQKPF
CASP8chr2202150040VMP1chr17579156561493442QSLCQSLRERCPRAVPGIGPSLQKPF
CASP8chr2202150040VMP1chr17579156561635457QSLCQSLRERCPRAVPGIGPSLQKPF
CASP8chr2202150040VMP1chr17579156561677528QSLCQSLRERCPRAVPGIGPSLQKPF

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Potential FusionNeoAntigen Information of CASP8-VMP1 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.
CASP8-VMP1_202150040_57915656.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)
CASP8-VMP1chr2202150040chr17579156561287HLA-B08:09SLRERCPRA0.98170.5497514
CASP8-VMP1chr2202150040chr17579156561287HLA-B50:02RERCPRAVP0.65130.5886716
CASP8-VMP1chr2202150040chr17579156561287HLA-B41:01RERCPRAVP0.37410.7655716
CASP8-VMP1chr2202150040chr17579156561287HLA-B50:01RERCPRAVP0.0190.7524716
CASP8-VMP1chr2202150040chr17579156561287HLA-B40:06RERCPRAVP0.98960.6091716
CASP8-VMP1chr2202150040chr17579156561287HLA-B50:04RERCPRAVP0.0190.7524716
CASP8-VMP1chr2202150040chr17579156561287HLA-B50:05RERCPRAVP0.0190.7524716

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Potential FusionNeoAntigen Information of CASP8-VMP1 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 CASP8-VMP1

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
5515LRERCPRAVPGIGPCASP8VMP1chr2202150040chr17579156561287

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CASP8-VMP1

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-B14:023BVN5515LRERCPRAVPGIGP-7.9962-8.1096
HLA-B14:023BVN5515LRERCPRAVPGIGP-5.70842-6.74372
HLA-B52:013W395515LRERCPRAVPGIGP-6.83737-6.95077
HLA-B52:013W395515LRERCPRAVPGIGP-4.4836-5.5189
HLA-A11:014UQ25515LRERCPRAVPGIGP-10.0067-10.1201
HLA-A11:014UQ25515LRERCPRAVPGIGP-9.03915-10.0745
HLA-A24:025HGA5515LRERCPRAVPGIGP-6.56204-6.67544
HLA-A24:025HGA5515LRERCPRAVPGIGP-5.42271-6.45801
HLA-B44:053DX85515LRERCPRAVPGIGP-7.85648-8.89178
HLA-B44:053DX85515LRERCPRAVPGIGP-5.3978-5.5112
HLA-A02:016TDR5515LRERCPRAVPGIGP-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of CASP8-VMP1

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
CASP8-VMP1chr2202150040chr1757915656514SLRERCPRAGAGCCTGAGAGAGCGATGTCCTCGTGC
CASP8-VMP1chr2202150040chr1757915656716RERCPRAVPGAGAGAGCGATGTCCTCGTGCTGTCCC

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 CASP8-VMP1

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
UCECCASP8-VMP1chr2202150040ENST00000264274chr1757915656ENST00000262291TCGA-EO-A3KW-01A

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Potential target of CAR-T therapy development for CASP8-VMP1

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
TgeneVMP1chr2:202150040chr17:57915656ENST00000262291912364_3840407.0TransmembraneHelical
TgeneVMP1chr2:202151224chr17:57915656ENST00000262291912364_3840407.0TransmembraneHelical

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 CASP8-VMP1

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 CASP8-VMP1

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