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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:BCL2L2-CAPN8

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: BCL2L2-CAPN8
FusionPDB ID: 9384
FusionGDB2.0 ID: 9384
HgeneTgene
Gene symbol

BCL2L2

CAPN8

Gene ID

599

388743

Gene nameBCL2 like 2calpain 8
SynonymsBCL-W|BCL2-L-2|BCLW|PPP1R51nCL-2
Cytomap

14q11.2

1q41

Type of geneprotein-codingprotein-coding
Descriptionbcl-2-like protein 2apoptosis regulator BCL-Wprotein phosphatase 1, regulatory subunit 51calpain-8new calpain 2stomach-specific M-type calpain
Modification date2020031320200313
UniProtAcc

Q92843

Main function of 5'-partner protein: FUNCTION: Promotes cell survival. Blocks dexamethasone-induced apoptosis. Mediates survival of postmitotic Sertoli cells by suppressing death-promoting activity of BAX. {ECO:0000269|PubMed:8761287}.

A6NHC0

Main function of 5'-partner protein: FUNCTION: Calcium-regulated non-lysosomal thiol-protease. Involved in membrane trafficking in the gastric surface mucus cells (pit cells) and may involve the membrane trafficking of mucus cells via interactions with coat protein. Proteolytically cleaves the beta-subunit of coatomer complex (By similarity). {ECO:0000250}.
Ensembl transtripts involved in fusion geneENST idsENST00000250405, ENST00000366873, 
ENST00000366872, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score4 X 2 X 2=1612 X 2 X 4=96
# samples 412
** MAII scorelog2(4/16*10)=1.32192809488736
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
log2(12/96*10)=0.321928094887362
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: BCL2L2 [Title/Abstract] AND CAPN8 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: BCL2L2 [Title/Abstract] AND CAPN8 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)BCL2L2(23777408)-CAPN8(223718212), # samples:1
Anticipated loss of major functional domain due to fusion event.BCL2L2-CAPN8 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.
BCL2L2-CAPN8 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.
BCL2L2-CAPN8 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.
BCL2L2-CAPN8 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


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/chr14:23777408/chr1:223718212)
- 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 BCL2L2 (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 CAPN8 (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)
ENST00000250405BCL2L2chr1423777408+ENST00000366872CAPN8chr1223718212-1156661205939244

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
ENST00000250405ENST00000366872BCL2L2chr1423777408+CAPN8chr1223718212-0.0070707310.9929293

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 BCL2L2-CAPN8

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
BCL2L2chr1423777408CAPN8chr1223718212661152TQLADWIHSSGGWEIYWETDYNHSGT

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Potential FusionNeoAntigen Information of BCL2L2-CAPN8 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.
BCL2L2-CAPN8_23777408_223718212.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)
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B58:01SSGGWEIYW0.99760.9733817
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B39:01IHSSGGWEI0.99690.8473615
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B18:01WEIYWETDY0.99660.78751221
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B38:01IHSSGGWEI0.99570.928615
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B38:02IHSSGGWEI0.99550.9206615
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B57:01SSGGWEIYW0.99540.9869817
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B39:06IHSSGGWEI0.99330.7881615
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B58:02SSGGWEIYW0.99060.978817
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B15:17SSGGWEIYW0.98460.9746817
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B15:17HSSGGWEIY0.97510.9278716
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B15:16SSGGWEIYW0.95670.8098817
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B57:03SSGGWEIYW0.94770.9927817
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B15:10IHSSGGWEI0.870.5699615
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B15:37IHSSGGWEI0.6950.6809615
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-A32:13SSGGWEIYW0.68220.9828817
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B15:18IHSSGGWEI0.54740.6736615
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B57:01HSSGGWEIYW0.99980.9872717
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B58:01HSSGGWEIYW0.99950.9738717
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B58:02HSSGGWEIYW0.99940.9732717
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B15:16HSSGGWEIYW0.99410.8604717
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B57:03HSSGGWEIYW0.98810.9934717
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B15:18IHSSGGWEIY0.94240.5076616
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B38:01WIHSSGGWEI0.08280.9536515
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B57:01IHSSGGWEIYW0.99960.9567617
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B38:01IHSSGGWEIYW0.96590.9031617
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B38:01DWIHSSGGWEI0.2060.974415
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B39:09IHSSGGWEI0.99720.5404615
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B39:12IHSSGGWEI0.99690.851615
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B39:05IHSSGGWEI0.99470.8225615
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B15:31HSSGGWEIY0.94050.8803716
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-C03:14HSSGGWEIY0.12190.9821716
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B18:04WEIYWETDY0.99770.80061221
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B39:31IHSSGGWEI0.99710.8485615
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B18:05WEIYWETDY0.99660.78751221
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B18:08WEIYWETDY0.99650.70931221
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B38:05IHSSGGWEI0.99570.928615
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B57:10SSGGWEIYW0.99540.9869817
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B18:03WEIYWETDY0.99520.77511221
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B57:04SSGGWEIYW0.99480.8983817
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B18:06WEIYWETDY0.99470.78811221
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B57:02SSGGWEIYW0.98580.9675817
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B58:06SSGGWEIYW0.98250.9567817
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B35:28HSSGGWEIY0.96490.9096716
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B15:09IHSSGGWEI0.95070.6296615
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B18:11WEIYWETDY0.94730.76411221
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B35:20HSSGGWEIY0.93040.9162716
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-A32:01SSGGWEIYW0.80740.9832817
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-C03:02HSSGGWEIY0.79150.9747716
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B39:11IHSSGGWEI0.62820.793615
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-C07:04IHSSGGWEI0.24450.9276615
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-C16:01HSSGGWEIY0.12070.9787716
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B57:10HSSGGWEIYW0.99980.9872717
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B57:04HSSGGWEIYW0.99970.8985717
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B58:06HSSGGWEIYW0.99880.9574717
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B57:02HSSGGWEIYW0.99750.9652717
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B38:05WIHSSGGWEI0.08280.9536515
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B57:10IHSSGGWEIYW0.99960.9567617
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B38:05IHSSGGWEIYW0.96590.9031617
BCL2L2-CAPN8chr1423777408chr1223718212661HLA-B38:05DWIHSSGGWEI0.2060.974415

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Potential FusionNeoAntigen Information of BCL2L2-CAPN8 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 BCL2L2-CAPN8

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
3721IHSSGGWEIYWETDBCL2L2CAPN8chr1423777408chr1223718212661

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of BCL2L2-CAPN8

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-B14:023BVN3721IHSSGGWEIYWETD-7.15543-7.26883
HLA-B14:023BVN3721IHSSGGWEIYWETD-4.77435-5.80965
HLA-B52:013W393721IHSSGGWEIYWETD-6.80875-6.92215
HLA-B52:013W393721IHSSGGWEIYWETD-4.20386-5.23916
HLA-A11:014UQ23721IHSSGGWEIYWETD-7.5194-8.5547
HLA-A11:014UQ23721IHSSGGWEIYWETD-6.9601-7.0735
HLA-A24:025HGA3721IHSSGGWEIYWETD-7.52403-7.63743
HLA-A24:025HGA3721IHSSGGWEIYWETD-5.82433-6.85963
HLA-B27:056PYJ3721IHSSGGWEIYWETD-3.28285-4.31815
HLA-B44:053DX83721IHSSGGWEIYWETD-5.91172-6.94702
HLA-B44:053DX83721IHSSGGWEIYWETD-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of BCL2L2-CAPN8

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
BCL2L2-CAPN8chr1423777408chr12237182121221WEIYWETDYTGGGAGATCTATTGGGAAACTGATTAT
BCL2L2-CAPN8chr1423777408chr1223718212415DWIHSSGGWEIGACTGGATCCACAGCAGTGGGGGCTGGGAGATC
BCL2L2-CAPN8chr1423777408chr1223718212515WIHSSGGWEITGGATCCACAGCAGTGGGGGCTGGGAGATC
BCL2L2-CAPN8chr1423777408chr1223718212615IHSSGGWEIATCCACAGCAGTGGGGGCTGGGAGATC
BCL2L2-CAPN8chr1423777408chr1223718212616IHSSGGWEIYATCCACAGCAGTGGGGGCTGGGAGATCTAT
BCL2L2-CAPN8chr1423777408chr1223718212617IHSSGGWEIYWATCCACAGCAGTGGGGGCTGGGAGATCTATTGG
BCL2L2-CAPN8chr1423777408chr1223718212716HSSGGWEIYCACAGCAGTGGGGGCTGGGAGATCTAT
BCL2L2-CAPN8chr1423777408chr1223718212717HSSGGWEIYWCACAGCAGTGGGGGCTGGGAGATCTATTGG
BCL2L2-CAPN8chr1423777408chr1223718212817SSGGWEIYWAGCAGTGGGGGCTGGGAGATCTATTGG

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 BCL2L2-CAPN8

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
STADBCL2L2-CAPN8chr1423777408ENST00000250405chr1223718212ENST00000366872TCGA-VQ-A8PD

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Potential target of CAR-T therapy development for BCL2L2-CAPN8

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 BCL2L2-CAPN8

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 BCL2L2-CAPN8

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