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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:RECK-UNC13B

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: RECK-UNC13B
FusionPDB ID: 73376
FusionGDB2.0 ID: 73376
HgeneTgene
Gene symbol

RECK

UNC13B

Gene ID

8434

10497

Gene namereversion inducing cysteine rich protein with kazal motifsunc-13 homolog B
SynonymsST15MUNC13|UNC13|Unc13h2|munc13-2
Cytomap

9p13.3

9p13.3

Type of geneprotein-codingprotein-coding
Descriptionreversion-inducing cysteine-rich protein with Kazal motifsmembrane-anchored glycoprotein (metastasis and invasion)suppression of tumorigenicity 15 (reversion-inducing-cysteine-rich protein with kazal motifs)suppression of tumorigenicity 5 (reversion-inprotein unc-13 homolog Bhomolog of rat Munc13 (diacylglycerol-binding)unc-13-like
Modification date2020032220200329
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000479053, ENST00000377966, 
ENST00000378495, ENST00000378496, 
ENST00000396787, ENST00000481299, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score9 X 7 X 6=37812 X 10 X 7=840
# samples 1013
** MAII scorelog2(10/378*10)=-1.91838623444635
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(13/840*10)=-2.69187770463767
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: RECK [Title/Abstract] AND UNC13B [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: RECK [Title/Abstract] AND UNC13B [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)RECK(36058898)-UNC13B(35366943), # samples:1
RECK(36058898)-UNC13B(35366944), # samples:1
Anticipated loss of major functional domain due to fusion event.RECK-UNC13B 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.
RECK-UNC13B 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.
RECK-UNC13B 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.
RECK-UNC13B 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
HgeneRECK

GO:1904684

negative regulation of metalloendopeptidase activity

18194466

TgeneUNC13B

GO:0043065

positive regulation of apoptotic process

10233166

TgeneUNC13B

GO:0050714

positive regulation of protein secretion

19641095

TgeneUNC13B

GO:0060478

acrosomal vesicle exocytosis

22248876

TgeneUNC13B

GO:0071333

cellular response to glucose stimulus

19641095



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/chr9:36058898/chr9:35366943)
- 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 RECK (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 UNC13B (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)
ENST00000377966RECKchr936058898+ENST00000396787UNC13Bchr935366943+460880046444651333
ENST00000377966RECKchr936058898+ENST00000378495UNC13Bchr935366943+571480046444081314
ENST00000377966RECKchr936058898+ENST00000378496UNC13Bchr935366943+448780046444651333
ENST00000377966RECKchr936058898+ENST00000396787UNC13Bchr935366944+460880046444651333
ENST00000377966RECKchr936058898+ENST00000378495UNC13Bchr935366944+571480046444081314
ENST00000377966RECKchr936058898+ENST00000378496UNC13Bchr935366944+448780046444651333

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
ENST00000377966ENST00000396787RECKchr936058898+UNC13Bchr935366943+0.0011469220.9988531
ENST00000377966ENST00000378495RECKchr936058898+UNC13Bchr935366943+0.0024362340.9975637
ENST00000377966ENST00000378496RECKchr936058898+UNC13Bchr935366943+0.0011874560.99881256
ENST00000377966ENST00000396787RECKchr936058898+UNC13Bchr935366944+0.0011469220.9988531
ENST00000377966ENST00000378495RECKchr936058898+UNC13Bchr935366944+0.0024362340.9975637
ENST00000377966ENST00000378496RECKchr936058898+UNC13Bchr935366944+0.0011874560.99881256

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 RECK-UNC13B

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
RECKchr936058898UNC13Bchr935366943800112LLQRAPDYCPETMIPDDGDPSLPQWL
RECKchr936058898UNC13Bchr935366944800112LLQRAPDYCPETMIPDDGDPSLPQWL

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Potential FusionNeoAntigen Information of RECK-UNC13B 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.
RECK-UNC13B_36058898_35366943.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)
RECK-UNC13Bchr936058898chr935366943800HLA-B35:08MIPDDGDPSL0.93420.95331222
RECK-UNC13Bchr936058898chr935366943800HLA-B35:03MIPDDGDPSL0.88340.96241222
RECK-UNC13Bchr936058898chr935366943800HLA-B35:01MIPDDGDPSL0.87250.96871222
RECK-UNC13Bchr936058898chr935366943800HLA-B35:04MIPDDGDPSL0.7820.98251222
RECK-UNC13Bchr936058898chr935366943800HLA-B35:02MIPDDGDPSL0.7820.98251222
RECK-UNC13Bchr936058898chr935366943800HLA-B35:08TMIPDDGDPSL0.99420.95571122
RECK-UNC13Bchr936058898chr935366943800HLA-B35:03TMIPDDGDPSL0.98320.96181122
RECK-UNC13Bchr936058898chr935366943800HLA-A02:60TMIPDDGDPSL0.98050.66921122
RECK-UNC13Bchr936058898chr935366943800HLA-A02:30TMIPDDGDPSL0.97960.65181122
RECK-UNC13Bchr936058898chr935366943800HLA-A02:24TMIPDDGDPSL0.97960.65181122
RECK-UNC13Bchr936058898chr935366943800HLA-A02:67TMIPDDGDPSL0.97960.65181122
RECK-UNC13Bchr936058898chr935366943800HLA-B35:02TMIPDDGDPSL0.97390.98641122
RECK-UNC13Bchr936058898chr935366943800HLA-B35:04TMIPDDGDPSL0.97390.98641122
RECK-UNC13Bchr936058898chr935366943800HLA-A02:16TMIPDDGDPSL0.97310.59831122
RECK-UNC13Bchr936058898chr935366943800HLA-A02:29TMIPDDGDPSL0.93510.6491122
RECK-UNC13Bchr936058898chr935366943800HLA-B82:01TMIPDDGDPSL0.92120.52381122
RECK-UNC13Bchr936058898chr935366943800HLA-A02:19TMIPDDGDPSL0.89250.63831122
RECK-UNC13Bchr936058898chr935366943800HLA-C05:09MIPDDGDPSL0.99960.96021222
RECK-UNC13Bchr936058898chr935366943800HLA-C04:10MIPDDGDPSL0.99940.79851222
RECK-UNC13Bchr936058898chr935366943800HLA-C04:07MIPDDGDPSL0.99940.81221222
RECK-UNC13Bchr936058898chr935366943800HLA-C08:15MIPDDGDPSL0.99910.97921222
RECK-UNC13Bchr936058898chr935366943800HLA-C01:17MIPDDGDPSL0.99560.97521222
RECK-UNC13Bchr936058898chr935366943800HLA-C01:30MIPDDGDPSL0.96540.96221222
RECK-UNC13Bchr936058898chr935366943800HLA-B07:12MIPDDGDPSL0.80810.65631222
RECK-UNC13Bchr936058898chr935366943800HLA-B35:12MIPDDGDPSL0.7820.98251222
RECK-UNC13Bchr936058898chr935366943800HLA-A02:07MIPDDGDPSL0.7460.68131222
RECK-UNC13Bchr936058898chr935366943800HLA-B39:10MIPDDGDPSL0.7040.96091222
RECK-UNC13Bchr936058898chr935366943800HLA-C05:09TMIPDDGDPSL0.99970.9481122
RECK-UNC13Bchr936058898chr935366943800HLA-C08:15TMIPDDGDPSL0.99960.97981122
RECK-UNC13Bchr936058898chr935366943800HLA-A02:07TMIPDDGDPSL0.98350.68411122
RECK-UNC13Bchr936058898chr935366943800HLA-A02:01TMIPDDGDPSL0.97960.65181122
RECK-UNC13Bchr936058898chr935366943800HLA-B35:12TMIPDDGDPSL0.97390.98641122
RECK-UNC13Bchr936058898chr935366943800HLA-B39:10TMIPDDGDPSL0.95490.96691122
RECK-UNC13Bchr936058898chr935366943800HLA-C05:01MIPDDGDPSL0.99960.96021222
RECK-UNC13Bchr936058898chr935366943800HLA-C04:03MIPDDGDPSL0.99950.85471222
RECK-UNC13Bchr936058898chr935366943800HLA-C04:01MIPDDGDPSL0.99940.81221222
RECK-UNC13Bchr936058898chr935366943800HLA-C01:03MIPDDGDPSL0.99910.9481222
RECK-UNC13Bchr936058898chr935366943800HLA-C08:02MIPDDGDPSL0.99910.97921222
RECK-UNC13Bchr936058898chr935366943800HLA-C01:02MIPDDGDPSL0.99690.97351222
RECK-UNC13Bchr936058898chr935366943800HLA-B35:77MIPDDGDPSL0.87250.96871222
RECK-UNC13Bchr936058898chr935366943800HLA-B35:13MIPDDGDPSL0.86230.96411222
RECK-UNC13Bchr936058898chr935366943800HLA-B35:09MIPDDGDPSL0.7820.98251222
RECK-UNC13Bchr936058898chr935366943800HLA-B35:22MIPDDGDPSL0.76570.50111222
RECK-UNC13Bchr936058898chr935366943800HLA-B39:11MIPDDGDPSL0.74810.90661222
RECK-UNC13Bchr936058898chr935366943800HLA-B67:01MIPDDGDPSL0.71070.90221222
RECK-UNC13Bchr936058898chr935366943800HLA-C05:01TMIPDDGDPSL0.99970.9481122
RECK-UNC13Bchr936058898chr935366943800HLA-C04:03TMIPDDGDPSL0.99970.86391122
RECK-UNC13Bchr936058898chr935366943800HLA-C08:02TMIPDDGDPSL0.99960.97981122
RECK-UNC13Bchr936058898chr935366943800HLA-A02:14TMIPDDGDPSL0.980.67241122
RECK-UNC13Bchr936058898chr935366943800HLA-B35:09TMIPDDGDPSL0.97390.98641122
RECK-UNC13Bchr936058898chr935366943800HLA-B35:22TMIPDDGDPSL0.96810.54891122
RECK-UNC13Bchr936058898chr935366943800HLA-B67:01TMIPDDGDPSL0.95940.93661122
RECK-UNC13Bchr936058898chr935366943800HLA-B40:21TMIPDDGDPSL0.94090.67861122
RECK-UNC13Bchr936058898chr935366943800HLA-B82:02TMIPDDGDPSL0.92120.52381122

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Potential FusionNeoAntigen Information of RECK-UNC13B 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 RECK-UNC13B

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
1483DYCPETMIPDDGDPRECKUNC13Bchr936058898chr935366943800

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of RECK-UNC13B

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-B14:023BVN1483DYCPETMIPDDGDP-7.15543-7.26883
HLA-B14:023BVN1483DYCPETMIPDDGDP-4.77435-5.80965
HLA-B52:013W391483DYCPETMIPDDGDP-6.80875-6.92215
HLA-B52:013W391483DYCPETMIPDDGDP-4.20386-5.23916
HLA-A11:014UQ21483DYCPETMIPDDGDP-7.5194-8.5547
HLA-A11:014UQ21483DYCPETMIPDDGDP-6.9601-7.0735
HLA-A24:025HGA1483DYCPETMIPDDGDP-7.52403-7.63743
HLA-A24:025HGA1483DYCPETMIPDDGDP-5.82433-6.85963
HLA-B27:056PYJ1483DYCPETMIPDDGDP-3.28285-4.31815
HLA-B44:053DX81483DYCPETMIPDDGDP-5.91172-6.94702
HLA-B44:053DX81483DYCPETMIPDDGDP-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of RECK-UNC13B

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
RECK-UNC13Bchr936058898chr9353669431122TMIPDDGDPSLACAATGATTCCAGATGATGGTGACCCCTCTCTG
RECK-UNC13Bchr936058898chr9353669431222MIPDDGDPSLATGATTCCAGATGATGGTGACCCCTCTCTG

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 RECK-UNC13B

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
GBMRECK-UNC13Bchr936058898ENST00000377966chr935366943ENST00000378495TCGA-12-0619

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Potential target of CAR-T therapy development for RECK-UNC13B

check button Predicted 3D structure. We used RoseTTAFold.
373_RECK-UNC13B_t000_.e2e.pdb


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
RECKchr936058898ENST00000377966UNC13Bchr935366943ENST00000378495
RECKchr936058898ENST00000377966UNC13Bchr935366943ENST00000378496

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Related Drugs to RECK-UNC13B

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 RECK-UNC13B

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