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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:MCC-DBN1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: MCC-DBN1
FusionPDB ID: 52152
FusionGDB2.0 ID: 52152
HgeneTgene
Gene symbol

MCC

DBN1

Gene ID

4163

1627

Gene nameMCC regulator of WNT signaling pathwaydrebrin 1
SynonymsMCC1D0S117E
Cytomap

5q22.2

5q35.3

Type of geneprotein-codingprotein-coding
Descriptioncolorectal mutant cancer proteinMCC, WNT signaling pathway regulatormutated in colorectal cancersdrebrindevelopmentally-regulated brain proteindrebrin Adrebrin Edrebrin E2
Modification date2020031320200320
UniProtAcc

Q9HCC0

Main function of 5'-partner protein: FUNCTION: Carboxyltransferase subunit of the 3-methylcrotonyl-CoA carboxylase, an enzyme that catalyzes the conversion of 3-methylcrotonyl-CoA to 3-methylglutaconyl-CoA, a critical step for leucine and isovaleric acid catabolism. {ECO:0000269|PubMed:17360195}.

Q16643

Main function of 5'-partner protein: FUNCTION: Actin cytoskeleton-organizing protein that plays a role in the formation of cell projections (PubMed:20215400). Required for actin polymerization at immunological synapses (IS) and for the recruitment of the chemokine receptor CXCR4 to IS (PubMed:20215400). Plays a role in dendritic spine morphogenesis and organization, including the localization of the dopamine receptor DRD1 to the dendritic spines (By similarity). Involved in memory-related synaptic plasticity in the hippocampus (By similarity). {ECO:0000250|UniProtKB:Q9QXS6, ECO:0000269|PubMed:20215400}.
Ensembl transtripts involved in fusion geneENST idsENST00000302475, ENST00000514701, 
ENST00000408903, ENST00000515367, 
ENST00000393563, ENST00000512501, 
ENST00000292385, ENST00000309007, 
ENST00000393565, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score11 X 8 X 5=44010 X 9 X 7=630
# samples 1210
** MAII scorelog2(12/440*10)=-1.87446911791614
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(10/630*10)=-2.65535182861255
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: MCC [Title/Abstract] AND DBN1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: MCC [Title/Abstract] AND DBN1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MCC(112630026)-DBN1(176887704), # samples:3
Anticipated loss of major functional domain due to fusion event.MCC-DBN1 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.
MCC-DBN1 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
HgeneMCC

GO:0045184

establishment of protein localization

18591935

HgeneMCC

GO:0050680

negative regulation of epithelial cell proliferation

18591935

HgeneMCC

GO:0090090

negative regulation of canonical Wnt signaling pathway

18591935

TgeneDBN1

GO:0051220

cytoplasmic sequestering of protein

28966017



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/chr5:112630026/chr5:176887704)
- 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 MCC (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 DBN1 (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)
ENST00000302475MCCchr5112630026-ENST00000309007DBN1chr5176887704-26256215641799411
ENST00000302475MCCchr5112630026-ENST00000292385DBN1chr5176887704-23066215641799411
ENST00000302475MCCchr5112630026-ENST00000393565DBN1chr5176887704-24356215641937457
ENST00000302475MCCchr5112630026-ENST00000309007DBN1chr5176887556-25656215641739391
ENST00000302475MCCchr5112630026-ENST00000292385DBN1chr5176887556-22466215641739391
ENST00000302475MCCchr5112630026-ENST00000393565DBN1chr5176887556-23756215641877437
ENST00000302475MCCchr5112630026-ENST00000393563DBN1chr5176887556-18066215641739391
ENST00000302475MCCchr5112630026-ENST00000512501DBN1chr5176887556-22576215641769401

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
ENST00000302475ENST00000309007MCCchr5112630026-DBN1chr5176887704-0.008764420.9912356
ENST00000302475ENST00000292385MCCchr5112630026-DBN1chr5176887704-0.0105337520.98946625
ENST00000302475ENST00000393565MCCchr5112630026-DBN1chr5176887704-0.0124287360.98757124
ENST00000302475ENST00000309007MCCchr5112630026-DBN1chr5176887556-0.0114458560.9885542
ENST00000302475ENST00000292385MCCchr5112630026-DBN1chr5176887556-0.0138886390.9861114
ENST00000302475ENST00000393565MCCchr5112630026-DBN1chr5176887556-0.0257919780.974208
ENST00000302475ENST00000393563MCCchr5112630026-DBN1chr5176887556-0.0144803110.98551977
ENST00000302475ENST00000512501MCCchr5112630026-DBN1chr5176887556-0.0461844430.9538155

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 MCC-DBN1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
MCCchr5112630026DBN1chr517688755662119MKYGNDSSAELSEEAAAIIAQRPDNP
MCCchr5112630026DBN1chr517688770462119MKYGNDSSAELSEGDHRDEEEETHMK

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Potential FusionNeoAntigen Information of MCC-DBN1 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.
MCC-DBN1_112630026_176887556.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)
MCC-DBN1chr5112630026chr5176887556621HLA-B45:01EEAAAIIA0.99950.94021220
MCC-DBN1chr5112630026chr5176887556621HLA-B50:02EEAAAIIA0.99950.71971220
MCC-DBN1chr5112630026chr5176887556621HLA-B45:01AELSEEAA0.99890.8998816
MCC-DBN1chr5112630026chr5176887556621HLA-B41:01AELSEEAA0.95320.9461816
MCC-DBN1chr5112630026chr5176887556621HLA-B45:01AELSEEAAA0.99310.8969817
MCC-DBN1chr5112630026chr5176887556621HLA-B45:01SEEAAAIIA0.99130.92531120
MCC-DBN1chr5112630026chr5176887556621HLA-B50:02AELSEEAAA0.98480.7862817
MCC-DBN1chr5112630026chr5176887556621HLA-B50:02SEEAAAIIA0.96620.71191120
MCC-DBN1chr5112630026chr5176887556621HLA-B41:01SEEAAAIIA0.40710.94141120
MCC-DBN1chr5112630026chr5176887556621HLA-B41:01AELSEEAAA0.40460.9281817
MCC-DBN1chr5112630026chr5176887556621HLA-B50:01AELSEEAAA0.31650.8532817
MCC-DBN1chr5112630026chr5176887556621HLA-B50:01SEEAAAIIA0.18050.73161120
MCC-DBN1chr5112630026chr5176887556621HLA-A66:01EEAAAIIAQR0.95280.55631222
MCC-DBN1chr5112630026chr5176887556621HLA-A26:03EEAAAIIAQR0.87780.58121222
MCC-DBN1chr5112630026chr5176887556621HLA-B45:01SAELSEEAAA0.75610.873717
MCC-DBN1chr5112630026chr5176887556621HLA-B50:02SAELSEEAAA0.69870.7756717
MCC-DBN1chr5112630026chr5176887556621HLA-B40:06AELSEEAAA0.99490.768817
MCC-DBN1chr5112630026chr5176887556621HLA-B40:06SEEAAAIIA0.98110.69521120
MCC-DBN1chr5112630026chr5176887556621HLA-B44:10AELSEEAAAI0.98230.7615818
MCC-DBN1chr5112630026chr5176887556621HLA-B18:06EEAAAIIAQ0.33870.96791221
MCC-DBN1chr5112630026chr5176887556621HLA-B50:05AELSEEAAA0.31650.8532817
MCC-DBN1chr5112630026chr5176887556621HLA-B50:04AELSEEAAA0.31650.8532817
MCC-DBN1chr5112630026chr5176887556621HLA-B50:04SEEAAAIIA0.18050.73161120
MCC-DBN1chr5112630026chr5176887556621HLA-B50:05SEEAAAIIA0.18050.73161120

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Potential FusionNeoAntigen Information of MCC-DBN1 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 MCC-DBN1

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
8993SSAELSEEAAAIIAMCCDBN1chr5112630026chr5176887556621

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of MCC-DBN1

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-B14:023BVN8993SSAELSEEAAAIIA-7.15543-7.26883
HLA-B14:023BVN8993SSAELSEEAAAIIA-4.77435-5.80965
HLA-B52:013W398993SSAELSEEAAAIIA-6.80875-6.92215
HLA-B52:013W398993SSAELSEEAAAIIA-4.20386-5.23916
HLA-A11:014UQ28993SSAELSEEAAAIIA-7.5194-8.5547
HLA-A11:014UQ28993SSAELSEEAAAIIA-6.9601-7.0735
HLA-A24:025HGA8993SSAELSEEAAAIIA-7.52403-7.63743
HLA-A24:025HGA8993SSAELSEEAAAIIA-5.82433-6.85963
HLA-B27:056PYJ8993SSAELSEEAAAIIA-3.28285-4.31815
HLA-B44:053DX88993SSAELSEEAAAIIA-5.91172-6.94702
HLA-B44:053DX88993SSAELSEEAAAIIA-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of MCC-DBN1

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
MCC-DBN1chr5112630026chr51768875561120SEEAAAIIAAGTGAGGAGGCAGCAGCTATTATTGCC
MCC-DBN1chr5112630026chr51768875561220EEAAAIIAGAGGAGGCAGCAGCTATTATTGCC
MCC-DBN1chr5112630026chr51768875561221EEAAAIIAQGAGGAGGCAGCAGCTATTATTGCCCAG
MCC-DBN1chr5112630026chr51768875561222EEAAAIIAQRGAGGAGGCAGCAGCTATTATTGCCCAGCGG
MCC-DBN1chr5112630026chr5176887556717SAELSEEAAATCGGCCGAGCTGAGTGAGGAGGCAGCAGCT
MCC-DBN1chr5112630026chr5176887556816AELSEEAAGCCGAGCTGAGTGAGGAGGCAGCA
MCC-DBN1chr5112630026chr5176887556817AELSEEAAAGCCGAGCTGAGTGAGGAGGCAGCAGCT
MCC-DBN1chr5112630026chr5176887556818AELSEEAAAIGCCGAGCTGAGTGAGGAGGCAGCAGCTATT

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 MCC-DBN1

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
LIHCMCC-DBN1chr5112630026ENST00000302475chr5176887556ENST00000292385TCGA-BC-A10T-01A

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Potential target of CAR-T therapy development for MCC-DBN1

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 MCC-DBN1

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 MCC-DBN1

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