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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:UIMC1-DBN1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: UIMC1-DBN1
FusionPDB ID: 96737
FusionGDB2.0 ID: 96737
HgeneTgene
Gene symbol

UIMC1

DBN1

Gene ID

51720

1627

Gene nameubiquitin interaction motif containing 1drebrin 1
SynonymsRAP80|X2HRIP110D0S117E
Cytomap

5q35.2

5q35.3

Type of geneprotein-codingprotein-coding
DescriptionBRCA1-A complex subunit RAP80receptor-associated protein 80retinoid X receptor-interacting protein 110drebrindevelopmentally-regulated brain proteindrebrin Adrebrin Edrebrin E2
Modification date2020032720200320
UniProtAcc.

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 idsENST00000377219, ENST00000377227, 
ENST00000506128, ENST00000511320, 
ENST00000503273, 
ENST00000393563, 
ENST00000512501, ENST00000292385, 
ENST00000309007, ENST00000393565, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score9 X 7 X 7=44110 X 9 X 7=630
# samples 1010
** MAII scorelog2(10/441*10)=-2.1407786557828
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: UIMC1 [Title/Abstract] AND DBN1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: UIMC1 [Title/Abstract] AND DBN1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)UIMC1(176370336)-DBN1(176895900), # samples:3
Anticipated loss of major functional domain due to fusion event.UIMC1-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.
UIMC1-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.
UIMC1-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.
UIMC1-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
HgeneUIMC1

GO:0045892

negative regulation of transcription, DNA-templated

12080054

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/chr5:176370336/chr5:176895900)
- 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 UIMC1 (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)
ENST00000377227UIMC1chr5176370336-ENST00000309007DBN1chr5176895900-4419173017013593630
ENST00000377227UIMC1chr5176370336-ENST00000292385DBN1chr5176895900-4100173017013593630
ENST00000377227UIMC1chr5176370336-ENST00000393565DBN1chr5176895900-4229173017013731676
ENST00000377219UIMC1chr5176370336-ENST00000309007DBN1chr5176895900-4453176417353627630
ENST00000377219UIMC1chr5176370336-ENST00000292385DBN1chr5176895900-4134176417353627630
ENST00000377219UIMC1chr5176370336-ENST00000393565DBN1chr5176895900-4263176417353765676
ENST00000506128UIMC1chr5176370336-ENST00000309007DBN1chr5176895900-3839115011213013630
ENST00000506128UIMC1chr5176370336-ENST00000292385DBN1chr5176895900-3520115011213013630
ENST00000506128UIMC1chr5176370336-ENST00000393565DBN1chr5176895900-3649115011213151676
ENST00000511320UIMC1chr5176370336-ENST00000309007DBN1chr5176895900-4396170716783570630
ENST00000511320UIMC1chr5176370336-ENST00000292385DBN1chr5176895900-4077170716783570630
ENST00000511320UIMC1chr5176370336-ENST00000393565DBN1chr5176895900-4206170716783708676

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
ENST00000377227ENST00000309007UIMC1chr5176370336-DBN1chr5176895900-0.0111239280.98887604
ENST00000377227ENST00000292385UIMC1chr5176370336-DBN1chr5176895900-0.0135254030.9864746
ENST00000377227ENST00000393565UIMC1chr5176370336-DBN1chr5176895900-0.0118166540.9881833
ENST00000377219ENST00000309007UIMC1chr5176370336-DBN1chr5176895900-0.0106443020.9893556
ENST00000377219ENST00000292385UIMC1chr5176370336-DBN1chr5176895900-0.0129431390.9870568
ENST00000377219ENST00000393565UIMC1chr5176370336-DBN1chr5176895900-0.0113047440.9886953
ENST00000506128ENST00000309007UIMC1chr5176370336-DBN1chr5176895900-0.0114600370.98854
ENST00000506128ENST00000292385UIMC1chr5176370336-DBN1chr5176895900-0.0129142160.98708576
ENST00000506128ENST00000393565UIMC1chr5176370336-DBN1chr5176895900-0.0113557120.98864424
ENST00000511320ENST00000309007UIMC1chr5176370336-DBN1chr5176895900-0.0116442220.98835576
ENST00000511320ENST00000292385UIMC1chr5176370336-DBN1chr5176895900-0.0144238290.98557615
ENST00000511320ENST00000393565UIMC1chr5176370336-DBN1chr5176895900-0.0123946260.98760533

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 UIMC1-DBN1

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

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Potential FusionNeoAntigen Information of UIMC1-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.

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)

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Potential FusionNeoAntigen Information of UIMC1-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 UIMC1-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.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of UIMC1-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

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Vaccine Design for the FusionNeoAntigens of UIMC1-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

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 UIMC1-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

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Potential target of CAR-T therapy development for UIMC1-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 UIMC1-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 UIMC1-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