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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:ANAPC4-RBPJ

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ANAPC4-RBPJ
FusionPDB ID: 4292
FusionGDB2.0 ID: 4292
HgeneTgene
Gene symbol

ANAPC4

RBPJ

Gene ID

29945

3516

Gene nameanaphase promoting complex subunit 4recombination signal binding protein for immunoglobulin kappa J region
SynonymsAPC4AOS3|CBF1|IGKJRB|IGKJRB1|KBF2|RBP-J|RBPJK|RBPSUH|SUH|csl
Cytomap

4p15.2

4p15.2

Type of geneprotein-codingprotein-coding
Descriptionanaphase-promoting complex subunit 4cyclosome subunit 4recombining binding protein suppressor of hairlessCBF-1H-2K binding factor-2RBP-J kappaRBP-JKimmunoglobulin kappa J region recombination signal binding protein 1renal carcinoma antigen NY-REN-30suppressor of hairless homolog
Modification date2020031320200329
UniProtAcc

Q9UJX5

Main function of 5'-partner protein: FUNCTION: Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains. {ECO:0000269|PubMed:18485873}.

RITA1

Main function of 5'-partner protein: 269
Ensembl transtripts involved in fusion geneENST idsENST00000315368, ENST00000510092, 
ENST00000511401, ENST00000342320, 
ENST00000504907, ENST00000507561, 
ENST00000342295, ENST00000345843, 
ENST00000348160, ENST00000355476, 
ENST00000361572, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score4 X 4 X 2=3213 X 11 X 7=1001
# samples 413
** MAII scorelog2(4/32*10)=0.321928094887362
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
log2(13/1001*10)=-2.94485844580754
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ANAPC4 [Title/Abstract] AND RBPJ [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ANAPC4 [Title/Abstract] AND RBPJ [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ANAPC4(25398521)-RBPJ(26407797), # samples:1
Anticipated loss of major functional domain due to fusion event.ANAPC4-RBPJ 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.
ANAPC4-RBPJ 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
HgeneANAPC4

GO:0070979

protein K11-linked ubiquitination

18485873

TgeneRBPJ

GO:0007221

positive regulation of transcription of Notch receptor target

21102556

TgeneRBPJ

GO:0045892

negative regulation of transcription, DNA-templated

10713164

TgeneRBPJ

GO:0061419

positive regulation of transcription from RNA polymerase II promoter in response to hypoxia

23303788



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/chr4:25398521/chr4:26407797)
- 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 ANAPC4 (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 RBPJ (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)
ENST00000315368ANAPC4chr425398521+ENST00000345843RBPJchr426407797+282013561422760872
ENST00000315368ANAPC4chr425398521+ENST00000342295RBPJchr426407797+341013561422760872
ENST00000315368ANAPC4chr425398521+ENST00000361572RBPJchr426407797+276113561422760873
ENST00000315368ANAPC4chr425398521+ENST00000348160RBPJchr426407797+282013561422760872
ENST00000315368ANAPC4chr425398521+ENST00000355476RBPJchr426407797+341013561422760872
ENST00000510092ANAPC4chr425398521+ENST00000345843RBPJchr426407797+27401276622680872
ENST00000510092ANAPC4chr425398521+ENST00000342295RBPJchr426407797+33301276622680872
ENST00000510092ANAPC4chr425398521+ENST00000361572RBPJchr426407797+26811276622680873
ENST00000510092ANAPC4chr425398521+ENST00000348160RBPJchr426407797+27401276622680872
ENST00000510092ANAPC4chr425398521+ENST00000355476RBPJchr426407797+33301276622680872

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
ENST00000315368ENST00000345843ANAPC4chr425398521+RBPJchr426407797+0.0006237630.99937624
ENST00000315368ENST00000342295ANAPC4chr425398521+RBPJchr426407797+0.0003720610.99962795
ENST00000315368ENST00000361572ANAPC4chr425398521+RBPJchr426407797+0.0006943660.9993056
ENST00000315368ENST00000348160ANAPC4chr425398521+RBPJchr426407797+0.0006237630.99937624
ENST00000315368ENST00000355476ANAPC4chr425398521+RBPJchr426407797+0.0003720610.99962795
ENST00000510092ENST00000345843ANAPC4chr425398521+RBPJchr426407797+0.0006614030.99933857
ENST00000510092ENST00000342295ANAPC4chr425398521+RBPJchr426407797+0.0003718440.9996282
ENST00000510092ENST00000361572ANAPC4chr425398521+RBPJchr426407797+0.0007470390.999253
ENST00000510092ENST00000348160ANAPC4chr425398521+RBPJchr426407797+0.0006614030.99933857
ENST00000510092ENST00000355476ANAPC4chr425398521+RBPJchr426407797+0.0003718440.9996282

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 ANAPC4-RBPJ

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 ANAPC4-RBPJ 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 ANAPC4-RBPJ 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 ANAPC4-RBPJ

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 ANAPC4-RBPJ

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 ANAPC4-RBPJ

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 ANAPC4-RBPJ

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 ANAPC4-RBPJ

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 ANAPC4-RBPJ

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 ANAPC4-RBPJ

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