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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:RBMS3-RBBP6

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: RBMS3-RBBP6
FusionPDB ID: 73043
FusionGDB2.0 ID: 73043
HgeneTgene
Gene symbol

RBMS3

RBBP6

Gene ID

27303

5930

Gene nameRNA binding motif single stranded interacting protein 3RB binding protein 6, ubiquitin ligase
Synonyms-MY038|P2P-R|PACT|RBQ-1|SNAMA
Cytomap

3p24.1

16p12.1

Type of geneprotein-codingprotein-coding
DescriptionRNA-binding motif, single-stranded-interacting protein 3RNA binding motif, single stranded interacting proteinRNA-binding proteinE3 ubiquitin-protein ligase RBBP6RB-binding Q-protein 1RING-type E3 ubiquitin transferase RBBP6p53-associated cellular protein of testisproliferation potential-related proteinprotein P2P-Rretinoblastoma binding protein 6retinoblastoma-binding Q pro
Modification date2020031320200313
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000273139, ENST00000383766, 
ENST00000383767, ENST00000396583, 
ENST00000434693, ENST00000445033, 
ENST00000452462, ENST00000456853, 
ENST00000473799, 
ENST00000348022, 
ENST00000381039, ENST00000452655, 
ENST00000319715, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score12 X 11 X 6=7926 X 6 X 5=180
# samples 126
** MAII scorelog2(12/792*10)=-2.72246602447109
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(6/180*10)=-1.58496250072116
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: RBMS3 [Title/Abstract] AND RBBP6 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: RBMS3 [Title/Abstract] AND RBBP6 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)RBMS3(29323247)-RBBP6(24564834), # samples:1
Anticipated loss of major functional domain due to fusion event.RBMS3-RBBP6 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.
RBMS3-RBBP6 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.
RBMS3-RBBP6 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.
RBMS3-RBBP6 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
TgeneRBBP6

GO:0006511

ubiquitin-dependent protein catabolic process

18851979



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/chr3:29323247/chr16:24564834)
- 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 RBMS3 (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 RBBP6 (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)
ENST00000434693RBMS3chr329323247+ENST00000319715RBBP6chr1624564834+626977535258501832
ENST00000396583RBMS3chr329323247+ENST00000319715RBBP6chr1624564834+59394452255201832
ENST00000383767RBMS3chr329323247+ENST00000319715RBBP6chr1624564834+59054111554861823
ENST00000445033RBMS3chr329323247+ENST00000319715RBBP6chr1624564834+587838411754591780
ENST00000273139RBMS3chr329323247+ENST00000319715RBBP6chr1624564834+57993053853801780
ENST00000383766RBMS3chr329323247+ENST00000319715RBBP6chr1624564834+57993053853801780
ENST00000452462RBMS3chr329323247+ENST00000319715RBBP6chr1624564834+569920513052801716
ENST00000456853RBMS3chr329323247+ENST00000319715RBBP6chr1624564834+56351416652161716

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
ENST00000434693ENST00000319715RBMS3chr329323247+RBBP6chr1624564834+0.0004662320.9995338
ENST00000396583ENST00000319715RBMS3chr329323247+RBBP6chr1624564834+0.0004005720.9995994
ENST00000383767ENST00000319715RBMS3chr329323247+RBBP6chr1624564834+0.0003927640.99960726
ENST00000445033ENST00000319715RBMS3chr329323247+RBBP6chr1624564834+0.0003792560.9996207
ENST00000273139ENST00000319715RBMS3chr329323247+RBBP6chr1624564834+0.0003543680.9996456
ENST00000383766ENST00000319715RBMS3chr329323247+RBBP6chr1624564834+0.0003543680.9996456
ENST00000452462ENST00000319715RBMS3chr329323247+RBBP6chr1624564834+0.0003627630.99963725
ENST00000456853ENST00000319715RBMS3chr329323247+RBBP6chr1624564834+0.0003610780.9996389

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 RBMS3-RBBP6

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
RBMS3chr329323247RBBP6chr16245648341411647TRSHSSSASSAESQDSKKKKKKKEKK
RBMS3chr329323247RBBP6chr162456483414125QYTYYYPHYLQTKIDDSSASISLAQL
RBMS3chr329323247RBBP6chr16245648342051647TRSHSSSASSAESQDSKKKKKKKEKK
RBMS3chr329323247RBBP6chr162456483420525QYTYYYPHYLQTKIDDSSASISLAQL
RBMS3chr329323247RBBP6chr16245648343051711TRSHSSSASSAESQDSKKKKKKKEKK
RBMS3chr329323247RBBP6chr162456483430589QYTYYYPHYLQTKIDDSSASISLAQL
RBMS3chr329323247RBBP6chr16245648343841711TRSHSSSASSAESQDSKKKKKKKEKK
RBMS3chr329323247RBBP6chr162456483438489QYTYYYPHYLQTKIDDSSASISLAQL
RBMS3chr329323247RBBP6chr1624564834411132QYTYYYPHYLQTKIDDSSASISLAQL
RBMS3chr329323247RBBP6chr16245648344111754TRSHSSSASSAESQDSKKKKKKKEKK
RBMS3chr329323247RBBP6chr1624564834445141QYTYYYPHYLQTKIDDSSASISLAQL
RBMS3chr329323247RBBP6chr16245648344451763TRSHSSSASSAESQDSKKKKKKKEKK
RBMS3chr329323247RBBP6chr1624564834775141QYTYYYPHYLQTKIDDSSASISLAQL
RBMS3chr329323247RBBP6chr16245648347751763TRSHSSSASSAESQDSKKKKKKKEKK

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Potential FusionNeoAntigen Information of RBMS3-RBBP6 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 RBMS3-RBBP6 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 RBMS3-RBBP6

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 RBMS3-RBBP6

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 RBMS3-RBBP6

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 RBMS3-RBBP6

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 RBMS3-RBBP6

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 RBMS3-RBBP6

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 RBMS3-RBBP6

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