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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:RBM4B-FADD

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: RBM4B-FADD
FusionPDB ID: 72942
FusionGDB2.0 ID: 72942
HgeneTgene
Gene symbol

RBM4B

FADD

Gene ID

83759

8772

Gene nameRNA binding motif protein 4BFas associated via death domain
SynonymsRBM30|RBM4L|ZCCHC15|ZCCHC21B|ZCRB3BGIG3|MORT1
Cytomap

11q13.2

11q13.3

Type of geneprotein-codingprotein-coding
DescriptionRNA-binding protein 4BRNA-binding motif protein 30zinc finger CCHC-type and RNA binding motif 3BFAS-associated death domain proteinFas (TNFRSF6)-associated via death domainFas-associating death domain-containing proteinFas-associating protein with death domaingrowth-inhibiting gene 3 proteinmediator of receptor-induced toxicity
Modification date2020032720200313
UniProtAcc.

Q13158

Main function of 5'-partner protein: FUNCTION: Apoptotic adaptor molecule that recruits caspase-8 or caspase-10 to the activated Fas (CD95) or TNFR-1 receptors. The resulting aggregate called the death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation. Active caspase-8 initiates the subsequent cascade of caspases mediating apoptosis. Involved in interferon-mediated antiviral immune response, playing a role in the positive regulation of interferon signaling. {ECO:0000269|PubMed:16762833, ECO:0000269|PubMed:19118384, ECO:0000269|PubMed:20935634, ECO:0000269|PubMed:21109225}.
Ensembl transtripts involved in fusion geneENST idsENST00000310046, ENST00000524637, 
ENST00000525754, ENST00000531969, 
ENST00000529195, ENST00000531036, 
ENST00000301838, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 5 X 3=905 X 2 X 4=40
# samples 66
** MAII scorelog2(6/90*10)=-0.584962500721156
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(6/40*10)=0.584962500721156
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: RBM4B [Title/Abstract] AND FADD [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: RBM4B [Title/Abstract] AND FADD [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)RBM4B(66444139)-FADD(70052239), # samples:2
Anticipated loss of major functional domain due to fusion event.RBM4B-FADD 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.
RBM4B-FADD 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.
RBM4B-FADD 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.
RBM4B-FADD 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.
RBM4B-FADD seems lost the major protein functional domain in Tgene partner, which is a tumor suppressor due to the frame-shifted 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
TgeneFADD

GO:0032757

positive regulation of interleukin-8 production

16127453

TgeneFADD

GO:0032760

positive regulation of tumor necrosis factor production

16127453

TgeneFADD

GO:0036462

TRAIL-activated apoptotic signaling pathway

21785459

TgeneFADD

GO:0043065

positive regulation of apoptotic process

11821383

TgeneFADD

GO:0045862

positive regulation of proteolysis

18387192

TgeneFADD

GO:0045944

positive regulation of transcription by RNA polymerase II

16127453

TgeneFADD

GO:0097190

apoptotic signaling pathway

11101870

TgeneFADD

GO:0097191

extrinsic apoptotic signaling pathway

21785459

TgeneFADD

GO:0097202

activation of cysteine-type endopeptidase activity

18387192



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/chr11:66444139/chr11:70052239)
- 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 RBM4B (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 FADD (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)
ENST00000531969RBM4Bchr1166444139-ENST00000301838FADDchr1170052239+174348573825250

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
ENST00000531969ENST00000301838RBM4Bchr1166444139-FADDchr1170052239+0.0064737710.9935262

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 RBM4B-FADD

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
RBM4Bchr1166444139FADDchr1170052239485135DAVEAIRGLDNTEFQDLCAAFNVICD

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Potential FusionNeoAntigen Information of RBM4B-FADD 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.
RBM4B-FADD_66444139_70052239.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)
RBM4B-FADDchr1166444139chr1170052239485HLA-B45:01TEFQDLCAA0.9970.95851120
RBM4B-FADDchr1166444139chr1170052239485HLA-B50:02TEFQDLCAA0.99620.75551120
RBM4B-FADDchr1166444139chr1170052239485HLA-B50:01TEFQDLCAA0.37470.88881120
RBM4B-FADDchr1166444139chr1170052239485HLA-B41:01TEFQDLCAA0.35430.97621120
RBM4B-FADDchr1166444139chr1170052239485HLA-B15:01AIRGLDNTEF0.99970.9124414
RBM4B-FADDchr1166444139chr1170052239485HLA-B44:03TEFQDLCAAF0.99890.98091121
RBM4B-FADDchr1166444139chr1170052239485HLA-B18:01TEFQDLCAAF0.99080.90511121
RBM4B-FADDchr1166444139chr1170052239485HLA-B40:06TEFQDLCAA0.99810.90581120
RBM4B-FADDchr1166444139chr1170052239485HLA-C07:95IRGLDNTEF0.97820.5836514
RBM4B-FADDchr1166444139chr1170052239485HLA-C07:27IRGLDNTEF0.97390.9177514
RBM4B-FADDchr1166444139chr1170052239485HLA-C07:67IRGLDNTEF0.81080.9339514
RBM4B-FADDchr1166444139chr1170052239485HLA-C07:80IRGLDNTEF0.81080.9339514
RBM4B-FADDchr1166444139chr1170052239485HLA-C07:46IRGLDNTEF0.80990.8657514
RBM4B-FADDchr1166444139chr1170052239485HLA-B15:21EFQDLCAAF0.78790.90231221
RBM4B-FADDchr1166444139chr1170052239485HLA-B15:07AIRGLDNTEF0.99960.7269414
RBM4B-FADDchr1166444139chr1170052239485HLA-B44:10TEFQDLCAAF0.98750.60591121
RBM4B-FADDchr1166444139chr1170052239485HLA-C07:02IRGLDNTEF0.81080.9339514
RBM4B-FADDchr1166444139chr1170052239485HLA-B50:04TEFQDLCAA0.37470.88881120
RBM4B-FADDchr1166444139chr1170052239485HLA-B50:05TEFQDLCAA0.37470.88881120
RBM4B-FADDchr1166444139chr1170052239485HLA-B15:125AIRGLDNTEF0.99970.9124414
RBM4B-FADDchr1166444139chr1170052239485HLA-B15:34AIRGLDNTEF0.99970.9124414
RBM4B-FADDchr1166444139chr1170052239485HLA-B15:33AIRGLDNTEF0.99970.9124414
RBM4B-FADDchr1166444139chr1170052239485HLA-B44:07TEFQDLCAAF0.99890.98091121
RBM4B-FADDchr1166444139chr1170052239485HLA-B44:13TEFQDLCAAF0.99890.98091121
RBM4B-FADDchr1166444139chr1170052239485HLA-B44:26TEFQDLCAAF0.99890.98091121
RBM4B-FADDchr1166444139chr1170052239485HLA-B18:05TEFQDLCAAF0.99080.90511121
RBM4B-FADDchr1166444139chr1170052239485HLA-B18:08TEFQDLCAAF0.99080.94341121
RBM4B-FADDchr1166444139chr1170052239485HLA-B18:06TEFQDLCAAF0.99040.92141121
RBM4B-FADDchr1166444139chr1170052239485HLA-B18:04TEFQDLCAAF0.99040.9121121
RBM4B-FADDchr1166444139chr1170052239485HLA-B18:03TEFQDLCAAF0.98180.90151121
RBM4B-FADDchr1166444139chr1170052239485HLA-B18:11TEFQDLCAAF0.97940.94921121
RBM4B-FADDchr1166444139chr1170052239485HLA-B15:53TEFQDLCAAF0.97310.93811121

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Potential FusionNeoAntigen Information of RBM4B-FADD 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.
RBM4B-FADD_66444139_70052239.msa

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)
RBM4B-FADDchr1166444139chr1170052239485DRB1-1201AVEAIRGLDNTEFQD116
RBM4B-FADDchr1166444139chr1170052239485DRB1-1201VEAIRGLDNTEFQDL217
RBM4B-FADDchr1166444139chr1170052239485DRB1-1203AVEAIRGLDNTEFQD116
RBM4B-FADDchr1166444139chr1170052239485DRB1-1203VEAIRGLDNTEFQDL217
RBM4B-FADDchr1166444139chr1170052239485DRB1-1205AVEAIRGLDNTEFQD116
RBM4B-FADDchr1166444139chr1170052239485DRB1-1205VEAIRGLDNTEFQDL217
RBM4B-FADDchr1166444139chr1170052239485DRB1-1206AVEAIRGLDNTEFQD116
RBM4B-FADDchr1166444139chr1170052239485DRB1-1206VEAIRGLDNTEFQDL217
RBM4B-FADDchr1166444139chr1170052239485DRB1-1207AVEAIRGLDNTEFQD116
RBM4B-FADDchr1166444139chr1170052239485DRB1-1207VEAIRGLDNTEFQDL217
RBM4B-FADDchr1166444139chr1170052239485DRB1-1208AVEAIRGLDNTEFQD116
RBM4B-FADDchr1166444139chr1170052239485DRB1-1208VEAIRGLDNTEFQDL217
RBM4B-FADDchr1166444139chr1170052239485DRB1-1210AVEAIRGLDNTEFQD116
RBM4B-FADDchr1166444139chr1170052239485DRB1-1210VEAIRGLDNTEFQDL217
RBM4B-FADDchr1166444139chr1170052239485DRB1-1211AVEAIRGLDNTEFQD116
RBM4B-FADDchr1166444139chr1170052239485DRB1-1211VEAIRGLDNTEFQDL217
RBM4B-FADDchr1166444139chr1170052239485DRB1-1212AVEAIRGLDNTEFQD116
RBM4B-FADDchr1166444139chr1170052239485DRB1-1212VEAIRGLDNTEFQDL217
RBM4B-FADDchr1166444139chr1170052239485DRB1-1212DAVEAIRGLDNTEFQ015
RBM4B-FADDchr1166444139chr1170052239485DRB1-1213AVEAIRGLDNTEFQD116
RBM4B-FADDchr1166444139chr1170052239485DRB1-1213VEAIRGLDNTEFQDL217
RBM4B-FADDchr1166444139chr1170052239485DRB1-1214AVEAIRGLDNTEFQD116
RBM4B-FADDchr1166444139chr1170052239485DRB1-1214VEAIRGLDNTEFQDL217
RBM4B-FADDchr1166444139chr1170052239485DRB1-1215AVEAIRGLDNTEFQD116
RBM4B-FADDchr1166444139chr1170052239485DRB1-1215VEAIRGLDNTEFQDL217
RBM4B-FADDchr1166444139chr1170052239485DRB1-1217AVEAIRGLDNTEFQD116
RBM4B-FADDchr1166444139chr1170052239485DRB1-1217VEAIRGLDNTEFQDL217
RBM4B-FADDchr1166444139chr1170052239485DRB1-1218AVEAIRGLDNTEFQD116
RBM4B-FADDchr1166444139chr1170052239485DRB1-1218VEAIRGLDNTEFQDL217
RBM4B-FADDchr1166444139chr1170052239485DRB1-1219AVEAIRGLDNTEFQD116
RBM4B-FADDchr1166444139chr1170052239485DRB1-1219VEAIRGLDNTEFQDL217
RBM4B-FADDchr1166444139chr1170052239485DRB1-1220AVEAIRGLDNTEFQD116
RBM4B-FADDchr1166444139chr1170052239485DRB1-1221AVEAIRGLDNTEFQD116
RBM4B-FADDchr1166444139chr1170052239485DRB1-1221VEAIRGLDNTEFQDL217
RBM4B-FADDchr1166444139chr1170052239485DRB1-1223AVEAIRGLDNTEFQD116
RBM4B-FADDchr1166444139chr1170052239485DRB1-1223VEAIRGLDNTEFQDL217

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Fusion breakpoint peptide structures of RBM4B-FADD

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
7871RGLDNTEFQDLCAARBM4BFADDchr1166444139chr1170052239485

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of RBM4B-FADD

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-B14:023BVN7871RGLDNTEFQDLCAA-7.15543-7.26883
HLA-B14:023BVN7871RGLDNTEFQDLCAA-4.77435-5.80965
HLA-B52:013W397871RGLDNTEFQDLCAA-6.80875-6.92215
HLA-B52:013W397871RGLDNTEFQDLCAA-4.20386-5.23916
HLA-A11:014UQ27871RGLDNTEFQDLCAA-7.5194-8.5547
HLA-A11:014UQ27871RGLDNTEFQDLCAA-6.9601-7.0735
HLA-A24:025HGA7871RGLDNTEFQDLCAA-7.52403-7.63743
HLA-A24:025HGA7871RGLDNTEFQDLCAA-5.82433-6.85963
HLA-B27:056PYJ7871RGLDNTEFQDLCAA-3.28285-4.31815
HLA-B44:053DX87871RGLDNTEFQDLCAA-5.91172-6.94702
HLA-B44:053DX87871RGLDNTEFQDLCAA-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of RBM4B-FADD

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
RBM4B-FADDchr1166444139chr11700522391120TEFQDLCAATTCAAGACCTGTGTGCAGCATTTAACG
RBM4B-FADDchr1166444139chr11700522391121TEFQDLCAAFTTCAAGACCTGTGTGCAGCATTTAACGTCA
RBM4B-FADDchr1166444139chr11700522391221EFQDLCAAFAAGACCTGTGTGCAGCATTTAACGTCA
RBM4B-FADDchr1166444139chr1170052239414AIRGLDNTEFGGGGCCTTGACAACACAGAGTTTCAAGACC
RBM4B-FADDchr1166444139chr1170052239514IRGLDNTEFGCCTTGACAACACAGAGTTTCAAGACC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
RBM4B-FADDchr1166444139chr1170052239015DAVEAIRGLDNTEFQTGGAGGCCATCAGGGGCCTTGACAACACAGAGTTTCAAGACCTGT
RBM4B-FADDchr1166444139chr1170052239116AVEAIRGLDNTEFQDAGGCCATCAGGGGCCTTGACAACACAGAGTTTCAAGACCTGTGTG
RBM4B-FADDchr1166444139chr1170052239217VEAIRGLDNTEFQDLCCATCAGGGGCCTTGACAACACAGAGTTTCAAGACCTGTGTGCAG

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Information of the samples that have these potential fusion neoantigens of RBM4B-FADD

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
SARCRBM4B-FADDchr1166444139ENST00000531969chr1170052239ENST00000301838TCGA-3B-A9HR-01A

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Potential target of CAR-T therapy development for RBM4B-FADD

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 RBM4B-FADD

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 RBM4B-FADD

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