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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:IL4R-RBBP6

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: IL4R-RBBP6
FusionPDB ID: 39565
FusionGDB2.0 ID: 39565
HgeneTgene
Gene symbol

IL4R

RBBP6

Gene ID

3566

5930

Gene nameinterleukin 4 receptorRB binding protein 6, ubiquitin ligase
SynonymsCD124|IL-4RA|IL4RAMY038|P2P-R|PACT|RBQ-1|SNAMA
Cytomap

16p12.1

16p12.1

Type of geneprotein-codingprotein-coding
Descriptioninterleukin-4 receptor subunit alphaIL-4 receptor subunit alphaIL4R nirs variant 1interleukin 13 receptorinterleukin-4 receptor alpha chainE3 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 date2020032220200313
UniProtAcc

P24394

Main function of 5'-partner protein: FUNCTION: Receptor for both interleukin 4 and interleukin 13. Couples to the JAK1/2/3-STAT6 pathway. The IL4 response is involved in promoting Th2 differentiation. The IL4/IL13 responses are involved in regulating IgE production and, chemokine and mucus production at sites of allergic inflammation. In certain cell types, can signal through activation of insulin receptor substrates, IRS1/IRS2. {ECO:0000269|PubMed:8124718}.; FUNCTION: Soluble IL4R (sIL4R) inhibits IL4-mediated cell proliferation and IL5 up-regulation by T-cells. {ECO:0000269|PubMed:8124718}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000380922, ENST00000170630, 
ENST00000395762, ENST00000449195, 
ENST00000543915, ENST00000565915, 
ENST00000319715, ENST00000348022, 
ENST00000381039, ENST00000452655, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score9 X 8 X 5=3606 X 6 X 5=180
# samples 106
** MAII scorelog2(10/360*10)=-1.84799690655495
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: IL4R [Title/Abstract] AND RBBP6 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: IL4R [Title/Abstract] AND RBBP6 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)IL4R(27351594)-RBBP6(24557483), # samples:1
Anticipated loss of major functional domain due to fusion event.IL4R-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.
IL4R-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.
IL4R-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.
IL4R-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/chr16:27351594/chr16:24557483)
- 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 IL4R (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)
ENST00000395762IL4Rchr1627351594+ENST00000319715RBBP6chr1624557483+596032923855411767
ENST00000395762IL4Rchr1627351594+ENST00000452655RBBP6chr1624557483+88632923851993
ENST00000395762IL4Rchr1627351594+ENST00000381039RBBP6chr1624557483+34403292383021927
ENST00000395762IL4Rchr1627351594+ENST00000348022RBBP6chr1624557483+585832923854391733
ENST00000543915IL4Rchr1627351594+ENST00000319715RBBP6chr1624557483+581418311353951760
ENST00000543915IL4Rchr1627351594+ENST00000452655RBBP6chr1624557483+740183270190
ENST00000543915IL4Rchr1627351594+ENST00000381039RBBP6chr1624557483+32941831132875920
ENST00000543915IL4Rchr1627351594+ENST00000348022RBBP6chr1624557483+571218311352931726
ENST00000449195IL4Rchr1627351594+ENST00000319715RBBP6chr1624557483+594331222155241767
ENST00000449195IL4Rchr1627351594+ENST00000452655RBBP6chr1624557483+86931222150293
ENST00000449195IL4Rchr1627351594+ENST00000381039RBBP6chr1624557483+34233122213004927
ENST00000449195IL4Rchr1627351594+ENST00000348022RBBP6chr1624557483+584131222154221733
ENST00000170630IL4Rchr1627351594+ENST00000319715RBBP6chr1624557483+5722912153031760
ENST00000170630IL4Rchr1627351594+ENST00000452655RBBP6chr1624557483+648912128186
ENST00000170630IL4Rchr1627351594+ENST00000381039RBBP6chr1624557483+320291212783920
ENST00000170630IL4Rchr1627351594+ENST00000348022RBBP6chr1624557483+5620912152011726

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
ENST00000395762ENST00000319715IL4Rchr1627351594+RBBP6chr1624557483+0.0004058380.99959415
ENST00000395762ENST00000452655IL4Rchr1627351594+RBBP6chr1624557483+0.303682450.69631755
ENST00000395762ENST00000381039IL4Rchr1627351594+RBBP6chr1624557483+0.0003572220.9996427
ENST00000395762ENST00000348022IL4Rchr1627351594+RBBP6chr1624557483+0.000405930.99959403
ENST00000543915ENST00000319715IL4Rchr1627351594+RBBP6chr1624557483+0.0003507430.9996493
ENST00000543915ENST00000452655IL4Rchr1627351594+RBBP6chr1624557483+0.224228130.7757719
ENST00000543915ENST00000381039IL4Rchr1627351594+RBBP6chr1624557483+0.0003656680.99963427
ENST00000543915ENST00000348022IL4Rchr1627351594+RBBP6chr1624557483+0.0003493560.9996506
ENST00000449195ENST00000319715IL4Rchr1627351594+RBBP6chr1624557483+0.0003988720.9996012
ENST00000449195ENST00000452655IL4Rchr1627351594+RBBP6chr1624557483+0.469979140.5300209
ENST00000449195ENST00000381039IL4Rchr1627351594+RBBP6chr1624557483+0.0003577930.99964225
ENST00000449195ENST00000348022IL4Rchr1627351594+RBBP6chr1624557483+0.0003990510.99960095
ENST00000170630ENST00000319715IL4Rchr1627351594+RBBP6chr1624557483+0.0003334850.9996666
ENST00000170630ENST00000452655IL4Rchr1627351594+RBBP6chr1624557483+0.267261270.7327387
ENST00000170630ENST00000381039IL4Rchr1627351594+RBBP6chr1624557483+0.0004024890.9995975
ENST00000170630ENST00000348022IL4Rchr1627351594+RBBP6chr1624557483+0.000326740.99967325

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 IL4R-RBBP6

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
IL4Rchr1627351594RBBP6chr16245574831831657TRSHSSSASSAESQDSKKKKKKKEKK
IL4Rchr1627351594RBBP6chr16245574831831691TRSHSSSASSAESQDSKKKKKKKEKK
IL4Rchr1627351594RBBP6chr1624557483183851TRSHSSSASSAESQDSKKKKKKKEKK
IL4Rchr1627351594RBBP6chr16245574833121664TRSHSSSASSAESQDSKKKKKKKEKK
IL4Rchr1627351594RBBP6chr16245574833121698TRSHSSSASSAESQDSKKKKKKKEKK
IL4Rchr1627351594RBBP6chr162455748331218LPMGWLCSGLLFPVSCLVLLQVASSE
IL4Rchr1627351594RBBP6chr1624557483312858TRSHSSSASSAESQDSKKKKKKKEKK
IL4Rchr1627351594RBBP6chr16245574833291664TRSHSSSASSAESQDSKKKKKKKEKK
IL4Rchr1627351594RBBP6chr16245574833291698TRSHSSSASSAESQDSKKKKKKKEKK
IL4Rchr1627351594RBBP6chr162455748332918LPMGWLCSGLLFPVSCLVLLQVASSE
IL4Rchr1627351594RBBP6chr1624557483329858TRSHSSSASSAESQDSKKKKKKKEKK
IL4Rchr1627351594RBBP6chr1624557483911657TRSHSSSASSAESQDSKKKKKKKEKK
IL4Rchr1627351594RBBP6chr1624557483911691TRSHSSSASSAESQDSKKKKKKKEKK
IL4Rchr1627351594RBBP6chr162455748391851TRSHSSSASSAESQDSKKKKKKKEKK

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Potential FusionNeoAntigen Information of IL4R-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 IL4R-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 IL4R-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 IL4R-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 IL4R-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 IL4R-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 IL4R-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 IL4R-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 IL4R-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