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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:RNF169-CBX1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: RNF169-CBX1
FusionPDB ID: 74880
FusionGDB2.0 ID: 74880
HgeneTgene
Gene symbol

RNF169

CBX1

Gene ID

254225

10951

Gene namering finger protein 169chromobox 1
Synonyms-CBX|HP1-BETA|HP1Hs-beta|HP1Hsbeta|M31|MOD1|p25beta
Cytomap

11q13.4

17q21.32

Type of geneprotein-codingprotein-coding
DescriptionE3 ubiquitin-protein ligase RNF169RING-type E3 ubiquitin transferase RNF169chromobox protein homolog 1HP1 beta homologchromobox homolog 1 (HP1 beta homolog Drosophila )heterochromatin protein 1 homolog betaheterochromatin protein 1-betaheterochromatin protein p25 betamodifier 1 protein
Modification date2020031320200313
UniProtAcc.

P83916

Main function of 5'-partner protein: FUNCTION: Component of heterochromatin. Recognizes and binds histone H3 tails methylated at 'Lys-9', leading to epigenetic repression. Interaction with lamin B receptor (LBR) can contribute to the association of the heterochromatin with the inner nuclear membrane. {ECO:0000250|UniProtKB:P83917}.
Ensembl transtripts involved in fusion geneENST idsENST00000299563, ENST00000225603, 
ENST00000393408, ENST00000495350, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score8 X 5 X 5=2009 X 7 X 5=315
# samples 911
** MAII scorelog2(9/200*10)=-1.15200309344505
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(11/315*10)=-1.51784830486262
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: RNF169 [Title/Abstract] AND CBX1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: RNF169 [Title/Abstract] AND CBX1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)RNF169(74528759)-CBX1(46154403), # samples:4
Anticipated loss of major functional domain due to fusion event.RNF169-CBX1 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.
RNF169-CBX1 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.
RNF169-CBX1 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.
RNF169-CBX1 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
HgeneRNF169

GO:0006974

cellular response to DNA damage stimulus

22733822

HgeneRNF169

GO:2000780

negative regulation of double-strand break repair

22742833



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/chr11:74528759/chr17:46154403)
- 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 RNF169 (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 CBX1 (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)
ENST00000299563RNF169chr1174528759+ENST00000393408CBX1chr1746153540-2656855131272419
ENST00000299563RNF169chr1174528759+ENST00000225603CBX1chr1746153540-2656855131272419
ENST00000299563RNF169chr1174528759+ENST00000495350CBX1chr1746153540-1208855131131372

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
ENST00000299563ENST00000393408RNF169chr1174528759+CBX1chr1746153540-0.0042578750.99574214
ENST00000299563ENST00000225603RNF169chr1174528759+CBX1chr1746153540-0.0042578750.99574214
ENST00000299563ENST00000495350RNF169chr1174528759+CBX1chr1746153540-0.084415910.9155841

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 RNF169-CBX1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
RNF169chr1174528759CBX1chr1746153540855281SKNNSYSLAFLAGEDNTWEPEENLDC

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Potential FusionNeoAntigen Information of RNF169-CBX1 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.
RNF169-CBX1_74528759_46153540.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)
RNF169-CBX1chr1174528759chr1746153540855HLA-B58:01FLAGEDNTW0.92780.9962918
RNF169-CBX1chr1174528759chr1746153540855HLA-B53:01FLAGEDNTW0.88480.8711918
RNF169-CBX1chr1174528759chr1746153540855HLA-A24:17AFLAGEDNTW0.97250.5172818
RNF169-CBX1chr1174528759chr1746153540855HLA-A31:08AFLAGEDNTW0.9550.583818
RNF169-CBX1chr1174528759chr1746153540855HLA-B57:01LAFLAGEDNTW0.99990.9949718
RNF169-CBX1chr1174528759chr1746153540855HLA-B58:02LAFLAGEDNTW0.99980.9854718
RNF169-CBX1chr1174528759chr1746153540855HLA-B58:01LAFLAGEDNTW0.99970.9918718
RNF169-CBX1chr1174528759chr1746153540855HLA-B57:03LAFLAGEDNTW0.99920.9974718
RNF169-CBX1chr1174528759chr1746153540855HLA-B53:01LAFLAGEDNTW0.99750.895718
RNF169-CBX1chr1174528759chr1746153540855HLA-B15:24FLAGEDNTW0.94510.9935918
RNF169-CBX1chr1174528759chr1746153540855HLA-B15:13FLAGEDNTW0.93170.9393918
RNF169-CBX1chr1174528759chr1746153540855HLA-B57:02FLAGEDNTW0.87110.9879918
RNF169-CBX1chr1174528759chr1746153540855HLA-B53:02FLAGEDNTW0.48690.9185918
RNF169-CBX1chr1174528759chr1746153540855HLA-A25:01FLAGEDNTW0.44530.9836918
RNF169-CBX1chr1174528759chr1746153540855HLA-B57:10LAFLAGEDNTW0.99990.9949718
RNF169-CBX1chr1174528759chr1746153540855HLA-B57:04LAFLAGEDNTW0.99980.9011718
RNF169-CBX1chr1174528759chr1746153540855HLA-B58:06LAFLAGEDNTW0.99940.9747718
RNF169-CBX1chr1174528759chr1746153540855HLA-B57:02LAFLAGEDNTW0.99930.9887718
RNF169-CBX1chr1174528759chr1746153540855HLA-B53:02LAFLAGEDNTW0.99790.8884718

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Potential FusionNeoAntigen Information of RNF169-CBX1 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 RNF169-CBX1

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
8721SLAFLAGEDNTWEPRNF169CBX1chr1174528759chr1746153540855

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of RNF169-CBX1

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-B14:023BVN8721SLAFLAGEDNTWEP-6.47793-6.68353
HLA-B14:023BVN8721SLAFLAGEDNTWEP-5.83009-7.77629
HLA-B14:023BVN8721SLAFLAGEDNTWEP-5.82672-6.03232
HLA-B14:023BVN8721SLAFLAGEDNTWEP-5.76076-6.59916
HLA-B14:023BVN8721SLAFLAGEDNTWEP-4.73297-5.57137
HLA-B14:023BVN8721SLAFLAGEDNTWEP-3.29133-5.23753
HLA-B52:013W398721SLAFLAGEDNTWEP-7.0275-7.2331
HLA-B52:013W398721SLAFLAGEDNTWEP-5.8192-6.0248
HLA-B52:013W398721SLAFLAGEDNTWEP-5.04167-5.88007
HLA-B52:013W398721SLAFLAGEDNTWEP-4.81649-5.65489
HLA-B52:013W398721SLAFLAGEDNTWEP-4.63072-6.57692
HLA-B52:013W398721SLAFLAGEDNTWEP-2.8402-4.7864
HLA-A11:014UQ28721SLAFLAGEDNTWEP-6.91469-7.12029
HLA-A11:014UQ28721SLAFLAGEDNTWEP-5.48682-5.69242
HLA-A24:025HGA8721SLAFLAGEDNTWEP-9.3147-9.5203
HLA-A24:025HGA8721SLAFLAGEDNTWEP-6.48244-7.32084
HLA-A24:025HGA8721SLAFLAGEDNTWEP-6.07021-6.90861
HLA-A24:025HGA8721SLAFLAGEDNTWEP-5.70199-7.64819
HLA-A24:025HGA8721SLAFLAGEDNTWEP-5.25723-5.46283
HLA-A24:025HGA8721SLAFLAGEDNTWEP-4.7731-6.7193
HLA-B27:056PYJ8721SLAFLAGEDNTWEP-3.71591-3.92151
HLA-B44:053DX88721SLAFLAGEDNTWEP-5.66137-5.86697
HLA-B44:053DX88721SLAFLAGEDNTWEP-4.6848-4.8904
HLA-B44:053DX88721SLAFLAGEDNTWEP-4.6782-5.5166
HLA-B44:053DX88721SLAFLAGEDNTWEP-4.45928-5.29768
HLA-B44:053DX88721SLAFLAGEDNTWEP-2.87692-4.82312
HLA-B44:053DX88721SLAFLAGEDNTWEP-2.23468-4.18088
HLA-A02:016TDR8721SLAFLAGEDNTWEP-3.40253-5.34873
HLA-A02:016TDR8721SLAFLAGEDNTWEP-1.26993-1.47553

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Vaccine Design for the FusionNeoAntigens of RNF169-CBX1

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
RNF169-CBX1chr1174528759chr1746153540718LAFLAGEDNTWCTTAGCTTTCCTGGCAGGTGAGGACAACACATG
RNF169-CBX1chr1174528759chr1746153540818AFLAGEDNTWAGCTTTCCTGGCAGGTGAGGACAACACATG
RNF169-CBX1chr1174528759chr1746153540918FLAGEDNTWTTTCCTGGCAGGTGAGGACAACACATG

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 RNF169-CBX1

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
BRCARNF169-CBX1chr1174528759ENST00000299563chr1746153540ENST00000225603TCGA-C8-A12Q-01A

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Potential target of CAR-T therapy development for RNF169-CBX1

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 RNF169-CBX1

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 RNF169-CBX1

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