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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:CPEB4-NRCAM

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CPEB4-NRCAM
FusionPDB ID: 18965
FusionGDB2.0 ID: 18965
HgeneTgene
Gene symbol

CPEB4

NRCAM

Gene ID

80315

4897

Gene namecytoplasmic polyadenylation element binding protein 4neuronal cell adhesion molecule
SynonymsCPE-BP4|hCPEB-4-
Cytomap

5q35.2

7q31.1

Type of geneprotein-codingprotein-coding
Descriptioncytoplasmic polyadenylation element-binding protein 4CPE-binding protein 4neuronal cell adhesion moleculeNgCAM-related cell adhesion moleculeneuronal surface protein Bravo
Modification date2020031320200313
UniProtAcc

Q17RY0

Main function of 5'-partner protein: FUNCTION: Sequence-specific RNA-binding protein that binds to the cytoplasmic polyadenylation element (CPE), an uridine-rich sequence element (consensus sequence 5'-UUUUUAU-3') within the mRNA 3'-UTR (PubMed:24990967). RNA binding results in a clear conformational change analogous to the Venus fly trap mechanism (PubMed:24990967). Regulates activation of unfolded protein response (UPR) in the process of adaptation to ER stress in liver, by maintaining translation of CPE-regulated mRNAs in conditions in which global protein synthesis is inhibited (By similarity). Required for cell cycle progression, specifically for cytokinesis and chromosomal segregation (PubMed:26398195). Plays a role as an oncogene promoting tumor growth and progression by positively regulating translation of t-plasminogen activator/PLAT (PubMed:22138752). Stimulates proliferation of melanocytes (PubMed:27857118). In contrast to CPEB1 and CPEB3, does not play role in synaptic plasticity, learning and memory (By similarity). {ECO:0000250|UniProtKB:Q7TN98, ECO:0000269|PubMed:22138752, ECO:0000269|PubMed:24990967, ECO:0000269|PubMed:26398195, ECO:0000269|PubMed:27857118}.

Q92823

Main function of 5'-partner protein: FUNCTION: Cell adhesion protein that is required for normal responses to cell-cell contacts in brain and in the peripheral nervous system. Plays a role in neurite outgrowth in response to contactin binding. Plays a role in mediating cell-cell contacts between Schwann cells and axons. Plays a role in the formation and maintenance of the nodes of Ranvier on myelinated axons. Nodes of Ranvier contain clustered sodium channels that are crucial for the saltatory propagation of action potentials along myelinated axons. During development, nodes of Ranvier are formed by the fusion of two heminodes. Required for normal clustering of sodium channels at heminodes; not required for the formation of mature nodes with normal sodium channel clusters. Required, together with GLDN, for maintaining NFASC and sodium channel clusters at mature nodes of Ranvier. {ECO:0000250|UniProtKB:Q810U4}.
Ensembl transtripts involved in fusion geneENST idsENST00000265085, ENST00000522336, 
ENST00000334035, ENST00000517880, 
ENST00000519467, ENST00000519835, 
ENST00000520867, 
ENST00000522550, 
ENST00000351718, ENST00000379022, 
ENST00000379024, ENST00000379028, 
ENST00000413765, ENST00000425651, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score4 X 3 X 4=487 X 5 X 5=175
# samples 47
** MAII scorelog2(4/48*10)=-0.263034405833794
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(7/175*10)=-1.32192809488736
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: CPEB4 [Title/Abstract] AND NRCAM [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CPEB4 [Title/Abstract] AND NRCAM [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CPEB4(173359503)-NRCAM(107800937), # samples:1
Anticipated loss of major functional domain due to fusion event.CPEB4-NRCAM 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.
CPEB4-NRCAM 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.
CPEB4-NRCAM 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.
CPEB4-NRCAM 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
TgeneNRCAM

GO:0045162

clustering of voltage-gated sodium channels

14602817



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/chr5:173359503/chr7:107800937)
- 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 CPEB4 (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 NRCAM (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)
ENST00000265085CPEB4chr5173359503+ENST00000379028NRCAMchr7107800937-5434271214543160568
ENST00000265085CPEB4chr5173359503+ENST00000413765NRCAMchr7107800937-5434271214543160568
ENST00000265085CPEB4chr5173359503+ENST00000351718NRCAMchr7107800937-5409271214543160568
ENST00000265085CPEB4chr5173359503+ENST00000379024NRCAMchr7107800937-4954271214543160568
ENST00000265085CPEB4chr5173359503+ENST00000379022NRCAMchr7107800937-2957271214542956501
ENST00000265085CPEB4chr5173359503+ENST00000425651NRCAMchr7107800937-3161271214543160569
ENST00000522336CPEB4chr5173359503+ENST00000379028NRCAMchr7107800937-2988266115714199
ENST00000522336CPEB4chr5173359503+ENST00000413765NRCAMchr7107800937-2988266115714199
ENST00000522336CPEB4chr5173359503+ENST00000351718NRCAMchr7107800937-2963266115714199
ENST00000522336CPEB4chr5173359503+ENST00000379024NRCAMchr7107800937-2508266115714199
ENST00000522336CPEB4chr5173359503+ENST00000379022NRCAMchr7107800937-511266115510132
ENST00000522336CPEB4chr5173359503+ENST00000425651NRCAMchr7107800937-715266115714200

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
ENST00000265085ENST00000379028CPEB4chr5173359503+NRCAMchr7107800937-0.0013637330.9986363
ENST00000265085ENST00000413765CPEB4chr5173359503+NRCAMchr7107800937-0.0013637330.9986363
ENST00000265085ENST00000351718CPEB4chr5173359503+NRCAMchr7107800937-0.0014356710.9985643
ENST00000265085ENST00000379024CPEB4chr5173359503+NRCAMchr7107800937-0.002033560.9979665
ENST00000265085ENST00000379022CPEB4chr5173359503+NRCAMchr7107800937-0.0088735520.9911265
ENST00000265085ENST00000425651CPEB4chr5173359503+NRCAMchr7107800937-0.0036417060.99635834
ENST00000522336ENST00000379028CPEB4chr5173359503+NRCAMchr7107800937-0.0005235090.9994765
ENST00000522336ENST00000413765CPEB4chr5173359503+NRCAMchr7107800937-0.0005235090.9994765
ENST00000522336ENST00000351718CPEB4chr5173359503+NRCAMchr7107800937-0.0005606380.9994393
ENST00000522336ENST00000379024CPEB4chr5173359503+NRCAMchr7107800937-0.0005805430.99941945
ENST00000522336ENST00000379022CPEB4chr5173359503+NRCAMchr7107800937-0.013339380.9866606
ENST00000522336ENST00000425651CPEB4chr5173359503+NRCAMchr7107800937-0.0016190750.9983809

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 CPEB4-NRCAM

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CPEB4chr5173359503NRCAMchr710780093726650YSYPGSDSSLLINAMASRQVDIATQG
CPEB4chr5173359503NRCAMchr71078009372712419YSYPGSDSSLLINAMASRQVDIATQG

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Potential FusionNeoAntigen Information of CPEB4-NRCAM 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.
CPEB4-NRCAM_173359503_107800937.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)
CPEB4-NRCAMchr5173359503chr71078009372712HLA-B35:01DSSLLINAM0.94210.846615
CPEB4-NRCAMchr5173359503chr71078009372712HLA-B35:02DSSLLINAM0.62960.8688615
CPEB4-NRCAMchr5173359503chr71078009372712HLA-B35:04DSSLLINAM0.62960.8688615
CPEB4-NRCAMchr5173359503chr71078009372712HLA-B51:08NAMASRQV0.99590.51751220
CPEB4-NRCAMchr5173359503chr71078009372712HLA-B35:12DSSLLINAM0.62960.8688615
CPEB4-NRCAMchr5173359503chr71078009372712HLA-B35:24DSSLLINAM0.97410.8314615
CPEB4-NRCAMchr5173359503chr71078009372712HLA-B35:77DSSLLINAM0.94210.846615
CPEB4-NRCAMchr5173359503chr71078009372712HLA-B35:23DSSLLINAM0.93640.7972615
CPEB4-NRCAMchr5173359503chr71078009372712HLA-B35:09DSSLLINAM0.62960.8688615
CPEB4-NRCAMchr5173359503chr71078009372712HLA-B18:07DSSLLINAM0.40980.8446615

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Potential FusionNeoAntigen Information of CPEB4-NRCAM 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.
CPEB4-NRCAM_173359503_107800937.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)
CPEB4-NRCAMchr5173359503chr71078009372712DRB1-0102SLLINAMASRQVDIA823
CPEB4-NRCAMchr5173359503chr71078009372712DRB1-0102SSLLINAMASRQVDI722
CPEB4-NRCAMchr5173359503chr71078009372712DRB1-0123SLLINAMASRQVDIA823
CPEB4-NRCAMchr5173359503chr71078009372712DRB1-0123SSLLINAMASRQVDI722
CPEB4-NRCAMchr5173359503chr71078009372712DRB1-0303DSSLLINAMASRQVD621
CPEB4-NRCAMchr5173359503chr71078009372712DRB1-1510SLLINAMASRQVDIA823
CPEB4-NRCAMchr5173359503chr71078009372712DRB1-1521SLLINAMASRQVDIA823
CPEB4-NRCAMchr5173359503chr71078009372712DRB1-1535SLLINAMASRQVDIA823
CPEB4-NRCAMchr5173359503chr71078009372712DRB1-1615SLLINAMASRQVDIA823
CPEB4-NRCAMchr5173359503chr71078009372712DRB1-1615SSLLINAMASRQVDI722
CPEB4-NRCAMchr5173359503chr71078009372712DRB1-1615DSSLLINAMASRQVD621

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Fusion breakpoint peptide structures of CPEB4-NRCAM

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
1423DSSLLINAMASRQVCPEB4NRCAMchr5173359503chr71078009372712

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CPEB4-NRCAM

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-B53:011A1O1423DSSLLINAMASRQV-1.20162-2.23692
HLA-B51:011E281423DSSLLINAMASRQV-4.67742-5.71272
HLA-B57:032BVO1423DSSLLINAMASRQV-3.57384-3.68724
HLA-A03:012XPG1423DSSLLINAMASRQV-2.81241-3.84771
HLA-A03:012XPG1423DSSLLINAMASRQV-2.75108-2.86448
HLA-B14:023BVN1423DSSLLINAMASRQV-6.6298-6.7432
HLA-B14:023BVN1423DSSLLINAMASRQV-5.03588-6.07118
HLA-B27:093CZF1423DSSLLINAMASRQV-2.72034-3.75564
HLA-B44:033DX71423DSSLLINAMASRQV-0.953592-1.98889
HLA-B52:013W391423DSSLLINAMASRQV-5.17052-5.28392
HLA-B52:013W391423DSSLLINAMASRQV-2.67174-3.70704
HLA-B18:014JQV1423DSSLLINAMASRQV-3.88279-3.99619
HLA-B18:014JQV1423DSSLLINAMASRQV-2.06796-3.10326
HLA-A11:014UQ21423DSSLLINAMASRQV-8.93359-9.04699
HLA-A11:014UQ21423DSSLLINAMASRQV-8.08854-9.12384
HLA-A24:025HGA1423DSSLLINAMASRQV-6.7667-6.8801
HLA-A24:025HGA1423DSSLLINAMASRQV-4.92764-5.96294
HLA-B57:015VUD1423DSSLLINAMASRQV-2.30317-3.33847
HLA-B27:056PYJ1423DSSLLINAMASRQV-4.30074-4.41414
HLA-B27:056PYJ1423DSSLLINAMASRQV-2.70769-3.74299
HLA-B27:036PZ51423DSSLLINAMASRQV-3.25646-4.29176
HLA-B27:036PZ51423DSSLLINAMASRQV-1.00133-1.11473
HLA-B44:053DX81423DSSLLINAMASRQV-5.00036-5.11376
HLA-B44:053DX81423DSSLLINAMASRQV-4.13613-5.17143
HLA-B07:025EO01423DSSLLINAMASRQV-1.03752-2.07282
HLA-A02:016TDR1423DSSLLINAMASRQV-5.74233-6.77763

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Vaccine Design for the FusionNeoAntigens of CPEB4-NRCAM

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
CPEB4-NRCAMchr5173359503chr71078009371220NAMASRQVATGCGATGGCAAGCCGGCAGGTGG
CPEB4-NRCAMchr5173359503chr7107800937615DSSLLINAMATAGCTCTCTGCTTATTAATGCGATGG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
CPEB4-NRCAMchr5173359503chr7107800937621DSSLLINAMASRQVDATAGCTCTCTGCTTATTAATGCGATGGCAAGCCGGCAGGTGGATA
CPEB4-NRCAMchr5173359503chr7107800937722SSLLINAMASRQVDIGCTCTCTGCTTATTAATGCGATGGCAAGCCGGCAGGTGGATATTG
CPEB4-NRCAMchr5173359503chr7107800937823SLLINAMASRQVDIACTCTGCTTATTAATGCGATGGCAAGCCGGCAGGTGGATATTGCAA

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Information of the samples that have these potential fusion neoantigens of CPEB4-NRCAM

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
GBMCPEB4-NRCAMchr5173359503ENST00000265085chr7107800937ENST00000351718TCGA-14-1823-01A

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Potential target of CAR-T therapy development for CPEB4-NRCAM

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
TgeneNRCAMchr5:173359503chr7:107800937ENST0000035171824281168_119001184.0TransmembraneHelical
TgeneNRCAMchr5:173359503chr7:107800937ENST0000037902426301168_119001193.0TransmembraneHelical
TgeneNRCAMchr5:173359503chr7:107800937ENST0000037902829331168_119001305.0TransmembraneHelical
TgeneNRCAMchr5:173359503chr7:107800937ENST0000042565126301168_119001305.0TransmembraneHelical

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 CPEB4-NRCAM

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 CPEB4-NRCAM

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