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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:PRKCA-CDH8

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PRKCA-CDH8
FusionPDB ID: 68695
FusionGDB2.0 ID: 68695
HgeneTgene
Gene symbol

PRKCA

CDH8

Gene ID

5578

1006

Gene nameprotein kinase C alphacadherin 8
SynonymsAAG6|PKC-alpha|PKCA|PKCI+/-|PKCalpha|PRKACANbla04261
Cytomap

17q24.2

16q21

Type of geneprotein-codingprotein-coding
Descriptionprotein kinase C alpha typePKC-Aaging-associated gene 6cadherin-8cadherin 8, type 2
Modification date2020032720200313
UniProtAcc

PICK1

Main function of 5'-partner protein: 415

P55286

Main function of 5'-partner protein: FUNCTION: Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types.
Ensembl transtripts involved in fusion geneENST idsENST00000413366, ENST00000583361, 
ENST00000580044, ENST00000299345, 
ENST00000577390, ENST00000577730, 
ENST00000584337, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score44 X 23 X 14=141686 X 4 X 4=96
# samples 466
** MAII scorelog2(46/14168*10)=-4.94485844580754
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(6/96*10)=-0.678071905112638
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: PRKCA [Title/Abstract] AND CDH8 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PRKCA [Title/Abstract] AND CDH8 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PRKCA(64685165)-CDH8(61935377), # samples:3
Anticipated loss of major functional domain due to fusion event.PRKCA-CDH8 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.
PRKCA-CDH8 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.
PRKCA-CDH8 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.
PRKCA-CDH8 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
HgenePRKCA

GO:0006468

protein phosphorylation

10770950

HgenePRKCA

GO:0035408

histone H3-T6 phosphorylation

20228790

HgenePRKCA

GO:0043536

positive regulation of blood vessel endothelial cell migration

20011604

HgenePRKCA

GO:0090330

regulation of platelet aggregation

12724315



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/chr17:64685165/chr16:61935377)
- 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 PRKCA (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 CDH8 (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)
ENST00000413366PRKCAchr1764685165+ENST00000577730CDH8chr1661935377-8502944142926970
ENST00000413366PRKCAchr1764685165+ENST00000299345CDH8chr1661935377-3465944142929971
ENST00000413366PRKCAchr1764685165+ENST00000577390CDH8chr1661935377-94589441430911025
ENST00000413366PRKCAchr1764685165+ENST00000584337CDH8chr1661935377-4156944142290758

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
ENST00000413366ENST00000577730PRKCAchr1764685165+CDH8chr1661935377-0.0001032640.99989676
ENST00000413366ENST00000299345PRKCAchr1764685165+CDH8chr1661935377-0.000285820.9997142
ENST00000413366ENST00000577390PRKCAchr1764685165+CDH8chr1661935377-0.0001382230.9998617
ENST00000413366ENST00000584337PRKCAchr1764685165+CDH8chr1661935377-0.0003763660.99962366

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 PRKCA-CDH8

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
PRKCAchr1764685165CDH8chr1661935377944308EGDEEGNMELRQKFELHTDLDPGSKK

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Potential FusionNeoAntigen Information of PRKCA-CDH8 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.
PRKCA-CDH8_64685165_61935377.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)
PRKCA-CDH8chr1764685165chr1661935377944HLA-B08:01ELRQKFEL0.99990.6982816
PRKCA-CDH8chr1764685165chr1661935377944HLA-B08:09ELRQKFEL0.99980.6284816
PRKCA-CDH8chr1764685165chr1661935377944HLA-B39:01QKFELHTDL0.99280.90471120
PRKCA-CDH8chr1764685165chr1661935377944HLA-B39:24QKFELHTDL0.99240.63331120
PRKCA-CDH8chr1764685165chr1661935377944HLA-B13:01MELRQKFEL0.99240.9306716
PRKCA-CDH8chr1764685165chr1661935377944HLA-B38:02QKFELHTDL0.9890.961120
PRKCA-CDH8chr1764685165chr1661935377944HLA-B44:03MELRQKFEL0.98710.9556716
PRKCA-CDH8chr1764685165chr1661935377944HLA-B47:01MELRQKFEL0.98460.6521716
PRKCA-CDH8chr1764685165chr1661935377944HLA-B39:13QKFELHTDL0.97990.91541120
PRKCA-CDH8chr1764685165chr1661935377944HLA-B18:01MELRQKFEL0.97160.8727716
PRKCA-CDH8chr1764685165chr1661935377944HLA-B14:02QKFELHTDL0.94730.69981120
PRKCA-CDH8chr1764685165chr1661935377944HLA-B14:01QKFELHTDL0.94730.69981120
PRKCA-CDH8chr1764685165chr1661935377944HLA-B41:01MELRQKFEL0.91530.9865716
PRKCA-CDH8chr1764685165chr1661935377944HLA-B39:13MELRQKFEL0.73940.9661716
PRKCA-CDH8chr1764685165chr1661935377944HLA-B15:10QKFELHTDL0.72970.6641120
PRKCA-CDH8chr1764685165chr1661935377944HLA-B48:01QKFELHTDL0.67390.56851120
PRKCA-CDH8chr1764685165chr1661935377944HLA-B15:37QKFELHTDL0.47670.62311120
PRKCA-CDH8chr1764685165chr1661935377944HLA-B48:01RQKFELHTDL0.96910.53331020
PRKCA-CDH8chr1764685165chr1661935377944HLA-B13:02RQKFELHTDL0.59910.54571020
PRKCA-CDH8chr1764685165chr1661935377944HLA-B13:01RQKFELHTDL0.54630.77771020
PRKCA-CDH8chr1764685165chr1661935377944HLA-B44:03EEGNMELRQKF0.99980.898314
PRKCA-CDH8chr1764685165chr1661935377944HLA-B18:01EEGNMELRQKF0.99330.818314
PRKCA-CDH8chr1764685165chr1661935377944HLA-B40:06MELRQKFEL0.99950.6837716
PRKCA-CDH8chr1764685165chr1661935377944HLA-B39:09QKFELHTDL0.99320.67721120
PRKCA-CDH8chr1764685165chr1661935377944HLA-B39:12QKFELHTDL0.99120.91891120
PRKCA-CDH8chr1764685165chr1661935377944HLA-B39:05QKFELHTDL0.9830.89941120
PRKCA-CDH8chr1764685165chr1661935377944HLA-B39:08MELRQKFEL0.7890.9355716
PRKCA-CDH8chr1764685165chr1661935377944HLA-B14:03QKFELHTDL0.36670.81271120
PRKCA-CDH8chr1764685165chr1661935377944HLA-B15:04RQKFELHTDL0.97150.75831020
PRKCA-CDH8chr1764685165chr1661935377944HLA-B15:07RQKFELHTDL0.96820.65571020
PRKCA-CDH8chr1764685165chr1661935377944HLA-B08:18ELRQKFEL0.99990.6982816
PRKCA-CDH8chr1764685165chr1661935377944HLA-B08:12ELRQKFEL0.99060.7869816
PRKCA-CDH8chr1764685165chr1661935377944HLA-B40:04MELRQKFEL0.99920.7336716
PRKCA-CDH8chr1764685165chr1661935377944HLA-B39:02QKFELHTDL0.99370.91721120
PRKCA-CDH8chr1764685165chr1661935377944HLA-B39:31QKFELHTDL0.99310.91961120
PRKCA-CDH8chr1764685165chr1661935377944HLA-B44:13MELRQKFEL0.98710.9556716
PRKCA-CDH8chr1764685165chr1661935377944HLA-B44:07MELRQKFEL0.98710.9556716
PRKCA-CDH8chr1764685165chr1661935377944HLA-B44:26MELRQKFEL0.98710.9556716
PRKCA-CDH8chr1764685165chr1661935377944HLA-B18:08MELRQKFEL0.97250.8614716
PRKCA-CDH8chr1764685165chr1661935377944HLA-B18:06MELRQKFEL0.97210.8787716
PRKCA-CDH8chr1764685165chr1661935377944HLA-B18:05MELRQKFEL0.97160.8727716
PRKCA-CDH8chr1764685165chr1661935377944HLA-B18:03MELRQKFEL0.96610.8657716
PRKCA-CDH8chr1764685165chr1661935377944HLA-B41:03MELRQKFEL0.90090.7767716
PRKCA-CDH8chr1764685165chr1661935377944HLA-B39:31MELRQKFEL0.85670.9651716
PRKCA-CDH8chr1764685165chr1661935377944HLA-B18:11MELRQKFEL0.82680.9235716
PRKCA-CDH8chr1764685165chr1661935377944HLA-B39:02MELRQKFEL0.82660.9685716
PRKCA-CDH8chr1764685165chr1661935377944HLA-B39:11MELRQKFEL0.79090.9456716
PRKCA-CDH8chr1764685165chr1661935377944HLA-B15:09QKFELHTDL0.65210.68821120
PRKCA-CDH8chr1764685165chr1661935377944HLA-B15:73RQKFELHTDL0.97170.70631020
PRKCA-CDH8chr1764685165chr1661935377944HLA-B15:68RQKFELHTDL0.97020.61351020
PRKCA-CDH8chr1764685165chr1661935377944HLA-B15:30RQKFELHTDL0.9350.84241020
PRKCA-CDH8chr1764685165chr1661935377944HLA-B15:35RQKFELHTDL0.9270.731020
PRKCA-CDH8chr1764685165chr1661935377944HLA-B40:21RQKFELHTDL0.54520.53051020
PRKCA-CDH8chr1764685165chr1661935377944HLA-B44:13EEGNMELRQKF0.99980.898314
PRKCA-CDH8chr1764685165chr1661935377944HLA-B44:26EEGNMELRQKF0.99980.898314
PRKCA-CDH8chr1764685165chr1661935377944HLA-B44:07EEGNMELRQKF0.99980.898314
PRKCA-CDH8chr1764685165chr1661935377944HLA-B18:11EEGNMELRQKF0.99820.7701314
PRKCA-CDH8chr1764685165chr1661935377944HLA-B18:06EEGNMELRQKF0.99410.8381314
PRKCA-CDH8chr1764685165chr1661935377944HLA-B18:08EEGNMELRQKF0.99410.8619314
PRKCA-CDH8chr1764685165chr1661935377944HLA-B18:03EEGNMELRQKF0.99380.8063314
PRKCA-CDH8chr1764685165chr1661935377944HLA-B18:05EEGNMELRQKF0.99330.818314

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Potential FusionNeoAntigen Information of PRKCA-CDH8 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.
PRKCA-CDH8_64685165_61935377.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)
PRKCA-CDH8chr1764685165chr1661935377944DRB1-0422QKFELHTDLDPGSKK1126

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Fusion breakpoint peptide structures of PRKCA-CDH8

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
6268NMELRQKFELHTDLPRKCACDH8chr1764685165chr1661935377944

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PRKCA-CDH8

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-B14:023BVN6268NMELRQKFELHTDL-7.9962-8.1096
HLA-B14:023BVN6268NMELRQKFELHTDL-5.70842-6.74372
HLA-B52:013W396268NMELRQKFELHTDL-6.83737-6.95077
HLA-B52:013W396268NMELRQKFELHTDL-4.4836-5.5189
HLA-A11:014UQ26268NMELRQKFELHTDL-10.0067-10.1201
HLA-A11:014UQ26268NMELRQKFELHTDL-9.03915-10.0745
HLA-A24:025HGA6268NMELRQKFELHTDL-6.56204-6.67544
HLA-A24:025HGA6268NMELRQKFELHTDL-5.42271-6.45801
HLA-B44:053DX86268NMELRQKFELHTDL-7.85648-8.89178
HLA-B44:053DX86268NMELRQKFELHTDL-5.3978-5.5112
HLA-A02:016TDR6268NMELRQKFELHTDL-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of PRKCA-CDH8

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
PRKCA-CDH8chr1764685165chr16619353771020RQKFELHTDLAAATTCGAGCTACACACAGACCTGGATCCT
PRKCA-CDH8chr1764685165chr16619353771120QKFELHTDLTTCGAGCTACACACAGACCTGGATCCT
PRKCA-CDH8chr1764685165chr1661935377314EEGNMELRQKFGGAAACATGGAACTCAGGCAGAAATTCGAGCTA
PRKCA-CDH8chr1764685165chr1661935377716MELRQKFELCTCAGGCAGAAATTCGAGCTACACACA
PRKCA-CDH8chr1764685165chr1661935377816ELRQKFELAGGCAGAAATTCGAGCTACACACA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
PRKCA-CDH8chr1764685165chr16619353771126QKFELHTDLDPGSKKTTCGAGCTACACACAGACCTGGATCCTGGGAGCAAAAAAATCAAG

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Information of the samples that have these potential fusion neoantigens of PRKCA-CDH8

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
BRCAPRKCA-CDH8chr1764685165ENST00000413366chr1661935377ENST00000299345TCGA-AC-A5XU-01A

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Potential target of CAR-T therapy development for PRKCA-CDH8

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
TgeneCDH8chr17:64685165chr16:61935377ENST00000577390112622_6420800.0TransmembraneHelical

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 PRKCA-CDH8

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 PRKCA-CDH8

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