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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:PRKD2-CKM

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PRKD2-CKM
FusionPDB ID: 68812
FusionGDB2.0 ID: 68812
HgeneTgene
Gene symbol

PRKD2

CKM

Gene ID

25865

1158

Gene nameprotein kinase D2creatine kinase, M-type
SynonymsHSPC187|PKD2|nPKC-D2CKMM|CPK-M|M-CK
Cytomap

19q13.32

19q13.32

Type of geneprotein-codingprotein-coding
Descriptionserine/threonine-protein kinase D2creatine kinase M-typecreatine kinase M chaincreatine kinase, musclecreatine phosphokinase M-type
Modification date2020032920200313
UniProtAcc.

P12532

Main function of 5'-partner protein: FUNCTION: Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate). Creatine kinase isoenzymes play a central role in energy transduction in tissues with large, fluctuating energy demands, such as skeletal muscle, heart, brain and spermatozoa.
Ensembl transtripts involved in fusion geneENST idsENST00000595515, ENST00000600194, 
ENST00000601806, ENST00000291281, 
ENST00000433867, ENST00000593492, 
ENST00000221476, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score9 X 8 X 9=6486 X 5 X 5=150
# samples 116
** MAII scorelog2(11/648*10)=-2.55849028935997
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(6/150*10)=-1.32192809488736
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: PRKD2 [Title/Abstract] AND CKM [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PRKD2 [Title/Abstract] AND CKM [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PRKD2(47207426)-CKM(45815178), # samples:2
Anticipated loss of major functional domain due to fusion event.PRKD2-CKM 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.
PRKD2-CKM 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.
PRKD2-CKM 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.
PRKD2-CKM 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.
PRKD2-CKM seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
PRKD2-CKM seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
PRKD2-CKM seems lost the major protein functional domain in Hgene partner, which is a kinase due to the frame-shifted ORF.
PRKD2-CKM seems lost the major protein functional domain in Tgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
PRKD2-CKM seems lost the major protein functional domain in Tgene partner, which is a essential gene 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
HgenePRKD2

GO:0006468

protein phosphorylation

22228765

HgenePRKD2

GO:0018105

peptidyl-serine phosphorylation

18440775

HgenePRKD2

GO:0045944

positive regulation of transcription by RNA polymerase II

17077180

HgenePRKD2

GO:0046777

protein autophosphorylation

17077180

HgenePRKD2

GO:0050852

T cell receptor signaling pathway

17077180



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/chr19:47207426/chr19:45815178)
- 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 PRKD2 (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 CKM (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)
ENST00000291281PRKD2chr1947207426-ENST00000221476CKMchr1945815178-211611151271779550
ENST00000433867PRKD2chr1947207426-ENST00000221476CKMchr1945815178-236813672172031604

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
ENST00000291281ENST00000221476PRKD2chr1947207426-CKMchr1945815178-0.053637530.9463625
ENST00000433867ENST00000221476PRKD2chr1947207426-CKMchr1945815178-0.054583810.9454162

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 PRKD2-CKM

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
PRKD2chr1947207426CKMchr19458151781115329LLKGLFRQGLQCKALNSLTGEFKGKY
PRKD2chr1947207426CKMchr19458151781367383LLKGLFRQGLQCKALNSLTGEFKGKY

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Potential FusionNeoAntigen Information of PRKD2-CKM 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.
PRKD2-CKM_47207426_45815178.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)
PRKD2-CKMchr1947207426chr19458151781115HLA-B48:01RQGLQCKAL0.93610.7581615
PRKD2-CKMchr1947207426chr19458151781115HLA-B39:13LQCKALNSL0.60090.8652918
PRKD2-CKMchr1947207426chr19458151781115HLA-B13:02LQCKALNSL0.40690.508918
PRKD2-CKMchr1947207426chr19458151781115HLA-B13:01LQCKALNSL0.31880.9411918
PRKD2-CKMchr1947207426chr19458151781115HLA-B57:03KALNSLTGEF0.9980.98511222
PRKD2-CKMchr1947207426chr19458151781115HLA-B15:04LQCKALNSL0.98010.6433918
PRKD2-CKMchr1947207426chr19458151781115HLA-B39:12FRQGLQCKAL0.97610.9325515
PRKD2-CKMchr1947207426chr19458151781115HLA-B15:73LQCKALNSL0.95480.7715918
PRKD2-CKMchr1947207426chr19458151781115HLA-B15:30LQCKALNSL0.86430.676918
PRKD2-CKMchr1947207426chr19458151781115HLA-B39:02LQCKALNSL0.7650.8702918
PRKD2-CKMchr1947207426chr19458151781115HLA-B57:02KALNSLTGEF0.95950.96081222

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Potential FusionNeoAntigen Information of PRKD2-CKM 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 PRKD2-CKM

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
8126RQGLQCKALNSLTGPRKD2CKMchr1947207426chr19458151781115

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PRKD2-CKM

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-B14:023BVN8126RQGLQCKALNSLTG-7.15543-7.26883
HLA-B14:023BVN8126RQGLQCKALNSLTG-4.77435-5.80965
HLA-B52:013W398126RQGLQCKALNSLTG-6.80875-6.92215
HLA-B52:013W398126RQGLQCKALNSLTG-4.20386-5.23916
HLA-A11:014UQ28126RQGLQCKALNSLTG-7.5194-8.5547
HLA-A11:014UQ28126RQGLQCKALNSLTG-6.9601-7.0735
HLA-A24:025HGA8126RQGLQCKALNSLTG-7.52403-7.63743
HLA-A24:025HGA8126RQGLQCKALNSLTG-5.82433-6.85963
HLA-B27:056PYJ8126RQGLQCKALNSLTG-3.28285-4.31815
HLA-B44:053DX88126RQGLQCKALNSLTG-5.91172-6.94702
HLA-B44:053DX88126RQGLQCKALNSLTG-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of PRKD2-CKM

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
PRKD2-CKMchr1947207426chr19458151781222KALNSLTGEFAAGCTCTCAACAGCCTGACGGGCGAGTTCA
PRKD2-CKMchr1947207426chr1945815178515FRQGLQCKALTCCGGCAGGGCCTGCAATGCAAAGCTCTCA
PRKD2-CKMchr1947207426chr1945815178615RQGLQCKALGGCAGGGCCTGCAATGCAAAGCTCTCA
PRKD2-CKMchr1947207426chr1945815178918LQCKALNSLTGCAATGCAAAGCTCTCAACAGCCTGA

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 PRKD2-CKM

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
BRCAPRKD2-CKMchr1947207426ENST00000291281chr1945815178ENST00000221476TCGA-BH-A0HX-01A

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Potential target of CAR-T therapy development for PRKD2-CKM

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 PRKD2-CKM

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 PRKD2-CKM

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