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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:PDSS2-DCLK1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PDSS2-DCLK1
FusionPDB ID: 64082
FusionGDB2.0 ID: 64082
HgeneTgene
Gene symbol

PDSS2

DCLK1

Gene ID

57107

9201

Gene namedecaprenyl diphosphate synthase subunit 2doublecortin like kinase 1
SynonymsC6orf210|COQ10D3|COQ1B|DLP1|bA59I9.3|hDLP1CL1|CLICK1|DCAMKL1|DCDC3A|DCLK
Cytomap

6q21

13q13.3

Type of geneprotein-codingprotein-coding
Descriptiondecaprenyl-diphosphate synthase subunit 2all-trans-decaprenyl-diphosphate synthase subunit 2decaprenyl pyrophosphate synthase subunit 2decaprenyl pyrophosphate synthetase subunit 2prenyl (decaprenyl) diphosphate synthase, subunit 2subunit 2 of decaprserine/threonine-protein kinase DCLK1doublecortin domain-containing protein 3Adoublecortin-like and CAM kinase-like 1
Modification date2020031320200320
UniProtAcc.

O15075

Main function of 5'-partner protein: FUNCTION: Probable kinase that may be involved in a calcium-signaling pathway controlling neuronal migration in the developing brain. May also participate in functions of the mature nervous system.
Ensembl transtripts involved in fusion geneENST idsENST00000369031, ENST00000369037, 
ENST00000453874, 
ENST00000379892, 
ENST00000379893, ENST00000460982, 
ENST00000255448, ENST00000360631, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score11 X 8 X 6=52810 X 9 X 7=630
# samples 1310
** MAII scorelog2(13/528*10)=-2.02202630633
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(10/630*10)=-2.65535182861255
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: PDSS2 [Title/Abstract] AND DCLK1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PDSS2 [Title/Abstract] AND DCLK1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PDSS2(107595233)-DCLK1(36413313), # samples:1
Anticipated loss of major functional domain due to fusion event.PDSS2-DCLK1 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.
PDSS2-DCLK1 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.
PDSS2-DCLK1 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.
PDSS2-DCLK1 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
HgenePDSS2

GO:0006744

ubiquinone biosynthetic process

16262699

HgenePDSS2

GO:0008299

isoprenoid biosynthetic process

16262699



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/chr6:107595233/chr13:36413313)
- 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 PDSS2 (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 DCLK1 (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)
ENST00000369037PDSS2chr6107595233-ENST00000360631DCLK1chr1336413313-52909082092095628
ENST00000369037PDSS2chr6107595233-ENST00000255448DCLK1chr1336413313-53649082092062617
ENST00000453874PDSS2chr6107595233-ENST00000360631DCLK1chr1336413313-52839012022088628
ENST00000453874PDSS2chr6107595233-ENST00000255448DCLK1chr1336413313-53579012022055617
ENST00000369031PDSS2chr6107595233-ENST00000360631DCLK1chr1336413313-52919092102096628
ENST00000369031PDSS2chr6107595233-ENST00000255448DCLK1chr1336413313-53659092102063617

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
ENST00000369037ENST00000360631PDSS2chr6107595233-DCLK1chr1336413313-0.0008464520.9991535
ENST00000369037ENST00000255448PDSS2chr6107595233-DCLK1chr1336413313-0.0008402970.9991597
ENST00000453874ENST00000360631PDSS2chr6107595233-DCLK1chr1336413313-0.0008455430.99915445
ENST00000453874ENST00000255448PDSS2chr6107595233-DCLK1chr1336413313-0.0008395820.9991604
ENST00000369031ENST00000360631PDSS2chr6107595233-DCLK1chr1336413313-0.0008526670.9991473
ENST00000369031ENST00000255448PDSS2chr6107595233-DCLK1chr1336413313-0.0008464980.9991535

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 PDSS2-DCLK1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
PDSS2chr6107595233DCLK1chr1336413313901233NACNGLALLQNTKSSQHGGSSTSLAS
PDSS2chr6107595233DCLK1chr1336413313908233NACNGLALLQNTKSSQHGGSSTSLAS
PDSS2chr6107595233DCLK1chr1336413313909233NACNGLALLQNTKSSQHGGSSTSLAS

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Potential FusionNeoAntigen Information of PDSS2-DCLK1 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.
PDSS2-DCLK1_107595233_36413313.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)
PDSS2-DCLK1chr6107595233chr1336413313909HLA-B15:04LQNTKSSQH0.84460.6745817
PDSS2-DCLK1chr6107595233chr1336413313909HLA-B15:50LQNTKSSQH0.98880.6955817

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Potential FusionNeoAntigen Information of PDSS2-DCLK1 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 PDSS2-DCLK1

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
388ALLQNTKSSQHGGSPDSS2DCLK1chr6107595233chr1336413313909

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PDSS2-DCLK1

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-B14:023BVN388ALLQNTKSSQHGGS-6.93863-7.05203
HLA-B14:023BVN388ALLQNTKSSQHGGS-4.13527-5.17057
HLA-B52:013W39388ALLQNTKSSQHGGS-6.86405-6.97745
HLA-B52:013W39388ALLQNTKSSQHGGS-3.72209-4.75739
HLA-A24:025HGA388ALLQNTKSSQHGGS-8.23297-9.26827
HLA-A24:025HGA388ALLQNTKSSQHGGS-5.62477-5.73817
HLA-B27:056PYJ388ALLQNTKSSQHGGS-5.8772-6.9125
HLA-B44:053DX8388ALLQNTKSSQHGGS-6.50682-6.62022
HLA-B44:053DX8388ALLQNTKSSQHGGS-4.20591-5.24121

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Vaccine Design for the FusionNeoAntigens of PDSS2-DCLK1

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
PDSS2-DCLK1chr6107595233chr1336413313817LQNTKSSQHCTACAGAACACCAAGAGCTCTCAGCAT

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 PDSS2-DCLK1

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
GBMPDSS2-DCLK1chr6107595233ENST00000369031chr1336413313ENST00000255448TCGA-06-5415-01A

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Potential target of CAR-T therapy development for PDSS2-DCLK1

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 PDSS2-DCLK1

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 PDSS2-DCLK1

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