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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:SPIDR-PRKDC

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: SPIDR-PRKDC
FusionPDB ID: 85795
FusionGDB2.0 ID: 85795
HgeneTgene
Gene symbol

SPIDR

PRKDC

Gene ID

23514

5591

Gene namescaffold protein involved in DNA repairprotein kinase, DNA-activated, catalytic subunit
SynonymsKIAA0146DNA-PKC|DNA-PKcs|DNAPK|DNAPKc|DNPK1|HYRC|HYRC1|IMD26|XRCC7|p350
Cytomap

8q11.21

8q11.21

Type of geneprotein-codingprotein-coding
DescriptionDNA repair-scaffolding proteinscaffolding protein involved in DNA repairDNA-dependent protein kinase catalytic subunitDNA-PK catalytic subunithyper-radiosensitivity of murine scid mutation, complementing 1p460protein kinase, DNA-activated, catalytic polypeptide
Modification date2020032020200322
UniProtAcc

Q14159

Main function of 5'-partner protein: FUNCTION: Plays a role in DNA double-strand break (DBS) repair via homologous recombination (HR). Serves as a scaffolding protein that helps to promote the recruitment of DNA-processing enzymes like the helicase BLM and recombinase RAD51 to site of DNA damage, and hence contributes to maintain genomic integrity. {ECO:0000269|PubMed:23509288, ECO:0000269|PubMed:23754376}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000521214, ENST00000297423, 
ENST00000518074, ENST00000541342, 
ENST00000517693, ENST00000518060, 
ENST00000314191, ENST00000338368, 
ENST00000523565, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score24 X 12 X 15=432018 X 20 X 5=1800
# samples 2719
** MAII scorelog2(27/4320*10)=-4
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(19/1800*10)=-3.24392558288609
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: SPIDR [Title/Abstract] AND PRKDC [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: SPIDR [Title/Abstract] AND PRKDC [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PRKDC(48706851)-SPIDR(48508373), # samples:1
PRKDC(48730011)-SPIDR(48508373), # samples:1
PRKDC(48839754)-SPIDR(48508373), # samples:1
PRKDC(48746757)-SPIDR(48191858), # samples:1
SPIDR(48353104)-PRKDC(48686938), # samples:1
Anticipated loss of major functional domain due to fusion event.PRKDC-SPIDR 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.
PRKDC-SPIDR 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.
SPIDR-PRKDC 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.
SPIDR-PRKDC 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.
SPIDR-PRKDC 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.
SPIDR-PRKDC 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.
PRKDC-SPIDR seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF.
PRKDC-SPIDR seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
PRKDC-SPIDR seems lost the major protein functional domain in Hgene partner, which is a kinase due to the frame-shifted ORF.
PRKDC-SPIDR 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
HgeneSPIDR

GO:0006974

cellular response to DNA damage stimulus

23509288

HgeneSPIDR

GO:0010569

regulation of double-strand break repair via homologous recombination

23754376

HgeneSPIDR

GO:0031334

positive regulation of protein complex assembly

23509288

HgeneSPIDR

GO:0070202

regulation of establishment of protein localization to chromosome

23509288

HgeneSPIDR

GO:0071479

cellular response to ionizing radiation

23509288|23754376

HgeneSPIDR

GO:0072711

cellular response to hydroxyurea

23509288

HgeneSPIDR

GO:0072757

cellular response to camptothecin

23509288

TgenePRKDC

GO:0002218

activation of innate immune response

28712728

TgenePRKDC

GO:0006468

protein phosphorylation

26237645

TgenePRKDC

GO:0006974

cellular response to DNA damage stimulus

26237645

TgenePRKDC

GO:0018105

peptidyl-serine phosphorylation

15194694|19303849

TgenePRKDC

GO:2001034

positive regulation of double-strand break repair via nonhomologous end joining

26237645



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/chr8:48706851/chr8:48508373)
- 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 SPIDR (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 PRKDC (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)
ENST00000297423SPIDRchr848353104+ENST00000338368PRKDCchr848686938-27511481511685544
ENST00000297423SPIDRchr848353104+ENST00000314191PRKDCchr848686938-27511481511685544
ENST00000518074SPIDRchr848353104+ENST00000338368PRKDCchr848686938-235810881711292373
ENST00000518074SPIDRchr848353104+ENST00000314191PRKDCchr848686938-235810881711292373
ENST00000541342SPIDRchr848353104+ENST00000338368PRKDCchr848686938-230310331461237363
ENST00000541342SPIDRchr848353104+ENST00000314191PRKDCchr848686938-230310331461237363

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
ENST00000297423ENST00000338368SPIDRchr848353104+PRKDCchr848686938-0.0102499840.98974997
ENST00000297423ENST00000314191SPIDRchr848353104+PRKDCchr848686938-0.0102499840.98974997
ENST00000518074ENST00000338368SPIDRchr848353104+PRKDCchr848686938-0.0019513330.99804866
ENST00000518074ENST00000314191SPIDRchr848353104+PRKDCchr848686938-0.0019513330.99804866
ENST00000541342ENST00000338368SPIDRchr848353104+PRKDCchr848686938-0.0017189720.998281
ENST00000541342ENST00000314191SPIDRchr848353104+PRKDCchr848686938-0.0017189720.998281

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 SPIDR-PRKDC

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
SPIDRchr848353104PRKDCchr8486869381033296GRPQDTVRIFPPCDELLLGHEKAPAF
SPIDRchr848353104PRKDCchr8486869381088306GRPQDTVRIFPPCDELLLGHEKAPAF
SPIDRchr848353104PRKDCchr8486869381481477GRPQDTVRIFPPCDELLLGHEKAPAF

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Potential FusionNeoAntigen Information of SPIDR-PRKDC 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.
SPIDR-PRKDC_48353104_48686938.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)
SPIDR-PRKDCchr848353104chr8486869381481HLA-B35:03FPPCDELLL0.96750.9163918
SPIDR-PRKDCchr848353104chr8486869381481HLA-A02:17RIFPPCDEL0.92690.5384716
SPIDR-PRKDCchr848353104chr8486869381481HLA-B35:02FPPCDELLL0.88850.971918
SPIDR-PRKDCchr848353104chr8486869381481HLA-B35:04FPPCDELLL0.88850.971918
SPIDR-PRKDCchr848353104chr8486869381481HLA-B48:01RIFPPCDEL0.3240.5606716
SPIDR-PRKDCchr848353104chr8486869381481HLA-B13:01RIFPPCDEL0.13490.9887716
SPIDR-PRKDCchr848353104chr8486869381481HLA-B27:07VRIFPPCDEL0.99970.5811616
SPIDR-PRKDCchr848353104chr8486869381481HLA-B27:07VRIFPPCDELL0.99990.5953617
SPIDR-PRKDCchr848353104chr8486869381481HLA-A02:20RIFPPCDELLL0.90240.7256718
SPIDR-PRKDCchr848353104chr8486869381481HLA-C03:07RIFPPCDEL0.99650.9918716
SPIDR-PRKDCchr848353104chr8486869381481HLA-C03:19RIFPPCDEL0.99210.993716
SPIDR-PRKDCchr848353104chr8486869381481HLA-C03:08RIFPPCDEL0.99070.9592716
SPIDR-PRKDCchr848353104chr8486869381481HLA-A02:05RIFPPCDEL0.93640.5418716
SPIDR-PRKDCchr848353104chr8486869381481HLA-C08:13RIFPPCDEL0.90060.9912716
SPIDR-PRKDCchr848353104chr8486869381481HLA-C08:04RIFPPCDEL0.90060.9912716
SPIDR-PRKDCchr848353104chr8486869381481HLA-B35:12FPPCDELLL0.88850.971918
SPIDR-PRKDCchr848353104chr8486869381481HLA-B39:10FPPCDELLL0.54490.957918
SPIDR-PRKDCchr848353104chr8486869381481HLA-C04:14IFPPCDELL0.45220.8901817
SPIDR-PRKDCchr848353104chr8486869381481HLA-C04:10IFPPCDELL0.40210.8153817
SPIDR-PRKDCchr848353104chr8486869381481HLA-C04:07IFPPCDELL0.38610.852817
SPIDR-PRKDCchr848353104chr8486869381481HLA-C01:30IFPPCDELL0.15930.97817
SPIDR-PRKDCchr848353104chr8486869381481HLA-C01:17IFPPCDELL0.0940.9455817
SPIDR-PRKDCchr848353104chr8486869381481HLA-B48:03RIFPPCDEL0.05330.5416716
SPIDR-PRKDCchr848353104chr8486869381481HLA-C03:03RIFPPCDEL0.98880.9921716
SPIDR-PRKDCchr848353104chr8486869381481HLA-C03:04RIFPPCDEL0.98880.9921716
SPIDR-PRKDCchr848353104chr8486869381481HLA-C03:05RIFPPCDEL0.97950.9594716
SPIDR-PRKDCchr848353104chr8486869381481HLA-A32:01RIFPPCDEL0.97620.9798716
SPIDR-PRKDCchr848353104chr8486869381481HLA-C03:06RIFPPCDEL0.95880.9921716
SPIDR-PRKDCchr848353104chr8486869381481HLA-B15:73RIFPPCDEL0.94660.9853716
SPIDR-PRKDCchr848353104chr8486869381481HLA-A02:14RIFPPCDEL0.9210.7441716
SPIDR-PRKDCchr848353104chr8486869381481HLA-B15:30RIFPPCDEL0.90220.9815716
SPIDR-PRKDCchr848353104chr8486869381481HLA-B07:13RIFPPCDEL0.89320.8829716
SPIDR-PRKDCchr848353104chr8486869381481HLA-B35:09FPPCDELLL0.88850.971918
SPIDR-PRKDCchr848353104chr8486869381481HLA-B35:13RIFPPCDEL0.60660.9752716
SPIDR-PRKDCchr848353104chr8486869381481HLA-C17:01RIFPPCDEL0.56540.9846716
SPIDR-PRKDCchr848353104chr8486869381481HLA-C01:03RIFPPCDEL0.52360.9542716
SPIDR-PRKDCchr848353104chr8486869381481HLA-C04:04IFPPCDELL0.44780.9483817
SPIDR-PRKDCchr848353104chr8486869381481HLA-C04:01IFPPCDELL0.38610.852817
SPIDR-PRKDCchr848353104chr8486869381481HLA-C18:01IFPPCDELL0.3520.8519817
SPIDR-PRKDCchr848353104chr8486869381481HLA-C01:03IFPPCDELL0.15190.9303817
SPIDR-PRKDCchr848353104chr8486869381481HLA-B40:21RIFPPCDEL0.10570.5815716
SPIDR-PRKDCchr848353104chr8486869381481HLA-C01:02IFPPCDELL0.09580.94817
SPIDR-PRKDCchr848353104chr8486869381481HLA-B40:12RIFPPCDEL0.05330.5416716
SPIDR-PRKDCchr848353104chr8486869381481HLA-B27:08VRIFPPCDEL0.99990.7091616
SPIDR-PRKDCchr848353104chr8486869381481HLA-B27:06VRIFPPCDEL0.99980.8233616
SPIDR-PRKDCchr848353104chr8486869381481HLA-B27:09VRIFPPCDEL0.99960.771616
SPIDR-PRKDCchr848353104chr8486869381481HLA-B40:21RIFPPCDELL0.37440.6151717
SPIDR-PRKDCchr848353104chr8486869381481HLA-B27:09VRIFPPCDELL0.99990.7358617
SPIDR-PRKDCchr848353104chr8486869381481HLA-B27:06VRIFPPCDELL0.99990.8275617
SPIDR-PRKDCchr848353104chr8486869381481HLA-A32:01RIFPPCDELLL0.99780.9843718
SPIDR-PRKDCchr848353104chr8486869381481HLA-A02:14RIFPPCDELLL0.97010.7363718

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Potential FusionNeoAntigen Information of SPIDR-PRKDC 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 SPIDR-PRKDC

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
10234VRIFPPCDELLLGHSPIDRPRKDCchr848353104chr8486869381481

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of SPIDR-PRKDC

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-B14:023BVN10234VRIFPPCDELLLGH-7.15543-7.26883
HLA-B14:023BVN10234VRIFPPCDELLLGH-4.77435-5.80965
HLA-B52:013W3910234VRIFPPCDELLLGH-6.80875-6.92215
HLA-B52:013W3910234VRIFPPCDELLLGH-4.20386-5.23916
HLA-A11:014UQ210234VRIFPPCDELLLGH-7.5194-8.5547
HLA-A11:014UQ210234VRIFPPCDELLLGH-6.9601-7.0735
HLA-A24:025HGA10234VRIFPPCDELLLGH-7.52403-7.63743
HLA-A24:025HGA10234VRIFPPCDELLLGH-5.82433-6.85963
HLA-B27:056PYJ10234VRIFPPCDELLLGH-3.28285-4.31815
HLA-B44:053DX810234VRIFPPCDELLLGH-5.91172-6.94702
HLA-B44:053DX810234VRIFPPCDELLLGH-4.24346-4.35686
HLA-B35:011A1N10234VRIFPPCDELLLGH-5.9251-6.0385
HLA-B35:011A1N10234VRIFPPCDELLLGH-4.80237-5.83767

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Vaccine Design for the FusionNeoAntigens of SPIDR-PRKDC

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
SPIDR-PRKDCchr848353104chr848686938616VRIFPPCDELTGTCCGGATCTTCCCTCCCTGTGATGAGCT
SPIDR-PRKDCchr848353104chr848686938617VRIFPPCDELLTGTCCGGATCTTCCCTCCCTGTGATGAGCTACT
SPIDR-PRKDCchr848353104chr848686938716RIFPPCDELCCGGATCTTCCCTCCCTGTGATGAGCT
SPIDR-PRKDCchr848353104chr848686938717RIFPPCDELLCCGGATCTTCCCTCCCTGTGATGAGCTACT
SPIDR-PRKDCchr848353104chr848686938718RIFPPCDELLLCCGGATCTTCCCTCCCTGTGATGAGCTACTCCT
SPIDR-PRKDCchr848353104chr848686938817IFPPCDELLGATCTTCCCTCCCTGTGATGAGCTACT
SPIDR-PRKDCchr848353104chr848686938918FPPCDELLLCTTCCCTCCCTGTGATGAGCTACTCCT

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 SPIDR-PRKDC

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
STADSPIDR-PRKDCchr848353104ENST00000297423chr848686938ENST00000314191TCGA-B7-5816-01A

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Potential target of CAR-T therapy development for SPIDR-PRKDC

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 SPIDR-PRKDC

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 SPIDR-PRKDC

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