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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:PRKDC-MYO5A

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PRKDC-MYO5A
FusionPDB ID: 68839
FusionGDB2.0 ID: 68839
HgeneTgene
Gene symbol

PRKDC

MYO5A

Gene ID

5591

4644

Gene nameprotein kinase, DNA-activated, catalytic subunitmyosin VA
SynonymsDNA-PKC|DNA-PKcs|DNAPK|DNAPKc|DNPK1|HYRC|HYRC1|IMD26|XRCC7|p350GS1|MYH12|MYO5|MYR12
Cytomap

8q11.21

15q21.2

Type of geneprotein-codingprotein-coding
DescriptionDNA-dependent protein kinase catalytic subunitDNA-PK catalytic subunithyper-radiosensitivity of murine scid mutation, complementing 1p460protein kinase, DNA-activated, catalytic polypeptideunconventional myosin-Vadilute myosin heavy chain, non-musclemyosin Vmyosin VA (heavy chain 12, myoxin)myosin, heavy polypeptide kinasemyosin-12myosin-Vamyoxin
Modification date2020032220200313
UniProtAcc.

Q9Y4I1

Main function of 5'-partner protein: FUNCTION: Processive actin-based motor that can move in large steps approximating the 36-nm pseudo-repeat of the actin filament. Involved in melanosome transport. Also mediates the transport of vesicles to the plasma membrane. May also be required for some polarization process involved in dendrite formation. {ECO:0000269|PubMed:10448864}.
Ensembl transtripts involved in fusion geneENST idsENST00000523565, ENST00000314191, 
ENST00000338368, 
ENST00000356338, 
ENST00000358212, ENST00000399231, 
ENST00000399233, ENST00000553916, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score24 X 28 X 10=672013 X 14 X 7=1274
# samples 2813
** MAII scorelog2(28/6720*10)=-4.58496250072116
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(13/1274*10)=-3.29278174922785
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: PRKDC [Title/Abstract] AND MYO5A [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PRKDC [Title/Abstract] AND MYO5A [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PRKDC(48730011)-MYO5A(52667657), # samples:2
Anticipated loss of major functional domain due to fusion event.PRKDC-MYO5A 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-MYO5A 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-MYO5A 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-MYO5A 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
HgenePRKDC

GO:0002218

activation of innate immune response

28712728

HgenePRKDC

GO:0006468

protein phosphorylation

26237645

HgenePRKDC

GO:0006974

cellular response to DNA damage stimulus

26237645

HgenePRKDC

GO:0018105

peptidyl-serine phosphorylation

15194694|19303849

HgenePRKDC

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/chr8:48730011/chr15:52667657)
- 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 PRKDC (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 MYO5A (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)
ENST00000338368PRKDCchr848730011-ENST00000399231MYO5Achr1552667657-19172961157127584233
ENST00000338368PRKDCchr848730011-ENST00000356338MYO5Achr1552667657-19088961157126774206
ENST00000338368PRKDCchr848730011-ENST00000358212MYO5Achr1552667657-19242961157128334258
ENST00000338368PRKDCchr848730011-ENST00000399233MYO5Achr1552667657-19158961157127494230
ENST00000338368PRKDCchr848730011-ENST00000553916MYO5Achr1552667657-13145961157127524231
ENST00000314191PRKDCchr848730011-ENST00000399231MYO5Achr1552667657-19172961157127584233
ENST00000314191PRKDCchr848730011-ENST00000356338MYO5Achr1552667657-19088961157126774206
ENST00000314191PRKDCchr848730011-ENST00000358212MYO5Achr1552667657-19242961157128334258
ENST00000314191PRKDCchr848730011-ENST00000399233MYO5Achr1552667657-19158961157127494230
ENST00000314191PRKDCchr848730011-ENST00000553916MYO5Achr1552667657-13145961157127524231

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
ENST00000338368ENST00000399231PRKDCchr848730011-MYO5Achr1552667657-0.0001479950.99985194
ENST00000338368ENST00000356338PRKDCchr848730011-MYO5Achr1552667657-0.0001999060.99980015
ENST00000338368ENST00000358212PRKDCchr848730011-MYO5Achr1552667657-0.0001341870.9998658
ENST00000338368ENST00000399233PRKDCchr848730011-MYO5Achr1552667657-0.0002699480.99973005
ENST00000338368ENST00000553916PRKDCchr848730011-MYO5Achr1552667657-0.0009038430.99909616
ENST00000314191ENST00000399231PRKDCchr848730011-MYO5Achr1552667657-0.0001479950.99985194
ENST00000314191ENST00000356338PRKDCchr848730011-MYO5Achr1552667657-0.0001999060.99980015
ENST00000314191ENST00000358212PRKDCchr848730011-MYO5Achr1552667657-0.0001341870.9998658
ENST00000314191ENST00000399233PRKDCchr848730011-MYO5Achr1552667657-0.0002699480.99973005
ENST00000314191ENST00000553916PRKDCchr848730011-MYO5Achr1552667657-0.0009038430.99909616

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 PRKDC-MYO5A

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
PRKDCchr848730011MYO5Achr155266765796113185DPMNIWDDIITNRYAKFLRRTKAATI

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Potential FusionNeoAntigen Information of PRKDC-MYO5A 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.
PRKDC-MYO5A_48730011_52667657.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)
PRKDC-MYO5Achr848730011chr15526676579611HLA-B18:01DDIITNRY0.99890.9065614
PRKDC-MYO5Achr848730011chr15526676579611HLA-B27:05NRYAKFLRR0.99910.92541120
PRKDC-MYO5Achr848730011chr15526676579611HLA-B27:04NRYAKFLRR0.99690.78341120
PRKDC-MYO5Achr848730011chr15526676579611HLA-B27:14NRYAKFLRR0.9990.85391120
PRKDC-MYO5Achr848730011chr15526676579611HLA-C15:06ITNRYAKFL0.98950.8789918
PRKDC-MYO5Achr848730011chr15526676579611HLA-B27:03NRYAKFLRR0.96410.9371120
PRKDC-MYO5Achr848730011chr15526676579611HLA-C04:07IWDDIITNRY0.99950.6064414
PRKDC-MYO5Achr848730011chr15526676579611HLA-C04:10IWDDIITNRY0.99940.5823414
PRKDC-MYO5Achr848730011chr15526676579611HLA-C04:14IWDDIITNRY0.85320.6352414
PRKDC-MYO5Achr848730011chr15526676579611HLA-B27:14NRYAKFLRRTK0.99910.80071122
PRKDC-MYO5Achr848730011chr15526676579611HLA-B15:31NIWDDIITNRY0.99740.7541314
PRKDC-MYO5Achr848730011chr15526676579611HLA-B18:04DDIITNRY0.99950.9169614
PRKDC-MYO5Achr848730011chr15526676579611HLA-B18:07DDIITNRY0.99920.8578614
PRKDC-MYO5Achr848730011chr15526676579611HLA-B18:05DDIITNRY0.99890.9065614
PRKDC-MYO5Achr848730011chr15526676579611HLA-B18:08DDIITNRY0.99890.7051614
PRKDC-MYO5Achr848730011chr15526676579611HLA-B18:03DDIITNRY0.99860.8982614
PRKDC-MYO5Achr848730011chr15526676579611HLA-B18:06DDIITNRY0.99860.9065614
PRKDC-MYO5Achr848730011chr15526676579611HLA-B18:11DDIITNRY0.98870.8716614
PRKDC-MYO5Achr848730011chr15526676579611HLA-B27:10NRYAKFLRR0.99830.89651120
PRKDC-MYO5Achr848730011chr15526676579611HLA-C15:05ITNRYAKFL0.9870.8847918
PRKDC-MYO5Achr848730011chr15526676579611HLA-C15:02ITNRYAKFL0.98490.8473918
PRKDC-MYO5Achr848730011chr15526676579611HLA-B18:08WDDIITNRY0.95290.697514
PRKDC-MYO5Achr848730011chr15526676579611HLA-C16:02ITNRYAKFL0.79170.9891918
PRKDC-MYO5Achr848730011chr15526676579611HLA-C04:01IWDDIITNRY0.99950.6064414
PRKDC-MYO5Achr848730011chr15526676579611HLA-C18:01IWDDIITNRY0.99820.6125414
PRKDC-MYO5Achr848730011chr15526676579611HLA-A25:01DIITNRYAKF0.99140.8433717
PRKDC-MYO5Achr848730011chr15526676579611HLA-B27:10TNRYAKFLRR0.95750.90471020
PRKDC-MYO5Achr848730011chr15526676579611HLA-A30:01RYAKFLRRTK0.95210.9251222
PRKDC-MYO5Achr848730011chr15526676579611HLA-B27:10NRYAKFLRRTK0.99910.83261122

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Potential FusionNeoAntigen Information of PRKDC-MYO5A 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 PRKDC-MYO5A

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
1030DDIITNRYAKFLRRPRKDCMYO5Achr848730011chr15526676579611

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PRKDC-MYO5A

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-B14:023BVN1030DDIITNRYAKFLRR-6.00367-7.03897
HLA-B14:023BVN1030DDIITNRYAKFLRR-5.39279-5.50619
HLA-B52:013W391030DDIITNRYAKFLRR-6.37513-6.48853
HLA-B52:013W391030DDIITNRYAKFLRR-5.71942-6.75472
HLA-A11:014UQ21030DDIITNRYAKFLRR-11.5708-11.6842
HLA-A11:014UQ21030DDIITNRYAKFLRR-8.11091-9.14621
HLA-A24:025HGA1030DDIITNRYAKFLRR-6.75661-6.87001
HLA-A24:025HGA1030DDIITNRYAKFLRR-5.30147-6.33677
HLA-B27:056PYJ1030DDIITNRYAKFLRR-4.27108-5.30638
HLA-B44:053DX81030DDIITNRYAKFLRR-6.47731-6.59071
HLA-B44:053DX81030DDIITNRYAKFLRR-3.23433-4.26963
HLA-B35:011A1N1030DDIITNRYAKFLRR-7.64663-7.76003
HLA-B35:011A1N1030DDIITNRYAKFLRR-5.01336-6.04866

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Vaccine Design for the FusionNeoAntigens of PRKDC-MYO5A

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
PRKDC-MYO5Achr848730011chr15526676571020TNRYAKFLRRCACAAATCGCTATGCTAAGTTTCTGCGCAG
PRKDC-MYO5Achr848730011chr15526676571120NRYAKFLRRAAATCGCTATGCTAAGTTTCTGCGCAG
PRKDC-MYO5Achr848730011chr15526676571122NRYAKFLRRTKAAATCGCTATGCTAAGTTTCTGCGCAGAACCAA
PRKDC-MYO5Achr848730011chr15526676571222RYAKFLRRTKTCGCTATGCTAAGTTTCTGCGCAGAACCAA
PRKDC-MYO5Achr848730011chr1552667657314NIWDDIITNRYGAACATCTGGGATGACATCATCACAAATCGCTA
PRKDC-MYO5Achr848730011chr1552667657414IWDDIITNRYCATCTGGGATGACATCATCACAAATCGCTA
PRKDC-MYO5Achr848730011chr1552667657514WDDIITNRYCTGGGATGACATCATCACAAATCGCTA
PRKDC-MYO5Achr848730011chr1552667657614DDIITNRYGGATGACATCATCACAAATCGCTA
PRKDC-MYO5Achr848730011chr1552667657717DIITNRYAKFTGACATCATCACAAATCGCTATGCTAAGTT
PRKDC-MYO5Achr848730011chr1552667657918ITNRYAKFLCATCACAAATCGCTATGCTAAGTTTCT

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 PRKDC-MYO5A

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
LUADPRKDC-MYO5Achr848730011ENST00000314191chr1552667657ENST00000356338TCGA-86-7713-01A

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Potential target of CAR-T therapy development for PRKDC-MYO5A

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 PRKDC-MYO5A

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 PRKDC-MYO5A

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
TgeneMYO5AC1836573GRISCELLI SYNDROME, TYPE 32GENOMICS_ENGLAND;ORPHANET
TgeneMYO5AC0023893Liver Cirrhosis, Experimental1CTD_human
TgeneMYO5AC0398794Hypopigmentation-immunodeficiency disease1GENOMICS_ENGLAND
TgeneMYO5AC1859194GRISCELLI SYNDROME, TYPE 11CTD_human;GENOMICS_ENGLAND;ORPHANET
TgeneMYO5AC1860157Elejalde Disease1GENOMICS_ENGLAND;ORPHANET
TgeneMYO5AC4721453Peripheral Nervous System Diseases1CTD_human