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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:PDXDC1-ATP2A1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PDXDC1-ATP2A1
FusionPDB ID: 64092
FusionGDB2.0 ID: 64092
HgeneTgene
Gene symbol

PDXDC1

ATP2A1

Gene ID

23042

487

Gene namepyridoxal dependent decarboxylase domain containing 1ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1
SynonymsLP8165ATP2A|SERCA1
Cytomap

16p13.11

16p11.2

Type of geneprotein-codingprotein-coding
Descriptionpyridoxal-dependent decarboxylase domain-containing protein 1sarcoplasmic/endoplasmic reticulum calcium ATPase 1ATPase, Ca++ transporting, cardiac muscle, fast twitch 1SR Ca(2+)-ATPase 1calcium pump 1calcium-transporting ATPase sarcoplasmic reticulum type, fast twitch skeletal muscle isoformendoplasmic reticul
Modification date2020031320200313
UniProtAcc.

O14983

Main function of 5'-partner protein: FUNCTION: Key regulator of striated muscle performance by acting as the major Ca(2+) ATPase responsible for the reuptake of cytosolic Ca(2+) into the sarcoplasmic reticulum. Catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen (By similarity). Contributes to calcium sequestration involved in muscular excitation/contraction (PubMed:10914677). {ECO:0000250|UniProtKB:P04191, ECO:0000269|PubMed:10914677}.
Ensembl transtripts involved in fusion geneENST idsENST00000396410, ENST00000450288, 
ENST00000455313, ENST00000535621, 
ENST00000569715, ENST00000325823, 
ENST00000447912, ENST00000563679, 
ENST00000565042, ENST00000357084, 
ENST00000395503, ENST00000536376, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score24 X 21 X 12=60482 X 2 X 2=8
# samples 272
** MAII scorelog2(27/6048*10)=-4.48542682717024
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(2/8*10)=1.32192809488736
Fusion gene context

PubMed: PDXDC1 [Title/Abstract] AND ATP2A1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PDXDC1 [Title/Abstract] AND ATP2A1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PDXDC1(15069077)-ATP2A1(28905476), # samples:1
Anticipated loss of major functional domain due to fusion event.PDXDC1-ATP2A1 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.
PDXDC1-ATP2A1 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
TgeneATP2A1

GO:0031448

positive regulation of fast-twitch skeletal muscle fiber contraction

12479237

TgeneATP2A1

GO:0090076

relaxation of skeletal muscle

8841193



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/chr16:15069077/chr16:28905476)
- 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 PDXDC1 (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 ATP2A1 (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)
ENST00000535621PDXDC1chr1615069077+ENST00000357084ATP2A1chr1628905476+2379209502119689
ENST00000535621PDXDC1chr1615069077+ENST00000395503ATP2A1chr1628905476+2466209502098682
ENST00000535621PDXDC1chr1615069077+ENST00000536376ATP2A1chr1628905476+2421209502098682
ENST00000455313PDXDC1chr1615069077+ENST00000357084ATP2A1chr1628905476+23111411202051643
ENST00000455313PDXDC1chr1615069077+ENST00000395503ATP2A1chr1628905476+23981411202030636
ENST00000455313PDXDC1chr1615069077+ENST00000536376ATP2A1chr1628905476+23531411202030636
ENST00000396410PDXDC1chr1615069077+ENST00000357084ATP2A1chr1628905476+2288118972028643
ENST00000396410PDXDC1chr1615069077+ENST00000395503ATP2A1chr1628905476+2375118972007636
ENST00000396410PDXDC1chr1615069077+ENST00000536376ATP2A1chr1628905476+2330118972007636
ENST00000569715PDXDC1chr1615069077+ENST00000357084ATP2A1chr1628905476+226898772008643
ENST00000569715PDXDC1chr1615069077+ENST00000395503ATP2A1chr1628905476+235598771987636
ENST00000569715PDXDC1chr1615069077+ENST00000536376ATP2A1chr1628905476+231098771987636
ENST00000450288PDXDC1chr1615069077+ENST00000357084ATP2A1chr1628905476+226292712002643
ENST00000450288PDXDC1chr1615069077+ENST00000395503ATP2A1chr1628905476+234992711981636
ENST00000450288PDXDC1chr1615069077+ENST00000536376ATP2A1chr1628905476+230492711981636

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
ENST00000535621ENST00000357084PDXDC1chr1615069077+ATP2A1chr1628905476+0.0045648090.9954352
ENST00000535621ENST00000395503PDXDC1chr1615069077+ATP2A1chr1628905476+0.0040465360.99595344
ENST00000535621ENST00000536376PDXDC1chr1615069077+ATP2A1chr1628905476+0.0040970380.99590296
ENST00000455313ENST00000357084PDXDC1chr1615069077+ATP2A1chr1628905476+0.004127080.9958729
ENST00000455313ENST00000395503PDXDC1chr1615069077+ATP2A1chr1628905476+0.0036204020.9963797
ENST00000455313ENST00000536376PDXDC1chr1615069077+ATP2A1chr1628905476+0.0036842890.9963158
ENST00000396410ENST00000357084PDXDC1chr1615069077+ATP2A1chr1628905476+0.0041053920.9958947
ENST00000396410ENST00000395503PDXDC1chr1615069077+ATP2A1chr1628905476+0.0035669060.99643314
ENST00000396410ENST00000536376PDXDC1chr1615069077+ATP2A1chr1628905476+0.0036608950.9963391
ENST00000569715ENST00000357084PDXDC1chr1615069077+ATP2A1chr1628905476+0.003961570.99603844
ENST00000569715ENST00000395503PDXDC1chr1615069077+ATP2A1chr1628905476+0.003442560.9965575
ENST00000569715ENST00000536376PDXDC1chr1615069077+ATP2A1chr1628905476+0.003535270.9964647
ENST00000450288ENST00000357084PDXDC1chr1615069077+ATP2A1chr1628905476+0.0040417710.99595827
ENST00000450288ENST00000395503PDXDC1chr1615069077+ATP2A1chr1628905476+0.0035334020.99646664
ENST00000450288ENST00000536376PDXDC1chr1615069077+ATP2A1chr1628905476+0.0036087090.99639124

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 PDXDC1-ATP2A1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
PDXDC1chr1615069077ATP2A1chr162890547620935GRSCGAREEEVEPGTARPPPAASAMD

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Potential FusionNeoAntigen Information of PDXDC1-ATP2A1 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.
PDXDC1-ATP2A1_15069077_28905476.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)
PDXDC1-ATP2A1chr1615069077chr1628905476209HLA-B50:02EEVEPGTA0.99930.724816
PDXDC1-ATP2A1chr1615069077chr1628905476209HLA-B45:01EEVEPGTA0.99910.8846816
PDXDC1-ATP2A1chr1615069077chr1628905476209HLA-B45:01EEEVEPGTA0.95210.9093716
PDXDC1-ATP2A1chr1615069077chr1628905476209HLA-B50:02EEEVEPGTA0.84520.7146716
PDXDC1-ATP2A1chr1615069077chr1628905476209HLA-B41:01REEEVEPGT0.15850.8576615
PDXDC1-ATP2A1chr1615069077chr1628905476209HLA-B45:01EEVEPGTARP0.98570.8281818
PDXDC1-ATP2A1chr1615069077chr1628905476209HLA-B50:02EEVEPGTARP0.96880.5604818
PDXDC1-ATP2A1chr1615069077chr1628905476209HLA-B45:01REEEVEPGTA0.95120.8191616
PDXDC1-ATP2A1chr1615069077chr1628905476209HLA-B50:02REEEVEPGTA0.92760.7437616
PDXDC1-ATP2A1chr1615069077chr1628905476209HLA-B50:01REEEVEPGTA0.73790.8753616
PDXDC1-ATP2A1chr1615069077chr1628905476209HLA-B41:01REEEVEPGTA0.71240.7071616
PDXDC1-ATP2A1chr1615069077chr1628905476209HLA-B45:01EEVEPGTARPP0.99960.8708819
PDXDC1-ATP2A1chr1615069077chr1628905476209HLA-B50:02EEVEPGTARPP0.99880.6508819
PDXDC1-ATP2A1chr1615069077chr1628905476209HLA-B56:01EPGTARPPPAA0.99850.77321122
PDXDC1-ATP2A1chr1615069077chr1628905476209HLA-B40:06REEEVEPGTA0.98450.6995616
PDXDC1-ATP2A1chr1615069077chr1628905476209HLA-B18:06EEVEPGTAR0.7160.8299817
PDXDC1-ATP2A1chr1615069077chr1628905476209HLA-B50:05REEEVEPGTA0.73790.8753616
PDXDC1-ATP2A1chr1615069077chr1628905476209HLA-B50:04REEEVEPGTA0.73790.8753616
PDXDC1-ATP2A1chr1615069077chr1628905476209HLA-B55:02EPGTARPPPAA0.99850.82921122

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Potential FusionNeoAntigen Information of PDXDC1-ATP2A1 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 PDXDC1-ATP2A1

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
7768REEEVEPGTARPPPPDXDC1ATP2A1chr1615069077chr1628905476209

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PDXDC1-ATP2A1

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-B14:023BVN7768REEEVEPGTARPPP-7.15543-7.26883
HLA-B14:023BVN7768REEEVEPGTARPPP-4.77435-5.80965
HLA-B52:013W397768REEEVEPGTARPPP-6.80875-6.92215
HLA-B52:013W397768REEEVEPGTARPPP-4.20386-5.23916
HLA-A11:014UQ27768REEEVEPGTARPPP-7.5194-8.5547
HLA-A11:014UQ27768REEEVEPGTARPPP-6.9601-7.0735
HLA-A24:025HGA7768REEEVEPGTARPPP-7.52403-7.63743
HLA-A24:025HGA7768REEEVEPGTARPPP-5.82433-6.85963
HLA-B27:056PYJ7768REEEVEPGTARPPP-3.28285-4.31815
HLA-B44:053DX87768REEEVEPGTARPPP-5.91172-6.94702
HLA-B44:053DX87768REEEVEPGTARPPP-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of PDXDC1-ATP2A1

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
PDXDC1-ATP2A1chr1615069077chr16289054761122EPGTARPPPAAGAGAAGATGTTTATCATTGACAAGGTGGATGGG
PDXDC1-ATP2A1chr1615069077chr1628905476615REEEVEPGTATGGACGCGTCCCTGGAGAAGATGTTT
PDXDC1-ATP2A1chr1615069077chr1628905476616REEEVEPGTAATGGACGCGTCCCTGGAGAAGATGTTTATC
PDXDC1-ATP2A1chr1615069077chr1628905476716EEEVEPGTAGACGCGTCCCTGGAGAAGATGTTTATC
PDXDC1-ATP2A1chr1615069077chr1628905476816EEVEPGTAGCGTCCCTGGAGAAGATGTTTATC
PDXDC1-ATP2A1chr1615069077chr1628905476817EEVEPGTARGCGTCCCTGGAGAAGATGTTTATCATT
PDXDC1-ATP2A1chr1615069077chr1628905476818EEVEPGTARPGCGTCCCTGGAGAAGATGTTTATCATTGAC
PDXDC1-ATP2A1chr1615069077chr1628905476819EEVEPGTARPPGCGTCCCTGGAGAAGATGTTTATCATTGACAAG

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 PDXDC1-ATP2A1

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
HNSCPDXDC1-ATP2A1chr1615069077ENST00000535621chr1628905476ENST00000357084TCGA-CN-6019

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Potential target of CAR-T therapy development for PDXDC1-ATP2A1

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
TgeneATP2A1chr16:15069077chr16:28905476ENST00000357084822758_77701002.0TransmembraneHelical%3B Name%3D5
TgeneATP2A1chr16:15069077chr16:28905476ENST00000357084822829_85101002.0TransmembraneHelical%3B Name%3D7
TgeneATP2A1chr16:15069077chr16:28905476ENST00000357084822898_91701002.0TransmembraneHelical%3B Name%3D8
TgeneATP2A1chr16:15069077chr16:28905476ENST00000357084822931_94901002.0TransmembraneHelical%3B Name%3D9
TgeneATP2A1chr16:15069077chr16:28905476ENST00000357084822965_98501002.0TransmembraneHelical%3B Name%3D10
TgeneATP2A1chr16:15069077chr16:28905476ENST00000395503823758_77701004.3333333333334TransmembraneHelical%3B Name%3D5
TgeneATP2A1chr16:15069077chr16:28905476ENST00000395503823829_85101004.3333333333334TransmembraneHelical%3B Name%3D7
TgeneATP2A1chr16:15069077chr16:28905476ENST00000395503823898_91701004.3333333333334TransmembraneHelical%3B Name%3D8
TgeneATP2A1chr16:15069077chr16:28905476ENST00000395503823931_94901004.3333333333334TransmembraneHelical%3B Name%3D9
TgeneATP2A1chr16:15069077chr16:28905476ENST00000395503823965_98501004.3333333333334TransmembraneHelical%3B Name%3D10

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 PDXDC1-ATP2A1

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 PDXDC1-ATP2A1

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