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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-ATG5

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PDSS2-ATG5
FusionPDB ID: 64077
FusionGDB2.0 ID: 64077
HgeneTgene
Gene symbol

PDSS2

ATG5

Gene ID

57107

9474

Gene namedecaprenyl diphosphate synthase subunit 2autophagy related 5
SynonymsC6orf210|COQ10D3|COQ1B|DLP1|bA59I9.3|hDLP1APG5|APG5-LIKE|APG5L|ASP|SCAR25|hAPG5
Cytomap

6q21

6q21

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 decaprautophagy protein 5APG5 autophagy 5-likeATG5 autophagy related 5 homologapoptosis-specific protein
Modification date2020031320200313
UniProtAcc.

Q9H1Y0

Main function of 5'-partner protein: FUNCTION: Involved in autophagic vesicle formation. Conjugation with ATG12, through a ubiquitin-like conjugating system involving ATG7 as an E1-like activating enzyme and ATG10 as an E2-like conjugating enzyme, is essential for its function. The ATG12-ATG5 conjugate acts as an E3-like enzyme which is required for lipidation of ATG8 family proteins and their association to the vesicle membranes. Involved in mitochondrial quality control after oxidative damage, and in subsequent cellular longevity. Plays a critical role in multiple aspects of lymphocyte development and is essential for both B and T lymphocyte survival and proliferation. Required for optimal processing and presentation of antigens for MHC II. Involved in the maintenance of axon morphology and membrane structures, as well as in normal adipocyte differentiation. Promotes primary ciliogenesis through removal of OFD1 from centriolar satellites and degradation of IFT20 via the autophagic pathway. {ECO:0000250|UniProtKB:Q99J83, ECO:0000269|PubMed:12207896, ECO:0000269|PubMed:20580051, ECO:0000269|PubMed:22170153, ECO:0000269|PubMed:26812546}.; FUNCTION: May play an important role in the apoptotic process, possibly within the modified cytoskeleton. Its expression is a relatively late event in the apoptotic process, occurring downstream of caspase activity. Plays a crucial role in IFN-gamma-induced autophagic cell death by interacting with FADD. {ECO:0000269|PubMed:15778222, ECO:0000269|PubMed:7796880}.; FUNCTION: (Microbial infection) May act as a proviral factor. In association with ATG12, negatively regulates the innate antiviral immune response by impairing the type I IFN production pathway upon vesicular stomatitis virus (VSV) infection (PubMed:17709747). Required for the translation of incoming hepatitis C virus (HCV) RNA and, thereby, for initiation of HCV replication, but not required once infection is established (PubMed:19666601). {ECO:0000269|PubMed:17709747, ECO:0000269|PubMed:19666601}.
Ensembl transtripts involved in fusion geneENST idsENST00000369031, ENST00000369037, 
ENST00000453874, 
ENST00000475645, 
ENST00000360666, ENST00000343245, 
ENST00000369070, ENST00000369076, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score11 X 8 X 6=52815 X 12 X 7=1260
# samples 1315
** MAII scorelog2(13/528*10)=-2.02202630633
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(15/1260*10)=-3.0703893278914
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: PDSS2 [Title/Abstract] AND ATG5 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PDSS2 [Title/Abstract] AND ATG5 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ATG5(106649847)-PDSS2(107475981), # samples:3
PDSS2(107780194)-ATG5(106649964), # samples:1
Anticipated loss of major functional domain due to fusion event.ATG5-PDSS2 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
ATG5-PDSS2 seems lost the major protein functional domain in Tgene partner, which is a tumor suppressor due to the frame-shifted ORF.
PDSS2-ATG5 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
PDSS2-ATG5 seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor 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
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/chr6:106649847/chr6:107475981)
- 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 ATG5 (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)
ENST00000369037PDSS2chr6107780194-ENST00000343245ATG5chr6106649964-2893574130828232
ENST00000369037PDSS2chr6107780194-ENST00000369070ATG5chr6106649964-2893574130828232
ENST00000369037PDSS2chr6107780194-ENST00000369076ATG5chr6106649964-2893574130828232
ENST00000453874PDSS2chr6107780194-ENST00000343245ATG5chr6106649964-2886567123821232
ENST00000453874PDSS2chr6107780194-ENST00000369070ATG5chr6106649964-2886567123821232
ENST00000453874PDSS2chr6107780194-ENST00000369076ATG5chr6106649964-2886567123821232
ENST00000369031PDSS2chr6107780194-ENST00000343245ATG5chr6106649964-2894575131829232
ENST00000369031PDSS2chr6107780194-ENST00000369070ATG5chr6106649964-2894575131829232
ENST00000369031PDSS2chr6107780194-ENST00000369076ATG5chr6106649964-2894575131829232

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
ENST00000369037ENST00000343245PDSS2chr6107780194-ATG5chr6106649964-0.71386190.28613815
ENST00000369037ENST00000369070PDSS2chr6107780194-ATG5chr6106649964-0.71386190.28613815
ENST00000369037ENST00000369076PDSS2chr6107780194-ATG5chr6106649964-0.71386190.28613815
ENST00000453874ENST00000343245PDSS2chr6107780194-ATG5chr6106649964-0.810617570.18938239
ENST00000453874ENST00000369070PDSS2chr6107780194-ATG5chr6106649964-0.810617570.18938239
ENST00000453874ENST00000369076PDSS2chr6107780194-ATG5chr6106649964-0.810617570.18938239
ENST00000369031ENST00000343245PDSS2chr6107780194-ATG5chr6106649964-0.62736650.37263355
ENST00000369031ENST00000369070PDSS2chr6107780194-ATG5chr6106649964-0.62736650.37263355
ENST00000369031ENST00000369076PDSS2chr6107780194-ATG5chr6106649964-0.62736650.37263355

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-ATG5

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
PDSS2chr6107780194ATG5chr6106649964567148AGGHSAPSAYHSQTTTERPFIQKLFR
PDSS2chr6107780194ATG5chr6106649964574148AGGHSAPSAYHSQTTTERPFIQKLFR
PDSS2chr6107780194ATG5chr6106649964575148AGGHSAPSAYHSQTTTERPFIQKLFR

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Potential FusionNeoAntigen Information of PDSS2-ATG5 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-ATG5_107780194_106649964.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-ATG5chr6107780194chr6106649964575HLA-B15:01SQTTTERPF0.99640.69681120
PDSS2-ATG5chr6107780194chr6106649964575HLA-B15:25SQTTTERPF0.87580.70081120
PDSS2-ATG5chr6107780194chr6106649964575HLA-B15:03SQTTTERPF0.64760.54081120
PDSS2-ATG5chr6107780194chr6106649964575HLA-B15:18SQTTTERPF0.58750.50451120
PDSS2-ATG5chr6107780194chr6106649964575HLA-B39:01YHSQTTTERPF0.99960.8352920
PDSS2-ATG5chr6107780194chr6106649964575HLA-B38:01YHSQTTTERPF0.99910.8706920
PDSS2-ATG5chr6107780194chr6106649964575HLA-B38:02YHSQTTTERPF0.99910.9014920
PDSS2-ATG5chr6107780194chr6106649964575HLA-B15:18YHSQTTTERPF0.99910.5149920
PDSS2-ATG5chr6107780194chr6106649964575HLA-B15:05SQTTTERPF0.67870.71361120
PDSS2-ATG5chr6107780194chr6106649964575HLA-B39:09YHSQTTTERPF0.99970.5545920
PDSS2-ATG5chr6107780194chr6106649964575HLA-B39:05YHSQTTTERPF0.9990.8113920
PDSS2-ATG5chr6107780194chr6106649964575HLA-B15:33SQTTTERPF0.99640.69681120
PDSS2-ATG5chr6107780194chr6106649964575HLA-B15:135SQTTTERPF0.99640.69881120
PDSS2-ATG5chr6107780194chr6106649964575HLA-B15:34SQTTTERPF0.99640.69681120
PDSS2-ATG5chr6107780194chr6106649964575HLA-B15:125SQTTTERPF0.99640.69681120
PDSS2-ATG5chr6107780194chr6106649964575HLA-B15:27SQTTTERPF0.99610.69031120
PDSS2-ATG5chr6107780194chr6106649964575HLA-B15:50SQTTTERPF0.9940.74151120
PDSS2-ATG5chr6107780194chr6106649964575HLA-B15:24SQTTTERPF0.99350.64891120
PDSS2-ATG5chr6107780194chr6106649964575HLA-B15:35SQTTTERPF0.96560.68131120
PDSS2-ATG5chr6107780194chr6106649964575HLA-B15:12SQTTTERPF0.96310.75391120
PDSS2-ATG5chr6107780194chr6106649964575HLA-B15:53SQTTTERPF0.95220.66191120
PDSS2-ATG5chr6107780194chr6106649964575HLA-B15:39SQTTTERPF0.88580.62861120
PDSS2-ATG5chr6107780194chr6106649964575HLA-B15:54SQTTTERPF0.83450.62381120
PDSS2-ATG5chr6107780194chr6106649964575HLA-B15:73SQTTTERPF0.74880.7631120
PDSS2-ATG5chr6107780194chr6106649964575HLA-B15:20SQTTTERPF0.65360.77391120
PDSS2-ATG5chr6107780194chr6106649964575HLA-B35:28SQTTTERPF0.63580.83031120
PDSS2-ATG5chr6107780194chr6106649964575HLA-B15:30SQTTTERPF0.5970.67021120
PDSS2-ATG5chr6107780194chr6106649964575HLA-B48:02SQTTTERPF0.53920.78511120
PDSS2-ATG5chr6107780194chr6106649964575HLA-B38:05YHSQTTTERPF0.99910.8706920
PDSS2-ATG5chr6107780194chr6106649964575HLA-B39:11YHSQTTTERPF0.99020.6416920

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Potential FusionNeoAntigen Information of PDSS2-ATG5 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.
PDSS2-ATG5_107780194_106649964.msa

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)
PDSS2-ATG5chr6107780194chr6106649964575DRB1-1446PSAYHSQTTTERPFI621
PDSS2-ATG5chr6107780194chr6106649964575DRB1-1446APSAYHSQTTTERPF520
PDSS2-ATG5chr6107780194chr6106649964575DRB5-0101PSAYHSQTTTERPFI621
PDSS2-ATG5chr6107780194chr6106649964575DRB5-0101APSAYHSQTTTERPF520
PDSS2-ATG5chr6107780194chr6106649964575DRB5-0101SAPSAYHSQTTTERP419
PDSS2-ATG5chr6107780194chr6106649964575DRB5-0102PSAYHSQTTTERPFI621
PDSS2-ATG5chr6107780194chr6106649964575DRB5-0102APSAYHSQTTTERPF520
PDSS2-ATG5chr6107780194chr6106649964575DRB5-0103PSAYHSQTTTERPFI621
PDSS2-ATG5chr6107780194chr6106649964575DRB5-0103APSAYHSQTTTERPF520
PDSS2-ATG5chr6107780194chr6106649964575DRB5-0104PSAYHSQTTTERPFI621
PDSS2-ATG5chr6107780194chr6106649964575DRB5-0104APSAYHSQTTTERPF520
PDSS2-ATG5chr6107780194chr6106649964575DRB5-0104SAPSAYHSQTTTERP419
PDSS2-ATG5chr6107780194chr6106649964575DRB5-0105PSAYHSQTTTERPFI621
PDSS2-ATG5chr6107780194chr6106649964575DRB5-0105APSAYHSQTTTERPF520
PDSS2-ATG5chr6107780194chr6106649964575DRB5-0105SAPSAYHSQTTTERP419
PDSS2-ATG5chr6107780194chr6106649964575DRB5-0108NPSAYHSQTTTERPFI621
PDSS2-ATG5chr6107780194chr6106649964575DRB5-0108NAPSAYHSQTTTERPF520
PDSS2-ATG5chr6107780194chr6106649964575DRB5-0111PSAYHSQTTTERPFI621
PDSS2-ATG5chr6107780194chr6106649964575DRB5-0111APSAYHSQTTTERPF520
PDSS2-ATG5chr6107780194chr6106649964575DRB5-0111SAPSAYHSQTTTERP419
PDSS2-ATG5chr6107780194chr6106649964575DRB5-0112APSAYHSQTTTERPF520
PDSS2-ATG5chr6107780194chr6106649964575DRB5-0112PSAYHSQTTTERPFI621
PDSS2-ATG5chr6107780194chr6106649964575DRB5-0113PSAYHSQTTTERPFI621
PDSS2-ATG5chr6107780194chr6106649964575DRB5-0113APSAYHSQTTTERPF520
PDSS2-ATG5chr6107780194chr6106649964575DRB5-0113SAPSAYHSQTTTERP419
PDSS2-ATG5chr6107780194chr6106649964575DRB5-0114PSAYHSQTTTERPFI621
PDSS2-ATG5chr6107780194chr6106649964575DRB5-0114APSAYHSQTTTERPF520
PDSS2-ATG5chr6107780194chr6106649964575DRB5-0114SAPSAYHSQTTTERP419
PDSS2-ATG5chr6107780194chr6106649964575DRB5-0203PSAYHSQTTTERPFI621
PDSS2-ATG5chr6107780194chr6106649964575DRB5-0203APSAYHSQTTTERPF520

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Fusion breakpoint peptide structures of PDSS2-ATG5

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
6977PSAYHSQTTTERPFPDSS2ATG5chr6107780194chr6106649964575

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PDSS2-ATG5

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-B52:013W396977PSAYHSQTTTERPF-5.34702-5.34702
HLA-B44:053DX86977PSAYHSQTTTERPF-3.7485-3.7485

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Vaccine Design for the FusionNeoAntigens of PDSS2-ATG5

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-ATG5chr6107780194chr61066499641120SQTTTERPFAGCCAGACAACGACTGAAAGACCTTTC
PDSS2-ATG5chr6107780194chr6106649964920YHSQTTTERPFTACCACAGCCAGACAACGACTGAAAGACCTTTC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
PDSS2-ATG5chr6107780194chr6106649964419SAPSAYHSQTTTERPTCAGCACCCTCTGCTTACCACAGCCAGACAACGACTGAAAGACCT
PDSS2-ATG5chr6107780194chr6106649964520APSAYHSQTTTERPFGCACCCTCTGCTTACCACAGCCAGACAACGACTGAAAGACCTTTC
PDSS2-ATG5chr6107780194chr6106649964621PSAYHSQTTTERPFICCCTCTGCTTACCACAGCCAGACAACGACTGAAAGACCTTTCATT

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Information of the samples that have these potential fusion neoantigens of PDSS2-ATG5

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
Non-CancerPDSS2-ATG5chr6107780194ENST00000369031chr6106649964ENST00000343245TCGA-BR-6564-11A

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Potential target of CAR-T therapy development for PDSS2-ATG5

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-ATG5

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-ATG5

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