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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:PARP2-ABCD4

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PARP2-ABCD4
FusionPDB ID: 62826
FusionGDB2.0 ID: 62826
HgeneTgene
Gene symbol

PARP2

ABCD4

Gene ID

10038

5826

Gene namepoly(ADP-ribose) polymerase 2ATP binding cassette subfamily D member 4
SynonymsADPRT2|ADPRTL2|ADPRTL3|ARTD2|PARP-2|pADPRT-2ABC41|EST352188|MAHCJ|P70R|P79R|PMP69|PXMP1L
Cytomap

14q11.2

14q24.3

Type of geneprotein-codingprotein-coding
Descriptionpoly [ADP-ribose] polymerase 2ADP-ribosyltransferase (NAD+; poly(ADP-ribose) polymerase)-like 2ADP-ribosyltransferase diphtheria toxin-like 2ADPRT-2DNA ADP-ribosyltransferase PARP2NAD(+) ADP-ribosyltransferase 2hPARP-2poly (ADP-ribose) polymerase fATP-binding cassette sub-family D member 469 kDa peroxisomal ABC-transporterATP-binding cassette, sub-family D (ALD), member 4PMP70-related proteinPXMP1-Lperoxisomal membrane protein 69
Modification date2020031320200313
UniProtAcc.

O14678

Main function of 5'-partner protein: FUNCTION: Lysosomal transporter that plays a role in the lysosomal release of vitamin B12 into the cytosol (PubMed:22922874). Targeted by LMBRD1 lysosomal chaperone from the endoplasmic reticulum to the lysosomal membrane (PubMed:27456980). Then forms a complex with lysosomal chaperone LMBRD1 and cytosolic MMACHC to transport cobalamin across the lysosomal membrane (PubMed:25535791). {ECO:0000269|PubMed:22922874, ECO:0000269|PubMed:27456980, ECO:0000303|PubMed:25535791}.
Ensembl transtripts involved in fusion geneENST idsENST00000250416, ENST00000429687, 
ENST00000527915, ENST00000555140, 
ENST00000557554, ENST00000557588, 
ENST00000298816, ENST00000356924, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score4 X 4 X 3=482 X 2 X 2=8
# samples 42
** MAII scorelog2(4/48*10)=-0.263034405833794
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(2/8*10)=1.32192809488736
Fusion gene context

PubMed: PARP2 [Title/Abstract] AND ABCD4 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PARP2 [Title/Abstract] AND ABCD4 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PARP2(20822406)-ABCD4(74755468), # samples:2
Anticipated loss of major functional domain due to fusion event.PARP2-ABCD4 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.
PARP2-ABCD4 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.
PARP2-ABCD4 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.
PARP2-ABCD4 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
HgenePARP2

GO:0018312

peptidyl-serine ADP-ribosylation

28190768

HgenePARP2

GO:0030592

DNA ADP-ribosylation

27471034

HgenePARP2

GO:0070212

protein poly-ADP-ribosylation

25043379



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/chr14:20822406/chr14:74755468)
- 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 PARP2 (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 ABCD4 (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)
ENST00000429687PARP2chr1420822406+ENST00000356924ABCD4chr1474755468-2226823601187375
ENST00000429687PARP2chr1420822406+ENST00000298816ABCD4chr1474755468-1250823601145361
ENST00000250416PARP2chr1420822406+ENST00000356924ABCD4chr1474755468-2232829271193388
ENST00000250416PARP2chr1420822406+ENST00000298816ABCD4chr1474755468-1256829271151374
ENST00000527915PARP2chr1420822406+ENST00000356924ABCD4chr1474755468-221080751171388
ENST00000527915PARP2chr1420822406+ENST00000298816ABCD4chr1474755468-123480751129374

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
ENST00000429687ENST00000356924PARP2chr1420822406+ABCD4chr1474755468-0.000486190.99951386
ENST00000429687ENST00000298816PARP2chr1420822406+ABCD4chr1474755468-0.002314560.99768543
ENST00000250416ENST00000356924PARP2chr1420822406+ABCD4chr1474755468-0.0003627640.99963725
ENST00000250416ENST00000298816PARP2chr1420822406+ABCD4chr1474755468-0.0023102810.9976897
ENST00000527915ENST00000356924PARP2chr1420822406+ABCD4chr1474755468-0.0003651930.99963474
ENST00000527915ENST00000298816PARP2chr1420822406+ABCD4chr1474755468-0.0023411620.99765885

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 PARP2-ABCD4

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
PARP2chr1420822406ABCD4chr1474755468807267MMEMKYNTKKAPLGSADDERILRFLE
PARP2chr1420822406ABCD4chr1474755468823254MMEMKYNTKKAPLGSADDERILRFLE
PARP2chr1420822406ABCD4chr1474755468829267MMEMKYNTKKAPLGSADDERILRFLE

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Potential FusionNeoAntigen Information of PARP2-ABCD4 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.

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)

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Potential FusionNeoAntigen Information of PARP2-ABCD4 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.
PARP2-ABCD4_20822406_74755468.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)
PARP2-ABCD4chr1420822406chr1474755468829DRB1-0103EMKYNTKKAPLGSAD217
PARP2-ABCD4chr1420822406chr1474755468829DRB1-0103MEMKYNTKKAPLGSA116
PARP2-ABCD4chr1420822406chr1474755468829DRB1-0454EMKYNTKKAPLGSAD217
PARP2-ABCD4chr1420822406chr1474755468829DRB1-0802EMKYNTKKAPLGSAD217
PARP2-ABCD4chr1420822406chr1474755468829DRB1-0802MEMKYNTKKAPLGSA116
PARP2-ABCD4chr1420822406chr1474755468829DRB1-0802MKYNTKKAPLGSADD318
PARP2-ABCD4chr1420822406chr1474755468829DRB1-0802MMEMKYNTKKAPLGS015
PARP2-ABCD4chr1420822406chr1474755468829DRB1-0807EMKYNTKKAPLGSAD217
PARP2-ABCD4chr1420822406chr1474755468829DRB1-0808EMKYNTKKAPLGSAD217
PARP2-ABCD4chr1420822406chr1474755468829DRB1-0808MEMKYNTKKAPLGSA116
PARP2-ABCD4chr1420822406chr1474755468829DRB1-0809EMKYNTKKAPLGSAD217
PARP2-ABCD4chr1420822406chr1474755468829DRB1-0809MEMKYNTKKAPLGSA116
PARP2-ABCD4chr1420822406chr1474755468829DRB1-0809MKYNTKKAPLGSADD318
PARP2-ABCD4chr1420822406chr1474755468829DRB1-0809MMEMKYNTKKAPLGS015
PARP2-ABCD4chr1420822406chr1474755468829DRB1-0811EMKYNTKKAPLGSAD217
PARP2-ABCD4chr1420822406chr1474755468829DRB1-0811MEMKYNTKKAPLGSA116
PARP2-ABCD4chr1420822406chr1474755468829DRB1-0813EMKYNTKKAPLGSAD217
PARP2-ABCD4chr1420822406chr1474755468829DRB1-0813MEMKYNTKKAPLGSA116
PARP2-ABCD4chr1420822406chr1474755468829DRB1-0813MMEMKYNTKKAPLGS015
PARP2-ABCD4chr1420822406chr1474755468829DRB1-0813MKYNTKKAPLGSADD318
PARP2-ABCD4chr1420822406chr1474755468829DRB1-0815EMKYNTKKAPLGSAD217
PARP2-ABCD4chr1420822406chr1474755468829DRB1-0815MEMKYNTKKAPLGSA116
PARP2-ABCD4chr1420822406chr1474755468829DRB1-0821EMKYNTKKAPLGSAD217
PARP2-ABCD4chr1420822406chr1474755468829DRB1-0821MEMKYNTKKAPLGSA116
PARP2-ABCD4chr1420822406chr1474755468829DRB1-0821MKYNTKKAPLGSADD318
PARP2-ABCD4chr1420822406chr1474755468829DRB1-0821MMEMKYNTKKAPLGS015
PARP2-ABCD4chr1420822406chr1474755468829DRB1-0824EMKYNTKKAPLGSAD217
PARP2-ABCD4chr1420822406chr1474755468829DRB1-0830EMKYNTKKAPLGSAD217
PARP2-ABCD4chr1420822406chr1474755468829DRB1-0830MEMKYNTKKAPLGSA116
PARP2-ABCD4chr1420822406chr1474755468829DRB1-1130EMKYNTKKAPLGSAD217
PARP2-ABCD4chr1420822406chr1474755468829DRB1-1130MEMKYNTKKAPLGSA116
PARP2-ABCD4chr1420822406chr1474755468829DRB1-1130MKYNTKKAPLGSADD318
PARP2-ABCD4chr1420822406chr1474755468829DRB1-1130MMEMKYNTKKAPLGS015
PARP2-ABCD4chr1420822406chr1474755468829DRB1-1145EMKYNTKKAPLGSAD217
PARP2-ABCD4chr1420822406chr1474755468829DRB1-1164EMKYNTKKAPLGSAD217
PARP2-ABCD4chr1420822406chr1474755468829DRB1-1347EMKYNTKKAPLGSAD217
PARP2-ABCD4chr1420822406chr1474755468829DRB1-1347MEMKYNTKKAPLGSA116
PARP2-ABCD4chr1420822406chr1474755468829DRB1-1367EMKYNTKKAPLGSAD217
PARP2-ABCD4chr1420822406chr1474755468829DRB1-1367MEMKYNTKKAPLGSA116
PARP2-ABCD4chr1420822406chr1474755468829DRB1-1367MKYNTKKAPLGSADD318
PARP2-ABCD4chr1420822406chr1474755468829DRB1-1367MMEMKYNTKKAPLGS015
PARP2-ABCD4chr1420822406chr1474755468829DRB1-1403EMKYNTKKAPLGSAD217
PARP2-ABCD4chr1420822406chr1474755468829DRB1-1427EMKYNTKKAPLGSAD217
PARP2-ABCD4chr1420822406chr1474755468829DRB1-1427MEMKYNTKKAPLGSA116
PARP2-ABCD4chr1420822406chr1474755468829DRB1-1440EMKYNTKKAPLGSAD217
PARP2-ABCD4chr1420822406chr1474755468829DRB1-1467EMKYNTKKAPLGSAD217
PARP2-ABCD4chr1420822406chr1474755468829DRB1-1477EMKYNTKKAPLGSAD217
PARP2-ABCD4chr1420822406chr1474755468829DRB5-0102EMKYNTKKAPLGSAD217
PARP2-ABCD4chr1420822406chr1474755468829DRB5-0103EMKYNTKKAPLGSAD217
PARP2-ABCD4chr1420822406chr1474755468829DRB5-0103MEMKYNTKKAPLGSA116
PARP2-ABCD4chr1420822406chr1474755468829DRB5-0108NEMKYNTKKAPLGSAD217

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Fusion breakpoint peptide structures of PARP2-ABCD4

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.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PARP2-ABCD4

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

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Vaccine Design for the FusionNeoAntigens of PARP2-ABCD4

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

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
PARP2-ABCD4chr1420822406chr1474755468015MMEMKYNTKKAPLGSTGATGGAAATGAAGTATAATACCAAGAAAGCCCCACTTGGTTCTG
PARP2-ABCD4chr1420822406chr1474755468116MEMKYNTKKAPLGSATGGAAATGAAGTATAATACCAAGAAAGCCCCACTTGGTTCTGCCG
PARP2-ABCD4chr1420822406chr1474755468217EMKYNTKKAPLGSADAAATGAAGTATAATACCAAGAAAGCCCCACTTGGTTCTGCCGATG
PARP2-ABCD4chr1420822406chr1474755468318MKYNTKKAPLGSADDTGAAGTATAATACCAAGAAAGCCCCACTTGGTTCTGCCGATGATG

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Information of the samples that have these potential fusion neoantigens of PARP2-ABCD4

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

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Potential target of CAR-T therapy development for PARP2-ABCD4

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 PARP2-ABCD4

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 PARP2-ABCD4

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