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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:PTBP3-ARID5A

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PTBP3-ARID5A
FusionPDB ID: 69847
FusionGDB2.0 ID: 69847
HgeneTgene
Gene symbol

PTBP3

ARID5A

Gene ID

9991

10865

Gene namepolypyrimidine tract binding protein 3AT-rich interaction domain 5A
SynonymsROD1MRF-1|MRF1|RP11-363D14
Cytomap

9q32

2q11.2

Type of geneprotein-codingprotein-coding
Descriptionpolypyrimidine tract-binding protein 3ROD1 regulator of differentiation 1fission yeast differentiation regulatorregulator of differentiation 1AT-rich interactive domain-containing protein 5AARID domain-containing protein 5AAT rich interactive domain 5A (MRF1-like)RFVG5814modulator recognition factor 1modulator recognition factor I
Modification date2020031320200320
UniProtAcc.

Q03989

Main function of 5'-partner protein: FUNCTION: Binds to AT-rich stretches in the modulator region upstream of the human cytomegalovirus major intermediate early gene enhancer. May act as repressor and down-regulate enhancer-dependent gene expressison (PubMed:8649988). May positively regulate chondrocyte-specific transcription such as of COL2A1 in collaboration with SOX9 and positively regulate histone H3 acetylation at chondrocyte-specific genes. May stimulate early-stage chondrocyte differentiation and inhibit later stage differention (By similarity). Can repress ESR1-mediated transcriptional activation; proposed to act as corepressor for selective nuclear hormone receptors (PubMed:15941852). As RNA-binding protein involved in the regulation of inflammatory response by stabilizing selective inflammation-related mRNAs, such as IL6, STAT3 and TBX21. Binds to stem loop structures located in the 3'UTRs of IL6, STAT3 and TBX21 mRNAs; at least for STAT3 prevents binding of ZC3H12A to the mRNA stem loop structure thus inhibiting its degradation activity. Contributes to elevated IL6 levels possibly implicated in autoimmunity processes. IL6-dependent stabilization of STAT3 mRNA may promote differentiation of naive CD4+ T-cells into T-helper Th17 cells. In CD4+ T-cells may also inhibit RORC-induced Th17 cell differentiation independently of IL6 signaling. Stabilization of TBX21 mRNA contributes to elevated interferon-gamma secretion in Th1 cells possibly implicated in the establishment of septic shock (By similarity). Stabilizes TNFRSF4/OX40 mRNA by binding to the conserved stem loop structure in its 3'UTR; thereby competing with the mRNA-destabilizing functions of RC3H1 and endoribonuclease ZC3H12A (By similarity). {ECO:0000250|UniProtKB:Q3U108, ECO:0000269|PubMed:15941852, ECO:0000269|PubMed:8649988}.
Ensembl transtripts involved in fusion geneENST idsENST00000374255, ENST00000458258, 
ENST00000334318, ENST00000343327, 
ENST00000374257, ENST00000487997, 
ENST00000454558, ENST00000357485, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score11 X 13 X 8=11442 X 1 X 2=4
# samples 172
** MAII scorelog2(17/1144*10)=-2.75048040064069
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(2/4*10)=2.32192809488736
Fusion gene context

PubMed: PTBP3 [Title/Abstract] AND ARID5A [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PTBP3 [Title/Abstract] AND ARID5A [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PTBP3(115060121)-ARID5A(97213139), # samples:1
Anticipated loss of major functional domain due to fusion event.PTBP3-ARID5A 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.
PTBP3-ARID5A 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.
PTBP3-ARID5A 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.
PTBP3-ARID5A 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
HgenePTBP3

GO:0033119

negative regulation of RNA splicing

18335065

TgeneARID5A

GO:0000122

negative regulation of transcription by RNA polymerase II

15941852

TgeneARID5A

GO:0071391

cellular response to estrogen stimulus

15941852



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/chr9:115060121/chr2:97213139)
- 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 PTBP3 (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 ARID5A (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)
ENST00000458258PTBP3chr9115060121-ENST00000357485ARID5Achr297213139+224213601916638
ENST00000374255PTBP3chr9115060121-ENST00000357485ARID5Achr297213139+23722661482046632

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
ENST00000458258ENST00000357485PTBP3chr9115060121-ARID5Achr297213139+0.0165508870.98344916
ENST00000374255ENST00000357485PTBP3chr9115060121-ARID5Achr297213139+0.0109132290.98908675

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 PTBP3-ARID5A

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
PTBP3chr9115060121ARID5Achr29721313913645NGPFTMNSSTPSTAAPVKGNRKQSTE
PTBP3chr9115060121ARID5Achr29721313926639NGPFTMNSSTPSTAAPVKGNRKQSTE

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Potential FusionNeoAntigen Information of PTBP3-ARID5A 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.
PTBP3-ARID5A_115060121_97213139.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)
PTBP3-ARID5Achr9115060121chr297213139266HLA-C01:17STPSTAAPV0.4040.9476817
PTBP3-ARID5Achr9115060121chr297213139266HLA-C01:30STPSTAAPV0.10870.9439817
PTBP3-ARID5Achr9115060121chr297213139266HLA-A69:01STPSTAAPV0.9750.6509817
PTBP3-ARID5Achr9115060121chr297213139266HLA-C01:02STPSTAAPV0.40550.9452817
PTBP3-ARID5Achr9115060121chr297213139266HLA-C01:03STPSTAAPV0.35870.9437817

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Potential FusionNeoAntigen Information of PTBP3-ARID5A 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.
PTBP3-ARID5A_115060121_97213139.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)
PTBP3-ARID5Achr9115060121chr297213139266DRB1-0401NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB1-0433NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB1-0434NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB1-0434GPFTMNSSTPSTAAP116
PTBP3-ARID5Achr9115060121chr297213139266DRB1-0435NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB1-0438NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB1-0447NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB1-0463NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB1-0464NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB1-0466NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB1-0472NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB1-0472GPFTMNSSTPSTAAP116
PTBP3-ARID5Achr9115060121chr297213139266DRB1-0474NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB1-0475NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB1-0476NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB1-1130NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB1-1153NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB1-1179NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB1-1336NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB1-1337NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB1-1367NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB1-1385NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB1-1396NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB1-1402NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB1-1409NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB1-1419NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB1-1424NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB1-1441NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB1-1446NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB1-1447NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB1-1451NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB1-1489NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB1-1494NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB1-1498NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0201NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0202NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0202GPFTMNSSTPSTAAP116
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0204NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0205NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0205GPFTMNSSTPSTAAP116
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0209NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0209GPFTMNSSTPSTAAP116
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0210NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0210GPFTMNSSTPSTAAP116
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0211NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0211GPFTMNSSTPSTAAP116
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0212NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0212GPFTMNSSTPSTAAP116
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0213NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0213GPFTMNSSTPSTAAP116
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0214NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0214GPFTMNSSTPSTAAP116
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0215NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0215GPFTMNSSTPSTAAP116
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0216NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0216GPFTMNSSTPSTAAP116
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0217NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0217GPFTMNSSTPSTAAP116
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0218NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0218GPFTMNSSTPSTAAP116
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0219NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0219GPFTMNSSTPSTAAP116
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0220NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0220GPFTMNSSTPSTAAP116
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0221NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0221GPFTMNSSTPSTAAP116
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0222NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0222GPFTMNSSTPSTAAP116
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0223NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0223GPFTMNSSTPSTAAP116
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0224NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0225NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0225GPFTMNSSTPSTAAP116
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0303NGPFTMNSSTPSTAA015
PTBP3-ARID5Achr9115060121chr297213139266DRB3-0303GPFTMNSSTPSTAAP116

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Fusion breakpoint peptide structures of PTBP3-ARID5A

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
6398NSSTPSTAAPVKGNPTBP3ARID5Achr9115060121chr297213139266

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PTBP3-ARID5A

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-B52:013W396398NSSTPSTAAPVKGN-7.90165-7.90165
HLA-B44:053DX86398NSSTPSTAAPVKGN-5.81679-5.81679

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Vaccine Design for the FusionNeoAntigens of PTBP3-ARID5A

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
PTBP3-ARID5Achr9115060121chr297213139817STPSTAAPVCTACTCCTTCTACAGCAGCCCCTGTCA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
PTBP3-ARID5Achr9115060121chr297213139015NGPFTMNSSTPSTAAACGGACCTTTTACCATGAATAGTTCTACTCCTTCTACAGCAGCCC
PTBP3-ARID5Achr9115060121chr297213139116GPFTMNSSTPSTAAPGACCTTTTACCATGAATAGTTCTACTCCTTCTACAGCAGCCCCTG

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Information of the samples that have these potential fusion neoantigens of PTBP3-ARID5A

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
STADPTBP3-ARID5Achr9115060121ENST00000374255chr297213139ENST00000357485TCGA-BR-8080-01A

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Potential target of CAR-T therapy development for PTBP3-ARID5A

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 PTBP3-ARID5A

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 PTBP3-ARID5A

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