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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:PTBP2-AUTS2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PTBP2-AUTS2
FusionPDB ID: 69840
FusionGDB2.0 ID: 69840
HgeneTgene
Gene symbol

PTBP2

AUTS2

Gene ID

58155

26053

Gene namepolypyrimidine tract binding protein 2activator of transcription and developmental regulator AUTS2
SynonymsPTBLP|brPTB|nPTBFBRSL2|MRD26
Cytomap

1p21.3

7q11.22

Type of geneprotein-codingprotein-coding
Descriptionpolypyrimidine tract-binding protein 2PTB-like proteinneural polypyrimidine tract binding proteinneurally-enriched homolog of PTBautism susceptibility gene 2 proteinAUTS2, activator of transcription and developmental regulatorautism susceptibility candidate 2autism-related protein 1
Modification date2020031320200313
UniProtAcc.

Q8WXX7

Main function of 5'-partner protein: FUNCTION: Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility (PubMed:25519132). The PRC1-like complex that contains PCGF5, RNF2, CSNK2B, RYBP and AUTS2 has decreased histone H2A ubiquitination activity, due to the phosphorylation of RNF2 by CSNK2B (PubMed:25519132). As a consequence, the complex mediates transcriptional activation (PubMed:25519132). In the cytoplasm, plays a role in axon and dendrite elongation and in neuronal migration during embryonic brain development. Promotes reorganization of the actin cytoskeleton, lamellipodia formation and neurite elongation via its interaction with RAC guanine nucleotide exchange factors, which then leads to the activation of RAC1 (By similarity). {ECO:0000250|UniProtKB:A0A087WPF7, ECO:0000269|PubMed:25519132}.
Ensembl transtripts involved in fusion geneENST idsENST00000482253, ENST00000370197, 
ENST00000370198, ENST00000426398, 
ENST00000609116, ENST00000394184, 
ENST00000541987, 
ENST00000342771, 
ENST00000406775, ENST00000403018, 
ENST00000489774, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score8 X 6 X 4=19225 X 24 X 10=6000
# samples 927
** MAII scorelog2(9/192*10)=-1.09310940439148
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(27/6000*10)=-4.47393118833241
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: PTBP2 [Title/Abstract] AND AUTS2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PTBP2 [Title/Abstract] AND AUTS2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PTBP2(97189150)-AUTS2(70240341), # samples:1
Anticipated loss of major functional domain due to fusion event.PTBP2-AUTS2 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.
PTBP2-AUTS2 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.
PTBP2-AUTS2 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.
PTBP2-AUTS2 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
HgenePTBP2

GO:0033119

negative regulation of RNA splicing

18335065

TgeneAUTS2

GO:0045944

positive regulation of transcription by RNA polymerase II

25519132

TgeneAUTS2

GO:0051571

positive regulation of histone H3-K4 methylation

25519132

TgeneAUTS2

GO:2000620

positive regulation of histone H4-K16 acetylation

25519132



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/chr1:97189150/chr7:70240341)
- 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 PTBP2 (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 AUTS2 (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)
ENST00000609116PTBP2chr197189150+ENST00000406775AUTS2chr770240341+3506121371998653
ENST00000609116PTBP2chr197189150+ENST00000342771AUTS2chr770240341+4071121371998653
ENST00000370197PTBP2chr197189150+ENST00000406775AUTS2chr770240341+347994101971653
ENST00000370197PTBP2chr197189150+ENST00000342771AUTS2chr770240341+404494101971653
ENST00000370198PTBP2chr197189150+ENST00000406775AUTS2chr770240341+347994101971653
ENST00000370198PTBP2chr197189150+ENST00000342771AUTS2chr770240341+404494101971653
ENST00000426398PTBP2chr197189150+ENST00000406775AUTS2chr770240341+346782281959643
ENST00000426398PTBP2chr197189150+ENST00000342771AUTS2chr770240341+403282281959643

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
ENST00000609116ENST00000406775PTBP2chr197189150+AUTS2chr770240341+0.0113555770.98864436
ENST00000609116ENST00000342771PTBP2chr197189150+AUTS2chr770240341+0.0074821890.9925178
ENST00000370197ENST00000406775PTBP2chr197189150+AUTS2chr770240341+0.0115379350.9884621
ENST00000370197ENST00000342771PTBP2chr197189150+AUTS2chr770240341+0.0076104550.9923895
ENST00000370198ENST00000406775PTBP2chr197189150+AUTS2chr770240341+0.0115379350.9884621
ENST00000370198ENST00000342771PTBP2chr197189150+AUTS2chr770240341+0.0076104550.9923895
ENST00000426398ENST00000406775PTBP2chr197189150+AUTS2chr770240341+0.0112061690.9887938
ENST00000426398ENST00000342771PTBP2chr197189150+AUTS2chr770240341+0.0073860050.99261403

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 PTBP2-AUTS2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
PTBP2chr197189150AUTS2chr77024034112128MDGIVTEVAVGVKLTDPFRPMLRKPG
PTBP2chr197189150AUTS2chr7702403418218MDGIVTEVAVGVKLTDPFRPMLRKPG
PTBP2chr197189150AUTS2chr7702403419428MDGIVTEVAVGVKLTDPFRPMLRKPG

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Potential FusionNeoAntigen Information of PTBP2-AUTS2 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.
PTBP2-AUTS2_97189150_70240341.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)
PTBP2-AUTS2chr197189150chr77024034194HLA-B44:03TEVAVGVKL0.99370.9896514
PTBP2-AUTS2chr197189150chr77024034194HLA-B50:02TEVAVGVKL0.99340.6477514
PTBP2-AUTS2chr197189150chr77024034194HLA-B13:01TEVAVGVKL0.98630.9704514
PTBP2-AUTS2chr197189150chr77024034194HLA-B47:01TEVAVGVKL0.98580.6933514
PTBP2-AUTS2chr197189150chr77024034194HLA-B18:01TEVAVGVKL0.95590.972514
PTBP2-AUTS2chr197189150chr77024034194HLA-B45:01TEVAVGVKL0.89720.9665514
PTBP2-AUTS2chr197189150chr77024034194HLA-B48:01TEVAVGVKL0.87080.5135514
PTBP2-AUTS2chr197189150chr77024034194HLA-B41:01TEVAVGVKL0.40720.9794514
PTBP2-AUTS2chr197189150chr77024034194HLA-B39:13TEVAVGVKL0.39240.9867514
PTBP2-AUTS2chr197189150chr77024034194HLA-B50:01TEVAVGVKL0.33550.7835514
PTBP2-AUTS2chr197189150chr77024034194HLA-A02:13KLTDPFRPML0.9720.70061222
PTBP2-AUTS2chr197189150chr77024034194HLA-A02:67KLTDPFRPML0.96870.67731222
PTBP2-AUTS2chr197189150chr77024034194HLA-A02:30KLTDPFRPML0.96870.67731222
PTBP2-AUTS2chr197189150chr77024034194HLA-A02:24KLTDPFRPML0.96870.67731222
PTBP2-AUTS2chr197189150chr77024034194HLA-A02:11KLTDPFRPML0.96760.69561222
PTBP2-AUTS2chr197189150chr77024034194HLA-A02:60KLTDPFRPML0.96740.61791222
PTBP2-AUTS2chr197189150chr77024034194HLA-A02:27KLTDPFRPML0.96460.62451222
PTBP2-AUTS2chr197189150chr77024034194HLA-A02:04KLTDPFRPML0.96260.58151222
PTBP2-AUTS2chr197189150chr77024034194HLA-A02:16KLTDPFRPML0.95190.59391222
PTBP2-AUTS2chr197189150chr77024034194HLA-A02:29KLTDPFRPML0.85490.68091222
PTBP2-AUTS2chr197189150chr77024034194HLA-A02:35KLTDPFRPML0.80870.69511222
PTBP2-AUTS2chr197189150chr77024034194HLA-A02:20KLTDPFRPML0.80760.68181222
PTBP2-AUTS2chr197189150chr77024034194HLA-A74:09KLTDPFRPMLR0.99420.72011223
PTBP2-AUTS2chr197189150chr77024034194HLA-A74:11KLTDPFRPMLR0.99420.72011223
PTBP2-AUTS2chr197189150chr77024034194HLA-A74:03KLTDPFRPMLR0.99420.72011223
PTBP2-AUTS2chr197189150chr77024034194HLA-A31:06KLTDPFRPMLR0.99130.54091223
PTBP2-AUTS2chr197189150chr77024034194HLA-A31:02KLTDPFRPMLR0.98790.69941223
PTBP2-AUTS2chr197189150chr77024034194HLA-B40:06TEVAVGVKL0.99890.7028514
PTBP2-AUTS2chr197189150chr77024034194HLA-B40:03TEVAVGVKL0.9880.5703514
PTBP2-AUTS2chr197189150chr77024034194HLA-B15:04KLTDPFRPM0.88080.88951221
PTBP2-AUTS2chr197189150chr77024034194HLA-B39:08TEVAVGVKL0.57560.9551514
PTBP2-AUTS2chr197189150chr77024034194HLA-A02:07KLTDPFRPML0.96990.72811222
PTBP2-AUTS2chr197189150chr77024034194HLA-A02:01KLTDPFRPML0.96870.67731222
PTBP2-AUTS2chr197189150chr77024034194HLA-A31:01KLTDPFRPMLR0.99410.69471223
PTBP2-AUTS2chr197189150chr77024034194HLA-B40:04TEVAVGVKL0.99860.7711514
PTBP2-AUTS2chr197189150chr77024034194HLA-B44:26TEVAVGVKL0.99370.9896514
PTBP2-AUTS2chr197189150chr77024034194HLA-B44:07TEVAVGVKL0.99370.9896514
PTBP2-AUTS2chr197189150chr77024034194HLA-B44:13TEVAVGVKL0.99370.9896514
PTBP2-AUTS2chr197189150chr77024034194HLA-B18:04TEVAVGVKL0.96720.9755514
PTBP2-AUTS2chr197189150chr77024034194HLA-B18:07TEVAVGVKL0.96360.9527514
PTBP2-AUTS2chr197189150chr77024034194HLA-B18:08TEVAVGVKL0.96140.9693514
PTBP2-AUTS2chr197189150chr77024034194HLA-B18:05TEVAVGVKL0.95590.972514
PTBP2-AUTS2chr197189150chr77024034194HLA-B18:06TEVAVGVKL0.93930.9744514
PTBP2-AUTS2chr197189150chr77024034194HLA-A32:01KLTDPFRPM0.93340.93111221
PTBP2-AUTS2chr197189150chr77024034194HLA-B18:03TEVAVGVKL0.91280.9698514
PTBP2-AUTS2chr197189150chr77024034194HLA-B18:11TEVAVGVKL0.77490.968514
PTBP2-AUTS2chr197189150chr77024034194HLA-B15:73KLTDPFRPM0.76040.81981221
PTBP2-AUTS2chr197189150chr77024034194HLA-B15:30KLTDPFRPM0.60660.81221221
PTBP2-AUTS2chr197189150chr77024034194HLA-B41:03TEVAVGVKL0.58540.7085514
PTBP2-AUTS2chr197189150chr77024034194HLA-B39:11TEVAVGVKL0.57420.9382514
PTBP2-AUTS2chr197189150chr77024034194HLA-B39:31TEVAVGVKL0.33850.9757514
PTBP2-AUTS2chr197189150chr77024034194HLA-B50:04TEVAVGVKL0.33550.7835514
PTBP2-AUTS2chr197189150chr77024034194HLA-B50:05TEVAVGVKL0.33550.7835514
PTBP2-AUTS2chr197189150chr77024034194HLA-B39:02TEVAVGVKL0.30730.9865514
PTBP2-AUTS2chr197189150chr77024034194HLA-B48:02TEVAVGVKL0.2020.9823514
PTBP2-AUTS2chr197189150chr77024034194HLA-A02:14KLTDPFRPML0.9470.7231222
PTBP2-AUTS2chr197189150chr77024034194HLA-B40:04VTEVAVGVKL0.60920.7932414
PTBP2-AUTS2chr197189150chr77024034194HLA-A74:01KLTDPFRPMLR0.99420.72011223

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Potential FusionNeoAntigen Information of PTBP2-AUTS2 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.
PTBP2-AUTS2_97189150_70240341.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)
PTBP2-AUTS2chr197189150chr77024034194DRB1-0111MDGIVTEVAVGVKLT015

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Fusion breakpoint peptide structures of PTBP2-AUTS2

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
2197EVAVGVKLTDPFRPPTBP2AUTS2chr197189150chr77024034194

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PTBP2-AUTS2

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-B14:023BVN2197EVAVGVKLTDPFRP-7.9962-8.1096
HLA-B14:023BVN2197EVAVGVKLTDPFRP-5.70842-6.74372
HLA-B52:013W392197EVAVGVKLTDPFRP-6.83737-6.95077
HLA-B52:013W392197EVAVGVKLTDPFRP-4.4836-5.5189
HLA-A11:014UQ22197EVAVGVKLTDPFRP-10.0067-10.1201
HLA-A11:014UQ22197EVAVGVKLTDPFRP-9.03915-10.0745
HLA-A24:025HGA2197EVAVGVKLTDPFRP-6.56204-6.67544
HLA-A24:025HGA2197EVAVGVKLTDPFRP-5.42271-6.45801
HLA-B44:053DX82197EVAVGVKLTDPFRP-7.85648-8.89178
HLA-B44:053DX82197EVAVGVKLTDPFRP-5.3978-5.5112
HLA-A02:016TDR2197EVAVGVKLTDPFRP-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of PTBP2-AUTS2

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
PTBP2-AUTS2chr197189150chr7702403411221KLTDPFRPMAAGTTGACAGATCCTTTCAGACCTATG
PTBP2-AUTS2chr197189150chr7702403411222KLTDPFRPMLAAGTTGACAGATCCTTTCAGACCTATGTTA
PTBP2-AUTS2chr197189150chr7702403411223KLTDPFRPMLRAAGTTGACAGATCCTTTCAGACCTATGTTAAGG
PTBP2-AUTS2chr197189150chr770240341414VTEVAVGVKLGTCACTGAGGTTGCAGTTGGCGTGAAGTTG
PTBP2-AUTS2chr197189150chr770240341514TEVAVGVKLACTGAGGTTGCAGTTGGCGTGAAGTTG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
PTBP2-AUTS2chr197189150chr770240341015MDGIVTEVAVGVKLTATGGACGGAATCGTCACTGAGGTTGCAGTTGGCGTGAAGTTGACA

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Information of the samples that have these potential fusion neoantigens of PTBP2-AUTS2

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
N/APTBP2-AUTS2chr197189150ENST00000370197chr770240341ENST00000342771DA721803

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Potential target of CAR-T therapy development for PTBP2-AUTS2

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 PTBP2-AUTS2

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 PTBP2-AUTS2

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