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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:USP6-PTRH2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: USP6-PTRH2
FusionPDB ID: 97623
FusionGDB2.0 ID: 97623
HgeneTgene
Gene symbol

USP6

PTRH2

Gene ID

9098

51651

Gene nameubiquitin specific peptidase 6peptidyl-tRNA hydrolase 2
SynonymsHRP1|TRE17|TRE2|TRESMCR|Tre-2|USP6-shortBIT1|CFAP37|CGI-147|IMNEPD|PTH|PTH 2|PTH2
Cytomap

17p13.2

17q23.1

Type of geneprotein-codingprotein-coding
Descriptionubiquitin carboxyl-terminal hydrolase 6TBC1D3 and USP32 fusiondeubiquitinating enzyme 6hyperpolymorphic gene 1proto-oncogene TRE-2ubiquitin specific peptidase 6 (Tre-2 oncogene)ubiquitin specific protease 6 (Tre-2 oncogene)ubiquitin thioesterase 6peptidyl-tRNA hydrolase 2, mitochondrialbcl-2 inhibitor of transcription 1cilia and flagella associated protein 37
Modification date2020032220200313
UniProtAcc

USP6NL

Main function of 5'-partner protein: 828		.
Ensembl transtripts involved in fusion geneENST idsENST00000332776, ENST00000250066, 
ENST00000304328, ENST00000574788, 
ENST00000572429, 		ENST00000393038, 
ENST00000409433, ENST00000470557, 
ENST00000537860, ENST00000579915, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score4 X 1 X 1=49 X 6 X 6=324
# samples 512
** MAII scorelog2(5/4*10)=3.64385618977473log2(12/324*10)=-1.43295940727611
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: USP6 [Title/Abstract] AND PTRH2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: USP6 [Title/Abstract] AND PTRH2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)USP6(5052062)-PTRH2(57775339), # samples:1
Anticipated loss of major functional domain due to fusion event.USP6-PTRH2 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.
USP6-PTRH2 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.
USP6-PTRH2 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.
USP6-PTRH2 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.
USP6-PTRH2 seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF.
USP6-PTRH2 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
USP6-PTRH2 seems lost the major protein functional domain in Tgene partner, which is a essential gene 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
HgeneUSP6

GO:0016579

protein deubiquitination

16127172

HgeneUSP6

GO:0060627

regulation of vesicle-mediated transport

15509780



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/chr17:5052062/chr17:57775339)
- 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 USP6 (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 PTRH2 (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)
ENST00000574788USP6chr175052062+ENST00000409433PTRH2chr1757775339-55444873219454121072
ENST00000574788USP6chr175052062+ENST00000470557PTRH2chr1757775339-55404873219454121072
ENST00000304328USP6chr175052062+ENST00000409433PTRH2chr1757775339-5224455328615092743
ENST00000304328USP6chr175052062+ENST00000470557PTRH2chr1757775339-5220455328615092743
ENST00000250066USP6chr175052062+ENST00000409433PTRH2chr1757775339-50134342166348811072
ENST00000250066USP6chr175052062+ENST00000470557PTRH2chr1757775339-50094342166348811072

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
ENST00000574788ENST00000409433USP6chr175052062+PTRH2chr1757775339-0.0133737530.9866262
ENST00000574788ENST00000470557USP6chr175052062+PTRH2chr1757775339-0.013567260.98643273
ENST00000304328ENST00000409433USP6chr175052062+PTRH2chr1757775339-0.0064861120.9935138
ENST00000304328ENST00000470557USP6chr175052062+PTRH2chr1757775339-0.0066069650.993393
ENST00000250066ENST00000409433USP6chr175052062+PTRH2chr1757775339-0.006156530.99384344
ENST00000250066ENST00000470557USP6chr175052062+PTRH2chr1757775339-0.0062597050.9937403

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 USP6-PTRH2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
USP6chr175052062PTRH2chr1757775339434236AQERKDILMKYDKGHRAGLPEDKGPE
USP6chr175052062PTRH2chr17577753394553182QLATCWQAEHCGEVHNKDMSWPEEMS
USP6chr175052062PTRH2chr1757775339487336AQERKDILMKYDKGHRAGLPEDKGPE

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Potential FusionNeoAntigen Information of USP6-PTRH2 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.
USP6-PTRH2_5052062_57775339.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)
USP6-PTRH2chr175052062chr17577753394553HLA-A26:02EVHNKDMSW0.98610.64871221
USP6-PTRH2chr175052062chr17577753394553HLA-A26:14EVHNKDMSW0.97370.69591221
USP6-PTRH2chr175052062chr17577753394553HLA-A26:15EVHNKDMSW0.97370.69591221
USP6-PTRH2chr175052062chr17577753394342HLA-B39:06MKYDKGHRA0.90820.7202817
USP6-PTRH2chr175052062chr17577753394553HLA-A26:03EVHNKDMSW0.87360.69611221
USP6-PTRH2chr175052062chr17577753394342HLA-B14:02MKYDKGHRA0.7850.8516817
USP6-PTRH2chr175052062chr17577753394342HLA-B14:01MKYDKGHRA0.7850.8516817
USP6-PTRH2chr175052062chr17577753394553HLA-A26:08EVHNKDMSW0.44810.51071221
USP6-PTRH2chr175052062chr17577753394553HLA-A32:13EVHNKDMSW0.26670.97351221
USP6-PTRH2chr175052062chr17577753394553HLA-B44:03GEVHNKDMSW0.99970.99121121
USP6-PTRH2chr175052062chr17577753394553HLA-B44:05GEVHNKDMSW0.99920.64691121
USP6-PTRH2chr175052062chr17577753394553HLA-A26:01EVHNKDMSW0.97370.69591221
USP6-PTRH2chr175052062chr17577753394342HLA-B73:01MKYDKGHRA0.84320.8403817
USP6-PTRH2chr175052062chr17577753394553HLA-B44:08GEVHNKDMSW0.99950.62881121
USP6-PTRH2chr175052062chr17577753394553HLA-B44:09GEVHNKDMSW0.99860.69721121
USP6-PTRH2chr175052062chr17577753394342HLA-C04:07KYDKGHRAGL0.99630.9236919
USP6-PTRH2chr175052062chr17577753394342HLA-C04:10KYDKGHRAGL0.99630.9245919
USP6-PTRH2chr175052062chr17577753394553HLA-B44:10GEVHNKDMSW0.93490.77581121
USP6-PTRH2chr175052062chr17577753394553HLA-A25:01EVHNKDMSW0.9960.93931221
USP6-PTRH2chr175052062chr17577753394553HLA-B15:13EVHNKDMSW0.83470.62331221
USP6-PTRH2chr175052062chr17577753394553HLA-B15:24EVHNKDMSW0.28880.88681221
USP6-PTRH2chr175052062chr17577753394553HLA-B44:26GEVHNKDMSW0.99970.99121121
USP6-PTRH2chr175052062chr17577753394553HLA-B44:13GEVHNKDMSW0.99970.99121121
USP6-PTRH2chr175052062chr17577753394553HLA-B44:07GEVHNKDMSW0.99970.99121121
USP6-PTRH2chr175052062chr17577753394342HLA-C04:01KYDKGHRAGL0.99630.9236919
USP6-PTRH2chr175052062chr17577753394342HLA-C18:01KYDKGHRAGL0.99040.923919
USP6-PTRH2chr175052062chr17577753394342HLA-A02:03LMKYDKGHRA0.88140.6045717
USP6-PTRH2chr175052062chr17577753394342HLA-A02:03ILMKYDKGHRA0.97490.5145617

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Potential FusionNeoAntigen Information of USP6-PTRH2 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.
USP6-PTRH2_5052062_57775339.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)
USP6-PTRH2chr175052062chr17577753394342DRB1-0437RKDILMKYDKGHRAG318
USP6-PTRH2chr175052062chr17577753394342DRB1-1102RKDILMKYDKGHRAG318
USP6-PTRH2chr175052062chr17577753394342DRB1-1116RKDILMKYDKGHRAG318
USP6-PTRH2chr175052062chr17577753394342DRB1-1165RKDILMKYDKGHRAG318
USP6-PTRH2chr175052062chr17577753394342DRB1-1170RKDILMKYDKGHRAG318
USP6-PTRH2chr175052062chr17577753394342DRB1-1186RKDILMKYDKGHRAG318
USP6-PTRH2chr175052062chr17577753394342DRB1-1301RKDILMKYDKGHRAG318
USP6-PTRH2chr175052062chr17577753394342DRB1-1315RKDILMKYDKGHRAG318
USP6-PTRH2chr175052062chr17577753394342DRB1-1315KDILMKYDKGHRAGL419
USP6-PTRH2chr175052062chr17577753394342DRB1-1316RKDILMKYDKGHRAG318
USP6-PTRH2chr175052062chr17577753394342DRB1-1317RKDILMKYDKGHRAG318
USP6-PTRH2chr175052062chr17577753394342DRB1-1317KDILMKYDKGHRAGL419
USP6-PTRH2chr175052062chr17577753394342DRB1-1322RKDILMKYDKGHRAG318
USP6-PTRH2chr175052062chr17577753394342DRB1-1327RKDILMKYDKGHRAG318
USP6-PTRH2chr175052062chr17577753394342DRB1-1335RKDILMKYDKGHRAG318
USP6-PTRH2chr175052062chr17577753394342DRB1-1351RKDILMKYDKGHRAG318
USP6-PTRH2chr175052062chr17577753394342DRB1-1352RKDILMKYDKGHRAG318
USP6-PTRH2chr175052062chr17577753394342DRB1-1357RKDILMKYDKGHRAG318
USP6-PTRH2chr175052062chr17577753394342DRB1-1357KDILMKYDKGHRAGL419
USP6-PTRH2chr175052062chr17577753394342DRB1-1359RKDILMKYDKGHRAG318
USP6-PTRH2chr175052062chr17577753394342DRB1-1361RKDILMKYDKGHRAG318
USP6-PTRH2chr175052062chr17577753394342DRB1-1364RKDILMKYDKGHRAG318
USP6-PTRH2chr175052062chr17577753394342DRB1-1368RKDILMKYDKGHRAG318
USP6-PTRH2chr175052062chr17577753394342DRB1-1369RKDILMKYDKGHRAG318
USP6-PTRH2chr175052062chr17577753394342DRB1-1371RKDILMKYDKGHRAG318
USP6-PTRH2chr175052062chr17577753394342DRB1-1379RKDILMKYDKGHRAG318
USP6-PTRH2chr175052062chr17577753394342DRB1-1380RKDILMKYDKGHRAG318
USP6-PTRH2chr175052062chr17577753394342DRB1-1383RKDILMKYDKGHRAG318
USP6-PTRH2chr175052062chr17577753394342DRB1-1387RKDILMKYDKGHRAG318
USP6-PTRH2chr175052062chr17577753394342DRB1-1391RKDILMKYDKGHRAG318
USP6-PTRH2chr175052062chr17577753394342DRB1-1392RKDILMKYDKGHRAG318
USP6-PTRH2chr175052062chr17577753394342DRB1-1398RKDILMKYDKGHRAG318
USP6-PTRH2chr175052062chr17577753394342DRB1-1525DILMKYDKGHRAGLP520
USP6-PTRH2chr175052062chr17577753394342DRB3-0204DILMKYDKGHRAGLP520

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Fusion breakpoint peptide structures of USP6-PTRH2

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
3803ILMKYDKGHRAGLPUSP6PTRH2chr175052062chr17577753394342
File nameBPseqHgeneTgeneHchrHbpTchrTbpAAlen
7127QAEHCGEVHNKDMSUSP6PTRH2chr175052062chr17577753394553

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of USP6-PTRH2

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-B14:023BVN3803ILMKYDKGHRAGLP-7.9962-8.1096
HLA-B14:023BVN3803ILMKYDKGHRAGLP-5.70842-6.74372
HLA-B52:013W393803ILMKYDKGHRAGLP-6.83737-6.95077
HLA-B52:013W393803ILMKYDKGHRAGLP-4.4836-5.5189
HLA-A11:014UQ23803ILMKYDKGHRAGLP-10.0067-10.1201
HLA-A11:014UQ23803ILMKYDKGHRAGLP-9.03915-10.0745
HLA-A24:025HGA3803ILMKYDKGHRAGLP-6.56204-6.67544
HLA-A24:025HGA3803ILMKYDKGHRAGLP-5.42271-6.45801
HLA-B44:053DX83803ILMKYDKGHRAGLP-7.85648-8.89178
HLA-B44:053DX83803ILMKYDKGHRAGLP-5.3978-5.5112
HLA-A02:016TDR3803ILMKYDKGHRAGLP-3.37154-4.40684
HLA-B14:023BVN7127QAEHCGEVHNKDMS-6.35597-6.46937
HLA-B14:023BVN7127QAEHCGEVHNKDMS-5.80319-6.83849
HLA-B52:013W397127QAEHCGEVHNKDMS-6.67268-6.78608
HLA-B52:013W397127QAEHCGEVHNKDMS-5.72753-6.76283
HLA-A11:014UQ27127QAEHCGEVHNKDMS-7.31441-7.42781
HLA-A11:014UQ27127QAEHCGEVHNKDMS-7.25126-8.28656
HLA-A24:025HGA7127QAEHCGEVHNKDMS-8.41244-8.52584
HLA-A24:025HGA7127QAEHCGEVHNKDMS-5.27978-6.31508
HLA-B44:053DX87127QAEHCGEVHNKDMS-4.03348-4.14688
HLA-B44:053DX87127QAEHCGEVHNKDMS-3.56413-4.59943
HLA-A02:016TDR7127QAEHCGEVHNKDMS-6.72173-7.75703

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Vaccine Design for the FusionNeoAntigens of USP6-PTRH2

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
USP6-PTRH2chr175052062chr17577753391121GEVHNKDMSWAAAATGATGCCCTCCAAATCCTTGGTTATG
USP6-PTRH2chr175052062chr17577753391221EVHNKDMSWATGATGCCCTCCAAATCCTTGGTTATG
USP6-PTRH2chr175052062chr1757775339617ILMKYDKGHRAATTGCAGTCCACCGAAAAATGATGCCCTCCAAA
USP6-PTRH2chr175052062chr1757775339717LMKYDKGHRAGCAGTCCACCGAAAAATGATGCCCTCCAAA
USP6-PTRH2chr175052062chr1757775339817MKYDKGHRAGTCCACCGAAAAATGATGCCCTCCAAA
USP6-PTRH2chr175052062chr1757775339919KYDKGHRAGLCACCGAAAAATGATGCCCTCCAAATCCTTG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
USP6-PTRH2chr175052062chr1757775339318RKDILMKYDKGHRAGGGTTACATCATTGCAGTCCACCGAAAAATGATGCCCTCCAAATCC
USP6-PTRH2chr175052062chr1757775339419KDILMKYDKGHRAGLTACATCATTGCAGTCCACCGAAAAATGATGCCCTCCAAATCCTTG
USP6-PTRH2chr175052062chr1757775339520DILMKYDKGHRAGLPATCATTGCAGTCCACCGAAAAATGATGCCCTCCAAATCCTTGGTT

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Information of the samples that have these potential fusion neoantigens of USP6-PTRH2

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
BRCAUSP6-PTRH2chr175052062ENST00000250066chr1757775339ENST00000409433TCGA-A2-A3XZ
BRCAUSP6-PTRH2chr175052062ENST00000304328chr1757775339ENST00000409433TCGA-A2-A3XZ

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Potential target of CAR-T therapy development for USP6-PTRH2

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 USP6-PTRH2

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 USP6-PTRH2

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