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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:TMEM170A-USP22

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TMEM170A-USP22
FusionPDB ID: 91780
FusionGDB2.0 ID: 91780
HgeneTgene
Gene symbol

TMEM170A

USP22

Gene ID

124491

23326

Gene nametransmembrane protein 170Aubiquitin specific peptidase 22
SynonymsTMEM170USP3L
Cytomap

16q23.1

17p11.2

Type of geneprotein-codingprotein-coding
Descriptiontransmembrane protein 170Atransmembrane protein 170ubiquitin carboxyl-terminal hydrolase 22deubiquitinating enzyme 22ubiquitin specific protease 22ubiquitin thioesterase 22ubiquitin thiolesterase 22ubiquitin-specific processing protease 22
Modification date2020031320200313
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000357613, ENST00000566980, 
ENST00000561878, ENST00000567796, 
ENST00000569276, ENST00000569540, 
ENST00000455117, ENST00000261497, 
ENST00000537526, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score7 X 6 X 7=29413 X 8 X 5=520
# samples 914
** MAII scorelog2(9/294*10)=-1.70781924850669
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(14/520*10)=-1.89308479608349
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: TMEM170A [Title/Abstract] AND USP22 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: TMEM170A [Title/Abstract] AND USP22 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TMEM170A(75485636)-USP22(20931987), # samples:1
Anticipated loss of major functional domain due to fusion event.TMEM170A-USP22 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.
TMEM170A-USP22 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.
TMEM170A-USP22 seems lost the major protein functional domain in Tgene partner, which is a epigenetic factor due to the frame-shifted ORF.
TMEM170A-USP22 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
TgeneUSP22

GO:0016574

histone ubiquitination

18469533

TgeneUSP22

GO:0016578

histone deubiquitination

18206972|18206973

TgeneUSP22

GO:0016579

protein deubiquitination

16378762



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/chr16:75485636/chr17:20931987)
- 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 TMEM170A (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 USP22 (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)
ENST00000566980TMEM170Achr1675485636-ENST00000261497USP22chr1720931987-5009168751574499
ENST00000566980TMEM170Achr1675485636-ENST00000537526USP22chr1720931987-5009168751574499

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
ENST00000566980ENST00000261497TMEM170Achr1675485636-USP22chr1720931987-0.0083184480.9916815
ENST00000566980ENST00000537526TMEM170Achr1675485636-USP22chr1720931987-0.0083184480.9916815

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 TMEM170A-USP22

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
TMEM170Achr1675485636USP22chr172093198716831DYWPSSPSDITNMAKSCICHVCGVHL

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Potential FusionNeoAntigen Information of TMEM170A-USP22 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.
TMEM170A-USP22_75485636_20931987.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)
TMEM170A-USP22chr1675485636chr1720931987168HLA-B35:04SPSDITNMA0.73740.7764514
TMEM170A-USP22chr1675485636chr1720931987168HLA-B35:02SPSDITNMA0.73740.7764514
TMEM170A-USP22chr1675485636chr1720931987168HLA-B35:12SPSDITNMA0.73740.7764514
TMEM170A-USP22chr1675485636chr1720931987168HLA-B39:10SPSDITNMA0.23260.7305514
TMEM170A-USP22chr1675485636chr1720931987168HLA-B35:09SPSDITNMA0.73740.7764514
TMEM170A-USP22chr1675485636chr1720931987168HLA-B67:01SPSDITNMA0.41060.6444514

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Potential FusionNeoAntigen Information of TMEM170A-USP22 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.

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)

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Fusion breakpoint peptide structures of TMEM170A-USP22

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
6979PSDITNMAKSCICHTMEM170AUSP22chr1675485636chr1720931987168

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of TMEM170A-USP22

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-B14:023BVN6979PSDITNMAKSCICH-6.12283-6.12283
HLA-A24:025HGA6979PSDITNMAKSCICH-7.36995-7.36995

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Vaccine Design for the FusionNeoAntigens of TMEM170A-USP22

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
TMEM170A-USP22chr1675485636chr1720931987514SPSDITNMATCACCCTCAGACATCACAAATATGGCC

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

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Information of the samples that have these potential fusion neoantigens of TMEM170A-USP22

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
PRADTMEM170A-USP22chr1675485636ENST00000566980chr1720931987ENST00000261497TCGA-CH-5790-01A

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Potential target of CAR-T therapy development for TMEM170A-USP22

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
HgeneTMEM170Achr16:75485636chr17:20931987ENST00000357613-2351_7178122.0TransmembraneHelical

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 TMEM170A-USP22

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 TMEM170A-USP22

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