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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:USP12-LNX2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: USP12-LNX2
FusionPDB ID: 97185
FusionGDB2.0 ID: 97185
HgeneTgene
Gene symbol

USP12

LNX2

Gene ID

219333

222484

Gene nameubiquitin specific peptidase 12ligand of numb-protein X 2
SynonymsUBH1|USP12L1PDZRN1
Cytomap

13q12.13

13q12.2

Type of geneprotein-codingprotein-coding
Descriptionubiquitin carboxyl-terminal hydrolase 12deubiquitinating enzyme 12ubiquitin specific protease 12 like 1ubiquitin thioesterase 12ubiquitin thiolesterase 12ubiquitin-hydrolyzing enzyme 1ubiquitin-specific-processing protease 12ligand of Numb protein X 2PDZ domain containing ring finger 1PDZ domain-containing RING finger protein 1numb-binding protein 2
Modification date2020031320200327
UniProtAcc.

Q8N448

Main function of 5'-partner protein:
Ensembl transtripts involved in fusion geneENST idsENST00000282344, ENST00000316334, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score11 X 9 X 6=5943 X 3 X 2=18
# samples 124
** MAII scorelog2(12/594*10)=-2.30742852519225
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(4/18*10)=1.15200309344505
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: USP12 [Title/Abstract] AND LNX2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: USP12 [Title/Abstract] AND LNX2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)USP12(27669737)-LNX2(28134122), # samples:1
USP12(27669738)-LNX2(28134122), # samples:1
Anticipated loss of major functional domain due to fusion event.USP12-LNX2 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.
USP12-LNX2 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.
USP12-LNX2 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.
USP12-LNX2 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
HgeneUSP12

GO:0016579

protein deubiquitination

19075014|24145035



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/chr13:27669737/chr13:28134122)
- 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 USP12 (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 LNX2 (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)
ENST00000282344USP12chr1327669737-ENST00000316334LNX2chr1328134122-41018301731678501
ENST00000282344USP12chr1327669738-ENST00000316334LNX2chr1328134122-41018301731678501

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
ENST00000282344ENST00000316334USP12chr1327669737-LNX2chr1328134122-0.0002259050.99977416
ENST00000282344ENST00000316334USP12chr1327669738-LNX2chr1328134122-0.0002259050.99977416

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 USP12-LNX2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
USP12chr1327669737LNX2chr1328134122830214EIFQGTLTNETRCLTCETASGERVNL
USP12chr1327669738LNX2chr1328134122830214EIFQGTLTNETRCLTCETASGERVNL

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Potential FusionNeoAntigen Information of USP12-LNX2 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.
USP12-LNX2_27669737_28134122.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)
USP12-LNX2chr1327669737chr1328134122830HLA-B39:06TRCLTCETA0.98420.91741019
USP12-LNX2chr1327669737chr1328134122830HLA-B73:01TRCLTCETA0.91690.81351019

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Potential FusionNeoAntigen Information of USP12-LNX2 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 USP12-LNX2

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
5733LTNETRCLTCETASUSP12LNX2chr1327669737chr1328134122830

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of USP12-LNX2

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-B14:023BVN5733LTNETRCLTCETAS-7.15543-7.26883
HLA-B14:023BVN5733LTNETRCLTCETAS-4.77435-5.80965
HLA-B52:013W395733LTNETRCLTCETAS-6.80875-6.92215
HLA-B52:013W395733LTNETRCLTCETAS-4.20386-5.23916
HLA-A11:014UQ25733LTNETRCLTCETAS-7.5194-8.5547
HLA-A11:014UQ25733LTNETRCLTCETAS-6.9601-7.0735
HLA-A24:025HGA5733LTNETRCLTCETAS-7.52403-7.63743
HLA-A24:025HGA5733LTNETRCLTCETAS-5.82433-6.85963
HLA-B27:056PYJ5733LTNETRCLTCETAS-3.28285-4.31815
HLA-B44:053DX85733LTNETRCLTCETAS-5.91172-6.94702
HLA-B44:053DX85733LTNETRCLTCETAS-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of USP12-LNX2

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
USP12-LNX2chr1327669737chr13281341221019TRCLTCETATGTGAAACTGCCAGTGGAGAGAGAGTG

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 USP12-LNX2

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
STADUSP12-LNX2chr1327669737ENST00000282344chr1328134122ENST00000316334TCGA-BR-4357

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Potential target of CAR-T therapy development for USP12-LNX2

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 USP12-LNX2

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 USP12-LNX2

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