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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:LUC7L3-USP22

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: LUC7L3-USP22
FusionPDB ID: 50357
FusionGDB2.0 ID: 50357
HgeneTgene
Gene symbol

LUC7L3

USP22

Gene ID

51747

23326

Gene nameLUC7 like 3 pre-mRNA splicing factorubiquitin specific peptidase 22
SynonymsCRA|CREAP-1|CROP|LUC7A|OA48-18|hLuc7AUSP3L
Cytomap

17q21.33

17p11.2

Type of geneprotein-codingprotein-coding
Descriptionluc7-like protein 3CRE-associated protein 1LUC7-like 3cAMP regulatory element-associated protein 1cisplatin resistance-associated-overexpressed proteinokadaic acid-inducible phosphoprotein OA48-18ubiquitin carboxyl-terminal hydrolase 22deubiquitinating enzyme 22ubiquitin specific protease 22ubiquitin thioesterase 22ubiquitin thiolesterase 22ubiquitin-specific processing protease 22
Modification date2020031320200313
UniProtAcc

O95232

Main function of 5'-partner protein: FUNCTION: Binds cAMP regulatory element DNA sequence. May play a role in RNA splicing. {ECO:0000269|PubMed:16462885}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000240304, ENST00000311571, 
ENST00000393227, ENST00000505658, 
ENST00000544170, ENST00000503798, 
ENST00000455117, ENST00000261497, 
ENST00000537526, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score18 X 13 X 8=187213 X 8 X 5=520
# samples 2214
** MAII scorelog2(22/1872*10)=-3.08900500605875
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: LUC7L3 [Title/Abstract] AND USP22 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: LUC7L3 [Title/Abstract] AND USP22 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)LUC7L3(48797192)-USP22(20931987), # samples:1
Anticipated loss of major functional domain due to fusion event.LUC7L3-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.
LUC7L3-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.
LUC7L3-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.
LUC7L3-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.
* 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/chr17:48797192/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 LUC7L3 (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)
ENST00000505658LUC7L3chr1748797192+ENST00000261497USP22chr1720931987-51292881531694513
ENST00000505658LUC7L3chr1748797192+ENST00000537526USP22chr1720931987-51292881531694513
ENST00000393227LUC7L3chr1748797192+ENST00000261497USP22chr1720931987-5074233981639513
ENST00000393227LUC7L3chr1748797192+ENST00000537526USP22chr1720931987-5074233981639513
ENST00000311571LUC7L3chr1748797192+ENST00000261497USP22chr1720931987-5070229941635513
ENST00000311571LUC7L3chr1748797192+ENST00000537526USP22chr1720931987-5070229941635513
ENST00000240304LUC7L3chr1748797192+ENST00000261497USP22chr1720931987-5070229941635513
ENST00000240304LUC7L3chr1748797192+ENST00000537526USP22chr1720931987-5070229941635513

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
ENST00000505658ENST00000261497LUC7L3chr1748797192+USP22chr1720931987-0.0039862650.99601376
ENST00000505658ENST00000537526LUC7L3chr1748797192+USP22chr1720931987-0.0039862650.99601376
ENST00000393227ENST00000261497LUC7L3chr1748797192+USP22chr1720931987-0.0039660640.99603397
ENST00000393227ENST00000537526LUC7L3chr1748797192+USP22chr1720931987-0.0039660640.99603397
ENST00000311571ENST00000261497LUC7L3chr1748797192+USP22chr1720931987-0.0040151910.9959848
ENST00000311571ENST00000537526LUC7L3chr1748797192+USP22chr1720931987-0.0040151910.9959848
ENST00000240304ENST00000261497LUC7L3chr1748797192+USP22chr1720931987-0.0040151910.9959848
ENST00000240304ENST00000537526LUC7L3chr1748797192+USP22chr1720931987-0.0040151910.9959848

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 LUC7L3-USP22

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
LUC7L3chr1748797192USP22chr172093198722945DEKRSNVRWDHESAKSCICHVCGVHL
LUC7L3chr1748797192USP22chr172093198723345DEKRSNVRWDHESAKSCICHVCGVHL
LUC7L3chr1748797192USP22chr172093198728845DEKRSNVRWDHESAKSCICHVCGVHL

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Potential FusionNeoAntigen Information of LUC7L3-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.
LUC7L3-USP22_48797192_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)
LUC7L3-USP22chr1748797192chr1720931987229HLA-B27:05VRWDHESAK0.9980.7441615
LUC7L3-USP22chr1748797192chr1720931987229HLA-B27:04VRWDHESAK0.98780.7234615
LUC7L3-USP22chr1748797192chr1720931987229HLA-B39:01DHESAKSCI0.95210.7148918
LUC7L3-USP22chr1748797192chr1720931987229HLA-B38:02DHESAKSCI0.92980.8357918
LUC7L3-USP22chr1748797192chr1720931987229HLA-B38:01DHESAKSCI0.92680.8151918
LUC7L3-USP22chr1748797192chr1720931987229HLA-B27:05SNVRWDHESAK0.99780.7321415
LUC7L3-USP22chr1748797192chr1720931987229HLA-B73:01VRWDHESA0.99630.9008614
LUC7L3-USP22chr1748797192chr1720931987229HLA-B27:14VRWDHESAK0.99380.7133615
LUC7L3-USP22chr1748797192chr1720931987229HLA-B39:05DHESAKSCI0.92490.6832918
LUC7L3-USP22chr1748797192chr1720931987229HLA-B27:03VRWDHESAK0.90640.7613615
LUC7L3-USP22chr1748797192chr1720931987229HLA-B27:14SNVRWDHESAK0.99630.6554415
LUC7L3-USP22chr1748797192chr1720931987229HLA-B27:08VRWDHESAK0.9970.6513615
LUC7L3-USP22chr1748797192chr1720931987229HLA-B27:10VRWDHESAK0.99640.8325615
LUC7L3-USP22chr1748797192chr1720931987229HLA-B38:05DHESAKSCI0.92680.8151918
LUC7L3-USP22chr1748797192chr1720931987229HLA-B27:10SNVRWDHESAK0.99640.808415

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Potential FusionNeoAntigen Information of LUC7L3-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 LUC7L3-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
10255VRWDHESAKSCICHLUC7L3USP22chr1748797192chr1720931987229

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of LUC7L3-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-B14:023BVN10255VRWDHESAKSCICH-7.9962-8.1096
HLA-B14:023BVN10255VRWDHESAKSCICH-5.70842-6.74372
HLA-B52:013W3910255VRWDHESAKSCICH-6.83737-6.95077
HLA-B52:013W3910255VRWDHESAKSCICH-4.4836-5.5189
HLA-A11:014UQ210255VRWDHESAKSCICH-10.0067-10.1201
HLA-A11:014UQ210255VRWDHESAKSCICH-9.03915-10.0745
HLA-A24:025HGA10255VRWDHESAKSCICH-6.56204-6.67544
HLA-A24:025HGA10255VRWDHESAKSCICH-5.42271-6.45801
HLA-B44:053DX810255VRWDHESAKSCICH-7.85648-8.89178
HLA-B44:053DX810255VRWDHESAKSCICH-5.3978-5.5112
HLA-B35:011A1N10255VRWDHESAKSCICH-6.27422-6.38762
HLA-B35:011A1N10255VRWDHESAKSCICH-5.27424-6.30954
HLA-A02:016TDR10255VRWDHESAKSCICH-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of LUC7L3-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
LUC7L3-USP22chr1748797192chr1720931987415SNVRWDHESAKAGCAACGTGCGGTGGGACCACGAGAGCGCCAAG
LUC7L3-USP22chr1748797192chr1720931987614VRWDHESAGTGCGGTGGGACCACGAGAGCGCC
LUC7L3-USP22chr1748797192chr1720931987615VRWDHESAKGTGCGGTGGGACCACGAGAGCGCCAAG
LUC7L3-USP22chr1748797192chr1720931987918DHESAKSCIGACCACGAGAGCGCCAAGTCCTGTATC

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 LUC7L3-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
Non-CancerLUC7L3-USP22chr1748797192ENST00000240304chr1720931987ENST00000261497ERR315333

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Potential target of CAR-T therapy development for LUC7L3-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

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 LUC7L3-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 LUC7L3-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