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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:NT5E-MDM2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NT5E-MDM2
FusionPDB ID: 60644
FusionGDB2.0 ID: 60644
HgeneTgene
Gene symbol

NT5E

MDM2

Gene ID

4907

4193

Gene name5'-nucleotidase ectoMDM2 proto-oncogene
SynonymsCALJA|CD73|E5NT|NT|NT5|NTE|eN|eNTACTFS|HDMX|LSKB|hdm2
Cytomap

6q14.3

12q15

Type of geneprotein-codingprotein-coding
Description5'-nucleotidase5'-NTPurine 5-Prime-Nucleotidaseecto-5'-nucleotidaseE3 ubiquitin-protein ligase Mdm2MDM2 oncogene, E3 ubiquitin protein ligaseMDM2 proto-oncogene, E3 ubiquitin protein ligaseMdm2, p53 E3 ubiquitin protein ligase homologMdm2, transformed 3T3 cell double minute 2, p53 binding proteindouble minute 2, hum
Modification date2020032920200329
UniProtAcc.

Q00987

Main function of 5'-partner protein: FUNCTION: E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome. Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Also acts as a ubiquitin ligase E3 toward itself and ARRB1. Permits the nuclear export of p53/TP53. Promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein. Inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradation. Component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in stabilizing p53/TP53. Also component of the TRIM28/KAP1-ERBB4-MDM2 complex which links growth factor and DNA damage response pathways. Mediates ubiquitination and subsequent proteasome degradation of DYRK2 in nucleus. Ubiquitinates IGF1R and SNAI1 and promotes them to proteasomal degradation (PubMed:12821780, PubMed:15053880, PubMed:15195100, PubMed:15632057, PubMed:16337594, PubMed:17290220, PubMed:19098711, PubMed:19219073, PubMed:19837670, PubMed:19965871, PubMed:20173098, PubMed:20385133, PubMed:20858735, PubMed:22128911). Ubiquitinates DCX, leading to DCX degradation and reduction of the dendritic spine density of olfactory bulb granule cells (By similarity). Ubiquitinates DLG4, leading to proteasomal degradation of DLG4 which is required for AMPA receptor endocytosis (By similarity). Negatively regulates NDUFS1, leading to decreased mitochondrial respiration, marked oxidative stress, and commitment to the mitochondrial pathway of apoptosis (PubMed:30879903). Binds NDUFS1 leading to its cytosolic retention rather than mitochondrial localization resulting in decreased supercomplex assembly (interactions between complex I and complex III), decreased complex I activity, ROS production, and apoptosis (PubMed:30879903). {ECO:0000250|UniProtKB:P23804, ECO:0000269|PubMed:12821780, ECO:0000269|PubMed:15053880, ECO:0000269|PubMed:15195100, ECO:0000269|PubMed:15632057, ECO:0000269|PubMed:16337594, ECO:0000269|PubMed:17290220, ECO:0000269|PubMed:19098711, ECO:0000269|PubMed:19219073, ECO:0000269|PubMed:19837670, ECO:0000269|PubMed:19965871, ECO:0000269|PubMed:20173098, ECO:0000269|PubMed:20385133, ECO:0000269|PubMed:20858735, ECO:0000269|PubMed:22128911, ECO:0000269|PubMed:30879903}.
Ensembl transtripts involved in fusion geneENST idsENST00000257770, ENST00000369646, 
ENST00000369651, 
ENST00000258148, 
ENST00000258149, ENST00000299252, 
ENST00000348801, ENST00000350057, 
ENST00000360430, ENST00000393410, 
ENST00000393412, ENST00000393413, 
ENST00000428863, ENST00000478070, 
ENST00000517852, ENST00000540827, 
ENST00000544125, ENST00000544561, 
ENST00000545204, ENST00000356290, 
ENST00000462284, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score4 X 3 X 3=3612 X 10 X 6=720
# samples 412
** MAII scorelog2(4/36*10)=0.15200309344505
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
log2(12/720*10)=-2.58496250072116
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: NT5E [Title/Abstract] AND MDM2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: NT5E [Title/Abstract] AND MDM2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NT5E(86160196)-MDM2(69207334), # samples:1
Anticipated loss of major functional domain due to fusion event.NT5E-MDM2 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.
NT5E-MDM2 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.
NT5E-MDM2 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.
NT5E-MDM2 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
HgeneNT5E

GO:0007159

leukocyte cell-cell adhesion

7595232

TgeneMDM2

GO:0000122

negative regulation of transcription by RNA polymerase II

9271120|17310983

TgeneMDM2

GO:0006511

ubiquitin-dependent protein catabolic process

11278372|15314173|16173922|17310983

TgeneMDM2

GO:0016567

protein ubiquitination

9450543|15878855|19656744|20153724

TgeneMDM2

GO:0031648

protein destabilization

9529249|10360174|15314173

TgeneMDM2

GO:0032436

positive regulation of proteasomal ubiquitin-dependent protein catabolic process

11278372

TgeneMDM2

GO:0034504

protein localization to nucleus

10360174

TgeneMDM2

GO:0042176

regulation of protein catabolic process

9153395

TgeneMDM2

GO:0043518

negative regulation of DNA damage response, signal transduction by p53 class mediator

9529249|10360174

TgeneMDM2

GO:0045184

establishment of protein localization

10360174

TgeneMDM2

GO:0045892

negative regulation of transcription, DNA-templated

9271120

TgeneMDM2

GO:0065003

protein-containing complex assembly

10608892|12915590

TgeneMDM2

GO:0071157

negative regulation of cell cycle arrest

9529249

TgeneMDM2

GO:0071480

cellular response to gamma radiation

16213212

TgeneMDM2

GO:0072717

cellular response to actinomycin D

15314173

TgeneMDM2

GO:1901797

negative regulation of signal transduction by p53 class mediator

16173922



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/chr6:86160196/chr12:69207334)
- 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 NT5E (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 MDM2 (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)
ENST00000369646NT5Echr686160196+ENST00000462284MDM2chr1269207334+7368388491782577
ENST00000369646NT5Echr686160196+ENST00000356290MDM2chr1269207334+6855388491272407
ENST00000257770NT5Echr686160196+ENST00000462284MDM2chr1269207334+7368388491782577
ENST00000257770NT5Echr686160196+ENST00000356290MDM2chr1269207334+6855388491272407
ENST00000369651NT5Echr686160196+ENST00000462284MDM2chr1269207334+7350370311764577
ENST00000369651NT5Echr686160196+ENST00000356290MDM2chr1269207334+6837370311254407

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
ENST00000369646ENST00000462284NT5Echr686160196+MDM2chr1269207334+0.0002701350.9997298
ENST00000369646ENST00000356290NT5Echr686160196+MDM2chr1269207334+7.87E-050.9999213
ENST00000257770ENST00000462284NT5Echr686160196+MDM2chr1269207334+0.0002701350.9997298
ENST00000257770ENST00000356290NT5Echr686160196+MDM2chr1269207334+7.87E-050.9999213
ENST00000369651ENST00000462284NT5Echr686160196+MDM2chr1269207334+0.0002671730.9997328
ENST00000369651ENST00000356290NT5Echr686160196+MDM2chr1269207334+7.76E-050.9999224

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 NT5E-MDM2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
NT5Echr686160196MDM2chr1269207334370113VAHFMNALRYDAMVRPKPLLLKLLKS
NT5Echr686160196MDM2chr1269207334388113VAHFMNALRYDAMVRPKPLLLKLLKS

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Potential FusionNeoAntigen Information of NT5E-MDM2 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.
NT5E-MDM2_86160196_69207334.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)
NT5E-MDM2chr686160196chr1269207334388HLA-B14:02DAMVRPKPL0.99780.62611019
NT5E-MDM2chr686160196chr1269207334388HLA-B14:01DAMVRPKPL0.99780.62611019
NT5E-MDM2chr686160196chr1269207334388HLA-A30:08MVRPKPLLL0.98110.61591221
NT5E-MDM2chr686160196chr1269207334388HLA-B15:17MVRPKPLLL0.9250.77191221
NT5E-MDM2chr686160196chr1269207334388HLA-B14:01MVRPKPLLL0.90.63241221
NT5E-MDM2chr686160196chr1269207334388HLA-B14:02MVRPKPLLL0.90.63241221
NT5E-MDM2chr686160196chr1269207334388HLA-B15:16MVRPKPLLL0.83230.51771221
NT5E-MDM2chr686160196chr1269207334388HLA-A32:13MVRPKPLLL0.72830.84111221
NT5E-MDM2chr686160196chr1269207334388HLA-B52:01MVRPKPLLL0.41330.59971221
NT5E-MDM2chr686160196chr1269207334388HLA-B13:01AMVRPKPLL0.02040.78641120
NT5E-MDM2chr686160196chr1269207334388HLA-B27:05LRYDAMVRPK0.99950.8332717
NT5E-MDM2chr686160196chr1269207334388HLA-A30:08AMVRPKPLLL0.74230.63081121
NT5E-MDM2chr686160196chr1269207334388HLA-C15:04MVRPKPLLL0.99810.76681221
NT5E-MDM2chr686160196chr1269207334388HLA-C03:08MVRPKPLLL0.99630.82091221
NT5E-MDM2chr686160196chr1269207334388HLA-B27:14LRYDAMVRP0.99490.8123716
NT5E-MDM2chr686160196chr1269207334388HLA-C15:06MVRPKPLLL0.99460.80861221
NT5E-MDM2chr686160196chr1269207334388HLA-C12:12MVRPKPLLL0.99440.89211221
NT5E-MDM2chr686160196chr1269207334388HLA-C03:19MVRPKPLLL0.99410.96831221
NT5E-MDM2chr686160196chr1269207334388HLA-C03:07MVRPKPLLL0.99410.95321221
NT5E-MDM2chr686160196chr1269207334388HLA-C06:03MVRPKPLLL0.99310.98651221
NT5E-MDM2chr686160196chr1269207334388HLA-C12:04MVRPKPLLL0.99290.98541221
NT5E-MDM2chr686160196chr1269207334388HLA-B51:07DAMVRPKPL0.98330.63281019
NT5E-MDM2chr686160196chr1269207334388HLA-B73:01LRYDAMVRP0.97360.7861716
NT5E-MDM2chr686160196chr1269207334388HLA-C12:16MVRPKPLLL0.96220.92261221
NT5E-MDM2chr686160196chr1269207334388HLA-C02:06MVRPKPLLL0.9610.8951221
NT5E-MDM2chr686160196chr1269207334388HLA-B14:03DAMVRPKPL0.95180.69131019
NT5E-MDM2chr686160196chr1269207334388HLA-C04:14MVRPKPLLL0.93120.80981221
NT5E-MDM2chr686160196chr1269207334388HLA-B15:04MVRPKPLLL0.92970.76051221
NT5E-MDM2chr686160196chr1269207334388HLA-C04:06MVRPKPLLL0.9120.8331221
NT5E-MDM2chr686160196chr1269207334388HLA-B15:07MVRPKPLLL0.90750.54261221
NT5E-MDM2chr686160196chr1269207334388HLA-C07:10MVRPKPLLL0.89780.91891221
NT5E-MDM2chr686160196chr1269207334388HLA-B14:03MVRPKPLLL0.89460.66261221
NT5E-MDM2chr686160196chr1269207334388HLA-C07:67MVRPKPLLL0.89120.89641221
NT5E-MDM2chr686160196chr1269207334388HLA-C07:80MVRPKPLLL0.89120.89641221
NT5E-MDM2chr686160196chr1269207334388HLA-C07:05MVRPKPLLL0.88720.95171221
NT5E-MDM2chr686160196chr1269207334388HLA-C07:19MVRPKPLLL0.85310.58141221
NT5E-MDM2chr686160196chr1269207334388HLA-C07:13MVRPKPLLL0.84930.84631221
NT5E-MDM2chr686160196chr1269207334388HLA-C07:29MVRPKPLLL0.82550.91961221
NT5E-MDM2chr686160196chr1269207334388HLA-C07:46MVRPKPLLL0.81980.78511221
NT5E-MDM2chr686160196chr1269207334388HLA-C08:13MVRPKPLLL0.81860.93321221
NT5E-MDM2chr686160196chr1269207334388HLA-C08:04MVRPKPLLL0.81860.93321221
NT5E-MDM2chr686160196chr1269207334388HLA-C07:27MVRPKPLLL0.78890.9211221
NT5E-MDM2chr686160196chr1269207334388HLA-C07:95MVRPKPLLL0.75920.59051221
NT5E-MDM2chr686160196chr1269207334388HLA-C03:14MVRPKPLLL0.75350.96951221
NT5E-MDM2chr686160196chr1269207334388HLA-C01:17MVRPKPLLL0.63650.91581221
NT5E-MDM2chr686160196chr1269207334388HLA-C01:30MVRPKPLLL0.57750.90941221
NT5E-MDM2chr686160196chr1269207334388HLA-B39:10MVRPKPLLL0.24190.8351221
NT5E-MDM2chr686160196chr1269207334388HLA-B27:14LRYDAMVRPK0.9990.7744717
NT5E-MDM2chr686160196chr1269207334388HLA-B27:03LRYDAMVRPK0.99170.8485717
NT5E-MDM2chr686160196chr1269207334388HLA-B73:01NALRYDAMVRP0.97920.686516
NT5E-MDM2chr686160196chr1269207334388HLA-C15:09MVRPKPLLL0.99810.76681221
NT5E-MDM2chr686160196chr1269207334388HLA-C03:04MVRPKPLLL0.99530.97591221
NT5E-MDM2chr686160196chr1269207334388HLA-C03:03MVRPKPLLL0.99530.97591221
NT5E-MDM2chr686160196chr1269207334388HLA-C06:17MVRPKPLLL0.99520.98381221
NT5E-MDM2chr686160196chr1269207334388HLA-C06:02MVRPKPLLL0.99520.98381221
NT5E-MDM2chr686160196chr1269207334388HLA-B07:13MVRPKPLLL0.99430.74371221
NT5E-MDM2chr686160196chr1269207334388HLA-C15:05MVRPKPLLL0.99260.80381221
NT5E-MDM2chr686160196chr1269207334388HLA-C12:03MVRPKPLLL0.99120.96151221
NT5E-MDM2chr686160196chr1269207334388HLA-C15:02MVRPKPLLL0.99060.70831221
NT5E-MDM2chr686160196chr1269207334388HLA-C03:67MVRPKPLLL0.98980.96091221
NT5E-MDM2chr686160196chr1269207334388HLA-C03:05MVRPKPLLL0.98970.86381221
NT5E-MDM2chr686160196chr1269207334388HLA-C03:17MVRPKPLLL0.98860.9521221
NT5E-MDM2chr686160196chr1269207334388HLA-C16:04MVRPKPLLL0.98220.9631221
NT5E-MDM2chr686160196chr1269207334388HLA-A30:01MVRPKPLLL0.98120.7361221
NT5E-MDM2chr686160196chr1269207334388HLA-C02:02MVRPKPLLL0.96540.95681221
NT5E-MDM2chr686160196chr1269207334388HLA-C16:01MVRPKPLLL0.96540.96561221
NT5E-MDM2chr686160196chr1269207334388HLA-C02:10MVRPKPLLL0.96540.95681221
NT5E-MDM2chr686160196chr1269207334388HLA-C16:02MVRPKPLLL0.9620.98461221
NT5E-MDM2chr686160196chr1269207334388HLA-C03:02MVRPKPLLL0.94610.95281221
NT5E-MDM2chr686160196chr1269207334388HLA-C06:08MVRPKPLLL0.94150.97241221
NT5E-MDM2chr686160196chr1269207334388HLA-A32:01MVRPKPLLL0.94150.82521221
NT5E-MDM2chr686160196chr1269207334388HLA-B15:35MVRPKPLLL0.93420.73511221
NT5E-MDM2chr686160196chr1269207334388HLA-B15:24MVRPKPLLL0.93130.74991221
NT5E-MDM2chr686160196chr1269207334388HLA-C07:04MVRPKPLLL0.92910.8271221
NT5E-MDM2chr686160196chr1269207334388HLA-C06:06MVRPKPLLL0.91570.98591221
NT5E-MDM2chr686160196chr1269207334388HLA-C12:02MVRPKPLLL0.90980.93961221
NT5E-MDM2chr686160196chr1269207334388HLA-C07:17MVRPKPLLL0.90020.94761221
NT5E-MDM2chr686160196chr1269207334388HLA-C04:04MVRPKPLLL0.89730.82231221
NT5E-MDM2chr686160196chr1269207334388HLA-C07:02MVRPKPLLL0.89120.89641221
NT5E-MDM2chr686160196chr1269207334388HLA-C07:22MVRPKPLLL0.88920.6421221
NT5E-MDM2chr686160196chr1269207334388HLA-A30:01RYDAMVRPK0.87790.7835817
NT5E-MDM2chr686160196chr1269207334388HLA-B15:73MVRPKPLLL0.87630.73421221
NT5E-MDM2chr686160196chr1269207334388HLA-B15:30MVRPKPLLL0.85720.74251221
NT5E-MDM2chr686160196chr1269207334388HLA-C03:06MVRPKPLLL0.84150.97721221
NT5E-MDM2chr686160196chr1269207334388HLA-B58:06MVRPKPLLL0.83060.75441221
NT5E-MDM2chr686160196chr1269207334388HLA-C07:01MVRPKPLLL0.77060.59151221
NT5E-MDM2chr686160196chr1269207334388HLA-C18:01MVRPKPLLL0.65820.77431221
NT5E-MDM2chr686160196chr1269207334388HLA-C01:02MVRPKPLLL0.65250.91041221
NT5E-MDM2chr686160196chr1269207334388HLA-B15:73AMVRPKPLL0.51470.76581120
NT5E-MDM2chr686160196chr1269207334388HLA-C01:03MVRPKPLLL0.46490.87731221
NT5E-MDM2chr686160196chr1269207334388HLA-C17:01MVRPKPLLL0.40120.68811221
NT5E-MDM2chr686160196chr1269207334388HLA-B15:30AMVRPKPLL0.35780.77721120
NT5E-MDM2chr686160196chr1269207334388HLA-B27:10LRYDAMVRPK0.99910.8457717
NT5E-MDM2chr686160196chr1269207334388HLA-A30:01MVRPKPLLLK0.99830.53221222
NT5E-MDM2chr686160196chr1269207334388HLA-A30:01AMVRPKPLLL0.74310.76051121

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Potential FusionNeoAntigen Information of NT5E-MDM2 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 NT5E-MDM2

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
407ALRYDAMVRPKPLLNT5EMDM2chr686160196chr1269207334388

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of NT5E-MDM2

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-B14:023BVN407ALRYDAMVRPKPLL-7.9962-8.1096
HLA-B14:023BVN407ALRYDAMVRPKPLL-5.70842-6.74372
HLA-B52:013W39407ALRYDAMVRPKPLL-6.83737-6.95077
HLA-B52:013W39407ALRYDAMVRPKPLL-4.4836-5.5189
HLA-A11:014UQ2407ALRYDAMVRPKPLL-10.0067-10.1201
HLA-A11:014UQ2407ALRYDAMVRPKPLL-9.03915-10.0745
HLA-A24:025HGA407ALRYDAMVRPKPLL-6.56204-6.67544
HLA-A24:025HGA407ALRYDAMVRPKPLL-5.42271-6.45801
HLA-B44:053DX8407ALRYDAMVRPKPLL-7.85648-8.89178
HLA-B44:053DX8407ALRYDAMVRPKPLL-5.3978-5.5112
HLA-A02:016TDR407ALRYDAMVRPKPLL-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of NT5E-MDM2

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
NT5E-MDM2chr686160196chr12692073341019DAMVRPKPLGATGCCATGGTTAGACCAAAGCCATTG
NT5E-MDM2chr686160196chr12692073341120AMVRPKPLLGCCATGGTTAGACCAAAGCCATTGCTT
NT5E-MDM2chr686160196chr12692073341121AMVRPKPLLLGCCATGGTTAGACCAAAGCCATTGCTTTTG
NT5E-MDM2chr686160196chr12692073341221MVRPKPLLLATGGTTAGACCAAAGCCATTGCTTTTG
NT5E-MDM2chr686160196chr12692073341222MVRPKPLLLKATGGTTAGACCAAAGCCATTGCTTTTGAAG
NT5E-MDM2chr686160196chr1269207334516NALRYDAMVRPAACGCCCTGCGCTACGATGCCATGGTTAGACCA
NT5E-MDM2chr686160196chr1269207334716LRYDAMVRPCTGCGCTACGATGCCATGGTTAGACCA
NT5E-MDM2chr686160196chr1269207334717LRYDAMVRPKCTGCGCTACGATGCCATGGTTAGACCAAAG
NT5E-MDM2chr686160196chr1269207334817RYDAMVRPKCGCTACGATGCCATGGTTAGACCAAAG

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 NT5E-MDM2

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
SARCNT5E-MDM2chr686160196ENST00000257770chr1269207334ENST00000356290TCGA-DX-A23Y-01A

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Potential target of CAR-T therapy development for NT5E-MDM2

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 NT5E-MDM2

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 NT5E-MDM2

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