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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:TMED4-ENG

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TMED4-ENG
FusionPDB ID: 91461
FusionGDB2.0 ID: 91461
HgeneTgene
Gene symbol

TMED4

ENG

Gene ID

222068

2022

Gene nametransmembrane p24 trafficking protein 4endoglin
SynonymsERS25|GMP25iso|HNLF|p24a3|p24alpha3END|HHT1|ORW1
Cytomap

7p13

9q34.11

Type of geneprotein-codingprotein-coding
Descriptiontransmembrane emp24 domain-containing protein 4endoplasmic reticulum stress-response protein 25 kDap24 family protein alpha-3putative NF-kappa-B-activating protein 156putative NFkB activating protein HNLFtransmembrane emp24 protein transport domain cendoglinCD105 antigen
Modification date2020032020200329
UniProtAcc.

Q8NFI3

Main function of 5'-partner protein: FUNCTION: Endoglycosidase that releases N-glycans from glycoproteins by cleaving the beta-1,4-glycosidic bond in the N,N'-diacetylchitobiose core. Involved in the processing of free oligosaccharides in the cytosol. {ECO:0000269|PubMed:12114544}.
Ensembl transtripts involved in fusion geneENST idsENST00000444131, ENST00000457408, 
ENST00000289577, ENST00000481238, 
ENST00000480266, ENST00000344849, 
ENST00000373203, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score3 X 2 X 1=66 X 7 X 4=168
# samples 36
** MAII scorelog2(3/6*10)=2.32192809488736log2(6/168*10)=-1.48542682717024
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: TMED4 [Title/Abstract] AND ENG [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: TMED4 [Title/Abstract] AND ENG [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TMED4(44620692)-ENG(130581112), # samples:1
Anticipated loss of major functional domain due to fusion event.TMED4-ENG 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.
TMED4-ENG 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.
TMED4-ENG 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.
TMED4-ENG 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.
TMED4-ENG seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target 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
TgeneENG

GO:0001934

positive regulation of protein phosphorylation

12015308

TgeneENG

GO:0010862

positive regulation of pathway-restricted SMAD protein phosphorylation

12015308

TgeneENG

GO:0017015

regulation of transforming growth factor beta receptor signaling pathway

15702480

TgeneENG

GO:0030336

negative regulation of cell migration

19736306

TgeneENG

GO:0030513

positive regulation of BMP signaling pathway

17068149

TgeneENG

GO:0031953

negative regulation of protein autophosphorylation

12015308



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/chr7:44620692/chr9:130581112)
- 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 TMED4 (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 ENG (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)
ENST00000457408TMED4chr744620692-ENST00000373203ENGchr9130581112-1923587531252399
ENST00000457408TMED4chr744620692-ENST00000344849ENGchr9130581112-2054587531153366

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
ENST00000457408ENST00000373203TMED4chr744620692-ENGchr9130581112-0.0514675830.9485324
ENST00000457408ENST00000344849TMED4chr744620692-ENGchr9130581112-0.0278660340.97213393

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 TMED4-ENG

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
TMED4chr744620692ENGchr9130581112587178QVEQIQKEQDYQRKKVHCLNMDSLSF

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Potential FusionNeoAntigen Information of TMED4-ENG 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.
TMED4-ENG_44620692_130581112.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)
TMED4-ENGchr744620692chr9130581112587HLA-B14:02QRKKVHCL0.99590.91681119
TMED4-ENGchr744620692chr9130581112587HLA-B14:01QRKKVHCL0.99590.91681119
TMED4-ENGchr744620692chr9130581112587HLA-B08:01QRKKVHCL0.99260.74721119
TMED4-ENGchr744620692chr9130581112587HLA-B08:09YQRKKVHC0.99260.73911018
TMED4-ENGchr744620692chr9130581112587HLA-B08:01YQRKKVHCL0.99820.66251019
TMED4-ENGchr744620692chr9130581112587HLA-B08:09YQRKKVHCL0.99550.8831019
TMED4-ENGchr744620692chr9130581112587HLA-B14:01YQRKKVHCL0.98950.8731019
TMED4-ENGchr744620692chr9130581112587HLA-B14:02YQRKKVHCL0.98950.8731019
TMED4-ENGchr744620692chr9130581112587HLA-B15:01YQRKKVHCL0.96660.92351019
TMED4-ENGchr744620692chr9130581112587HLA-B39:24YQRKKVHCL0.96510.69371019
TMED4-ENGchr744620692chr9130581112587HLA-B15:03YQRKKVHCL0.53980.78311019
TMED4-ENGchr744620692chr9130581112587HLA-B07:10YQRKKVHCL0.36450.71341019
TMED4-ENGchr744620692chr9130581112587HLA-B13:02YQRKKVHCL0.3330.6631019
TMED4-ENGchr744620692chr9130581112587HLA-B39:13YQRKKVHCL0.29360.97411019
TMED4-ENGchr744620692chr9130581112587HLA-B13:01YQRKKVHCL0.21230.89311019
TMED4-ENGchr744620692chr9130581112587HLA-B08:01DYQRKKVHCL0.90120.6652919
TMED4-ENGchr744620692chr9130581112587HLA-B39:12QRKKVHCL0.97440.97971119
TMED4-ENGchr744620692chr9130581112587HLA-B14:03QRKKVHCL0.80610.90821119
TMED4-ENGchr744620692chr9130581112587HLA-B42:02YQRKKVHCL0.99850.671019
TMED4-ENGchr744620692chr9130581112587HLA-C12:12YQRKKVHCL0.91680.97541019
TMED4-ENGchr744620692chr9130581112587HLA-B15:04YQRKKVHCL0.87670.92911019
TMED4-ENGchr744620692chr9130581112587HLA-B15:07YQRKKVHCL0.84040.82841019
TMED4-ENGchr744620692chr9130581112587HLA-A02:05YQRKKVHCL0.81690.52451019
TMED4-ENGchr744620692chr9130581112587HLA-B39:12YQRKKVHCL0.73440.97241019
TMED4-ENGchr744620692chr9130581112587HLA-B39:09YQRKKVHCL0.7170.86141019
TMED4-ENGchr744620692chr9130581112587HLA-C07:05YQRKKVHCL0.69850.96721019
TMED4-ENGchr744620692chr9130581112587HLA-C12:16YQRKKVHCL0.6190.98351019
TMED4-ENGchr744620692chr9130581112587HLA-C07:19YQRKKVHCL0.56020.78011019
TMED4-ENGchr744620692chr9130581112587HLA-C07:80YQRKKVHCL0.55850.95531019
TMED4-ENGchr744620692chr9130581112587HLA-C07:67YQRKKVHCL0.55850.95531019
TMED4-ENGchr744620692chr9130581112587HLA-C07:13YQRKKVHCL0.55290.91041019
TMED4-ENGchr744620692chr9130581112587HLA-C07:46YQRKKVHCL0.54150.89261019
TMED4-ENGchr744620692chr9130581112587HLA-C07:10YQRKKVHCL0.52810.97041019
TMED4-ENGchr744620692chr9130581112587HLA-C07:27YQRKKVHCL0.51880.95451019
TMED4-ENGchr744620692chr9130581112587HLA-C07:95YQRKKVHCL0.50290.80131019
TMED4-ENGchr744620692chr9130581112587HLA-C07:29YQRKKVHCL0.49320.94851019
TMED4-ENGchr744620692chr9130581112587HLA-B14:03YQRKKVHCL0.48990.93841019
TMED4-ENGchr744620692chr9130581112587HLA-B08:18QRKKVHCL0.99260.74721119
TMED4-ENGchr744620692chr9130581112587HLA-B08:18YQRKKVHCL0.99820.66251019
TMED4-ENGchr744620692chr9130581112587HLA-B15:27YQRKKVHCL0.96670.92681019
TMED4-ENGchr744620692chr9130581112587HLA-B15:33YQRKKVHCL0.96660.92351019
TMED4-ENGchr744620692chr9130581112587HLA-B15:125YQRKKVHCL0.96660.92351019
TMED4-ENGchr744620692chr9130581112587HLA-B15:34YQRKKVHCL0.96660.92351019
TMED4-ENGchr744620692chr9130581112587HLA-B15:135YQRKKVHCL0.96020.91841019
TMED4-ENGchr744620692chr9130581112587HLA-B15:24YQRKKVHCL0.94950.87261019
TMED4-ENGchr744620692chr9130581112587HLA-B15:50YQRKKVHCL0.91940.97961019
TMED4-ENGchr744620692chr9130581112587HLA-B15:73YQRKKVHCL0.89730.90011019
TMED4-ENGchr744620692chr9130581112587HLA-C06:02YQRKKVHCL0.87150.99821019
TMED4-ENGchr744620692chr9130581112587HLA-C06:17YQRKKVHCL0.87150.99821019
TMED4-ENGchr744620692chr9130581112587HLA-B15:35YQRKKVHCL0.84470.921019
TMED4-ENGchr744620692chr9130581112587HLA-B08:12YQRKKVHCL0.82530.80821019
TMED4-ENGchr744620692chr9130581112587HLA-B15:68YQRKKVHCL0.79580.77871019
TMED4-ENGchr744620692chr9130581112587HLA-B15:54YQRKKVHCL0.79160.90381019
TMED4-ENGchr744620692chr9130581112587HLA-B15:53YQRKKVHCL0.78610.91971019
TMED4-ENGchr744620692chr9130581112587HLA-C06:08YQRKKVHCL0.73910.99671019
TMED4-ENGchr744620692chr9130581112587HLA-B15:30YQRKKVHCL0.7240.94561019
TMED4-ENGchr744620692chr9130581112587HLA-B39:02YQRKKVHCL0.6940.97491019
TMED4-ENGchr744620692chr9130581112587HLA-C07:22YQRKKVHCL0.6320.88241019
TMED4-ENGchr744620692chr9130581112587HLA-C07:04YQRKKVHCL0.61330.93871019
TMED4-ENGchr744620692chr9130581112587HLA-C07:02YQRKKVHCL0.55850.95531019
TMED4-ENGchr744620692chr9130581112587HLA-B15:12YQRKKVHCL0.53980.8931019
TMED4-ENGchr744620692chr9130581112587HLA-C07:01YQRKKVHCL0.52930.73971019
TMED4-ENGchr744620692chr9130581112587HLA-C03:67YQRKKVHCL0.44480.95081019
TMED4-ENGchr744620692chr9130581112587HLA-C06:06YQRKKVHCL0.42060.99631019
TMED4-ENGchr744620692chr9130581112587HLA-B48:05YQRKKVHCL0.36280.54481019
TMED4-ENGchr744620692chr9130581112587HLA-B15:68RKKVHCLNM0.15410.84461221
TMED4-ENGchr744620692chr9130581112587HLA-B08:18DYQRKKVHCL0.90120.6652919

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Potential FusionNeoAntigen Information of TMED4-ENG 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.
TMED4-ENG_44620692_130581112.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)
TMED4-ENGchr744620692chr9130581112587DRB5-0106VEQIQKEQDYQRKKV116
TMED4-ENGchr744620692chr9130581112587DRB5-0106QVEQIQKEQDYQRKK015
TMED4-ENGchr744620692chr9130581112587DRB5-0205VEQIQKEQDYQRKKV116
TMED4-ENGchr744620692chr9130581112587DRB5-0205QVEQIQKEQDYQRKK015

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Fusion breakpoint peptide structures of TMED4-ENG

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
4216KEQDYQRKKVHCLNTMED4ENGchr744620692chr9130581112587

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of TMED4-ENG

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-B14:023BVN4216KEQDYQRKKVHCLN-8.62545-8.73885
HLA-B14:023BVN4216KEQDYQRKKVHCLN-3.26321-4.29851
HLA-B52:013W394216KEQDYQRKKVHCLN-6.23413-6.34753
HLA-B52:013W394216KEQDYQRKKVHCLN-4.55402-5.58932
HLA-A24:025HGA4216KEQDYQRKKVHCLN-8.62578-8.73918
HLA-A24:025HGA4216KEQDYQRKKVHCLN-6.438-7.4733
HLA-B44:053DX84216KEQDYQRKKVHCLN-5.68484-5.79824
HLA-B44:053DX84216KEQDYQRKKVHCLN-3.64855-4.68385
HLA-A02:016TDR4216KEQDYQRKKVHCLN-5.14764-6.18294

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Vaccine Design for the FusionNeoAntigens of TMED4-ENG

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
TMED4-ENGchr744620692chr91305811121018YQRKKVHCTACCAAAGGAAAAAGGTGCACTGC
TMED4-ENGchr744620692chr91305811121019YQRKKVHCLTACCAAAGGAAAAAGGTGCACTGCCTC
TMED4-ENGchr744620692chr91305811121119QRKKVHCLCAAAGGAAAAAGGTGCACTGCCTC
TMED4-ENGchr744620692chr91305811121221RKKVHCLNMAGGAAAAAGGTGCACTGCCTCAACATG
TMED4-ENGchr744620692chr9130581112919DYQRKKVHCLGATTACCAAAGGAAAAAGGTGCACTGCCTC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
TMED4-ENGchr744620692chr9130581112015QVEQIQKEQDYQRKKCAGGTGGAACAGATTCAGAAGGAGCAGGATTACCAAAGGAAAAAG
TMED4-ENGchr744620692chr9130581112116VEQIQKEQDYQRKKVGTGGAACAGATTCAGAAGGAGCAGGATTACCAAAGGAAAAAGGTG

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Information of the samples that have these potential fusion neoantigens of TMED4-ENG

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
N/ATMED4-ENGchr744620692ENST00000457408chr9130581112ENST00000344849AK123738

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Potential target of CAR-T therapy development for TMED4-ENG

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
TgeneENGchr7:44620692chr9:130581112ENST00000344849914587_6110626.0TransmembraneHelical
TgeneENGchr7:44620692chr9:130581112ENST00000373203915587_6110659.0TransmembraneHelical

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 TMED4-ENG

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 TMED4-ENG

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