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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:TFG-MET

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TFG-MET
FusionPDB ID: 90359
FusionGDB2.0 ID: 90359
HgeneTgene
Gene symbol

TFG

MET

Gene ID

10342

8731

Gene nametrafficking from ER to golgi regulatorRNA guanine-7 methyltransferase
SynonymsHMSNP|SPG57|TF6|TRKT3CMT1|CMT1c|MET|Met|RG7MT1|cm1p|hCMT1|hMet
Cytomap

3q12.2

18p11.21

Type of geneprotein-codingprotein-coding
Descriptionprotein TFGTRK-fusedTRK-fused gene proteinTRKT3 oncogenemRNA cap guanine-N7 methyltransferaseRNA (guanine-7-) methyltransferasehcm1pmRNA (guanine-7-)methyltransferasemRNA (guanine-N(7)-)-methyltransferasemRNA cap methyltransferase
Modification date2020031320200329
UniProtAcc

Q92734

Main function of 5'-partner protein: FUNCTION: Plays a role in the normal dynamic function of the endoplasmic reticulum (ER) and its associated microtubules (PubMed:23479643, PubMed:27813252). Required for secretory cargo traffic from the endoplasmic reticulum to the Golgi apparatus (PubMed:21478858). {ECO:0000269|PubMed:21478858, ECO:0000269|PubMed:23479643, ECO:0000269|PubMed:27813252}.

Q9H1A3

Main function of 5'-partner protein:
Ensembl transtripts involved in fusion geneENST idsENST00000481203, ENST00000240851, 
ENST00000418917, ENST00000476228, 
ENST00000490574, 
ENST00000318493, 
ENST00000397752, ENST00000436117, 
ENST00000495962, ENST00000539704, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score13 X 14 X 7=127414 X 18 X 10=2520
# samples 1927
** MAII scorelog2(19/1274*10)=-2.74529395392535
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(27/2520*10)=-3.22239242133645
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: TFG [Title/Abstract] AND MET [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: TFG [Title/Abstract] AND MET [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MET(116412043)-TFG(100455420), # samples:3
TFG(100451516)-MET(116414935), # samples:3
Anticipated loss of major functional domain due to fusion event.MET-TFG 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.
MET-TFG 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.
TFG-MET 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.
TFG-MET 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.
TFG-MET 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.
TFG-MET 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
TgeneMET

GO:0006370

7-methylguanosine mRNA capping

27422871



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/chr3:116412043/chr7:100455420)
- 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 TFG (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 MET (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)
ENST00000418917TFGchr3100451516+ENST00000397752METchr7116414935+41016941021838578
ENST00000418917TFGchr3100451516+ENST00000318493METchr7116414935+20576941021838578
ENST00000490574TFGchr3100451516+ENST00000397752METchr7116414935+4084677851821578
ENST00000490574TFGchr3100451516+ENST00000318493METchr7116414935+2040677851821578
ENST00000240851TFGchr3100451516+ENST00000397752METchr7116414935+43279203282064578
ENST00000240851TFGchr3100451516+ENST00000318493METchr7116414935+22839203282064578
ENST00000476228TFGchr3100451516+ENST00000397752METchr7116414935+41467391471883578
ENST00000476228TFGchr3100451516+ENST00000318493METchr7116414935+21027391471883578
ENST00000418917TFGchr3100451516+ENST00000397752METchr7116414934+41016941021838578
ENST00000418917TFGchr3100451516+ENST00000318493METchr7116414934+20576941021838578
ENST00000490574TFGchr3100451516+ENST00000397752METchr7116414934+4084677851821578
ENST00000490574TFGchr3100451516+ENST00000318493METchr7116414934+2040677851821578
ENST00000240851TFGchr3100451516+ENST00000397752METchr7116414934+43279203282064578
ENST00000240851TFGchr3100451516+ENST00000318493METchr7116414934+22839203282064578
ENST00000476228TFGchr3100451516+ENST00000397752METchr7116414934+41467391471883578
ENST00000476228TFGchr3100451516+ENST00000318493METchr7116414934+21027391471883578

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
ENST00000418917ENST00000397752TFGchr3100451516+METchr7116414935+0.0001652840.99983466
ENST00000418917ENST00000318493TFGchr3100451516+METchr7116414935+0.0004525330.9995474
ENST00000490574ENST00000397752TFGchr3100451516+METchr7116414935+0.0001672760.99983275
ENST00000490574ENST00000318493TFGchr3100451516+METchr7116414935+0.0004516730.99954826
ENST00000240851ENST00000397752TFGchr3100451516+METchr7116414935+0.000175130.99982494
ENST00000240851ENST00000318493TFGchr3100451516+METchr7116414935+0.0004100660.99959
ENST00000476228ENST00000397752TFGchr3100451516+METchr7116414935+0.0001808580.9998192
ENST00000476228ENST00000318493TFGchr3100451516+METchr7116414935+0.0004774960.99952257
ENST00000418917ENST00000397752TFGchr3100451516+METchr7116414934+0.0001652840.99983466
ENST00000418917ENST00000318493TFGchr3100451516+METchr7116414934+0.0004525330.9995474
ENST00000490574ENST00000397752TFGchr3100451516+METchr7116414934+0.0001672760.99983275
ENST00000490574ENST00000318493TFGchr3100451516+METchr7116414934+0.0004516730.99954826
ENST00000240851ENST00000397752TFGchr3100451516+METchr7116414934+0.000175130.99982494
ENST00000240851ENST00000318493TFGchr3100451516+METchr7116414934+0.0004100660.99959
ENST00000476228ENST00000397752TFGchr3100451516+METchr7116414934+0.0001808580.9998192
ENST00000476228ENST00000318493TFGchr3100451516+METchr7116414934+0.0004774960.99952257

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 TFG-MET

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
TFGchr3100451516METchr7116414934677197VMSAFGLTDDQVSDQFPNSSQNGSCR
TFGchr3100451516METchr7116414934694197VMSAFGLTDDQVSDQFPNSSQNGSCR
TFGchr3100451516METchr7116414934739197VMSAFGLTDDQVSDQFPNSSQNGSCR
TFGchr3100451516METchr7116414934920197VMSAFGLTDDQVSDQFPNSSQNGSCR
TFGchr3100451516METchr7116414935677197VMSAFGLTDDQVSDQFPNSSQNGSCR
TFGchr3100451516METchr7116414935694197VMSAFGLTDDQVSDQFPNSSQNGSCR
TFGchr3100451516METchr7116414935739197VMSAFGLTDDQVSDQFPNSSQNGSCR
TFGchr3100451516METchr7116414935920197VMSAFGLTDDQVSDQFPNSSQNGSCR

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Potential FusionNeoAntigen Information of TFG-MET 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.
TFG-MET_100451516_116414934.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)
TFG-METchr3100451516chr7116414934920HLA-B39:08TDDQVSDQF0.26180.835716
TFG-METchr3100451516chr7116414934920HLA-C05:09LTDDQVSDQF0.99990.9757616
TFG-METchr3100451516chr7116414934920HLA-C08:15LTDDQVSDQF0.99990.9854616
TFG-METchr3100451516chr7116414934920HLA-C04:03LTDDQVSDQF10.9407616
TFG-METchr3100451516chr7116414934920HLA-C08:02LTDDQVSDQF0.99990.9854616
TFG-METchr3100451516chr7116414934920HLA-C05:01LTDDQVSDQF0.99990.9757616
TFG-METchr3100451516chr7116414934920HLA-B57:02LTDDQVSDQF0.98420.8399616

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Potential FusionNeoAntigen Information of TFG-MET 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 TFG-MET

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
5684LTDDQVSDQFPNSSTFGMETchr3100451516chr7116414934920

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of TFG-MET

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-B14:023BVN5684LTDDQVSDQFPNSS-7.9962-8.1096
HLA-B14:023BVN5684LTDDQVSDQFPNSS-5.70842-6.74372
HLA-B52:013W395684LTDDQVSDQFPNSS-6.83737-6.95077
HLA-B52:013W395684LTDDQVSDQFPNSS-4.4836-5.5189
HLA-A11:014UQ25684LTDDQVSDQFPNSS-10.0067-10.1201
HLA-A11:014UQ25684LTDDQVSDQFPNSS-9.03915-10.0745
HLA-A24:025HGA5684LTDDQVSDQFPNSS-6.56204-6.67544
HLA-A24:025HGA5684LTDDQVSDQFPNSS-5.42271-6.45801
HLA-B44:053DX85684LTDDQVSDQFPNSS-7.85648-8.89178
HLA-B44:053DX85684LTDDQVSDQFPNSS-5.3978-5.5112
HLA-A02:016TDR5684LTDDQVSDQFPNSS-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of TFG-MET

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
TFG-METchr3100451516chr7116414934616LTDDQVSDQFTAACAGATGATCAGGTTTCAGATCAGTTTC
TFG-METchr3100451516chr7116414934716TDDQVSDQFCAGATGATCAGGTTTCAGATCAGTTTC

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 TFG-MET

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
THCATFG-METchr3100451516ENST00000240851chr7116414934ENST00000318493TCGA-FK-A3S3

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Potential target of CAR-T therapy development for TFG-MET

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
TgeneMETchr3:100451516chr7:116414934ENST0000043611709933_9550765.0TransmembraneHelical
TgeneMETchr3:100451516chr7:116414935ENST0000043611709933_9550765.0TransmembraneHelical

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 TFG-MET

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 TFG-MET

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
HgeneTFGC3714897SPASTIC PARAPLEGIA 57, AUTOSOMAL RECESSIVE5CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT
HgeneTFGC1858338Neuropathy, hereditary motor and sensory, Okinawa type4CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT
HgeneTFGC0238463Papillary thyroid carcinoma2ORPHANET
HgeneTFGC0442874Neuropathy1GENOMICS_ENGLAND
HgeneTFGC1275278Extraskeletal Myxoid Chondrosarcoma1GENOMICS_ENGLAND;ORPHANET
HgeneTFGC3714756Intellectual Disability1GENOMICS_ENGLAND