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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:MTF2-FNBP1L

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: MTF2-FNBP1L
FusionPDB ID: 55646
FusionGDB2.0 ID: 55646
HgeneTgene
Gene symbol

MTF2

FNBP1L

Gene ID

22823

54874

Gene namemetal response element binding transcription factor 2formin binding protein 1 like
SynonymsM96|PCL2|TDRD19A|dJ976O13.2C1orf39|TOCA1
Cytomap

1p22.1

1p22.1

Type of geneprotein-codingprotein-coding
Descriptionmetal-response element-binding transcription factor 2hPCl2metal regulatory transcription factor 2metal-response element DNA-binding protein M96polycomb-like 2polycomb-like protein 2putative DNA binding proteintudor domain containing 19Aformin-binding protein 1-liketoca-1transducer of Cdc42-dependent actin assembly 1transducer of Cdc42-dependent actin assembly protein 1
Modification date2020031320200313
UniProtAcc

Q9Y483

Main function of 5'-partner protein: FUNCTION: Polycomb group (PcG) protein that specifically binds histone H3 trimethylated at 'Lys-36' (H3K36me3) and recruits the PRC2 complex, thus enhancing PRC2 H3K27me3 methylation activity (PubMed:23142980, PubMed:23228662, PubMed:31959557). Regulates the transcriptional networks during embryonic stem cell self-renewal and differentiation (By similarity). Promotes recruitment of the PRC2 complex to the inactive X chromosome in differentiating XX ES cells and PRC2 recruitment to target genes in undifferentiated ES cells (By similarity). Required to repress Hox genes by enhancing H3K27me3 methylation of the PRC2 complex (By similarity). In some conditions may act as an inhibitor of PRC2 activity: able to activate the CDKN2A gene and promote cellular senescence by suppressing the catalytic activity of the PRC2 complex locally (By similarity). Binds to the metal-regulating-element (MRE) of MT1A gene promoter (By similarity). {ECO:0000250|UniProtKB:Q02395, ECO:0000269|PubMed:23142980, ECO:0000269|PubMed:23228662, ECO:0000269|PubMed:31959557}.

Q5T0N5

Main function of 5'-partner protein: FUNCTION: Required to coordinate membrane tubulation with reorganization of the actin cytoskeleton during endocytosis. May bind to lipids such as phosphatidylinositol 4,5-bisphosphate and phosphatidylserine and promote membrane invagination and the formation of tubules. Also promotes CDC42-induced actin polymerization by activating the WASL/N-WASP-WASPIP/WIP complex, the predominant form of WASL/N-WASP in cells. Actin polymerization may promote the fission of membrane tubules to form endocytic vesicles. Essential for autophagy of intracellular bacterial pathogens. {ECO:0000269|PubMed:15260990, ECO:0000269|PubMed:16326391, ECO:0000269|PubMed:19342671}.
Ensembl transtripts involved in fusion geneENST idsENST00000471953, ENST00000540243, 
ENST00000545708, ENST00000370298, 
ENST00000370303, 
ENST00000260506, 
ENST00000271234, ENST00000370253, 
ENST00000370256, ENST00000604705, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score11 X 4 X 6=26410 X 7 X 4=280
# samples 1310
** MAII scorelog2(13/264*10)=-1.02202630633
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(10/280*10)=-1.48542682717024
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: MTF2 [Title/Abstract] AND FNBP1L [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: MTF2 [Title/Abstract] AND FNBP1L [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MTF2(93545088)-FNBP1L(93987639), # samples:2
Anticipated loss of major functional domain due to fusion event.MTF2-FNBP1L 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.
MTF2-FNBP1L 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.
MTF2-FNBP1L 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.
MTF2-FNBP1L 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
TgeneFNBP1L

GO:0006900

vesicle budding from membrane

20730103

TgeneFNBP1L

GO:0010324

membrane invagination

20730103

TgeneFNBP1L

GO:0016050

vesicle organization

20730103

TgeneFNBP1L

GO:0030050

vesicle transport along actin filament

20730103

TgeneFNBP1L

GO:0051491

positive regulation of filopodium assembly

20730103

TgeneFNBP1L

GO:0072583

clathrin-dependent endocytosis

20730103

TgeneFNBP1L

GO:0097320

plasma membrane tubulation

20730103



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/chr1:93545088/chr1:93987639)
- 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 MTF2 (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 FNBP1L (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)
ENST00000370298MTF2chr193545088+ENST00000370256FNBP1Lchr193987639+42002942891956555
ENST00000370298MTF2chr193545088+ENST00000260506FNBP1Lchr193987639+53442942891809506
ENST00000370298MTF2chr193545088+ENST00000271234FNBP1Lchr193987639+42152942891971560
ENST00000370298MTF2chr193545088+ENST00000604705FNBP1Lchr193987639+19842942891983565
ENST00000370298MTF2chr193545088+ENST00000370253FNBP1Lchr193987639+40432942891797502
ENST00000370303MTF2chr193545088+ENST00000370256FNBP1Lchr193987639+41272212161883555
ENST00000370303MTF2chr193545088+ENST00000260506FNBP1Lchr193987639+52712212161736506
ENST00000370303MTF2chr193545088+ENST00000271234FNBP1Lchr193987639+41422212161898560
ENST00000370303MTF2chr193545088+ENST00000604705FNBP1Lchr193987639+19112212161910564
ENST00000370303MTF2chr193545088+ENST00000370253FNBP1Lchr193987639+39702212161724502

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
ENST00000370298ENST00000370256MTF2chr193545088+FNBP1Lchr193987639+0.0002376490.99976236
ENST00000370298ENST00000260506MTF2chr193545088+FNBP1Lchr193987639+0.0001290590.9998709
ENST00000370298ENST00000271234MTF2chr193545088+FNBP1Lchr193987639+0.000226210.9997738
ENST00000370298ENST00000604705MTF2chr193545088+FNBP1Lchr193987639+0.0019540170.9980459
ENST00000370298ENST00000370253MTF2chr193545088+FNBP1Lchr193987639+0.0001695720.99983037
ENST00000370303ENST00000370256MTF2chr193545088+FNBP1Lchr193987639+0.0002286910.9997713
ENST00000370303ENST00000260506MTF2chr193545088+FNBP1Lchr193987639+0.0001250520.99987495
ENST00000370303ENST00000271234MTF2chr193545088+FNBP1Lchr193987639+0.0002175480.9997825
ENST00000370303ENST00000604705MTF2chr193545088+FNBP1Lchr193987639+0.0018404170.9981596
ENST00000370303ENST00000370253MTF2chr193545088+FNBP1Lchr193987639+0.0001627840.99983716

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 MTF2-FNBP1L

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

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Potential FusionNeoAntigen Information of MTF2-FNBP1L 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.

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)

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Potential FusionNeoAntigen Information of MTF2-FNBP1L 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 MTF2-FNBP1L

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.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of MTF2-FNBP1L

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

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Vaccine Design for the FusionNeoAntigens of MTF2-FNBP1L

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

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 MTF2-FNBP1L

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

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Potential target of CAR-T therapy development for MTF2-FNBP1L

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 MTF2-FNBP1L

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 MTF2-FNBP1L

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