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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:NUP214-TOM1L2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NUP214-TOM1L2
FusionPDB ID: 61044
FusionGDB2.0 ID: 61044
HgeneTgene
Gene symbol

NUP214

TOM1L2

Gene ID

8021

146691

Gene namenucleoporin 214target of myb1 like 2 membrane trafficking protein
SynonymsCAIN|CAN|IIAE9-
Cytomap

9q34.13

17p11.2

Type of geneprotein-codingprotein-coding
Descriptionnuclear pore complex protein Nup214CAN protein, putative oncogenenucleoporin 214kDaTOM1-like protein 2target of Myb-like protein 2target of myb1-like 2
Modification date2020032220200313
UniProtAcc

P35658

Main function of 5'-partner protein: FUNCTION: Part of the nuclear pore complex (PubMed:9049309). Has a critical role in nucleocytoplasmic transport (PubMed:31178128). May serve as a docking site in the receptor-mediated import of substrates across the nuclear pore complex (PubMed:31178128, PubMed:8108440). {ECO:0000269|PubMed:31178128, ECO:0000269|PubMed:9049309, ECO:0000303|PubMed:8108440}.; FUNCTION: (Microbial infection) Required for capsid disassembly of the human adenovirus 5 (HadV-5) leading to release of the viral genome to the nucleus (in vitro). {ECO:0000269|PubMed:25410864}.		.
Ensembl transtripts involved in fusion geneENST idsENST00000465486, ENST00000359428, 
ENST00000411637, ENST00000451030, 
ENST00000483497, 		ENST00000318094, 
ENST00000379504, ENST00000395739, 
ENST00000535933, ENST00000540946, 
ENST00000542206, ENST00000581396, 
ENST00000478943, ENST00000577517, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score11 X 15 X 5=8258 X 8 X 4=256
# samples 148
** MAII scorelog2(14/825*10)=-2.55896729218821
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(8/256*10)=-1.67807190511264
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: NUP214 [Title/Abstract] AND TOM1L2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: NUP214 [Title/Abstract] AND TOM1L2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NUP214(134072803)-TOM1L2(17810845), # samples:2
TOM1L2(17875576)-NUP214(134072603), # samples:1
Anticipated loss of major functional domain due to fusion event.NUP214-TOM1L2 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.
NUP214-TOM1L2 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.
NUP214-TOM1L2 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.
NUP214-TOM1L2 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.
TOM1L2-NUP214 seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted ORF.
TOM1L2-NUP214 seems lost the major protein functional domain in Tgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
TOM1L2-NUP214 seems lost the major protein functional domain in Tgene partner, which is a CGC 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
TgeneTOM1L2

GO:0007165

signal transduction

16479011

TgeneTOM1L2

GO:0045839

negative regulation of mitotic nuclear division

16479011



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/chr9:134072803/chr17:17810845)
- 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 NUP214 (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 TOM1L2 (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)
ENST00000359428NUP214chr9134072803+ENST00000581396TOM1L2chr1717810845-1090754642167852254
ENST00000359428NUP214chr9134072803+ENST00000379504TOM1L2chr1717810845-774654642169352304
ENST00000359428NUP214chr9134072803+ENST00000318094TOM1L2chr1717810845-758754642168002259
ENST00000359428NUP214chr9134072803+ENST00000395739TOM1L2chr1717810845-708754642168002259
ENST00000359428NUP214chr9134072803+ENST00000535933TOM1L2chr1717810845-705354642168632280
ENST00000359428NUP214chr9134072803+ENST00000540946TOM1L2chr1717810845-674854642165812186
ENST00000359428NUP214chr9134072803+ENST00000542206TOM1L2chr1717810845-664554642165782185
ENST00000411637NUP214chr9134072803+ENST00000581396TOM1L2chr1717810845-108525409867302240
ENST00000411637NUP214chr9134072803+ENST00000379504TOM1L2chr1717810845-76915409868802290
ENST00000411637NUP214chr9134072803+ENST00000318094TOM1L2chr1717810845-75325409867452245
ENST00000411637NUP214chr9134072803+ENST00000395739TOM1L2chr1717810845-70325409867452245
ENST00000411637NUP214chr9134072803+ENST00000535933TOM1L2chr1717810845-69985409868082266
ENST00000411637NUP214chr9134072803+ENST00000540946TOM1L2chr1717810845-66935409865262172
ENST00000411637NUP214chr9134072803+ENST00000542206TOM1L2chr1717810845-65905409865232171
ENST00000451030NUP214chr9134072803+ENST00000581396TOM1L2chr1717810845-108775434067552251
ENST00000451030NUP214chr9134072803+ENST00000379504TOM1L2chr1717810845-77165434069052301
ENST00000451030NUP214chr9134072803+ENST00000318094TOM1L2chr1717810845-75575434067702256
ENST00000451030NUP214chr9134072803+ENST00000395739TOM1L2chr1717810845-70575434067702256
ENST00000451030NUP214chr9134072803+ENST00000535933TOM1L2chr1717810845-70235434068332277
ENST00000451030NUP214chr9134072803+ENST00000540946TOM1L2chr1717810845-67185434065512183
ENST00000451030NUP214chr9134072803+ENST00000542206TOM1L2chr1717810845-66155434065482182
ENST00000483497NUP214chr9134072803+ENST00000581396TOM1L2chr1717810845-7549210626934271052
ENST00000483497NUP214chr9134072803+ENST00000379504TOM1L2chr1717810845-4388210626935771102
ENST00000483497NUP214chr9134072803+ENST00000318094TOM1L2chr1717810845-4229210626934421057
ENST00000483497NUP214chr9134072803+ENST00000395739TOM1L2chr1717810845-3729210626934421057
ENST00000483497NUP214chr9134072803+ENST00000535933TOM1L2chr1717810845-3695210626935051078
ENST00000483497NUP214chr9134072803+ENST00000540946TOM1L2chr1717810845-339021062693223984
ENST00000483497NUP214chr9134072803+ENST00000542206TOM1L2chr1717810845-328721062693220983

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
ENST00000359428ENST00000581396NUP214chr9134072803+TOM1L2chr1717810845-0.0019049190.9980951
ENST00000359428ENST00000379504NUP214chr9134072803+TOM1L2chr1717810845-0.0023152780.9976847
ENST00000359428ENST00000318094NUP214chr9134072803+TOM1L2chr1717810845-0.002874710.9971253
ENST00000359428ENST00000395739NUP214chr9134072803+TOM1L2chr1717810845-0.0026234480.99737656
ENST00000359428ENST00000535933NUP214chr9134072803+TOM1L2chr1717810845-0.0021833190.9978167
ENST00000359428ENST00000540946NUP214chr9134072803+TOM1L2chr1717810845-0.0012290780.9987709
ENST00000359428ENST00000542206NUP214chr9134072803+TOM1L2chr1717810845-0.00125150.99874854
ENST00000411637ENST00000581396NUP214chr9134072803+TOM1L2chr1717810845-0.002114580.9978854
ENST00000411637ENST00000379504NUP214chr9134072803+TOM1L2chr1717810845-0.0026161550.9973839
ENST00000411637ENST00000318094NUP214chr9134072803+TOM1L2chr1717810845-0.003252790.99674726
ENST00000411637ENST00000395739NUP214chr9134072803+TOM1L2chr1717810845-0.0029685350.99703145
ENST00000411637ENST00000535933NUP214chr9134072803+TOM1L2chr1717810845-0.0024814250.99751866
ENST00000411637ENST00000540946NUP214chr9134072803+TOM1L2chr1717810845-0.0013755520.99862444
ENST00000411637ENST00000542206NUP214chr9134072803+TOM1L2chr1717810845-0.0013853120.99861467
ENST00000451030ENST00000581396NUP214chr9134072803+TOM1L2chr1717810845-0.0021169280.997883
ENST00000451030ENST00000379504NUP214chr9134072803+TOM1L2chr1717810845-0.0026260280.99737394
ENST00000451030ENST00000318094NUP214chr9134072803+TOM1L2chr1717810845-0.0032564130.99674356
ENST00000451030ENST00000395739NUP214chr9134072803+TOM1L2chr1717810845-0.0029778510.9970221
ENST00000451030ENST00000535933NUP214chr9134072803+TOM1L2chr1717810845-0.0024930730.9975069
ENST00000451030ENST00000540946NUP214chr9134072803+TOM1L2chr1717810845-0.001381150.99861884
ENST00000451030ENST00000542206NUP214chr9134072803+TOM1L2chr1717810845-0.0013918740.9986082
ENST00000483497ENST00000581396NUP214chr9134072803+TOM1L2chr1717810845-0.0043626930.99563736
ENST00000483497ENST00000379504NUP214chr9134072803+TOM1L2chr1717810845-0.0055878320.9944121
ENST00000483497ENST00000318094NUP214chr9134072803+TOM1L2chr1717810845-0.0071991920.99280083
ENST00000483497ENST00000395739NUP214chr9134072803+TOM1L2chr1717810845-0.0066254020.9933745
ENST00000483497ENST00000535933NUP214chr9134072803+TOM1L2chr1717810845-0.0054607420.9945392
ENST00000483497ENST00000540946NUP214chr9134072803+TOM1L2chr1717810845-0.0034997820.99650025
ENST00000483497ENST00000542206NUP214chr9134072803+TOM1L2chr1717810845-0.003734370.9962656

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 NUP214-TOM1L2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
NUP214chr9134072803TOM1L2chr17178108452106612TAATSGFSFCQASEKATDGSLQSEDW
NUP214chr9134072803TOM1L2chr171781084554091800TAATSGFSFCQASEKATDGSLQSEDW
NUP214chr9134072803TOM1L2chr171781084554341811TAATSGFSFCQASEKATDGSLQSEDW
NUP214chr9134072803TOM1L2chr171781084554641814TAATSGFSFCQASEKATDGSLQSEDW

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Potential FusionNeoAntigen Information of NUP214-TOM1L2 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.
NUP214-TOM1L2_134072803_17810845.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)
NUP214-TOM1L2chr9134072803chr17178108455464HLA-B41:01SEKATDGSL0.44980.88671221
NUP214-TOM1L2chr9134072803chr17178108455464HLA-B39:13SEKATDGSL0.44910.93181221
NUP214-TOM1L2chr9134072803chr17178108455464HLA-B39:08SEKATDGSL0.61460.87411221
NUP214-TOM1L2chr9134072803chr17178108455464HLA-B40:04SEKATDGSL0.99590.7381221
NUP214-TOM1L2chr9134072803chr17178108455464HLA-B41:03SEKATDGSL0.72710.5851221
NUP214-TOM1L2chr9134072803chr17178108455464HLA-B39:02SEKATDGSL0.41750.93321221
NUP214-TOM1L2chr9134072803chr17178108455464HLA-B15:53SEKATDGSL0.16140.88891221

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Potential FusionNeoAntigen Information of NUP214-TOM1L2 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.
NUP214-TOM1L2_134072803_17810845.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)
NUP214-TOM1L2chr9134072803chr17178108455464DRB5-0101TSGFSFCQASEKATD318
NUP214-TOM1L2chr9134072803chr17178108455464DRB5-0105TSGFSFCQASEKATD318
NUP214-TOM1L2chr9134072803chr17178108455464DRB5-0113TSGFSFCQASEKATD318
NUP214-TOM1L2chr9134072803chr17178108455464DRB5-0114TSGFSFCQASEKATD318

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Fusion breakpoint peptide structures of NUP214-TOM1L2

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
2565FSFCQASEKATDGSNUP214TOM1L2chr9134072803chr17178108455464

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of NUP214-TOM1L2

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-B14:023BVN2565FSFCQASEKATDGS-4.62424-5.65954
HLA-B14:023BVN2565FSFCQASEKATDGS-4.1114-4.2248
HLA-B52:013W392565FSFCQASEKATDGS-6.8001-6.9135
HLA-B52:013W392565FSFCQASEKATDGS-6.46104-7.49634
HLA-A24:025HGA2565FSFCQASEKATDGS-9.1447-9.2581
HLA-A24:025HGA2565FSFCQASEKATDGS-6.01279-7.04809
HLA-B44:053DX82565FSFCQASEKATDGS-5.02862-5.14202
HLA-B44:053DX82565FSFCQASEKATDGS-4.60714-5.64244

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Vaccine Design for the FusionNeoAntigens of NUP214-TOM1L2

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
NUP214-TOM1L2chr9134072803chr17178108451221SEKATDGSLCAGAAAAGGCAACAGATGGCTCCCTGC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
NUP214-TOM1L2chr9134072803chr1717810845318TSGFSFCQASEKATDCCTCTGGGTTCAGCTTTTGCCAAGCTTCAGAAAAGGCAACAGATG

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Information of the samples that have these potential fusion neoantigens of NUP214-TOM1L2

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
BRCANUP214-TOM1L2chr9134072803ENST00000359428chr1717810845ENST00000318094TCGA-C8-A135-01A

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Potential target of CAR-T therapy development for NUP214-TOM1L2

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 NUP214-TOM1L2

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 NUP214-TOM1L2

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
HgeneNUP214C0025958Microcephaly1GENOMICS_ENGLAND
HgeneNUP214C0543888Epileptic encephalopathy1GENOMICS_ENGLAND
HgeneNUP214C1836830Developmental regression1GENOMICS_ENGLAND
HgeneNUP214C1961099Precursor T-Cell Lymphoblastic Leukemia-Lymphoma1ORPHANET