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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:NFE2L1-SLC39A11

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NFE2L1-SLC39A11
FusionPDB ID: 58829
FusionGDB2.0 ID: 58829
HgeneTgene
Gene symbol

NFE2L1

SLC39A11

Gene ID

4779

201266

Gene namenuclear factor, erythroid 2 like 1solute carrier family 39 member 11
SynonymsLCR-F1|NRF1|TCF11C17orf26|ZIP-11|ZIP11
Cytomap

17q21.32

17q24.3-q25.1

Type of geneprotein-codingprotein-coding
Descriptionendoplasmic reticulum membrane sensor NFE2L1NF-E2-related factor 1NFE2-related factor 1TCF-11locus control region-factor 1nuclear factor erythroid 2-related factor 1nuclear factor, erythroid derived 2, like 1protein NRF1, p120 formtranscription fazinc transporter ZIP11Zrt- and Irt-like protein 11solute carrier family 39 (metal ion transporter), member 11
Modification date2020031320200313
UniProtAcc

Q14494

Main function of 5'-partner protein: FUNCTION: [Endoplasmic reticulum membrane sensor NFE2L1]: Endoplasmic reticulum membrane sensor that translocates into the nucleus in response to various stresses to act as a transcription factor (PubMed:20932482, PubMed:24448410). Constitutes a precursor of the transcription factor NRF1 (By similarity). Able to detect various cellular stresses, such as cholesterol excess, oxidative stress or proteasome inhibition (PubMed:20932482). In response to stress, it is released from the endoplasmic reticulum membrane following cleavage by the protease DDI2 and translocates into the nucleus to form the transcription factor NRF1 (By similarity). Acts as a key sensor of cholesterol excess: in excess cholesterol conditions, the endoplasmic reticulum membrane form of the protein directly binds cholesterol via its CRAC motif, preventing cleavage and release of the transcription factor NRF1, thereby allowing expression of genes promoting cholesterol removal, such as CD36 (By similarity). Involved in proteasome homeostasis: in response to proteasome inhibition, it is released from the endoplasmic reticulum membrane, translocates to the nucleus and activates expression of genes encoding proteasome subunits (PubMed:20932482). {ECO:0000250|UniProtKB:Q61985, ECO:0000269|PubMed:20932482, ECO:0000269|PubMed:24448410}.; FUNCTION: [Transcription factor NRF1]: CNC-type bZIP family transcription factor that translocates to the nucleus and regulates expression of target genes in response to various stresses (PubMed:8932385, PubMed:9421508). Heterodimerizes with small-Maf proteins (MAFF, MAFG or MAFK) and binds DNA motifs including the antioxidant response elements (AREs), which regulate expression of genes involved in oxidative stress response (PubMed:8932385, PubMed:9421508). Activates or represses expression of target genes, depending on the context (PubMed:8932385, PubMed:9421508). Plays a key role in cholesterol homeostasis by acting as a sensor of cholesterol excess: in low cholesterol conditions, translocates into the nucleus and represses expression of genes involved in defense against cholesterol excess, such as CD36 (By similarity). In excess cholesterol conditions, the endoplasmic reticulum membrane form of the protein directly binds cholesterol via its CRAC motif, preventing cleavage and release of the transcription factor NRF1, thereby allowing expression of genes promoting cholesterol removal (By similarity). Critical for redox balance in response to oxidative stress: acts by binding the AREs motifs on promoters and mediating activation of oxidative stress response genes, such as GCLC, GCLM, GSS, MT1 and MT2 (By similarity). Plays an essential role during fetal liver hematopoiesis: probably has a protective function against oxidative stress and is involved in lipid homeostasis in the liver (By similarity). Involved in proteasome homeostasis: in response to proteasome inhibition, mediates the 'bounce-back' of proteasome subunits by translocating into the nucleus and activating expression of genes encoding proteasome subunits (PubMed:20932482). Also involved in regulating glucose flux (By similarity). Together with CEBPB; represses expression of DSPP during odontoblast differentiation (PubMed:15308669). In response to ascorbic acid induction, activates expression of SP7/Osterix in osteoblasts. {ECO:0000250|UniProtKB:Q61985, ECO:0000269|PubMed:15308669, ECO:0000269|PubMed:20932482, ECO:0000269|PubMed:8932385, ECO:0000269|PubMed:9421508}.
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Ensembl transtripts involved in fusion geneENST idsENST00000357480, ENST00000361665, 
ENST00000362042, ENST00000536222, 
ENST00000582155, ENST00000583378, 
ENST00000585291, ENST00000579481, 
ENST00000579732, ENST00000579988, 
ENST00000255559, ENST00000542342, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score18 X 12 X 13=280824 X 14 X 9=3024
# samples 2029
** MAII scorelog2(20/2808*10)=-3.81147103052984
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(29/3024*10)=-3.38233333420614
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: NFE2L1 [Title/Abstract] AND SLC39A11 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: NFE2L1 [Title/Abstract] AND SLC39A11 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NFE2L1(46134864)-SLC39A11(70944014), # samples:3
Anticipated loss of major functional domain due to fusion event.NFE2L1-SLC39A11 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.
NFE2L1-SLC39A11 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.
NFE2L1-SLC39A11 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.
NFE2L1-SLC39A11 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


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/chr17:46134864/chr17:70944014)
- 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 NFE2L1 (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 SLC39A11 (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)
ENST00000362042NFE2L1chr1746134864+ENST00000255559SLC39A11chr1770944014-392515886162289557
ENST00000362042NFE2L1chr1746134864+ENST00000542342SLC39A11chr1770944014-394515886162310564
ENST00000585291NFE2L1chr1746134864+ENST00000255559SLC39A11chr1770944014-353411972911898535
ENST00000585291NFE2L1chr1746134864+ENST00000542342SLC39A11chr1770944014-355411972911919542
ENST00000357480NFE2L1chr1746134864+ENST00000255559SLC39A11chr1770944014-382414876052188527
ENST00000357480NFE2L1chr1746134864+ENST00000542342SLC39A11chr1770944014-384414876052209534
ENST00000361665NFE2L1chr1746134864+ENST00000255559SLC39A11chr1770944014-388015436042244546
ENST00000361665NFE2L1chr1746134864+ENST00000542342SLC39A11chr1770944014-390015436042265553
ENST00000582155NFE2L1chr1746134864+ENST00000255559SLC39A11chr1770944014-2796459511160369
ENST00000582155NFE2L1chr1746134864+ENST00000542342SLC39A11chr1770944014-2816459511181376
ENST00000583378NFE2L1chr1746134864+ENST00000255559SLC39A11chr1770944014-2746409341110358
ENST00000583378NFE2L1chr1746134864+ENST00000542342SLC39A11chr1770944014-2766409341131365
ENST00000536222NFE2L1chr1746134864+ENST00000255559SLC39A11chr1770944014-31508132611514417
ENST00000536222NFE2L1chr1746134864+ENST00000542342SLC39A11chr1770944014-31708132611535424

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
ENST00000362042ENST00000255559NFE2L1chr1746134864+SLC39A11chr1770944014-0.0009359730.999064
ENST00000362042ENST00000542342NFE2L1chr1746134864+SLC39A11chr1770944014-0.0009327750.99906725
ENST00000585291ENST00000255559NFE2L1chr1746134864+SLC39A11chr1770944014-0.0009309860.99906904
ENST00000585291ENST00000542342NFE2L1chr1746134864+SLC39A11chr1770944014-0.0010472440.99895275
ENST00000357480ENST00000255559NFE2L1chr1746134864+SLC39A11chr1770944014-0.0006879030.99931204
ENST00000357480ENST00000542342NFE2L1chr1746134864+SLC39A11chr1770944014-0.0007774540.9992225
ENST00000361665ENST00000255559NFE2L1chr1746134864+SLC39A11chr1770944014-0.0008825560.99911743
ENST00000361665ENST00000542342NFE2L1chr1746134864+SLC39A11chr1770944014-0.0009306810.9990694
ENST00000582155ENST00000255559NFE2L1chr1746134864+SLC39A11chr1770944014-0.0018275850.9981724
ENST00000582155ENST00000542342NFE2L1chr1746134864+SLC39A11chr1770944014-0.0019095410.99809045
ENST00000583378ENST00000255559NFE2L1chr1746134864+SLC39A11chr1770944014-0.0018406890.99815935
ENST00000583378ENST00000542342NFE2L1chr1746134864+SLC39A11chr1770944014-0.0012740810.99872595
ENST00000536222ENST00000255559NFE2L1chr1746134864+SLC39A11chr1770944014-0.006524070.993476
ENST00000536222ENST00000542342NFE2L1chr1746134864+SLC39A11chr1770944014-0.0066424150.9933576

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 NFE2L1-SLC39A11

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
NFE2L1chr1746134864SLC39A11chr17709440141197301EQQWQDLMSIMEMQGAAEDPQTTLAL
NFE2L1chr1746134864SLC39A11chr17709440141487293EQQWQDLMSIMEMQGAAEDPQTTLAL
NFE2L1chr1746134864SLC39A11chr17709440141543312EQQWQDLMSIMEMQGAAEDPQTTLAL
NFE2L1chr1746134864SLC39A11chr17709440141588323EQQWQDLMSIMEMQGAAEDPQTTLAL
NFE2L1chr1746134864SLC39A11chr1770944014409124EQQWQDLMSIMEMQGAAEDPQTTLAL
NFE2L1chr1746134864SLC39A11chr1770944014459135EQQWQDLMSIMEMQGAAEDPQTTLAL
NFE2L1chr1746134864SLC39A11chr1770944014813183EQQWQDLMSIMEMQGAAEDPQTTLAL

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Potential FusionNeoAntigen Information of NFE2L1-SLC39A11 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.
NFE2L1-SLC39A11_46134864_70944014.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)
NFE2L1-SLC39A11chr1746134864chr17709440141487HLA-B45:01MEMQGAAEDP0.96030.93551020
NFE2L1-SLC39A11chr1746134864chr17709440141487HLA-B50:02MEMQGAAEDP0.94170.70111020

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Potential FusionNeoAntigen Information of NFE2L1-SLC39A11 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 NFE2L1-SLC39A11

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
5308LMSIMEMQGAAEDPNFE2L1SLC39A11chr1746134864chr17709440141487

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of NFE2L1-SLC39A11

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-B14:023BVN5308LMSIMEMQGAAEDP-7.9962-8.1096
HLA-B14:023BVN5308LMSIMEMQGAAEDP-5.70842-6.74372
HLA-B52:013W395308LMSIMEMQGAAEDP-6.83737-6.95077
HLA-B52:013W395308LMSIMEMQGAAEDP-4.4836-5.5189
HLA-A11:014UQ25308LMSIMEMQGAAEDP-10.0067-10.1201
HLA-A11:014UQ25308LMSIMEMQGAAEDP-9.03915-10.0745
HLA-A24:025HGA5308LMSIMEMQGAAEDP-6.56204-6.67544
HLA-A24:025HGA5308LMSIMEMQGAAEDP-5.42271-6.45801
HLA-B44:053DX85308LMSIMEMQGAAEDP-7.85648-8.89178
HLA-B44:053DX85308LMSIMEMQGAAEDP-5.3978-5.5112
HLA-A02:016TDR5308LMSIMEMQGAAEDP-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of NFE2L1-SLC39A11

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
NFE2L1-SLC39A11chr1746134864chr17709440141020MEMQGAAEDPGAAATGCAGGGTGCAGCAGAAGACCCCCAG

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 NFE2L1-SLC39A11

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
SKCMNFE2L1-SLC39A11chr1746134864ENST00000357480chr1770944014ENST00000255559TCGA-EB-A4XL-01A

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Potential target of CAR-T therapy development for NFE2L1-SLC39A11

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
HgeneNFE2L1chr17:46134864chr17:70944014ENST00000357480+457_24294743.0TransmembraneHelical%3B Signal-anchor for type II membrane protein
HgeneNFE2L1chr17:46134864chr17:70944014ENST00000362042+567_24324773.0TransmembraneHelical%3B Signal-anchor for type II membrane protein
HgeneNFE2L1chr17:46134864chr17:70944014ENST00000585291+567_24294743.0TransmembraneHelical%3B Signal-anchor for type II membrane protein
TgeneSLC39A11chr17:46134864chr17:70944014ENST00000255559310194_2140336.0TransmembraneHelical
TgeneSLC39A11chr17:46134864chr17:70944014ENST00000255559310263_2850336.0TransmembraneHelical
TgeneSLC39A11chr17:46134864chr17:70944014ENST00000255559310290_3070336.0TransmembraneHelical
TgeneSLC39A11chr17:46134864chr17:70944014ENST00000255559310322_3420336.0TransmembraneHelical
TgeneSLC39A11chr17:46134864chr17:70944014ENST00000542342310194_2140343.0TransmembraneHelical
TgeneSLC39A11chr17:46134864chr17:70944014ENST00000542342310263_2850343.0TransmembraneHelical
TgeneSLC39A11chr17:46134864chr17:70944014ENST00000542342310290_3070343.0TransmembraneHelical
TgeneSLC39A11chr17:46134864chr17:70944014ENST00000542342310322_3420343.0TransmembraneHelical

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 NFE2L1-SLC39A11

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 NFE2L1-SLC39A11

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