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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:CYP2E1-NEBL

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CYP2E1-NEBL
FusionPDB ID: 21062
FusionGDB2.0 ID: 21062
HgeneTgene
Gene symbol

CYP2E1

NEBL

Gene ID

1571

10529

Gene namecytochrome P450 family 2 subfamily E member 1nebulette
SynonymsCPE1|CYP2E|P450-J|P450C2EC10orf113|LASP2|LNEBL|bA165O3.1
Cytomap

10q26.3

10p12.31

Type of geneprotein-codingprotein-coding
Descriptioncytochrome P450 2E14-nitrophenol 2-hydroxylaseCYPIIE1cytochrome P450, family 2, subfamily E, polypeptide 1cytochrome P450, subfamily IIE (ethanol-inducible), polypeptide 1cytochrome P450-Jflavoprotein-linked monooxygenasemicrosomal monooxygenasexenebuletteLIM and SH3 protein 2LIM-nebuletteactin-binding Z-disk protein
Modification date2020031520200313
UniProtAcc

P05181

Main function of 5'-partner protein: FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of fatty acids (PubMed:10553002, PubMed:18577768). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10553002, PubMed:18577768). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates fatty acids specifically at the omega-1 position displaying the highest catalytic activity for saturated fatty acids (PubMed:10553002, PubMed:18577768). May be involved in the oxidative metabolism of xenobiotics (Probable). {ECO:0000269|PubMed:10553002, ECO:0000269|PubMed:18577768, ECO:0000305|PubMed:9348445}.

O76041

Main function of 5'-partner protein: FUNCTION: Binds to actin and plays an important role in the assembly of the Z-disk. May functionally link sarcomeric actin to the desmin intermediate filaments in the heart muscle sarcomeres (PubMed:27733623). Isoform 2 might play a role in the assembly of focal adhesion (PubMed:15004028). {ECO:0000269|PubMed:15004028, ECO:0000269|PubMed:27733623}.
Ensembl transtripts involved in fusion geneENST idsENST00000252945, ENST00000463117, 
ENST00000480558, 
ENST00000377119, 
ENST00000464278, ENST00000377122, 
ENST00000377159, ENST00000417816, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score8 X 5 X 3=12012 X 11 X 6=792
# samples 813
** MAII scorelog2(8/120*10)=-0.584962500721156
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(13/792*10)=-2.60698880705116
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: CYP2E1 [Title/Abstract] AND NEBL [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CYP2E1 [Title/Abstract] AND NEBL [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CYP2E1(135341076)-NEBL(21101869), # samples:1
Anticipated loss of major functional domain due to fusion event.CYP2E1-NEBL 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.
CYP2E1-NEBL 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.
CYP2E1-NEBL 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.
CYP2E1-NEBL 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
HgeneCYP2E1

GO:0002933

lipid hydroxylation

10553002

HgeneCYP2E1

GO:0016098

monoterpenoid metabolic process

16401082

HgeneCYP2E1

GO:0017144

drug metabolic process

19219744

HgeneCYP2E1

GO:0018960

4-nitrophenol metabolic process

9348445

HgeneCYP2E1

GO:0046483

heterocycle metabolic process

19651758

HgeneCYP2E1

GO:0055114

oxidation-reduction process

16401082|19219744



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/chr10:135341076/chr10:21101869)
- 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 CYP2E1 (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 NEBL (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)
ENST00000463117CYP2E1chr10135341076+ENST00000377122NEBLchr1021101869-69224492001147315
ENST00000463117CYP2E1chr10135341076+ENST00000417816NEBLchr1021101869-2746449200904234
ENST00000463117CYP2E1chr10135341076+ENST00000377159NEBLchr1021101869-1181449200904234
ENST00000252945CYP2E1chr10135341076+ENST00000377122NEBLchr1021101869-668321033908291
ENST00000252945CYP2E1chr10135341076+ENST00000417816NEBLchr1021101869-250721033665210
ENST00000252945CYP2E1chr10135341076+ENST00000377159NEBLchr1021101869-94221033665210

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
ENST00000463117ENST00000377122CYP2E1chr10135341076+NEBLchr1021101869-0.0001561790.99984384
ENST00000463117ENST00000417816CYP2E1chr10135341076+NEBLchr1021101869-0.0006270270.999373
ENST00000463117ENST00000377159CYP2E1chr10135341076+NEBLchr1021101869-0.0025345550.9974655
ENST00000252945ENST00000377122CYP2E1chr10135341076+NEBLchr1021101869-8.55E-050.9999144
ENST00000252945ENST00000417816CYP2E1chr10135341076+NEBLchr1021101869-0.0003001670.99969983
ENST00000252945ENST00000377159CYP2E1chr10135341076+NEBLchr1021101869-0.0009534170.9990466

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 CYP2E1-NEBL

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CYP2E1chr10135341076NEBLchr102110186921059QLELKNIPKSFTRVKYHEDFEKTKGR
CYP2E1chr10135341076NEBLchr102110186944983QLELKNIPKSFTRVKYHEDFEKTKGR

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Potential FusionNeoAntigen Information of CYP2E1-NEBL 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.
CYP2E1-NEBL_135341076_21101869.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)
CYP2E1-NEBLchr10135341076chr1021101869210HLA-B08:09IPKSFTRV0.99350.5248614
CYP2E1-NEBLchr10135341076chr1021101869210HLA-B27:02TRVKYHEDF0.9970.61831120
CYP2E1-NEBLchr10135341076chr1021101869210HLA-B35:01IPKSFTRVKY0.93550.739616
CYP2E1-NEBLchr10135341076chr1021101869210HLA-C15:04KSFTRVKY0.99430.6428816
CYP2E1-NEBLchr10135341076chr1021101869210HLA-C07:95TRVKYHEDF0.98420.66931120
CYP2E1-NEBLchr10135341076chr1021101869210HLA-C07:46TRVKYHEDF0.80050.86471120
CYP2E1-NEBLchr10135341076chr1021101869210HLA-C07:80TRVKYHEDF0.79220.91951120
CYP2E1-NEBLchr10135341076chr1021101869210HLA-C07:67TRVKYHEDF0.79220.91951120
CYP2E1-NEBLchr10135341076chr1021101869210HLA-C07:10TRVKYHEDF0.78970.95741120
CYP2E1-NEBLchr10135341076chr1021101869210HLA-A02:07NIPKSFTRV0.70580.6169514
CYP2E1-NEBLchr10135341076chr1021101869210HLA-C01:30NIPKSFTRV0.25410.9508514
CYP2E1-NEBLchr10135341076chr1021101869210HLA-C01:17NIPKSFTRV0.23640.9169514
CYP2E1-NEBLchr10135341076chr1021101869210HLA-C15:09KSFTRVKY0.99430.6428816
CYP2E1-NEBLchr10135341076chr1021101869210HLA-C16:02KSFTRVKY0.95950.9601816
CYP2E1-NEBLchr10135341076chr1021101869210HLA-C16:01KSFTRVKY0.90450.9157816
CYP2E1-NEBLchr10135341076chr1021101869210HLA-A30:01KSFTRVKYH0.97880.6335817
CYP2E1-NEBLchr10135341076chr1021101869210HLA-A68:02NIPKSFTRV0.96030.6242514
CYP2E1-NEBLchr10135341076chr1021101869210HLA-A69:01NIPKSFTRV0.90450.6869514
CYP2E1-NEBLchr10135341076chr1021101869210HLA-C07:02TRVKYHEDF0.79220.91951120
CYP2E1-NEBLchr10135341076chr1021101869210HLA-C07:22TRVKYHEDF0.6470.67941120
CYP2E1-NEBLchr10135341076chr1021101869210HLA-C01:02NIPKSFTRV0.17650.9107514
CYP2E1-NEBLchr10135341076chr1021101869210HLA-C01:03NIPKSFTRV0.14130.8996514
CYP2E1-NEBLchr10135341076chr1021101869210HLA-A30:01RVKYHEDFEK0.9930.92011222
CYP2E1-NEBLchr10135341076chr1021101869210HLA-B35:77IPKSFTRVKY0.93550.739616
CYP2E1-NEBLchr10135341076chr1021101869210HLA-B35:23IPKSFTRVKY0.92920.7371616
CYP2E1-NEBLchr10135341076chr1021101869210HLA-B35:24IPKSFTRVKY0.89820.7461616
CYP2E1-NEBLchr10135341076chr1021101869210HLA-B15:11IPKSFTRVKY0.89660.6656616
CYP2E1-NEBLchr10135341076chr1021101869210HLA-B15:08IPKSFTRVKY0.89070.6564616
CYP2E1-NEBLchr10135341076chr1021101869210HLA-B35:43IPKSFTRVKY0.88260.6515616
CYP2E1-NEBLchr10135341076chr1021101869210HLA-B35:11IPKSFTRVKY0.87870.674616
CYP2E1-NEBLchr10135341076chr1021101869210HLA-B18:07IPKSFTRVKY0.37380.7028616

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Potential FusionNeoAntigen Information of CYP2E1-NEBL 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.
CYP2E1-NEBL_135341076_21101869.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)
CYP2E1-NEBLchr10135341076chr1021101869210DRB1-0803PKSFTRVKYHEDFEK722
CYP2E1-NEBLchr10135341076chr1021101869210DRB1-0814PKSFTRVKYHEDFEK722
CYP2E1-NEBLchr10135341076chr1021101869210DRB1-0823PKSFTRVKYHEDFEK722
CYP2E1-NEBLchr10135341076chr1021101869210DRB1-0827PKSFTRVKYHEDFEK722
CYP2E1-NEBLchr10135341076chr1021101869210DRB1-0832PKSFTRVKYHEDFEK722
CYP2E1-NEBLchr10135341076chr1021101869210DRB1-0832IPKSFTRVKYHEDFE621
CYP2E1-NEBLchr10135341076chr1021101869210DRB1-0833PKSFTRVKYHEDFEK722
CYP2E1-NEBLchr10135341076chr1021101869210DRB1-0835PKSFTRVKYHEDFEK722
CYP2E1-NEBLchr10135341076chr1021101869210DRB1-0836PKSFTRVKYHEDFEK722
CYP2E1-NEBLchr10135341076chr1021101869210DRB1-0837PKSFTRVKYHEDFEK722
CYP2E1-NEBLchr10135341076chr1021101869210DRB1-0837IPKSFTRVKYHEDFE621
CYP2E1-NEBLchr10135341076chr1021101869210DRB1-0838PKSFTRVKYHEDFEK722
CYP2E1-NEBLchr10135341076chr1021101869210DRB1-1463PKSFTRVKYHEDFEK722
CYP2E1-NEBLchr10135341076chr1021101869210DRB1-1463IPKSFTRVKYHEDFE621
CYP2E1-NEBLchr10135341076chr1021101869210DRB1-1485PKSFTRVKYHEDFEK722
CYP2E1-NEBLchr10135341076chr1021101869210DRB5-0106FTRVKYHEDFEKTKG1025
CYP2E1-NEBLchr10135341076chr1021101869210DRB5-0202FTRVKYHEDFEKTKG1025

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Fusion breakpoint peptide structures of CYP2E1-NEBL

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
3891IPKSFTRVKYHEDFCYP2E1NEBLchr10135341076chr1021101869210

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CYP2E1-NEBL

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-B14:023BVN3891IPKSFTRVKYHEDF-7.15543-7.26883
HLA-B14:023BVN3891IPKSFTRVKYHEDF-4.77435-5.80965
HLA-B52:013W393891IPKSFTRVKYHEDF-6.80875-6.92215
HLA-B52:013W393891IPKSFTRVKYHEDF-4.20386-5.23916
HLA-A11:014UQ23891IPKSFTRVKYHEDF-7.5194-8.5547
HLA-A11:014UQ23891IPKSFTRVKYHEDF-6.9601-7.0735
HLA-A24:025HGA3891IPKSFTRVKYHEDF-7.52403-7.63743
HLA-A24:025HGA3891IPKSFTRVKYHEDF-5.82433-6.85963
HLA-B27:056PYJ3891IPKSFTRVKYHEDF-3.28285-4.31815
HLA-B44:053DX83891IPKSFTRVKYHEDF-5.91172-6.94702
HLA-B44:053DX83891IPKSFTRVKYHEDF-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of CYP2E1-NEBL

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
CYP2E1-NEBLchr10135341076chr10211018691120TRVKYHEDFACCCGGGTAAAATACCATGAAGATTTT
CYP2E1-NEBLchr10135341076chr10211018691222RVKYHEDFEKCGGGTAAAATACCATGAAGATTTTGAAAAA
CYP2E1-NEBLchr10135341076chr1021101869514NIPKSFTRVAATATTCCCAAGTCCTTCACCCGGGTA
CYP2E1-NEBLchr10135341076chr1021101869614IPKSFTRVATTCCCAAGTCCTTCACCCGGGTA
CYP2E1-NEBLchr10135341076chr1021101869616IPKSFTRVKYATTCCCAAGTCCTTCACCCGGGTAAAATAC
CYP2E1-NEBLchr10135341076chr1021101869816KSFTRVKYAAGTCCTTCACCCGGGTAAAATAC
CYP2E1-NEBLchr10135341076chr1021101869817KSFTRVKYHAAGTCCTTCACCCGGGTAAAATACCAT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
CYP2E1-NEBLchr10135341076chr10211018691025FTRVKYHEDFEKTKGTTCACCCGGGTAAAATACCATGAAGATTTTGAAAAAACAAAGGGG
CYP2E1-NEBLchr10135341076chr1021101869621IPKSFTRVKYHEDFEATTCCCAAGTCCTTCACCCGGGTAAAATACCATGAAGATTTTGAA
CYP2E1-NEBLchr10135341076chr1021101869722PKSFTRVKYHEDFEKCCCAAGTCCTTCACCCGGGTAAAATACCATGAAGATTTTGAAAAA

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Information of the samples that have these potential fusion neoantigens of CYP2E1-NEBL

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
Non-CancerCYP2E1-NEBLchr10135341076ENST00000252945chr1021101869ENST00000377122TCGA-DD-A1EB-11A

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Potential target of CAR-T therapy development for CYP2E1-NEBL

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 CYP2E1-NEBL

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 CYP2E1-NEBL

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