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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:NAV3-CDH4

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NAV3-CDH4
FusionPDB ID: 57355
FusionGDB2.0 ID: 57355
HgeneTgene
Gene symbol

NAV3

CDH4

Gene ID

89795

1002

Gene nameneuron navigator 3cadherin 4
SynonymsPOMFIL1|STEERIN3|unc53H3CAD4|R-CAD|RCAD
Cytomap

12q21.2

20q13.33

Type of geneprotein-codingprotein-coding
Descriptionneuron navigator 3pore membrane and/or filament interacting like protein 1unc-53 homolog 3cadherin-4R-cadherincadherin 4, type 1, R-cadherin (retinal)cadherin 4, type 1, preproproteinretinal cadherin
Modification date2020031320200313
UniProtAcc

Q8IVL0

Main function of 5'-partner protein: FUNCTION: May regulate IL2 production by T-cells. May be involved in neuron regeneration. {ECO:0000269|PubMed:16166283}.

P55283

Main function of 5'-partner protein: FUNCTION: Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. May play an important role in retinal development.
Ensembl transtripts involved in fusion geneENST idsENST00000228327, ENST00000266692, 
ENST00000397909, ENST00000536525, 
ENST00000541270, ENST00000552300, 
ENST00000360469, ENST00000543233, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score17 X 11 X 4=74816 X 14 X 7=1568
# samples 1521
** MAII scorelog2(15/748*10)=-2.31807576939176
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(21/1568*10)=-2.90046432644909
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: NAV3 [Title/Abstract] AND CDH4 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: NAV3 [Title/Abstract] AND CDH4 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NAV3(78553066)-CDH4(60469966), # samples:1
Anticipated loss of major functional domain due to fusion event.NAV3-CDH4 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.
NAV3-CDH4 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.
NAV3-CDH4 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.
NAV3-CDH4 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/chr12:78553066/chr20:60469966)
- 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 NAV3 (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 CDH4 (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)
ENST00000536525NAV3chr1278553066+ENST00000360469CDH4chr2060469966+10415504217367422189
ENST00000536525NAV3chr1278553066+ENST00000543233CDH4chr2060469966+7049504217367422189
ENST00000397909NAV3chr1278553066+ENST00000360469CDH4chr2060469966+10415504217367422189
ENST00000397909NAV3chr1278553066+ENST00000543233CDH4chr2060469966+7049504217367422189
ENST00000228327NAV3chr1278553066+ENST00000360469CDH4chr2060469966+10415504217367422189
ENST00000228327NAV3chr1278553066+ENST00000543233CDH4chr2060469966+7049504217367422189
ENST00000266692NAV3chr1278553066+ENST00000360469CDH4chr2060469966+9884451117362112012
ENST00000266692NAV3chr1278553066+ENST00000543233CDH4chr2060469966+6518451117362112012

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
ENST00000536525ENST00000360469NAV3chr1278553066+CDH4chr2060469966+0.0015446410.9984554
ENST00000536525ENST00000543233NAV3chr1278553066+CDH4chr2060469966+0.0023831580.9976169
ENST00000397909ENST00000360469NAV3chr1278553066+CDH4chr2060469966+0.0015446410.9984554
ENST00000397909ENST00000543233NAV3chr1278553066+CDH4chr2060469966+0.0023831580.9976169
ENST00000228327ENST00000360469NAV3chr1278553066+CDH4chr2060469966+0.0014949210.9985051
ENST00000228327ENST00000543233NAV3chr1278553066+CDH4chr2060469966+0.0023014290.9976986
ENST00000266692ENST00000360469NAV3chr1278553066+CDH4chr2060469966+0.0017960430.998204
ENST00000266692ENST00000543233NAV3chr1278553066+CDH4chr2060469966+0.0028070280.99719304

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 NAV3-CDH4

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
NAV3chr1278553066CDH4chr206046996645111446GRLQSLTMTAEQKKVQQYTVIVQATD
NAV3chr1278553066CDH4chr206046996650421623GRLQSLTMTAEQKKVQQYTVIVQATD

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Potential FusionNeoAntigen Information of NAV3-CDH4 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.
NAV3-CDH4_78553066_60469966.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)
NAV3-CDH4chr1278553066chr20604699665042HLA-B15:02EQKKVQQY0.97170.84731018
NAV3-CDH4chr1278553066chr20604699665042HLA-B18:01EQKKVQQY0.93530.87091018
NAV3-CDH4chr1278553066chr20604699665042HLA-B44:03AEQKKVQQY0.99950.8931918
NAV3-CDH4chr1278553066chr20604699665042HLA-B18:01AEQKKVQQY0.97340.8063918
NAV3-CDH4chr1278553066chr20604699665042HLA-B45:01AEQKKVQQY0.74080.8619918
NAV3-CDH4chr1278553066chr20604699665042HLA-B50:02AEQKKVQQY0.65180.5051918
NAV3-CDH4chr1278553066chr20604699665042HLA-B41:01AEQKKVQQY0.2860.8645918
NAV3-CDH4chr1278553066chr20604699665042HLA-B15:03AEQKKVQQY0.24390.6092918
NAV3-CDH4chr1278553066chr20604699665042HLA-B50:01AEQKKVQQY0.07490.7187918
NAV3-CDH4chr1278553066chr20604699665042HLA-B44:03AEQKKVQQYT0.88510.8515919
NAV3-CDH4chr1278553066chr20604699665042HLA-B44:03TAEQKKVQQY0.76280.9023818
NAV3-CDH4chr1278553066chr20604699665042HLA-B15:17MTAEQKKVQQY0.99910.7871718
NAV3-CDH4chr1278553066chr20604699665042HLA-B44:03MTAEQKKVQQY0.87790.8902718
NAV3-CDH4chr1278553066chr20604699665042HLA-B15:135EQKKVQQY0.99970.78651018
NAV3-CDH4chr1278553066chr20604699665042HLA-B15:50EQKKVQQY0.9990.76671018
NAV3-CDH4chr1278553066chr20604699665042HLA-B15:12EQKKVQQY0.99530.83871018
NAV3-CDH4chr1278553066chr20604699665042HLA-B15:53EQKKVQQY0.99290.77111018
NAV3-CDH4chr1278553066chr20604699665042HLA-B15:54EQKKVQQY0.95830.73881018
NAV3-CDH4chr1278553066chr20604699665042HLA-B18:06EQKKVQQY0.95540.86811018
NAV3-CDH4chr1278553066chr20604699665042HLA-B18:04EQKKVQQY0.95150.88541018
NAV3-CDH4chr1278553066chr20604699665042HLA-B18:07EQKKVQQY0.94530.83421018
NAV3-CDH4chr1278553066chr20604699665042HLA-B18:08EQKKVQQY0.93910.85521018
NAV3-CDH4chr1278553066chr20604699665042HLA-B18:11EQKKVQQY0.93580.73141018
NAV3-CDH4chr1278553066chr20604699665042HLA-B18:05EQKKVQQY0.93530.87091018
NAV3-CDH4chr1278553066chr20604699665042HLA-B18:03EQKKVQQY0.92170.86141018
NAV3-CDH4chr1278553066chr20604699665042HLA-B44:26AEQKKVQQY0.99950.8931918
NAV3-CDH4chr1278553066chr20604699665042HLA-B44:13AEQKKVQQY0.99950.8931918
NAV3-CDH4chr1278553066chr20604699665042HLA-B44:07AEQKKVQQY0.99950.8931918
NAV3-CDH4chr1278553066chr20604699665042HLA-B18:04AEQKKVQQY0.98450.828918
NAV3-CDH4chr1278553066chr20604699665042HLA-B18:07AEQKKVQQY0.97940.7868918
NAV3-CDH4chr1278553066chr20604699665042HLA-B18:08AEQKKVQQY0.97460.8071918
NAV3-CDH4chr1278553066chr20604699665042HLA-B18:05AEQKKVQQY0.97340.8063918
NAV3-CDH4chr1278553066chr20604699665042HLA-B18:03AEQKKVQQY0.95510.7954918
NAV3-CDH4chr1278553066chr20604699665042HLA-B18:06AEQKKVQQY0.94690.7964918
NAV3-CDH4chr1278553066chr20604699665042HLA-B15:135AEQKKVQQY0.91140.79918
NAV3-CDH4chr1278553066chr20604699665042HLA-B15:50AEQKKVQQY0.86120.8206918
NAV3-CDH4chr1278553066chr20604699665042HLA-B18:11AEQKKVQQY0.81380.7324918
NAV3-CDH4chr1278553066chr20604699665042HLA-B15:12AEQKKVQQY0.78240.8184918
NAV3-CDH4chr1278553066chr20604699665042HLA-B40:04AEQKKVQQY0.63050.6391918
NAV3-CDH4chr1278553066chr20604699665042HLA-B15:53AEQKKVQQY0.63020.7511918
NAV3-CDH4chr1278553066chr20604699665042HLA-B15:20AEQKKVQQY0.57180.8148918
NAV3-CDH4chr1278553066chr20604699665042HLA-B35:28AEQKKVQQY0.52670.8251918
NAV3-CDH4chr1278553066chr20604699665042HLA-B35:20AEQKKVQQY0.48490.8535918
NAV3-CDH4chr1278553066chr20604699665042HLA-B15:54AEQKKVQQY0.33540.7195918
NAV3-CDH4chr1278553066chr20604699665042HLA-B41:03AEQKKVQQY0.28180.554918
NAV3-CDH4chr1278553066chr20604699665042HLA-B48:02AEQKKVQQY0.21490.8025918
NAV3-CDH4chr1278553066chr20604699665042HLA-B15:68AEQKKVQQY0.11160.5043918
NAV3-CDH4chr1278553066chr20604699665042HLA-B50:05AEQKKVQQY0.07490.7187918
NAV3-CDH4chr1278553066chr20604699665042HLA-B50:04AEQKKVQQY0.07490.7187918
NAV3-CDH4chr1278553066chr20604699665042HLA-B44:26AEQKKVQQYT0.88510.8515919
NAV3-CDH4chr1278553066chr20604699665042HLA-B44:13AEQKKVQQYT0.88510.8515919
NAV3-CDH4chr1278553066chr20604699665042HLA-B44:07AEQKKVQQYT0.88510.8515919
NAV3-CDH4chr1278553066chr20604699665042HLA-B44:26TAEQKKVQQY0.76280.9023818
NAV3-CDH4chr1278553066chr20604699665042HLA-B44:13TAEQKKVQQY0.76280.9023818
NAV3-CDH4chr1278553066chr20604699665042HLA-B44:07TAEQKKVQQY0.76280.9023818
NAV3-CDH4chr1278553066chr20604699665042HLA-B18:11TAEQKKVQQY0.59740.6793818
NAV3-CDH4chr1278553066chr20604699665042HLA-B57:04MTAEQKKVQQY0.99970.6816718
NAV3-CDH4chr1278553066chr20604699665042HLA-A25:01MTAEQKKVQQY0.98830.8445718
NAV3-CDH4chr1278553066chr20604699665042HLA-B44:13MTAEQKKVQQY0.87790.8902718
NAV3-CDH4chr1278553066chr20604699665042HLA-B44:26MTAEQKKVQQY0.87790.8902718
NAV3-CDH4chr1278553066chr20604699665042HLA-B44:07MTAEQKKVQQY0.87790.8902718

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Potential FusionNeoAntigen Information of NAV3-CDH4 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.
NAV3-CDH4_78553066_60469966.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)
NAV3-CDH4chr1278553066chr20604699665042DRB1-0465QKKVQQYTVIVQATD1126
NAV3-CDH4chr1278553066chr20604699665042DRB1-0473QKKVQQYTVIVQATD1126
NAV3-CDH4chr1278553066chr20604699665042DRB1-1457QKKVQQYTVIVQATD1126

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Fusion breakpoint peptide structures of NAV3-CDH4

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
9514TMTAEQKKVQQYTVNAV3CDH4chr1278553066chr20604699665042

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of NAV3-CDH4

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-B14:023BVN9514TMTAEQKKVQQYTV-7.9962-8.1096
HLA-B14:023BVN9514TMTAEQKKVQQYTV-5.70842-6.74372
HLA-B52:013W399514TMTAEQKKVQQYTV-6.83737-6.95077
HLA-B52:013W399514TMTAEQKKVQQYTV-4.4836-5.5189
HLA-A11:014UQ29514TMTAEQKKVQQYTV-10.0067-10.1201
HLA-A11:014UQ29514TMTAEQKKVQQYTV-9.03915-10.0745
HLA-A24:025HGA9514TMTAEQKKVQQYTV-6.56204-6.67544
HLA-A24:025HGA9514TMTAEQKKVQQYTV-5.42271-6.45801
HLA-B44:053DX89514TMTAEQKKVQQYTV-7.85648-8.89178
HLA-B44:053DX89514TMTAEQKKVQQYTV-5.3978-5.5112
HLA-A02:016TDR9514TMTAEQKKVQQYTV-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of NAV3-CDH4

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
NAV3-CDH4chr1278553066chr20604699661018EQKKVQQYGAACAAAAGAAAGTTCAGCAGTAC
NAV3-CDH4chr1278553066chr2060469966718MTAEQKKVQQYATGACAGCGGAACAAAAGAAAGTTCAGCAGTAC
NAV3-CDH4chr1278553066chr2060469966818TAEQKKVQQYACAGCGGAACAAAAGAAAGTTCAGCAGTAC
NAV3-CDH4chr1278553066chr2060469966918AEQKKVQQYGCGGAACAAAAGAAAGTTCAGCAGTAC
NAV3-CDH4chr1278553066chr2060469966919AEQKKVQQYTGCGGAACAAAAGAAAGTTCAGCAGTACACA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
NAV3-CDH4chr1278553066chr20604699661126QKKVQQYTVIVQATDCAAAAGAAAGTTCAGCAGTACACAGTCATCGTTCAGGCCACAGAT

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Information of the samples that have these potential fusion neoantigens of NAV3-CDH4

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
SARCNAV3-CDH4chr1278553066ENST00000228327chr2060469966ENST00000360469TCGA-DX-AB2F-01A

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Potential target of CAR-T therapy development for NAV3-CDH4

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
TgeneCDH4chr12:78553066chr20:60469966ENST00000360469616735_7560917.0TransmembraneHelical
TgeneCDH4chr12:78553066chr20:60469966ENST00000543233515735_7560843.0TransmembraneHelical

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 NAV3-CDH4

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 NAV3-CDH4

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