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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:KDM4A-OPRD1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: KDM4A-OPRD1
FusionPDB ID: 41784
FusionGDB2.0 ID: 41784
HgeneTgene
Gene symbol

KDM4A

OPRD1

Gene ID

9682

4985

Gene namelysine demethylase 4Aopioid receptor delta 1
SynonymsJHDM3A|JMJD2|JMJD2A|TDRD14ADOP|DOR|DOR1|OPRD
Cytomap

1p34.2-p34.1

1p35.3

Type of geneprotein-codingprotein-coding
Descriptionlysine-specific demethylase 4AjmjC domain-containing histone demethylation protein 3Ajumonji C domain-containing histone demethylase 3Ajumonji domain containing 2jumonji domain containing 2Ajumonji domain-containing protein 2Alysine (K)-specific demdelta-type opioid receptorD-OR-1DOR-1delta opioid receptor 1opioid receptor delta 1 isoform DOR-1Bopioid receptor delta 1 isoform DOR-1Copioid receptor delta 1 isoform DOR-1Dopioid receptor delta 1 isoform DOR-1E
Modification date2020031320200313
UniProtAcc

O75164

Main function of 5'-partner protein: FUNCTION: Histone demethylase that specifically demethylates 'Lys-9' and 'Lys-36' residues of histone H3, thereby playing a central role in histone code (PubMed:26741168). Does not demethylate histone H3 'Lys-4', H3 'Lys-27' nor H4 'Lys-20'. Demethylates trimethylated H3 'Lys-9' and H3 'Lys-36' residue, while it has no activity on mono- and dimethylated residues. Demethylation of Lys residue generates formaldehyde and succinate. Participates in transcriptional repression of ASCL2 and E2F-responsive promoters via the recruitment of histone deacetylases and NCOR1, respectively. {ECO:0000269|PubMed:16024779, ECO:0000269|PubMed:16603238, ECO:0000269|PubMed:26741168}.; FUNCTION: [Isoform 2]: Crucial for muscle differentiation, promotes transcriptional activation of the Myog gene by directing the removal of repressive chromatin marks at its promoter. Lacks the N-terminal demethylase domain. {ECO:0000269|PubMed:21694756}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000463151, ENST00000372396, 
ENST00000234961, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score13 X 11 X 10=14302 X 2 X 2=8
# samples 152
** MAII scorelog2(15/1430*10)=-3.25298074116987
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(2/8*10)=1.32192809488736
Fusion gene context

PubMed: KDM4A [Title/Abstract] AND OPRD1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: KDM4A [Title/Abstract] AND OPRD1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)KDM4A(44121437)-OPRD1(29185466), # samples:2
Anticipated loss of major functional domain due to fusion event.KDM4A-OPRD1 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.
KDM4A-OPRD1 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.
KDM4A-OPRD1 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.
KDM4A-OPRD1 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
HgeneKDM4A

GO:0016577

histone demethylation

16024779

HgeneKDM4A

GO:0045892

negative regulation of transcription, DNA-templated

16024779

HgeneKDM4A

GO:0070544

histone H3-K36 demethylation

21914792

TgeneOPRD1

GO:0007186

G protein-coupled receptor signaling pathway

16325578

TgeneOPRD1

GO:0010629

negative regulation of gene expression

24613828

TgeneOPRD1

GO:0031333

negative regulation of protein complex assembly

24613828

TgeneOPRD1

GO:0033138

positive regulation of peptidyl-serine phosphorylation

24613828

TgeneOPRD1

GO:0051881

regulation of mitochondrial membrane potential

24613828

TgeneOPRD1

GO:0071456

cellular response to hypoxia

24613828

TgeneOPRD1

GO:0097237

cellular response to toxic substance

24613828



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/chr1:44121437/chr1:29185466)
- 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 KDM4A (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 OPRD1 (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)
ENST00000372396KDM4Achr144121437+ENST00000234961OPRD1chr129185466+17534481341339401

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
ENST00000372396ENST00000234961KDM4Achr144121437+OPRD1chr129185466+0.0037628070.99623716

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 KDM4A-OPRD1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
KDM4Achr144121437OPRD1chr129185466448105TVREFRKIANSDKYTKMKTATNIYIF

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Potential FusionNeoAntigen Information of KDM4A-OPRD1 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.
KDM4A-OPRD1_44121437_29185466.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)
KDM4A-OPRD1chr144121437chr129185466448HLA-B39:06DKYTKMKTA0.90930.77121120
KDM4A-OPRD1chr144121437chr129185466448HLA-B15:03RKIANSDKY0.0320.581514
KDM4A-OPRD1chr144121437chr129185466448HLA-C05:09NSDKYTKM10.8471917
KDM4A-OPRD1chr144121437chr129185466448HLA-C04:10NSDKYTKM10.5629917
KDM4A-OPRD1chr144121437chr129185466448HLA-C04:07NSDKYTKM10.5745917
KDM4A-OPRD1chr144121437chr129185466448HLA-C08:15NSDKYTKM10.9423917
KDM4A-OPRD1chr144121437chr129185466448HLA-C05:01NSDKYTKM10.8471917
KDM4A-OPRD1chr144121437chr129185466448HLA-C04:03NSDKYTKM10.6406917
KDM4A-OPRD1chr144121437chr129185466448HLA-C08:02NSDKYTKM10.9423917
KDM4A-OPRD1chr144121437chr129185466448HLA-C18:01NSDKYTKM10.6101917
KDM4A-OPRD1chr144121437chr129185466448HLA-C04:01NSDKYTKM10.5745917
KDM4A-OPRD1chr144121437chr129185466448HLA-B48:02RKIANSDKY0.04710.808514
KDM4A-OPRD1chr144121437chr129185466448HLA-B15:53RKIANSDKY0.03540.8093514
KDM4A-OPRD1chr144121437chr129185466448HLA-B15:54RKIANSDKY0.02120.7924514

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Potential FusionNeoAntigen Information of KDM4A-OPRD1 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.
KDM4A-OPRD1_44121437_29185466.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)
KDM4A-OPRD1chr144121437chr129185466448DRB1-0419NSDKYTKMKTATNIY924
KDM4A-OPRD1chr144121437chr129185466448DRB1-0419SDKYTKMKTATNIYI1025
KDM4A-OPRD1chr144121437chr129185466448DRB1-0431NSDKYTKMKTATNIY924
KDM4A-OPRD1chr144121437chr129185466448DRB1-0431SDKYTKMKTATNIYI1025
KDM4A-OPRD1chr144121437chr129185466448DRB1-0443NSDKYTKMKTATNIY924
KDM4A-OPRD1chr144121437chr129185466448DRB1-0447NSDKYTKMKTATNIY924
KDM4A-OPRD1chr144121437chr129185466448DRB1-0447SDKYTKMKTATNIYI1025
KDM4A-OPRD1chr144121437chr129185466448DRB1-0447ANSDKYTKMKTATNI823
KDM4A-OPRD1chr144121437chr129185466448DRB1-0454NSDKYTKMKTATNIY924
KDM4A-OPRD1chr144121437chr129185466448DRB1-0454SDKYTKMKTATNIYI1025
KDM4A-OPRD1chr144121437chr129185466448DRB1-0454ANSDKYTKMKTATNI823
KDM4A-OPRD1chr144121437chr129185466448DRB1-0461NSDKYTKMKTATNIY924
KDM4A-OPRD1chr144121437chr129185466448DRB1-0461SDKYTKMKTATNIYI1025
KDM4A-OPRD1chr144121437chr129185466448DRB1-0475NSDKYTKMKTATNIY924
KDM4A-OPRD1chr144121437chr129185466448DRB1-0475SDKYTKMKTATNIYI1025
KDM4A-OPRD1chr144121437chr129185466448DRB1-0486NSDKYTKMKTATNIY924
KDM4A-OPRD1chr144121437chr129185466448DRB1-1001NSDKYTKMKTATNIY924
KDM4A-OPRD1chr144121437chr129185466448DRB1-1001SDKYTKMKTATNIYI1025
KDM4A-OPRD1chr144121437chr129185466448DRB1-1001ANSDKYTKMKTATNI823
KDM4A-OPRD1chr144121437chr129185466448DRB1-1001DKYTKMKTATNIYIF1126
KDM4A-OPRD1chr144121437chr129185466448DRB1-1003NSDKYTKMKTATNIY924
KDM4A-OPRD1chr144121437chr129185466448DRB1-1003SDKYTKMKTATNIYI1025
KDM4A-OPRD1chr144121437chr129185466448DRB1-1003ANSDKYTKMKTATNI823
KDM4A-OPRD1chr144121437chr129185466448DRB1-1003DKYTKMKTATNIYIF1126
KDM4A-OPRD1chr144121437chr129185466448DRB1-1130NSDKYTKMKTATNIY924
KDM4A-OPRD1chr144121437chr129185466448DRB1-1130SDKYTKMKTATNIYI1025
KDM4A-OPRD1chr144121437chr129185466448DRB5-0101VREFRKIANSDKYTK116
KDM4A-OPRD1chr144121437chr129185466448DRB5-0101TVREFRKIANSDKYT015
KDM4A-OPRD1chr144121437chr129185466448DRB5-0101REFRKIANSDKYTKM217
KDM4A-OPRD1chr144121437chr129185466448DRB5-0102VREFRKIANSDKYTK116
KDM4A-OPRD1chr144121437chr129185466448DRB5-0103VREFRKIANSDKYTK116
KDM4A-OPRD1chr144121437chr129185466448DRB5-0104VREFRKIANSDKYTK116
KDM4A-OPRD1chr144121437chr129185466448DRB5-0104TVREFRKIANSDKYT015
KDM4A-OPRD1chr144121437chr129185466448DRB5-0105VREFRKIANSDKYTK116
KDM4A-OPRD1chr144121437chr129185466448DRB5-0105TVREFRKIANSDKYT015
KDM4A-OPRD1chr144121437chr129185466448DRB5-0105REFRKIANSDKYTKM217
KDM4A-OPRD1chr144121437chr129185466448DRB5-0108NVREFRKIANSDKYTK116
KDM4A-OPRD1chr144121437chr129185466448DRB5-0111VREFRKIANSDKYTK116
KDM4A-OPRD1chr144121437chr129185466448DRB5-0113VREFRKIANSDKYTK116
KDM4A-OPRD1chr144121437chr129185466448DRB5-0113TVREFRKIANSDKYT015
KDM4A-OPRD1chr144121437chr129185466448DRB5-0113REFRKIANSDKYTKM217
KDM4A-OPRD1chr144121437chr129185466448DRB5-0114VREFRKIANSDKYTK116
KDM4A-OPRD1chr144121437chr129185466448DRB5-0114TVREFRKIANSDKYT015
KDM4A-OPRD1chr144121437chr129185466448DRB5-0114REFRKIANSDKYTKM217

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Fusion breakpoint peptide structures of KDM4A-OPRD1

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
4286KIANSDKYTKMKTAKDM4AOPRD1chr144121437chr129185466448

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of KDM4A-OPRD1

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-B14:023BVN4286KIANSDKYTKMKTA-7.15543-7.26883
HLA-B14:023BVN4286KIANSDKYTKMKTA-4.77435-5.80965
HLA-B52:013W394286KIANSDKYTKMKTA-6.80875-6.92215
HLA-B52:013W394286KIANSDKYTKMKTA-4.20386-5.23916
HLA-A11:014UQ24286KIANSDKYTKMKTA-7.5194-8.5547
HLA-A11:014UQ24286KIANSDKYTKMKTA-6.9601-7.0735
HLA-A24:025HGA4286KIANSDKYTKMKTA-7.52403-7.63743
HLA-A24:025HGA4286KIANSDKYTKMKTA-5.82433-6.85963
HLA-B27:056PYJ4286KIANSDKYTKMKTA-3.28285-4.31815
HLA-B44:053DX84286KIANSDKYTKMKTA-5.91172-6.94702
HLA-B44:053DX84286KIANSDKYTKMKTA-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of KDM4A-OPRD1

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
KDM4A-OPRD1chr144121437chr1291854661120DKYTKMKTACGATAAGTACACTAAGATGAAGACGGC
KDM4A-OPRD1chr144121437chr129185466514RKIANSDKYCCGCAAGATAGCCAATAGCGATAAGTA
KDM4A-OPRD1chr144121437chr129185466917NSDKYTKMCAATAGCGATAAGTACACTAAGAT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
KDM4A-OPRD1chr144121437chr129185466015TVREFRKIANSDKYTGACTGTTCGAGAGTTCCGCAAGATAGCCAATAGCGATAAGTACAC
KDM4A-OPRD1chr144121437chr129185466116VREFRKIANSDKYTKTGTTCGAGAGTTCCGCAAGATAGCCAATAGCGATAAGTACACTAA
KDM4A-OPRD1chr144121437chr1291854661025SDKYTKMKTATNIYITAGCGATAAGTACACTAAGATGAAGACGGCCACCAACATCTACAT
KDM4A-OPRD1chr144121437chr1291854661126DKYTKMKTATNIYIFCGATAAGTACACTAAGATGAAGACGGCCACCAACATCTACATCTT
KDM4A-OPRD1chr144121437chr129185466217REFRKIANSDKYTKMTCGAGAGTTCCGCAAGATAGCCAATAGCGATAAGTACACTAAGAT
KDM4A-OPRD1chr144121437chr129185466823ANSDKYTKMKTATNIAGCCAATAGCGATAAGTACACTAAGATGAAGACGGCCACCAACAT
KDM4A-OPRD1chr144121437chr129185466924NSDKYTKMKTATNIYCAATAGCGATAAGTACACTAAGATGAAGACGGCCACCAACATCTA

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Information of the samples that have these potential fusion neoantigens of KDM4A-OPRD1

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
CHOLKDM4A-OPRD1chr144121437ENST00000372396chr129185466ENST00000234961TCGA-W5-AA36-01A

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Potential target of CAR-T therapy development for KDM4A-OPRD1

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
TgeneOPRD1chr1:44121437chr1:29185466ENST0000023496103123_1440373.0TransmembraneHelical%3B Name%3D3
TgeneOPRD1chr1:44121437chr1:29185466ENST0000023496103164_1860373.0TransmembraneHelical%3B Name%3D4
TgeneOPRD1chr1:44121437chr1:29185466ENST0000023496103207_2380373.0TransmembraneHelical%3B Name%3D5
TgeneOPRD1chr1:44121437chr1:29185466ENST0000023496103262_2840373.0TransmembraneHelical%3B Name%3D6
TgeneOPRD1chr1:44121437chr1:29185466ENST0000023496103300_3210373.0TransmembraneHelical%3B Name%3D7
TgeneOPRD1chr1:44121437chr1:29185466ENST000002349610386_1100373.0TransmembraneHelical%3B Name%3D2

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 KDM4A-OPRD1

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 KDM4A-OPRD1

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