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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:ARFGEF2-TSHZ2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ARFGEF2-TSHZ2
FusionPDB ID: 5878
FusionGDB2.0 ID: 5878
HgeneTgene
Gene symbol

ARFGEF2

TSHZ2

Gene ID

10564

128553

Gene nameADP ribosylation factor guanine nucleotide exchange factor 2teashirt zinc finger homeobox 2
SynonymsBIG2|PVNH2|dJ1164I10.1C20orf17|OVC10-2|TSH2|ZABC2|ZNF218
Cytomap

20q13.13

20q13.2

Type of geneprotein-codingprotein-coding
Descriptionbrefeldin A-inhibited guanine nucleotide-exchange protein 2ADP-ribosylation factor guanine nucleotide-exchange factor 2 (brefeldin A-inhibited)brefeldin A-inhibited GEP 2teashirt homolog 2cell growth-inhibiting protein 7ovarian cancer-related protein 10-2serologically defined colon cancer antigen 33 liketeashirt family zinc finger 2zinc finger protein 218
Modification date2020031320200313
UniProtAcc

Q9Y6D5

Main function of 5'-partner protein: FUNCTION: Promotes guanine-nucleotide exchange on ARF1 and ARF3 and to a lower extent on ARF5 and ARF6. Promotes the activation of ARF1/ARF5/ARF6 through replacement of GDP with GTP. Involved in the regulation of Golgi vesicular transport. Required for the integrity of the endosomal compartment. Involved in trafficking from the trans-Golgi network (TGN) to endosomes and is required for membrane association of the AP-1 complex and GGA1. Seems to be involved in recycling of the transferrin receptor from recycling endosomes to the plasma membrane. Probably is involved in the exit of GABA(A) receptors from the endoplasmic reticulum. Involved in constitutive release of tumor necrosis factor receptor 1 via exosome-like vesicles; the function seems to involve PKA and specifically PRKAR2B. Proposed to act as A kinase-anchoring protein (AKAP) and may mediate crosstalk between Arf and PKA pathways. {ECO:0000269|PubMed:12051703, ECO:0000269|PubMed:12571360, ECO:0000269|PubMed:15385626, ECO:0000269|PubMed:16477018, ECO:0000269|PubMed:17276987, ECO:0000269|PubMed:18625701, ECO:0000269|PubMed:20360857}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000371917, ENST00000493140, 
ENST00000329613, ENST00000371497, 
ENST00000603338, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score15 X 13 X 9=175540 X 23 X 9=8280
# samples 1550
** MAII scorelog2(15/1755*10)=-3.54843662469604
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(50/8280*10)=-4.0496307677246
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ARFGEF2 [Title/Abstract] AND TSHZ2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ARFGEF2 [Title/Abstract] AND TSHZ2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ARFGEF2(47580435)-TSHZ2(51870038), # samples:3
Anticipated loss of major functional domain due to fusion event.ARFGEF2-TSHZ2 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.
ARFGEF2-TSHZ2 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.
ARFGEF2-TSHZ2 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.
ARFGEF2-TSHZ2 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.
ARFGEF2-TSHZ2 seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
ARFGEF2-TSHZ2 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
ARFGEF2-TSHZ2 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
ARFGEF2-TSHZ2 seems lost the major protein functional domain in Tgene partner, which is a transcription factor 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
HgeneARFGEF2

GO:0001881

receptor recycling

16477018

HgeneARFGEF2

GO:0035556

intracellular signal transduction

12571360



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/chr20:47580435/chr20:51870038)
- 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 ARFGEF2 (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 TSHZ2 (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)
ENST00000371917ARFGEF2chr2047580435+ENST00000371497TSHZ2chr2051870038+12167907039711323
ENST00000371917ARFGEF2chr2047580435+ENST00000603338TSHZ2chr2051870038+4316907039711323

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
ENST00000371917ENST00000371497ARFGEF2chr2047580435+TSHZ2chr2051870038+0.0001508150.9998492
ENST00000371917ENST00000603338ARFGEF2chr2047580435+TSHZ2chr2051870038+0.0016656010.99833447

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 ARFGEF2-TSHZ2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ARFGEF2chr2047580435TSHZ2chr2051870038907302KDILEDVVTSAIKGYAQEEQLKEEEE

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Potential FusionNeoAntigen Information of ARFGEF2-TSHZ2 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.
ARFGEF2-TSHZ2_47580435_51870038.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)
ARFGEF2-TSHZ2chr2047580435chr2051870038907HLA-C15:04VVTSAIKGY0.25890.8608615
ARFGEF2-TSHZ2chr2047580435chr2051870038907HLA-A25:01VVTSAIKGY0.32220.7226615
ARFGEF2-TSHZ2chr2047580435chr2051870038907HLA-C15:09VVTSAIKGY0.25890.8608615
ARFGEF2-TSHZ2chr2047580435chr2051870038907HLA-A25:01DVVTSAIKGY0.98510.81515
ARFGEF2-TSHZ2chr2047580435chr2051870038907HLA-A25:01EDVVTSAIKGY0.87110.7488415

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Potential FusionNeoAntigen Information of ARFGEF2-TSHZ2 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.
ARFGEF2-TSHZ2_47580435_51870038.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)
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-0804EDVVTSAIKGYAQEE419
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-0804LEDVVTSAIKGYAQE318
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-0818IKGYAQEEQLKEEEE1126
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-0820EDVVTSAIKGYAQEE419
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-0820LEDVVTSAIKGYAQE318
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-0828EDVVTSAIKGYAQEE419
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-0831EDVVTSAIKGYAQEE419
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-0831LEDVVTSAIKGYAQE318
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-0840IKGYAQEEQLKEEEE1126
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-0840AIKGYAQEEQLKEEE1025
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-1104EDVVTSAIKGYAQEE419
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-1106EDVVTSAIKGYAQEE419
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-1125EDVVTSAIKGYAQEE419
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-1135EDVVTSAIKGYAQEE419
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-1138EDVVTSAIKGYAQEE419
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-1143EDVVTSAIKGYAQEE419
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-1144EDVVTSAIKGYAQEE419
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-1146EDVVTSAIKGYAQEE419
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-1147EDVVTSAIKGYAQEE419
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-1150EDVVTSAIKGYAQEE419
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-1150LEDVVTSAIKGYAQE318
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-1154EDVVTSAIKGYAQEE419
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-1154LEDVVTSAIKGYAQE318
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-1156EDVVTSAIKGYAQEE419
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-1156LEDVVTSAIKGYAQE318
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-1158EDVVTSAIKGYAQEE419
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-1160EDVVTSAIKGYAQEE419
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-1167EDVVTSAIKGYAQEE419
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-1177EDVVTSAIKGYAQEE419
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-1178EDVVTSAIKGYAQEE419
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-1183EDVVTSAIKGYAQEE419
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-1184EDVVTSAIKGYAQEE419
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-1188EDVVTSAIKGYAQEE419
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-1188LEDVVTSAIKGYAQE318
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-1189EDVVTSAIKGYAQEE419
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-13101IKGYAQEEQLKEEEE1126
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-13101AIKGYAQEEQLKEEE1025
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-1310IKGYAQEEQLKEEEE1126
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-1310AIKGYAQEEQLKEEE1025
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-1311EDVVTSAIKGYAQEE419
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-1318EDVVTSAIKGYAQEE419
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-1342EDVVTSAIKGYAQEE419
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-1388IKGYAQEEQLKEEEE1126
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-1415EDVVTSAIKGYAQEE419
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-1415LEDVVTSAIKGYAQE318
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-1473EDVVTSAIKGYAQEE419
ARFGEF2-TSHZ2chr2047580435chr2051870038907DRB1-1484EDVVTSAIKGYAQEE419

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Fusion breakpoint peptide structures of ARFGEF2-TSHZ2

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
10379VVTSAIKGYAQEEQARFGEF2TSHZ2chr2047580435chr2051870038907

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ARFGEF2-TSHZ2

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-B14:023BVN10379VVTSAIKGYAQEEQ-7.9962-8.1096
HLA-B14:023BVN10379VVTSAIKGYAQEEQ-5.70842-6.74372
HLA-B52:013W3910379VVTSAIKGYAQEEQ-6.83737-6.95077
HLA-B52:013W3910379VVTSAIKGYAQEEQ-4.4836-5.5189
HLA-A11:014UQ210379VVTSAIKGYAQEEQ-10.0067-10.1201
HLA-A11:014UQ210379VVTSAIKGYAQEEQ-9.03915-10.0745
HLA-A24:025HGA10379VVTSAIKGYAQEEQ-6.56204-6.67544
HLA-A24:025HGA10379VVTSAIKGYAQEEQ-5.42271-6.45801
HLA-B44:053DX810379VVTSAIKGYAQEEQ-7.85648-8.89178
HLA-B44:053DX810379VVTSAIKGYAQEEQ-5.3978-5.5112
HLA-B35:011A1N10379VVTSAIKGYAQEEQ-6.27422-6.38762
HLA-B35:011A1N10379VVTSAIKGYAQEEQ-5.27424-6.30954
HLA-A02:016TDR10379VVTSAIKGYAQEEQ-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of ARFGEF2-TSHZ2

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
ARFGEF2-TSHZ2chr2047580435chr2051870038415EDVVTSAIKGYAAGATGTAGTCACATCTGCCATTAAAGGCTACG
ARFGEF2-TSHZ2chr2047580435chr2051870038515DVVTSAIKGYATGTAGTCACATCTGCCATTAAAGGCTACG
ARFGEF2-TSHZ2chr2047580435chr2051870038615VVTSAIKGYTAGTCACATCTGCCATTAAAGGCTACG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
ARFGEF2-TSHZ2chr2047580435chr20518700381025AIKGYAQEEQLKEEECCATTAAAGGCTACGCCCAGGAGGAACAGCTGAAAGAAGAGGAGG
ARFGEF2-TSHZ2chr2047580435chr20518700381126IKGYAQEEQLKEEEETTAAAGGCTACGCCCAGGAGGAACAGCTGAAAGAAGAGGAGGAAA
ARFGEF2-TSHZ2chr2047580435chr2051870038318LEDVVTSAIKGYAQETGGAAGATGTAGTCACATCTGCCATTAAAGGCTACGCCCAGGAGG
ARFGEF2-TSHZ2chr2047580435chr2051870038419EDVVTSAIKGYAQEEAAGATGTAGTCACATCTGCCATTAAAGGCTACGCCCAGGAGGAAC

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Information of the samples that have these potential fusion neoantigens of ARFGEF2-TSHZ2

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
BRCAARFGEF2-TSHZ2chr2047580435ENST00000371917chr2051870038ENST00000371497TCGA-A8-A09D-01A

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Potential target of CAR-T therapy development for ARFGEF2-TSHZ2

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 ARFGEF2-TSHZ2

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 ARFGEF2-TSHZ2

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