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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:CDH1-YWHAH

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CDH1-YWHAH
FusionPDB ID: 15049
FusionGDB2.0 ID: 15049
HgeneTgene
Gene symbol

CDH1

YWHAH

Gene ID

51343

7533

Gene namefizzy and cell division cycle 20 related 1tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta
SynonymsCDC20C|CDH1|FZR|FZR2|HCDH|HCDH1YWHA1
Cytomap

19p13.3

22q12.3

Type of geneprotein-codingprotein-coding
Descriptionfizzy-related protein homologCDC20 homolog 1CDC20-like 1bCDC20-like protein 1cdh1/Hct1 homologfizzy/cell division cycle 20 related 114-3-3 protein eta14-3-3 etatyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, eta polypeptide
Modification date2020031320200327
UniProtAcc

Q9H159

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.
.
Ensembl transtripts involved in fusion geneENST idsENST00000261769, ENST00000422392, 
ENST00000562836, 
ENST00000471374, 
ENST00000248975, ENST00000397492, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score21 X 16 X 8=26889 X 7 X 6=378
# samples 2913
** MAII scorelog2(29/2688*10)=-3.21240833276383
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(13/378*10)=-1.53987461119262
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: CDH1 [Title/Abstract] AND YWHAH [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CDH1 [Title/Abstract] AND YWHAH [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CDH1(68772314)-YWHAH(32352126), # samples:1
Anticipated loss of major functional domain due to fusion event.CDH1-YWHAH 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.
CDH1-YWHAH 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.
CDH1-YWHAH seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF.
CDH1-YWHAH seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor 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
HgeneCDH1

GO:0031145

anaphase-promoting complex-dependent catabolic process

18662541|21596315

HgeneCDH1

GO:0072425

signal transduction involved in G2 DNA damage checkpoint

18662541

HgeneCDH1

GO:1904668

positive regulation of ubiquitin protein ligase activity

11459826

TgeneYWHAH

GO:0002028

regulation of sodium ion transport

16728661

TgeneYWHAH

GO:0006713

glucocorticoid catabolic process

15790729

TgeneYWHAH

GO:0042921

glucocorticoid receptor signaling pathway

15790729

TgeneYWHAH

GO:0045893

positive regulation of transcription, DNA-templated

15790729

TgeneYWHAH

GO:0086010

membrane depolarization during action potential

16728661

TgeneYWHAH

GO:2000649

regulation of sodium ion transmembrane transporter activity

16728661



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/chr16:68772314/chr22:32352126)
- 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 CDH1 (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 YWHAH (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)
ENST00000261769CDH1chr1668772314+ENST00000397492YWHAHchr2232352126+1819354451007320
ENST00000422392CDH1chr1668772314+ENST00000397492YWHAHchr2232352126+169222735880281

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
ENST00000261769ENST00000397492CDH1chr1668772314+YWHAHchr2232352126+0.0016050610.9983949
ENST00000422392ENST00000397492CDH1chr1668772314+YWHAHchr2232352126+0.0010977390.9989022

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 CDH1-YWHAH

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CDH1chr1668772314YWHAHchr223235212622764PGATWREAASWAEVTELNEPLSNEDR
CDH1chr1668772314YWHAHchr2232352126354103PGATWREAASWAEVTELNEPLSNEDR

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Potential FusionNeoAntigen Information of CDH1-YWHAH 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.
CDH1-YWHAH_68772314_32352126.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)
CDH1-YWHAHchr1668772314chr2232352126354HLA-B40:02REAASWAEV0.99960.5974514
CDH1-YWHAHchr1668772314chr2232352126354HLA-B45:01REAASWAEV0.99810.9541514
CDH1-YWHAHchr1668772314chr2232352126354HLA-B50:02REAASWAEV0.99790.8625514
CDH1-YWHAHchr1668772314chr2232352126354HLA-B15:17ASWAEVTEL0.99260.9603817
CDH1-YWHAHchr1668772314chr2232352126354HLA-B40:01REAASWAEV0.99230.7714514
CDH1-YWHAHchr1668772314chr2232352126354HLA-B45:01AEVTELNEP0.99060.88761120
CDH1-YWHAHchr1668772314chr2232352126354HLA-B15:16ASWAEVTEL0.99020.8807817
CDH1-YWHAHchr1668772314chr2232352126354HLA-B50:02AEVTELNEP0.97630.65321120
CDH1-YWHAHchr1668772314chr2232352126354HLA-A02:21ASWAEVTEL0.84780.7709817
CDH1-YWHAHchr1668772314chr2232352126354HLA-B41:01REAASWAEV0.62470.9246514
CDH1-YWHAHchr1668772314chr2232352126354HLA-B50:01REAASWAEV0.62440.9889514
CDH1-YWHAHchr1668772314chr2232352126354HLA-B39:13REAASWAEV0.54470.9762514
CDH1-YWHAHchr1668772314chr2232352126354HLA-B40:05REAASWAEV0.52850.7811514
CDH1-YWHAHchr1668772314chr2232352126354HLA-B41:01AEVTELNEP0.41220.91731120
CDH1-YWHAHchr1668772314chr2232352126354HLA-B13:01ASWAEVTEL0.33790.9908817
CDH1-YWHAHchr1668772314chr2232352126354HLA-B50:01AEVTELNEP0.32320.79061120
CDH1-YWHAHchr1668772314chr2232352126354HLA-C04:14SWAEVTEL0.96960.9582917
CDH1-YWHAHchr1668772314chr2232352126354HLA-C15:04ASWAEVTEL0.99970.9652817
CDH1-YWHAHchr1668772314chr2232352126354HLA-C03:19ASWAEVTEL0.99970.9964817
CDH1-YWHAHchr1668772314chr2232352126354HLA-C03:07ASWAEVTEL0.99970.9919817
CDH1-YWHAHchr1668772314chr2232352126354HLA-B40:06REAASWAEV0.99960.9216514
CDH1-YWHAHchr1668772314chr2232352126354HLA-C15:06ASWAEVTEL0.99950.965817
CDH1-YWHAHchr1668772314chr2232352126354HLA-C03:08ASWAEVTEL0.99950.9364817
CDH1-YWHAHchr1668772314chr2232352126354HLA-C04:06ASWAEVTEL0.99850.9574817
CDH1-YWHAHchr1668772314chr2232352126354HLA-C08:13ASWAEVTEL0.99510.991817
CDH1-YWHAHchr1668772314chr2232352126354HLA-C08:04ASWAEVTEL0.99510.991817
CDH1-YWHAHchr1668772314chr2232352126354HLA-C06:03ASWAEVTEL0.99080.9965817
CDH1-YWHAHchr1668772314chr2232352126354HLA-C12:04ASWAEVTEL0.99010.9967817
CDH1-YWHAHchr1668772314chr2232352126354HLA-B48:03REAASWAEV0.98530.8366514
CDH1-YWHAHchr1668772314chr2232352126354HLA-B40:06AEVTELNEP0.98160.70691120
CDH1-YWHAHchr1668772314chr2232352126354HLA-C08:03ASWAEVTEL0.95380.9956817
CDH1-YWHAHchr1668772314chr2232352126354HLA-C02:06ASWAEVTEL0.87260.9888817
CDH1-YWHAHchr1668772314chr2232352126354HLA-B39:08REAASWAEV0.45880.9486514
CDH1-YWHAHchr1668772314chr2232352126354HLA-C04:04SWAEVTEL0.97380.9472917
CDH1-YWHAHchr1668772314chr2232352126354HLA-C14:02SWAEVTEL0.91240.9735917
CDH1-YWHAHchr1668772314chr2232352126354HLA-C14:03SWAEVTEL0.91240.9735917
CDH1-YWHAHchr1668772314chr2232352126354HLA-C15:09ASWAEVTEL0.99970.9652817
CDH1-YWHAHchr1668772314chr2232352126354HLA-C03:04ASWAEVTEL0.99960.9955817
CDH1-YWHAHchr1668772314chr2232352126354HLA-C03:03ASWAEVTEL0.99960.9955817
CDH1-YWHAHchr1668772314chr2232352126354HLA-C15:02ASWAEVTEL0.99960.9508817
CDH1-YWHAHchr1668772314chr2232352126354HLA-C15:05ASWAEVTEL0.99950.9606817
CDH1-YWHAHchr1668772314chr2232352126354HLA-B40:40REAASWAEV0.99950.6271514
CDH1-YWHAHchr1668772314chr2232352126354HLA-C03:05ASWAEVTEL0.99940.9584817
CDH1-YWHAHchr1668772314chr2232352126354HLA-C03:17ASWAEVTEL0.99940.9883817
CDH1-YWHAHchr1668772314chr2232352126354HLA-B40:04REAASWAEV0.99730.9392514
CDH1-YWHAHchr1668772314chr2232352126354HLA-A25:01EVTELNEPL0.99630.87141221
CDH1-YWHAHchr1668772314chr2232352126354HLA-B40:36REAASWAEV0.99330.7502514
CDH1-YWHAHchr1668772314chr2232352126354HLA-A68:02EVTELNEPL0.99280.51161221
CDH1-YWHAHchr1668772314chr2232352126354HLA-C16:02ASWAEVTEL0.99250.9961817
CDH1-YWHAHchr1668772314chr2232352126354HLA-C03:06ASWAEVTEL0.98850.9965817
CDH1-YWHAHchr1668772314chr2232352126354HLA-B40:49REAASWAEV0.98610.7866514
CDH1-YWHAHchr1668772314chr2232352126354HLA-B40:12REAASWAEV0.98530.8366514
CDH1-YWHAHchr1668772314chr2232352126354HLA-A69:01EVTELNEPL0.9750.70221221
CDH1-YWHAHchr1668772314chr2232352126354HLA-C08:01ASWAEVTEL0.95380.9956817
CDH1-YWHAHchr1668772314chr2232352126354HLA-B35:13ASWAEVTEL0.8860.9297817
CDH1-YWHAHchr1668772314chr2232352126354HLA-A02:14ASWAEVTEL0.85250.7353817
CDH1-YWHAHchr1668772314chr2232352126354HLA-A02:06ASWAEVTEL0.84780.7709817
CDH1-YWHAHchr1668772314chr2232352126354HLA-B41:03REAASWAEV0.79220.7658514
CDH1-YWHAHchr1668772314chr2232352126354HLA-C17:01ASWAEVTEL0.74740.9862817
CDH1-YWHAHchr1668772314chr2232352126354HLA-B50:04REAASWAEV0.62440.9889514
CDH1-YWHAHchr1668772314chr2232352126354HLA-B50:05REAASWAEV0.62440.9889514
CDH1-YWHAHchr1668772314chr2232352126354HLA-B50:05AEVTELNEP0.32320.79061120
CDH1-YWHAHchr1668772314chr2232352126354HLA-B50:04AEVTELNEP0.32320.79061120
CDH1-YWHAHchr1668772314chr2232352126354HLA-B07:13ASWAEVTEL0.29490.8468817
CDH1-YWHAHchr1668772314chr2232352126354HLA-B40:21ASWAEVTEL0.2020.5738817
CDH1-YWHAHchr1668772314chr2232352126354HLA-B40:04AEVTELNEPL0.99390.74041121
CDH1-YWHAHchr1668772314chr2232352126354HLA-B41:03AEVTELNEPL0.69350.56361121

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Potential FusionNeoAntigen Information of CDH1-YWHAH 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.
CDH1-YWHAH_68772314_32352126.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)
CDH1-YWHAHchr1668772314chr2232352126354DRB1-0903GATWREAASWAEVTE116
CDH1-YWHAHchr1668772314chr2232352126354DRB1-0908GATWREAASWAEVTE116

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Fusion breakpoint peptide structures of CDH1-YWHAH

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
1506EAASWAEVTELNEPCDH1YWHAHchr1668772314chr2232352126354

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CDH1-YWHAH

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-B14:023BVN1506EAASWAEVTELNEP-7.15543-7.26883
HLA-B14:023BVN1506EAASWAEVTELNEP-4.77435-5.80965
HLA-B52:013W391506EAASWAEVTELNEP-6.80875-6.92215
HLA-B52:013W391506EAASWAEVTELNEP-4.20386-5.23916
HLA-A11:014UQ21506EAASWAEVTELNEP-7.5194-8.5547
HLA-A11:014UQ21506EAASWAEVTELNEP-6.9601-7.0735
HLA-A24:025HGA1506EAASWAEVTELNEP-7.52403-7.63743
HLA-A24:025HGA1506EAASWAEVTELNEP-5.82433-6.85963
HLA-B27:056PYJ1506EAASWAEVTELNEP-3.28285-4.31815
HLA-B44:053DX81506EAASWAEVTELNEP-5.91172-6.94702
HLA-B44:053DX81506EAASWAEVTELNEP-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of CDH1-YWHAH

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
CDH1-YWHAHchr1668772314chr22323521261120AEVTELNEPGCAGAGGTGACAGAGCTGAATGAACCT
CDH1-YWHAHchr1668772314chr22323521261121AEVTELNEPLGCAGAGGTGACAGAGCTGAATGAACCTCTC
CDH1-YWHAHchr1668772314chr22323521261221EVTELNEPLGAGGTGACAGAGCTGAATGAACCTCTC
CDH1-YWHAHchr1668772314chr2232352126514REAASWAEVAGAGAGGCCGCGTCCTGGGCAGAGGTG
CDH1-YWHAHchr1668772314chr2232352126817ASWAEVTELGCGTCCTGGGCAGAGGTGACAGAGCTG
CDH1-YWHAHchr1668772314chr2232352126917SWAEVTELTCCTGGGCAGAGGTGACAGAGCTG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
CDH1-YWHAHchr1668772314chr2232352126116GATWREAASWAEVTEGGCGCCACCTGGAGAGAGGCCGCGTCCTGGGCAGAGGTGACAGAG

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Information of the samples that have these potential fusion neoantigens of CDH1-YWHAH

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
STADCDH1-YWHAHchr1668772314ENST00000261769chr2232352126ENST00000397492TCGA-CD-5799-01A

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Potential target of CAR-T therapy development for CDH1-YWHAH

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 CDH1-YWHAH

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 CDH1-YWHAH

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