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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:TTK-TMEM63B

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TTK-TMEM63B
FusionPDB ID: 95136
FusionGDB2.0 ID: 95136
HgeneTgene
Gene symbol

TTK

TMEM63B

Gene ID

7272

55362

Gene nameTTK protein kinasetransmembrane protein 63B
SynonymsCT96|ESK|MPH1|MPS1|MPS1L1|PYTC6orf110
Cytomap

6q14.1

6p21.1

Type of geneprotein-codingprotein-coding
Descriptiondual specificity protein kinase TTKcancer/testis antigen 96monopolar spindle 1 kinasemonopolar spindle 1-like 1phosphotyrosine picked threonine kinasephosphotyrosine picked threonine-protein kinaseCSC1-like protein 2
Modification date2020031320200313
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000230510, ENST00000369798, 
ENST00000509894, ENST00000515751, 
ENST00000527188, ENST00000259746, 
ENST00000323267, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score2 X 2 X 2=83 X 5 X 3=45
# samples 35
** MAII scorelog2(3/8*10)=1.90689059560852log2(5/45*10)=0.15200309344505
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: TTK [Title/Abstract] AND TMEM63B [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: TTK [Title/Abstract] AND TMEM63B [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TTK(80721265)-TMEM63B(44119583), # samples:2
Anticipated loss of major functional domain due to fusion event.TTK-TMEM63B 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.
TTK-TMEM63B 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/chr6:80721265/chr6:44119583)
- 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 TTK (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 TMEM63B (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)
ENST00000509894TTKchr680721265+ENST00000259746TMEM63Bchr644119583+301915578292382517
ENST00000509894TTKchr680721265+ENST00000323267TMEM63Bchr644119583+301815578292382517
ENST00000230510TTKchr680721265+ENST00000259746TMEM63Bchr644119583+277113095812134517
ENST00000230510TTKchr680721265+ENST00000323267TMEM63Bchr644119583+277013095812134517
ENST00000369798TTKchr680721265+ENST00000259746TMEM63Bchr644119583+23018391111664517
ENST00000369798TTKchr680721265+ENST00000323267TMEM63Bchr644119583+23008391111664517
ENST00000509894TTKchr680721265+ENST00000259746TMEM63Bchr644119582+301915578292382517
ENST00000509894TTKchr680721265+ENST00000323267TMEM63Bchr644119582+301815578292382517
ENST00000230510TTKchr680721265+ENST00000259746TMEM63Bchr644119582+277113095812134517
ENST00000230510TTKchr680721265+ENST00000323267TMEM63Bchr644119582+277013095812134517
ENST00000369798TTKchr680721265+ENST00000259746TMEM63Bchr644119582+23018391111664517
ENST00000369798TTKchr680721265+ENST00000323267TMEM63Bchr644119582+23008391111664517

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
ENST00000509894ENST00000259746TTKchr680721265+TMEM63Bchr644119583+0.0012814030.9987186
ENST00000509894ENST00000323267TTKchr680721265+TMEM63Bchr644119583+0.0012681830.9987318
ENST00000230510ENST00000259746TTKchr680721265+TMEM63Bchr644119583+0.0013166890.9986833
ENST00000230510ENST00000323267TTKchr680721265+TMEM63Bchr644119583+0.0013054430.9986946
ENST00000369798ENST00000259746TTKchr680721265+TMEM63Bchr644119583+0.0009392720.9990607
ENST00000369798ENST00000323267TTKchr680721265+TMEM63Bchr644119583+0.0009308940.99906915
ENST00000509894ENST00000259746TTKchr680721265+TMEM63Bchr644119582+0.0012814030.9987186
ENST00000509894ENST00000323267TTKchr680721265+TMEM63Bchr644119582+0.0012681830.9987318
ENST00000230510ENST00000259746TTKchr680721265+TMEM63Bchr644119582+0.0013166890.9986833
ENST00000230510ENST00000323267TTKchr680721265+TMEM63Bchr644119582+0.0013054430.9986946
ENST00000369798ENST00000259746TTKchr680721265+TMEM63Bchr644119582+0.0009392720.9990607
ENST00000369798ENST00000323267TTKchr680721265+TMEM63Bchr644119582+0.0009308940.99906915

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 TTK-TMEM63B

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
TTKchr680721265TMEM63Bchr6441195821309243SRGQTTKARFLYGCVFLPDNGAFFVN
TTKchr680721265TMEM63Bchr6441195821557243SRGQTTKARFLYGCVFLPDNGAFFVN
TTKchr680721265TMEM63Bchr644119582839243SRGQTTKARFLYGCVFLPDNGAFFVN
TTKchr680721265TMEM63Bchr6441195831309243SRGQTTKARFLYGCVFLPDNGAFFVN
TTKchr680721265TMEM63Bchr6441195831557243SRGQTTKARFLYGCVFLPDNGAFFVN
TTKchr680721265TMEM63Bchr644119583839243SRGQTTKARFLYGCVFLPDNGAFFVN

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Potential FusionNeoAntigen Information of TTK-TMEM63B 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.
TTK-TMEM63B_80721265_44119582.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)
TTK-TMEM63Bchr680721265chr6441195821309HLA-B27:04ARFLYGCVF0.99910.8488716
TTK-TMEM63Bchr680721265chr6441195821309HLA-B27:02ARFLYGCVF0.99910.7656716
TTK-TMEM63Bchr680721265chr6441195821309HLA-B27:05ARFLYGCVF0.9990.9366716
TTK-TMEM63Bchr680721265chr6441195821309HLA-B27:07ARFLYGCVF0.99290.5804716
TTK-TMEM63Bchr680721265chr6441195821309HLA-B15:03ARFLYGCVF0.44330.9242716
TTK-TMEM63Bchr680721265chr6441195821309HLA-B15:18ARFLYGCVF0.38090.8787716
TTK-TMEM63Bchr680721265chr6441195821309HLA-B27:05ARFLYGCVFL0.99980.9482717
TTK-TMEM63Bchr680721265chr6441195821309HLA-B27:02ARFLYGCVFL0.99980.7914717
TTK-TMEM63Bchr680721265chr6441195821309HLA-B27:04ARFLYGCVFL0.99970.8882717
TTK-TMEM63Bchr680721265chr6441195821309HLA-B27:07ARFLYGCVFL0.99970.6585717
TTK-TMEM63Bchr680721265chr6441195821309HLA-B27:02KARFLYGCVF0.98860.5726616
TTK-TMEM63Bchr680721265chr6441195821309HLA-B27:14ARFLYGCVF0.99860.8778716
TTK-TMEM63Bchr680721265chr6441195821309HLA-C07:95ARFLYGCVF0.99440.7743716
TTK-TMEM63Bchr680721265chr6441195821309HLA-C07:05ARFLYGCVF0.98650.9695716
TTK-TMEM63Bchr680721265chr6441195821309HLA-B27:03ARFLYGCVF0.98530.9428716
TTK-TMEM63Bchr680721265chr6441195821309HLA-C07:27ARFLYGCVF0.98470.9688716
TTK-TMEM63Bchr680721265chr6441195821309HLA-C07:46ARFLYGCVF0.8240.9225716
TTK-TMEM63Bchr680721265chr6441195821309HLA-C07:67ARFLYGCVF0.8220.9587716
TTK-TMEM63Bchr680721265chr6441195821309HLA-C07:80ARFLYGCVF0.8220.9587716
TTK-TMEM63Bchr680721265chr6441195821309HLA-C07:10ARFLYGCVF0.80640.9701716
TTK-TMEM63Bchr680721265chr6441195821309HLA-C12:16ARFLYGCVF0.1190.9818716
TTK-TMEM63Bchr680721265chr6441195821309HLA-B27:14ARFLYGCVFL0.99980.8848717
TTK-TMEM63Bchr680721265chr6441195821309HLA-B27:03ARFLYGCVFL0.9960.9525717
TTK-TMEM63Bchr680721265chr6441195821309HLA-B27:10ARFLYGCVF0.99910.935716
TTK-TMEM63Bchr680721265chr6441195821309HLA-B27:08ARFLYGCVF0.9990.8598716
TTK-TMEM63Bchr680721265chr6441195821309HLA-B27:06ARFLYGCVF0.99890.8366716
TTK-TMEM63Bchr680721265chr6441195821309HLA-C07:01ARFLYGCVF0.99610.7431716
TTK-TMEM63Bchr680721265chr6441195821309HLA-B27:09ARFLYGCVF0.99120.9366716
TTK-TMEM63Bchr680721265chr6441195821309HLA-C07:02ARFLYGCVF0.8220.9587716
TTK-TMEM63Bchr680721265chr6441195821309HLA-C07:22ARFLYGCVF0.73390.7918716
TTK-TMEM63Bchr680721265chr6441195821309HLA-B15:68ARFLYGCVF0.13330.779716
TTK-TMEM63Bchr680721265chr6441195821309HLA-B27:10ARFLYGCVFL0.99970.9542717
TTK-TMEM63Bchr680721265chr6441195821309HLA-B27:08ARFLYGCVFL0.99970.8841717
TTK-TMEM63Bchr680721265chr6441195821309HLA-B27:06ARFLYGCVFL0.99970.8932717
TTK-TMEM63Bchr680721265chr6441195821309HLA-B27:09ARFLYGCVFL0.99950.9463717

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Potential FusionNeoAntigen Information of TTK-TMEM63B 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.
TTK-TMEM63B_80721265_44119582.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)
TTK-TMEM63Bchr680721265chr6441195821309DRB3-0101YGCVFLPDNGAFFVN1126
TTK-TMEM63Bchr680721265chr6441195821309DRB3-0104YGCVFLPDNGAFFVN1126
TTK-TMEM63Bchr680721265chr6441195821309DRB3-0105YGCVFLPDNGAFFVN1126
TTK-TMEM63Bchr680721265chr6441195821309DRB3-0108YGCVFLPDNGAFFVN1126
TTK-TMEM63Bchr680721265chr6441195821309DRB3-0111YGCVFLPDNGAFFVN1126
TTK-TMEM63Bchr680721265chr6441195821309DRB3-0112YGCVFLPDNGAFFVN1126
TTK-TMEM63Bchr680721265chr6441195821309DRB3-0113YGCVFLPDNGAFFVN1126
TTK-TMEM63Bchr680721265chr6441195821309DRB3-0114YGCVFLPDNGAFFVN1126

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Fusion breakpoint peptide structures of TTK-TMEM63B

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
4124KARFLYGCVFLPDNTTKTMEM63Bchr680721265chr6441195821309

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of TTK-TMEM63B

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-B14:023BVN4124KARFLYGCVFLPDN-7.15543-7.26883
HLA-B14:023BVN4124KARFLYGCVFLPDN-4.77435-5.80965
HLA-B52:013W394124KARFLYGCVFLPDN-6.80875-6.92215
HLA-B52:013W394124KARFLYGCVFLPDN-4.20386-5.23916
HLA-A11:014UQ24124KARFLYGCVFLPDN-7.5194-8.5547
HLA-A11:014UQ24124KARFLYGCVFLPDN-6.9601-7.0735
HLA-A24:025HGA4124KARFLYGCVFLPDN-7.52403-7.63743
HLA-A24:025HGA4124KARFLYGCVFLPDN-5.82433-6.85963
HLA-B27:056PYJ4124KARFLYGCVFLPDN-3.28285-4.31815
HLA-B44:053DX84124KARFLYGCVFLPDN-5.91172-6.94702
HLA-B44:053DX84124KARFLYGCVFLPDN-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of TTK-TMEM63B

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
TTK-TMEM63Bchr680721265chr644119582616KARFLYGCVFTAAAGCCAGGTTTTTATATGGGTGTGTGTT
TTK-TMEM63Bchr680721265chr644119582716ARFLYGCVFAGCCAGGTTTTTATATGGGTGTGTGTT
TTK-TMEM63Bchr680721265chr644119582717ARFLYGCVFLAGCCAGGTTTTTATATGGGTGTGTGTTCCT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
TTK-TMEM63Bchr680721265chr6441195821126YGCVFLPDNGAFFVNATATGGGTGTGTGTTCCTGCCCGACAACGGCGCCTTCTTCGTGAA

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Information of the samples that have these potential fusion neoantigens of TTK-TMEM63B

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
SARCTTK-TMEM63Bchr680721265ENST00000230510chr644119582ENST00000259746TCGA-DX-A23Y

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Potential target of CAR-T therapy development for TTK-TMEM63B

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
TgeneTMEM63Bchr6:80721265chr6:44119582ENST000002597461724560_5800833.0TransmembraneHelical
TgeneTMEM63Bchr6:80721265chr6:44119582ENST000002597461724630_6500833.0TransmembraneHelical
TgeneTMEM63Bchr6:80721265chr6:44119582ENST000002597461724678_6980833.0TransmembraneHelical
TgeneTMEM63Bchr6:80721265chr6:44119582ENST000002597461724711_7310833.0TransmembraneHelical
TgeneTMEM63Bchr6:80721265chr6:44119582ENST000003232671724560_5800833.0TransmembraneHelical
TgeneTMEM63Bchr6:80721265chr6:44119582ENST000003232671724630_6500833.0TransmembraneHelical
TgeneTMEM63Bchr6:80721265chr6:44119582ENST000003232671724678_6980833.0TransmembraneHelical
TgeneTMEM63Bchr6:80721265chr6:44119582ENST000003232671724711_7310833.0TransmembraneHelical
TgeneTMEM63Bchr6:80721265chr6:44119583ENST000002597461724560_5800833.0TransmembraneHelical
TgeneTMEM63Bchr6:80721265chr6:44119583ENST000002597461724630_6500833.0TransmembraneHelical
TgeneTMEM63Bchr6:80721265chr6:44119583ENST000002597461724678_6980833.0TransmembraneHelical
TgeneTMEM63Bchr6:80721265chr6:44119583ENST000002597461724711_7310833.0TransmembraneHelical
TgeneTMEM63Bchr6:80721265chr6:44119583ENST000003232671724560_5800833.0TransmembraneHelical
TgeneTMEM63Bchr6:80721265chr6:44119583ENST000003232671724630_6500833.0TransmembraneHelical
TgeneTMEM63Bchr6:80721265chr6:44119583ENST000003232671724678_6980833.0TransmembraneHelical
TgeneTMEM63Bchr6:80721265chr6:44119583ENST000003232671724711_7310833.0TransmembraneHelical

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 TTK-TMEM63B

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 TTK-TMEM63B

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