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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:TESK2-GNA12

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TESK2-GNA12
FusionPDB ID: 90129
FusionGDB2.0 ID: 90129
HgeneTgene
Gene symbol

TESK2

GNA12

Gene ID

10420

2768

Gene nametestis associated actin remodelling kinase 2G protein subunit alpha 12
Synonyms-NNX3|RMP|gep
Cytomap

1p34.1

7p22.3-p22.2

Type of geneprotein-codingprotein-coding
Descriptiondual specificity testis-specific protein kinase 2testicular protein kinase 2testis-specific kinase 2guanine nucleotide-binding protein subunit alpha-12WUGSC:H_GS165O14.2g alpha-12guanine nucleotide binding protein (G protein) alpha 12
Modification date2020032020200313
UniProtAcc.

Q03113

Main function of 5'-partner protein: FUNCTION: Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems (PubMed:22609986, PubMed:15525651, PubMed:15240885, PubMed:17565996, PubMed:12515866, PubMed:16787920, PubMed:16705036, PubMed:23762476, PubMed:27084452). Activates effector molecule RhoA by binding and activating RhoGEFs (ARHGEF12/LARG) (PubMed:15240885, PubMed:12515866, PubMed:16202387). GNA12-dependent Rho signaling subsequently regulates transcription factor AP-1 (activating protein-1) (By similarity). GNA12-dependent Rho signaling also regulates protein phosphatese 2A activation causing dephosphorylation of its target proteins (PubMed:15525651, PubMed:17565996). Promotes tumor cell invasion and metastasis by activating RhoA/ROCK signaling pathway and up-regulating proinflammatory cytokine production (PubMed:23762476, PubMed:16787920, PubMed:16705036, PubMed:27084452). Inhibits CDH1-mediated cell adhesion in process independent from Rho activation (PubMed:11976333, PubMed:16787920). Together with NAPA promotes CDH5 localization to plasma membrane (PubMed:15980433). May play a role in the control of cell migration through the TOR signaling cascade (PubMed:22609986). {ECO:0000250|UniProtKB:P27600, ECO:0000269|PubMed:11976333, ECO:0000269|PubMed:12515866, ECO:0000269|PubMed:15240885, ECO:0000269|PubMed:15525651, ECO:0000269|PubMed:15980433, ECO:0000269|PubMed:16705036, ECO:0000269|PubMed:16787920, ECO:0000269|PubMed:17565996, ECO:0000269|PubMed:22609986, ECO:0000269|PubMed:23762476, ECO:0000269|PubMed:27084452}.
Ensembl transtripts involved in fusion geneENST idsENST00000341771, ENST00000372084, 
ENST00000372086, ENST00000538496, 
ENST00000451835, ENST00000486676, 
ENST00000396960, ENST00000407653, 
ENST00000407904, ENST00000491117, 
ENST00000275364, ENST00000544127, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score11 X 8 X 7=6167 X 6 X 4=168
# samples 139
** MAII scorelog2(13/616*10)=-2.24441872766645
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(9/168*10)=-0.900464326449086
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: TESK2 [Title/Abstract] AND GNA12 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: TESK2 [Title/Abstract] AND GNA12 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TESK2(45851584)-GNA12(2834777), # samples:3
Anticipated loss of major functional domain due to fusion event.TESK2-GNA12 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.
TESK2-GNA12 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.
TESK2-GNA12 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.
TESK2-GNA12 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.
TESK2-GNA12 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
TESK2-GNA12 seems lost the major protein functional domain in Hgene partner, which is a kinase 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


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/chr1:45851584/chr7:2834777)
- 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 TESK2 (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 GNA12 (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)
ENST00000372084TESK2chr145851584-ENST00000275364GNA12chr72834777-4313407141243409
ENST00000372084TESK2chr145851584-ENST00000544127GNA12chr72834777-1560407141192392

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
ENST00000372084ENST00000275364TESK2chr145851584-GNA12chr72834777-0.0026023760.99739766
ENST00000372084ENST00000544127TESK2chr145851584-GNA12chr72834777-0.0056590090.994341

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 TESK2-GNA12

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
TESK2chr145851584GNA12chr72834777407131VCVHQGQLHALTEGSRVLVDARDKLG

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Potential FusionNeoAntigen Information of TESK2-GNA12 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.
TESK2-GNA12_45851584_2834777.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)
TESK2-GNA12chr145851584chr72834777407HLA-A02:22ALTEGSRVL0.96770.6327918
TESK2-GNA12chr145851584chr72834777407HLA-A02:13ALTEGSRVL0.94330.7621918
TESK2-GNA12chr145851584chr72834777407HLA-A02:27ALTEGSRVL0.92930.6911918
TESK2-GNA12chr145851584chr72834777407HLA-A02:38ALTEGSRVL0.83970.7848918
TESK2-GNA12chr145851584chr72834777407HLA-A02:19ALTEGSRVL0.75350.5917918
TESK2-GNA12chr145851584chr72834777407HLA-A02:13ALTEGSRVLV0.9920.6494919
TESK2-GNA12chr145851584chr72834777407HLA-A02:27ALTEGSRVLV0.98870.5656919
TESK2-GNA12chr145851584chr72834777407HLA-A02:38ALTEGSRVLV0.97440.7045919
TESK2-GNA12chr145851584chr72834777407HLA-B39:01LHALTEGSRVL0.99980.9267718
TESK2-GNA12chr145851584chr72834777407HLA-B38:01LHALTEGSRVL0.99960.9805718
TESK2-GNA12chr145851584chr72834777407HLA-B38:02LHALTEGSRVL0.99960.9829718
TESK2-GNA12chr145851584chr72834777407HLA-B15:10LHALTEGSRVL0.99960.5297718
TESK2-GNA12chr145851584chr72834777407HLA-B15:37LHALTEGSRVL0.98770.5792718
TESK2-GNA12chr145851584chr72834777407HLA-C01:17ALTEGSRVL0.88480.9767918
TESK2-GNA12chr145851584chr72834777407HLA-C01:30ALTEGSRVL0.68480.9777918
TESK2-GNA12chr145851584chr72834777407HLA-C03:19HALTEGSRVL0.99950.9913818
TESK2-GNA12chr145851584chr72834777407HLA-C03:08HALTEGSRVL0.99930.944818
TESK2-GNA12chr145851584chr72834777407HLA-B39:05LHALTEGSRVL0.99960.9154718
TESK2-GNA12chr145851584chr72834777407HLA-C01:03ALTEGSRVL0.97860.9533918
TESK2-GNA12chr145851584chr72834777407HLA-A02:03ALTEGSRVL0.9640.7006918
TESK2-GNA12chr145851584chr72834777407HLA-C01:02ALTEGSRVL0.91740.9759918
TESK2-GNA12chr145851584chr72834777407HLA-C03:67ALTEGSRVL0.87350.9834918
TESK2-GNA12chr145851584chr72834777407HLA-B15:73ALTEGSRVL0.82420.9578918
TESK2-GNA12chr145851584chr72834777407HLA-B15:30ALTEGSRVL0.72540.924918
TESK2-GNA12chr145851584chr72834777407HLA-B07:13ALTEGSRVL0.54850.8532918
TESK2-GNA12chr145851584chr72834777407HLA-C03:03HALTEGSRVL0.99950.9883818
TESK2-GNA12chr145851584chr72834777407HLA-C03:04HALTEGSRVL0.99950.9883818
TESK2-GNA12chr145851584chr72834777407HLA-C03:05HALTEGSRVL0.99930.9396818
TESK2-GNA12chr145851584chr72834777407HLA-C03:17HALTEGSRVL0.99920.977818
TESK2-GNA12chr145851584chr72834777407HLA-A02:03ALTEGSRVLV0.99620.5717919
TESK2-GNA12chr145851584chr72834777407HLA-C03:06HALTEGSRVL0.95650.989818
TESK2-GNA12chr145851584chr72834777407HLA-B35:13HALTEGSRVL0.87640.9126818
TESK2-GNA12chr145851584chr72834777407HLA-B38:05LHALTEGSRVL0.99960.9805718
TESK2-GNA12chr145851584chr72834777407HLA-B15:09LHALTEGSRVL0.99940.7901718
TESK2-GNA12chr145851584chr72834777407HLA-B39:11LHALTEGSRVL0.99720.9081718

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Potential FusionNeoAntigen Information of TESK2-GNA12 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.
TESK2-GNA12_45851584_2834777.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)
TESK2-GNA12chr145851584chr72834777407DRB1-0301TEGSRVLVDARDKLG1126
TESK2-GNA12chr145851584chr72834777407DRB1-0303TEGSRVLVDARDKLG1126
TESK2-GNA12chr145851584chr72834777407DRB1-0307TEGSRVLVDARDKLG1126
TESK2-GNA12chr145851584chr72834777407DRB1-0310TEGSRVLVDARDKLG1126
TESK2-GNA12chr145851584chr72834777407DRB1-0310LTEGSRVLVDARDKL1025
TESK2-GNA12chr145851584chr72834777407DRB1-0313TEGSRVLVDARDKLG1126
TESK2-GNA12chr145851584chr72834777407DRB1-0315TEGSRVLVDARDKLG1126
TESK2-GNA12chr145851584chr72834777407DRB1-0318TEGSRVLVDARDKLG1126
TESK2-GNA12chr145851584chr72834777407DRB1-0320TEGSRVLVDARDKLG1126
TESK2-GNA12chr145851584chr72834777407DRB1-0322TEGSRVLVDARDKLG1126
TESK2-GNA12chr145851584chr72834777407DRB1-0324TEGSRVLVDARDKLG1126
TESK2-GNA12chr145851584chr72834777407DRB1-0326TEGSRVLVDARDKLG1126
TESK2-GNA12chr145851584chr72834777407DRB1-0328TEGSRVLVDARDKLG1126
TESK2-GNA12chr145851584chr72834777407DRB1-0330TEGSRVLVDARDKLG1126
TESK2-GNA12chr145851584chr72834777407DRB1-0332TEGSRVLVDARDKLG1126
TESK2-GNA12chr145851584chr72834777407DRB1-0334TEGSRVLVDARDKLG1126
TESK2-GNA12chr145851584chr72834777407DRB1-0336TEGSRVLVDARDKLG1126
TESK2-GNA12chr145851584chr72834777407DRB1-0342TEGSRVLVDARDKLG1126
TESK2-GNA12chr145851584chr72834777407DRB1-0344TEGSRVLVDARDKLG1126
TESK2-GNA12chr145851584chr72834777407DRB1-0346TEGSRVLVDARDKLG1126
TESK2-GNA12chr145851584chr72834777407DRB1-0348TEGSRVLVDARDKLG1126
TESK2-GNA12chr145851584chr72834777407DRB1-0350TEGSRVLVDARDKLG1126
TESK2-GNA12chr145851584chr72834777407DRB1-0352TEGSRVLVDARDKLG1126
TESK2-GNA12chr145851584chr72834777407DRB1-0354TEGSRVLVDARDKLG1126
TESK2-GNA12chr145851584chr72834777407DRB1-1107TEGSRVLVDARDKLG1126
TESK2-GNA12chr145851584chr72834777407DRB1-1394TEGSRVLVDARDKLG1126
TESK2-GNA12chr145851584chr72834777407DRB1-1476TEGSRVLVDARDKLG1126
TESK2-GNA12chr145851584chr72834777407DRB1-1479TEGSRVLVDARDKLG1126

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Fusion breakpoint peptide structures of TESK2-GNA12

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
7379QLHALTEGSRVLVDTESK2GNA12chr145851584chr72834777407

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of TESK2-GNA12

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-B14:023BVN7379QLHALTEGSRVLVD-7.15543-7.26883
HLA-B14:023BVN7379QLHALTEGSRVLVD-4.77435-5.80965
HLA-B52:013W397379QLHALTEGSRVLVD-6.80875-6.92215
HLA-B52:013W397379QLHALTEGSRVLVD-4.20386-5.23916
HLA-A11:014UQ27379QLHALTEGSRVLVD-7.5194-8.5547
HLA-A11:014UQ27379QLHALTEGSRVLVD-6.9601-7.0735
HLA-A24:025HGA7379QLHALTEGSRVLVD-7.52403-7.63743
HLA-A24:025HGA7379QLHALTEGSRVLVD-5.82433-6.85963
HLA-B27:056PYJ7379QLHALTEGSRVLVD-3.28285-4.31815
HLA-B44:053DX87379QLHALTEGSRVLVD-5.91172-6.94702
HLA-B44:053DX87379QLHALTEGSRVLVD-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of TESK2-GNA12

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
TESK2-GNA12chr145851584chr72834777718LHALTEGSRVLTTGCATGCACTTACAGAGGGCTCAAGGGTTCTT
TESK2-GNA12chr145851584chr72834777818HALTEGSRVLCATGCACTTACAGAGGGCTCAAGGGTTCTT
TESK2-GNA12chr145851584chr72834777918ALTEGSRVLGCACTTACAGAGGGCTCAAGGGTTCTT
TESK2-GNA12chr145851584chr72834777919ALTEGSRVLVGCACTTACAGAGGGCTCAAGGGTTCTTGTT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
TESK2-GNA12chr145851584chr728347771025LTEGSRVLVDARDKLCTTACAGAGGGCTCAAGGGTTCTTGTTGATGCACGAGATAAGCTT
TESK2-GNA12chr145851584chr728347771126TEGSRVLVDARDKLGACAGAGGGCTCAAGGGTTCTTGTTGATGCACGAGATAAGCTTGGC

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Information of the samples that have these potential fusion neoantigens of TESK2-GNA12

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
CESCTESK2-GNA12chr145851584ENST00000372084chr72834777ENST00000275364TCGA-EK-A2IR-01A

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Potential target of CAR-T therapy development for TESK2-GNA12

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 TESK2-GNA12

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 TESK2-GNA12

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