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Center for Computational Systems Medicine
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Fusion Gene Summary

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Fusion Gene ORF analysis

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Fusion Genomic Features

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Fusion Protein Features

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Fusion Gene Sequence

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Fusion Gene PPI analysis

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Related Drugs

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Related Diseases

Fusion gene:TLK2-CRADD (FusionGDB2 ID:91153)

Fusion Gene Summary for TLK2-CRADD

check button Fusion gene summary
Fusion gene informationFusion gene name: TLK2-CRADD
Fusion gene ID: 91153
HgeneTgene
Gene symbol

TLK2

CRADD

Gene ID

11011

8738

Gene nametousled like kinase 2CASP2 and RIPK1 domain containing adaptor with death domain
SynonymsHsHPK|MRD57|PKU-ALPHAMRT34|RAIDD
Cytomap

17q23.2

12q22

Type of geneprotein-codingprotein-coding
Descriptionserine/threonine-protein kinase tousled-like 2death domain-containing protein CRADDCRADD/LYZ fusionRIP-associated ICH1/CED3-homologous protein with death domaincaspase and RIP adaptor with death domaindeath adaptor molecule RAIDDdeath domain containing protein CRADD
Modification date2020031320200313
UniProtAcc.

P78560

Ensembl transtripts involved in fusion geneENST00000326270, ENST00000343388, 
ENST00000346027, ENST00000542523, 
ENST00000582809, ENST00000577616, 
ENST00000548330, ENST00000332896, 
ENST00000541813, ENST00000542893, 
ENST00000548483, ENST00000552033, 
ENST00000552983, 
Fusion gene scores* DoF score18 X 11 X 9=17829 X 7 X 6=378
# samples 2413
** MAII scorelog2(24/1782*10)=-2.8923910259134
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
Context

PubMed: TLK2 [Title/Abstract] AND CRADD [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointTLK2(60613698)-CRADD(94243745), # samples:1
Anticipated loss of major functional domain due to fusion event.
* 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
HgeneTLK2

GO:0001672

regulation of chromatin assembly or disassembly

12660173

HgeneTLK2

GO:0006468

protein phosphorylation

12660173

HgeneTLK2

GO:0006974

cellular response to DNA damage stimulus

12660173

HgeneTLK2

GO:0018105

peptidyl-serine phosphorylation

20016786

HgeneTLK2

GO:0035556

intracellular signal transduction

12660173

HgeneTLK2

GO:0071480

cellular response to gamma radiation

12660173

TgeneCRADD

GO:0043065

positive regulation of apoptotic process

11821383


check buttonFusion gene breakpoints across TLK2 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

check buttonFusion gene breakpoints across CRADD (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

check button Fusion gene information from two resources (ChiTars 5.0 and ChimerDB 4.0)
* All genome coordinats were lifted-over on hg19.
* Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser.
SourceDiseaseSampleHgeneHchrHbpHstrandTgeneTchrTbpTstrand
ChimerDB4Non-CancerTCGA-BC-A10Z-11ATLK2chr17

60613698

+CRADDchr12

94243745

+


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Fusion Gene ORF analysis for TLK2-CRADD

check button Open reading frame (ORF) analsis of fusion genes based on Ensembl gene isoform structure.
* Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser.
ORFHenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrand
5CDS-3UTRENST00000326270ENST00000548330TLK2chr17

60613698

+CRADDchr12

94243745

+
5CDS-3UTRENST00000343388ENST00000548330TLK2chr17

60613698

+CRADDchr12

94243745

+
5CDS-3UTRENST00000346027ENST00000548330TLK2chr17

60613698

+CRADDchr12

94243745

+
5CDS-3UTRENST00000542523ENST00000548330TLK2chr17

60613698

+CRADDchr12

94243745

+
5CDS-3UTRENST00000582809ENST00000548330TLK2chr17

60613698

+CRADDchr12

94243745

+
5CDS-intronENST00000326270ENST00000332896TLK2chr17

60613698

+CRADDchr12

94243745

+
5CDS-intronENST00000326270ENST00000541813TLK2chr17

60613698

+CRADDchr12

94243745

+
5CDS-intronENST00000326270ENST00000542893TLK2chr17

60613698

+CRADDchr12

94243745

+
5CDS-intronENST00000326270ENST00000548483TLK2chr17

60613698

+CRADDchr12

94243745

+
5CDS-intronENST00000326270ENST00000552033TLK2chr17

60613698

+CRADDchr12

94243745

+
5CDS-intronENST00000326270ENST00000552983TLK2chr17

60613698

+CRADDchr12

94243745

+
5CDS-intronENST00000343388ENST00000332896TLK2chr17

60613698

+CRADDchr12

94243745

+
5CDS-intronENST00000343388ENST00000541813TLK2chr17

60613698

+CRADDchr12

94243745

+
5CDS-intronENST00000343388ENST00000542893TLK2chr17

60613698

+CRADDchr12

94243745

+
5CDS-intronENST00000343388ENST00000548483TLK2chr17

60613698

+CRADDchr12

94243745

+
5CDS-intronENST00000343388ENST00000552033TLK2chr17

60613698

+CRADDchr12

94243745

+
5CDS-intronENST00000343388ENST00000552983TLK2chr17

60613698

+CRADDchr12

94243745

+
5CDS-intronENST00000346027ENST00000332896TLK2chr17

60613698

+CRADDchr12

94243745

+
5CDS-intronENST00000346027ENST00000541813TLK2chr17

60613698

+CRADDchr12

94243745

+
5CDS-intronENST00000346027ENST00000542893TLK2chr17

60613698

+CRADDchr12

94243745

+
5CDS-intronENST00000346027ENST00000548483TLK2chr17

60613698

+CRADDchr12

94243745

+
5CDS-intronENST00000346027ENST00000552033TLK2chr17

60613698

+CRADDchr12

94243745

+
5CDS-intronENST00000346027ENST00000552983TLK2chr17

60613698

+CRADDchr12

94243745

+
5CDS-intronENST00000542523ENST00000332896TLK2chr17

60613698

+CRADDchr12

94243745

+
5CDS-intronENST00000542523ENST00000541813TLK2chr17

60613698

+CRADDchr12

94243745

+
5CDS-intronENST00000542523ENST00000542893TLK2chr17

60613698

+CRADDchr12

94243745

+
5CDS-intronENST00000542523ENST00000548483TLK2chr17

60613698

+CRADDchr12

94243745

+
5CDS-intronENST00000542523ENST00000552033TLK2chr17

60613698

+CRADDchr12

94243745

+
5CDS-intronENST00000542523ENST00000552983TLK2chr17

60613698

+CRADDchr12

94243745

+
5CDS-intronENST00000582809ENST00000332896TLK2chr17

60613698

+CRADDchr12

94243745

+
5CDS-intronENST00000582809ENST00000541813TLK2chr17

60613698

+CRADDchr12

94243745

+
5CDS-intronENST00000582809ENST00000542893TLK2chr17

60613698

+CRADDchr12

94243745

+
5CDS-intronENST00000582809ENST00000548483TLK2chr17

60613698

+CRADDchr12

94243745

+
5CDS-intronENST00000582809ENST00000552033TLK2chr17

60613698

+CRADDchr12

94243745

+
5CDS-intronENST00000582809ENST00000552983TLK2chr17

60613698

+CRADDchr12

94243745

+
intron-3UTRENST00000577616ENST00000548330TLK2chr17

60613698

+CRADDchr12

94243745

+
intron-intronENST00000577616ENST00000332896TLK2chr17

60613698

+CRADDchr12

94243745

+
intron-intronENST00000577616ENST00000541813TLK2chr17

60613698

+CRADDchr12

94243745

+
intron-intronENST00000577616ENST00000542893TLK2chr17

60613698

+CRADDchr12

94243745

+
intron-intronENST00000577616ENST00000548483TLK2chr17

60613698

+CRADDchr12

94243745

+
intron-intronENST00000577616ENST00000552033TLK2chr17

60613698

+CRADDchr12

94243745

+
intron-intronENST00000577616ENST00000552983TLK2chr17

60613698

+CRADDchr12

94243745

+

check buttonORFfinder result based on the fusion transcript sequence of in-frame fusion genes.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)		BP loci
(transcript)		Predicted start
(transcript)		Predicted stop
(transcript)		Seq length
(amino acids)

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

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Fusion Genomic Features for TLK2-CRADD


check buttonFusionAI prediction of the potential fusion gene breakpoint based on the pre-mature RNA sequence context (+/- 5kb of individual partner genes, total 20kb length sequence). FusionAI is a fusion gene breakpoint classifier based on convolutional neural network by comparing the fusion positive and negative sequence context of ~ 20K fusion gene data. From here, we can have the relative potentency of the 20K genomic sequence how individual sequnce will be likely used as the gene fusion breakpoints.
HgeneHchrHbpHstrandTgeneTchrTbpTstrand1-pp (fusion gene breakpoint)
TLK2chr1760613698+CRADDchr1294243745+2.79E-070.99999976
TLK2chr1760613698+CRADDchr1294243745+2.79E-070.99999976

check buttonDistribution of 44 human genomic features loci across 20kb length fusion breakpoint regions. We integrated a total of 44 different types of human genomic feature loci information across five big categories including virus integration sites, repeats, structural variants, chromatin states, and gene expression regulation. More details are in help page.

check buttonDistribution of 44 human genomic features loci across 20kb length fusion breakpoint regions that are ovelapped with the top 1% feature importance score regions. More details are in help page.
genomic feature of top 1%

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Fusion Protein Features for TLK2-CRADD


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/:60613698/:94243745)
- 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 buttonMain function of each fusion partner protein. (from UniProt)
HgeneTgene
.CRADD

P78560

FUNCTION: Transcriptional activator which is required for calcium-dependent dendritic growth and branching in cortical neurons. Recruits CREB-binding protein (CREBBP) to nuclear bodies. Component of the CREST-BRG1 complex, a multiprotein complex that regulates promoter activation by orchestrating a calcium-dependent release of a repressor complex and a recruitment of an activator complex. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex. At the same time, there is increased recruitment of CREBBP to the promoter by a CREST-dependent mechanism, which leads to transcriptional activation. The CREST-BRG1 complex also binds to the NR2B promoter, and activity-dependent induction of NR2B expression involves a release of HDAC1 and recruitment of CREBBP (By similarity). {ECO:0000250}.FUNCTION: Adapter protein that associates with PIDD1 and the caspase CASP2 to form the PIDDosome, a complex that activates CASP2 and triggers apoptosis (PubMed:9044836, PubMed:15073321, PubMed:16652156, PubMed:17159900, PubMed:17289572). Also recruits CASP2 to the TNFR-1 signaling complex through its interaction with RIPK1 and TRADD and may play a role in the tumor necrosis factor-mediated signaling pathway (PubMed:8985253). {ECO:0000269|PubMed:15073321, ECO:0000269|PubMed:16652156, ECO:0000269|PubMed:17159900, ECO:0000269|PubMed:17289572, ECO:0000269|PubMed:8985253, ECO:0000269|PubMed:9044836}.

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, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at

download page


* Minus value of BPloci means that the break pointn is located before the CDS.
- In-frame and retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

- In-frame and not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note


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Fusion Gene Sequence for TLK2-CRADD


check button For in-frame fusion transcripts, we provide the fusion transcript sequences and fusion amino acid sequences. To have fusion amino acid sequence, we ran ORFfinder and chose the longest ORF among the all predicted ones.

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Fusion Gene PPI Analysis for TLK2-CRADD


check button Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in

ChiPPI page.


check button Protein-protein interactors with each fusion partner protein in wild-type (BIOGRID-3.4.160)
HgeneHgene's interactorsTgeneTgene's interactors


check button - Retained PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenStill interaction with


check button - Lost PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


check button - Retained PPIs, but lost function due to frame-shift fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


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Related Drugs for TLK2-CRADD


check button Drugs targeting genes involved in this fusion gene.
(DrugBank Version 5.1.8 2021-05-08)
PartnerGeneUniProtAccDrugBank IDDrug nameDrug activityDrug typeDrug status

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Related Diseases for TLK2-CRADD


check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource