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Center for Computational Systems Medicine level1
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Fusion Gene Summary

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Fusion Gene Sample Information

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Fusion ORF Analysis

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Fusion Amino Acid Sequences

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Fusion Protein Functional Features

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Fusion Protein-Protein Interaction

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Related drugs with this fusion protein

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Related disease with this fusion protein

Fusion Protein:USP18-DAPK2

Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: USP18-DAPK2
FusionPDB ID: 97251
FusionGDB2.0 ID: 97251
HgeneTgene
Gene symbol

USP18

DAPK2

Gene ID

11274

23604

Gene nameubiquitin specific peptidase 18death associated protein kinase 2
SynonymsISG43|PTORCH2|UBP43DRP-1|DRP1
Cytomap

22q11.21

15q22.31

Type of geneprotein-codingprotein-coding
Descriptionubl carboxyl-terminal hydrolase 1843 kDa ISG15-specific proteaseISG15-specific-processing proteasehUBP43ubiquitin specific protease 18ubl thioesterase 18ubl thiolesterase 18death-associated protein kinase 2DAP kinase 2DAP-kinase-related protein 1 beta isoform
Modification date2020031320200313
UniProtAcc.

Q9UIK4

Ensembl transtripts involved in fusion geneENST idsENST00000215794, ENST00000558482, 
ENST00000261891, ENST00000457488, 
ENST00000558069, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score5 X 6 X 4=1208 X 9 X 8=576
# samples 513
** MAII scorelog2(5/120*10)=-1.26303440583379
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(13/576*10)=-2.14755718841386
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)

PubMed: USP18 [Title/Abstract] AND DAPK2 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)USP18(18643035)-DAPK2(64275953), # samples:1
Anticipated loss of major functional domain due to fusion event.USP18-DAPK2 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.
USP18-DAPK2 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.
USP18-DAPK2 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.
USP18-DAPK2 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
TgeneDAPK2

GO:0006468

protein phosphorylation

10376525

TgeneDAPK2

GO:0035556

intracellular signal transduction

10376525


check buttonFusion gene breakpoints across USP18 (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 DAPK2 (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 Gene Sample Information

check buttonFusion gene information from FusionGDB2.0.
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
ChimerDB4LIHCTCGA-DD-A73F-01AUSP18chr22

18643035

+DAPK2chr15

64275953

-


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Fusion ORF Analysis


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)
ENST00000215794USP18chr2218643035+ENST00000261891DAPK2chr1564275953-31896844301704424
ENST00000215794USP18chr2218643035+ENST00000457488DAPK2chr1564275953-23026844301704424
ENST00000215794USP18chr2218643035+ENST00000558069DAPK2chr1564275953-20596844302058543

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
ENST00000215794ENST00000261891USP18chr2218643035+DAPK2chr1564275953-0.0013698830.99863017
ENST00000215794ENST00000457488USP18chr2218643035+DAPK2chr1564275953-0.0026956150.9973043
ENST00000215794ENST00000558069USP18chr2218643035+DAPK2chr1564275953-0.0061937890.99380624

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Fusion Amino Acid Sequences


check button For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among the all predicted ones.
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

>97251_97251_1_USP18-DAPK2_USP18_chr22_18643035_ENST00000215794_DAPK2_chr15_64275953_ENST00000261891_length(amino acids)=424AA_BP=84
MSKAFGLLRQICQSILAESSQSPADLEEKKEEDSNMKREQPRERPRAWDYPHGLVGLHNIGQTCCLNSLIQVFVMNVDFTRILKSGQFAI
VKKCREKSTGLEYAAKFIKKRQSRASRRGVSREEIEREVSILRQVLHHNVITLHDVYENRTDVVLILELVSGGELFDFLAQKESLSEEEA
TSFIKQILDGVNYLHTKKIAHFDLKPENIMLLDKNIPIPHIKLIDFGLAHEIEDGVEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVI
TYILLSGASPFLGDTKQETLANITAVSYDFDEEFFSQTSELAKDFIRKLLVKETRKRLTIQEALRHPWITPVDNQQAMVRRESVVNLENF

--------------------------------------------------------------

>97251_97251_2_USP18-DAPK2_USP18_chr22_18643035_ENST00000215794_DAPK2_chr15_64275953_ENST00000457488_length(amino acids)=424AA_BP=84
MSKAFGLLRQICQSILAESSQSPADLEEKKEEDSNMKREQPRERPRAWDYPHGLVGLHNIGQTCCLNSLIQVFVMNVDFTRILKSGQFAI
VKKCREKSTGLEYAAKFIKKRQSRASRRGVSREEIEREVSILRQVLHHNVITLHDVYENRTDVVLILELVSGGELFDFLAQKESLSEEEA
TSFIKQILDGVNYLHTKKIAHFDLKPENIMLLDKNIPIPHIKLIDFGLAHEIEDGVEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVI
TYILLSGASPFLGDTKQETLANITAVSYDFDEEFFSQTSELAKDFIRKLLVKETRKRLTIQEALRHPWITPVDNQQAMVRRESVVNLENF

--------------------------------------------------------------

>97251_97251_3_USP18-DAPK2_USP18_chr22_18643035_ENST00000215794_DAPK2_chr15_64275953_ENST00000558069_length(amino acids)=543AA_BP=84
MSKAFGLLRQICQSILAESSQSPADLEEKKEEDSNMKREQPRERPRAWDYPHGLVGLHNIGQTCCLNSLIQVFVMNVDFTRILKSGQFAI
VKKCREKSTGLEYAAKFIKKRQSRASRRGVSREEIEREVSILRQVLHHNVITLHDVYENRTDVVLILELVSGGELFDFLAQKESLSEEEA
TSFIKQILDGVNYLHTKKIAHFDLKPENIMLLDKNIPIPHIKLIDFGLAHEIEDGVEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVI
TYILLSGASPFLGDTKQETLANITAVSYDFDEEFFSQTSELAKDFIRKLLVKETRKRLTIQEALRHPWITSKGEGRAPEQRKTEPTQLKT
KHLREYTLKCHSSMPPNNSYVNFERFACVVEDVARVDLGCRALVEAHDTIQDDVEALVSIFNEKEAWYREENESARHDLSQLRYEFRKVE
SLKKLLREDIQATGCSLGSMARKLDHLQAQFEILRQELSADLQWIQELVGSFQLESGSSEGLGSTFYQDTSESLSELLSRSCTEEFLAGW

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Fusion Protein Functional Features


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/chr22:18643035/chr15:64275953)
- 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
.DAPK2

Q9UIK4

FUNCTION: Might normally function as a transcriptional repressor. EWS-fusion-proteins (EFPS) may play a role in the tumorigenic process. They may disturb gene expression by mimicking, or interfering with the normal function of CTD-POLII within the transcription initiation complex. They may also contribute to an aberrant activation of the fusion protein target genes.FUNCTION: Calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways that trigger cell survival, apoptosis, and autophagy. Regulates both type I apoptotic and type II autophagic cell death signals, depending on the cellular setting. The former is caspase-dependent, while the latter is caspase-independent and is characterized by the accumulation of autophagic vesicles. Acts as a mediator of anoikis and a suppressor of beta-catenin-dependent anchorage-independent growth of malignant epithelial cells. May play a role in granulocytic maturation (PubMed:17347302). Regulates granulocytic motility by controlling cell spreading and polarization (PubMed:24163421). {ECO:0000269|PubMed:17347302, ECO:0000269|PubMed:24163421, ECO:0000269|PubMed:26047703}.; FUNCTION: Isoform 2 is not regulated by calmodulin. It can phosphorylate MYL9. It can induce membrane blebbing and autophagic cell death.

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.
- Retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
TgeneDAPK2chr22:18643035chr15:64275953ENST0000026189101129_3730.666666666666668371.0Nucleotide bindingATP
TgeneDAPK2chr22:18643035chr15:64275953ENST0000045748811229_3730.666666666666668371.0Nucleotide bindingATP
TgeneDAPK2chr22:18643035chr15:64275953ENST0000055806911029_3730.666666666666668489.0Nucleotide bindingATP
TgeneDAPK2chr22:18643035chr15:64275953ENST00000261891011277_34430.666666666666668371.0RegionNote=Calmodulin-binding
TgeneDAPK2chr22:18643035chr15:64275953ENST00000261891011292_30130.666666666666668371.0RegionAutoinhibitory domain
TgeneDAPK2chr22:18643035chr15:64275953ENST00000457488112277_34430.666666666666668371.0RegionNote=Calmodulin-binding
TgeneDAPK2chr22:18643035chr15:64275953ENST00000457488112292_30130.666666666666668371.0RegionAutoinhibitory domain
TgeneDAPK2chr22:18643035chr15:64275953ENST00000558069110277_34430.666666666666668489.0RegionNote=Calmodulin-binding
TgeneDAPK2chr22:18643035chr15:64275953ENST00000558069110292_30130.666666666666668489.0RegionAutoinhibitory domain

- Not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneUSP18chr22:18643035chr15:64275953ENST00000215794+31155_37084.66666666666667373.0DomainNote=USP
TgeneDAPK2chr22:18643035chr15:64275953ENST0000026189101123_28530.666666666666668371.0DomainProtein kinase
TgeneDAPK2chr22:18643035chr15:64275953ENST0000045748811223_28530.666666666666668371.0DomainProtein kinase
TgeneDAPK2chr22:18643035chr15:64275953ENST0000055806911023_28530.666666666666668489.0DomainProtein kinase


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Fusion Protein-Protein Interaction


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 from validated records (BIOGRID-3.4.160)
GenePPI interactors


check button Protein-protein interactors based on sequence similarity (STRING)
GeneSTRING network
USP18
DAPK2


check button - Retained interactions in fusion protein (protein functional feature from UniProt).
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenStill interaction with


check button - Lost interactions due to fusion (protein functional feature from UniProt).
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


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Related Drugs to USP18-DAPK2


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 USP18-DAPK2


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