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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:SRI-DKK1 (FusionGDB2 ID:86404)

Fusion Gene Summary for SRI-DKK1

check button Fusion gene summary
Fusion gene informationFusion gene name: SRI-DKK1
Fusion gene ID: 86404
HgeneTgene
Gene symbol

SRI

DKK1

Gene ID

6717

22943

Gene namesorcindickkopf WNT signaling pathway inhibitor 1
SynonymsCP-22|CP22|SCN|V19DKK-1|SK
Cytomap

7q21.12

10q21.1

Type of geneprotein-codingprotein-coding
Descriptionsorcin22 kDa proteinH_RG167B05.1calcium binding protein amplified in mutlidrug-resistant cellsdickkopf-related protein 1dickkopf 1 homologdickkopf-1 likedickkopf-like protein 1
Modification date2020031320200329
UniProtAcc..
Ensembl transtripts involved in fusion geneENST00000265729, ENST00000394641, 
ENST00000419179, ENST00000431660, 
ENST00000490437, 
ENST00000467359, 
ENST00000373970, 
Fusion gene scores* DoF score6 X 5 X 4=1201 X 1 X 1=1
# samples 71
** MAII scorelog2(7/120*10)=-0.777607578663552
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(1/1*10)=3.32192809488736
Context

PubMed: SRI [Title/Abstract] AND DKK1 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointSRI(87840197)-DKK1(54076557), # samples:1
Anticipated loss of major functional domain due to fusion event.SRI-DKK1 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
SRI-DKK1 seems lost the major protein functional domain in Tgene 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
HgeneSRI

GO:0060315

negative regulation of ryanodine-sensitive calcium-release channel activity

17699613

TgeneDKK1

GO:0000122

negative regulation of transcription by RNA polymerase II

20723538

TgeneDKK1

GO:0002090

regulation of receptor internalization

17804805

TgeneDKK1

GO:0030178

negative regulation of Wnt signaling pathway

15020244|22615920

TgeneDKK1

GO:0032091

negative regulation of protein binding

20093360

TgeneDKK1

GO:0033137

negative regulation of peptidyl-serine phosphorylation

20723538

TgeneDKK1

GO:0042662

negative regulation of mesodermal cell fate specification

20559569

TgeneDKK1

GO:0042663

regulation of endodermal cell fate specification

20559569

TgeneDKK1

GO:0043507

positive regulation of JUN kinase activity

23164821

TgeneDKK1

GO:0060394

negative regulation of pathway-restricted SMAD protein phosphorylation

20559569

TgeneDKK1

GO:0090090

negative regulation of canonical Wnt signaling pathway

11433302|11448771|11742004|12857724|17804805|18044981|20039315|20093360|22902902

TgeneDKK1

GO:1901296

negative regulation of canonical Wnt signaling pathway involved in cardiac muscle cell fate commitment

20559569

TgeneDKK1

GO:1904723

negative regulation of Wnt-Frizzled-LRP5/6 complex assembly

11448771|20093360

TgeneDKK1

GO:2000726

negative regulation of cardiac muscle cell differentiation

20559569


check buttonFusion gene breakpoints across SRI (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 DKK1 (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
ChiTaRS5.0N/ABQ225130SRIchr7

87840197

-DKK1chr10

54076557

+


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Fusion Gene ORF analysis for SRI-DKK1

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-intronENST00000265729ENST00000467359SRIchr7

87840197

-DKK1chr10

54076557

+
5CDS-intronENST00000394641ENST00000467359SRIchr7

87840197

-DKK1chr10

54076557

+
5CDS-intronENST00000419179ENST00000467359SRIchr7

87840197

-DKK1chr10

54076557

+
5CDS-intronENST00000431660ENST00000467359SRIchr7

87840197

-DKK1chr10

54076557

+
5CDS-intronENST00000490437ENST00000467359SRIchr7

87840197

-DKK1chr10

54076557

+
Frame-shiftENST00000265729ENST00000373970SRIchr7

87840197

-DKK1chr10

54076557

+
Frame-shiftENST00000394641ENST00000373970SRIchr7

87840197

-DKK1chr10

54076557

+
Frame-shiftENST00000419179ENST00000373970SRIchr7

87840197

-DKK1chr10

54076557

+
Frame-shiftENST00000431660ENST00000373970SRIchr7

87840197

-DKK1chr10

54076557

+
Frame-shiftENST00000490437ENST00000373970SRIchr7

87840197

-DKK1chr10

54076557

+

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 SRI-DKK1


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)

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.

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Fusion Protein Features for SRI-DKK1


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/:87840197/:54076557)
- 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
..
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: 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}.

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 SRI-DKK1


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 SRI-DKK1


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 SRI-DKK1


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 SRI-DKK1


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