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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:ZZZ3-NCK1 (FusionGDB2 ID:103338)

Fusion Gene Summary for ZZZ3-NCK1

check button Fusion gene summary
Fusion gene informationFusion gene name: ZZZ3-NCK1
Fusion gene ID: 103338
HgeneTgene
Gene symbol

ZZZ3

NCK1

Gene ID

26009

4690

Gene namezinc finger ZZ-type containing 3NCK adaptor protein 1
SynonymsATAC1NCK|NCKalpha|nck-1
Cytomap

1p31.1

3q22.3

Type of geneprotein-codingprotein-coding
DescriptionZZ-type zinc finger-containing protein 3ATAC component 1 homologzinc finger, ZZ domain containing 3cytoplasmic protein NCK1NCK tyrosine kinaseSH2/SH3 adaptor protein NCK-alphamelanoma NCK proteinnon-catalytic region of tyrosine kinase
Modification date2020032020200327
UniProtAcc.

P16333

Ensembl transtripts involved in fusion geneENST00000370801, ENST00000370798, 
ENST00000476275, 
ENST00000288986, 
ENST00000481752, ENST00000469404, 
Fusion gene scores* DoF score13 X 9 X 9=10539 X 5 X 9=405
# samples 1412
** MAII scorelog2(14/1053*10)=-2.91100670408075
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(12/405*10)=-1.75488750216347
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: ZZZ3 [Title/Abstract] AND NCK1 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointZZZ3(78148270)-NCK1(136646826), # 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
TgeneNCK1

GO:0033137

negative regulation of peptidyl-serine phosphorylation

14676213|16835242

TgeneNCK1

GO:0036493

positive regulation of translation in response to endoplasmic reticulum stress

14676213

TgeneNCK1

GO:0045944

positive regulation of transcription by RNA polymerase II

10026169

TgeneNCK1

GO:0060548

negative regulation of cell death

18835251

TgeneNCK1

GO:0070262

peptidyl-serine dephosphorylation

16835242

TgeneNCK1

GO:1902237

positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway

14676213

TgeneNCK1

GO:1903676

positive regulation of cap-dependent translational initiation

11959995

TgeneNCK1

GO:1903679

positive regulation of cap-independent translational initiation

11959995

TgeneNCK1

GO:1903898

negative regulation of PERK-mediated unfolded protein response

14676213

TgeneNCK1

GO:1903912

negative regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation

14676213|16835242

TgeneNCK1

GO:1990441

negative regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress

16835242


check buttonFusion gene breakpoints across ZZZ3 (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 NCK1 (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
ChimerDB4BRCATCGA-AC-A6IW-01AZZZ3chr1

78148270

-NCK1chr3

136646826

+


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Fusion Gene ORF analysis for ZZZ3-NCK1

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
5UTR-5UTRENST00000370801ENST00000288986ZZZ3chr1

78148270

-NCK1chr3

136646826

+
5UTR-5UTRENST00000370801ENST00000481752ZZZ3chr1

78148270

-NCK1chr3

136646826

+
5UTR-intronENST00000370801ENST00000469404ZZZ3chr1

78148270

-NCK1chr3

136646826

+
intron-5UTRENST00000370798ENST00000288986ZZZ3chr1

78148270

-NCK1chr3

136646826

+
intron-5UTRENST00000370798ENST00000481752ZZZ3chr1

78148270

-NCK1chr3

136646826

+
intron-5UTRENST00000476275ENST00000288986ZZZ3chr1

78148270

-NCK1chr3

136646826

+
intron-5UTRENST00000476275ENST00000481752ZZZ3chr1

78148270

-NCK1chr3

136646826

+
intron-intronENST00000370798ENST00000469404ZZZ3chr1

78148270

-NCK1chr3

136646826

+
intron-intronENST00000476275ENST00000469404ZZZ3chr1

78148270

-NCK1chr3

136646826

+

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 ZZZ3-NCK1


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)
ZZZ3chr178148269-NCK1chr3136646825+2.79E-050.9999721
ZZZ3chr178148269-NCK1chr3136646825+2.79E-050.9999721

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 ZZZ3-NCK1


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/:78148270/:136646826)
- 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
.NCK1

P16333

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 which associates with tyrosine-phosphorylated growth factor receptors, such as KDR and PDGFRB, or their cellular substrates. Maintains low levels of EIF2S1 phosphorylation by promoting its dephosphorylation by PP1. Plays a role in the DNA damage response, not in the detection of the damage by ATM/ATR, but for efficient activation of downstream effectors, such as that of CHEK2. Plays a role in ELK1-dependent transcriptional activation in response to activated Ras signaling. Modulates the activation of EIF2AK2/PKR by dsRNA. May play a role in cell adhesion and migration through interaction with ephrin receptors. {ECO:0000269|PubMed:10026169, ECO:0000269|PubMed:16835242, ECO:0000269|PubMed:17803907, ECO:0000269|PubMed:18835251, ECO:0000269|PubMed:23358419, ECO:0000269|PubMed:9430661}.

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 ZZZ3-NCK1


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 ZZZ3-NCK1


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 ZZZ3-NCK1


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 ZZZ3-NCK1


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