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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:NLK-RPS3 (FusionGDB2 ID:59356)

Fusion Gene Summary for NLK-RPS3

check button Fusion gene summary
Fusion gene informationFusion gene name: NLK-RPS3
Fusion gene ID: 59356
HgeneTgene
Gene symbol

NLK

RPS3

Gene ID

51701

6188

Gene namenemo like kinaseribosomal protein S3
Synonyms-S3
Cytomap

17q11.2

11q13.4

Type of geneprotein-codingprotein-coding
Descriptionserine/threonine-protein kinase NLK40S ribosomal protein S3IMR-90 ribosomal protein S3small ribosomal subunit protein uS3
Modification date2020031320200327
UniProtAcc

Q9UBE8

.
Ensembl transtripts involved in fusion geneENST00000407008, ENST00000582037, 
ENST00000583517, 		ENST00000531188, 
ENST00000278572, ENST00000524851, 
ENST00000526608, ENST00000527446, 
ENST00000529285, ENST00000530164, 
ENST00000534440, 
Fusion gene scores* DoF score18 X 10 X 9=162017 X 19 X 5=1615
# samples 2022
** MAII scorelog2(20/1620*10)=-3.01792190799726
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(22/1615*10)=-2.87595873605663
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: NLK [Title/Abstract] AND RPS3 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointNLK(26404134)-RPS3(75116730), # 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
HgeneNLK

GO:0050821

protein stabilization

25512613

TgeneRPS3

GO:0006979

response to oxidative stress

23911537

TgeneRPS3

GO:0017148

negative regulation of translation

20217897

TgeneRPS3

GO:0031397

negative regulation of protein ubiquitination

19656744

TgeneRPS3

GO:0032079

positive regulation of endodeoxyribonuclease activity

18973764

TgeneRPS3

GO:0042769

DNA damage response, detection of DNA damage

23911537

TgeneRPS3

GO:0045739

positive regulation of DNA repair

23911537

TgeneRPS3

GO:0061481

response to TNF agonist

20041225

TgeneRPS3

GO:0070301

cellular response to hydrogen peroxide

23911537

TgeneRPS3

GO:1901224

positive regulation of NIK/NF-kappaB signaling

20041225

TgeneRPS3

GO:1902546

positive regulation of DNA N-glycosylase activity

15518571

TgeneRPS3

GO:1905053

positive regulation of base-excision repair

18973764

TgeneRPS3

GO:2001235

positive regulation of apoptotic signaling pathway

14988002


check buttonFusion gene breakpoints across NLK (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 RPS3 (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/ABI493957NLKchr17

26404134

+RPS3chr11

75116730

-


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Fusion Gene ORF analysis for NLK-RPS3

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
intron-3UTRENST00000407008ENST00000531188NLKchr17

26404134

+RPS3chr11

75116730

-
intron-3UTRENST00000582037ENST00000531188NLKchr17

26404134

+RPS3chr11

75116730

-
intron-3UTRENST00000583517ENST00000531188NLKchr17

26404134

+RPS3chr11

75116730

-
intron-intronENST00000407008ENST00000278572NLKchr17

26404134

+RPS3chr11

75116730

-
intron-intronENST00000407008ENST00000524851NLKchr17

26404134

+RPS3chr11

75116730

-
intron-intronENST00000407008ENST00000526608NLKchr17

26404134

+RPS3chr11

75116730

-
intron-intronENST00000407008ENST00000527446NLKchr17

26404134

+RPS3chr11

75116730

-
intron-intronENST00000407008ENST00000529285NLKchr17

26404134

+RPS3chr11

75116730

-
intron-intronENST00000407008ENST00000530164NLKchr17

26404134

+RPS3chr11

75116730

-
intron-intronENST00000407008ENST00000534440NLKchr17

26404134

+RPS3chr11

75116730

-
intron-intronENST00000582037ENST00000278572NLKchr17

26404134

+RPS3chr11

75116730

-
intron-intronENST00000582037ENST00000524851NLKchr17

26404134

+RPS3chr11

75116730

-
intron-intronENST00000582037ENST00000526608NLKchr17

26404134

+RPS3chr11

75116730

-
intron-intronENST00000582037ENST00000527446NLKchr17

26404134

+RPS3chr11

75116730

-
intron-intronENST00000582037ENST00000529285NLKchr17

26404134

+RPS3chr11

75116730

-
intron-intronENST00000582037ENST00000530164NLKchr17

26404134

+RPS3chr11

75116730

-
intron-intronENST00000582037ENST00000534440NLKchr17

26404134

+RPS3chr11

75116730

-
intron-intronENST00000583517ENST00000278572NLKchr17

26404134

+RPS3chr11

75116730

-
intron-intronENST00000583517ENST00000524851NLKchr17

26404134

+RPS3chr11

75116730

-
intron-intronENST00000583517ENST00000526608NLKchr17

26404134

+RPS3chr11

75116730

-
intron-intronENST00000583517ENST00000527446NLKchr17

26404134

+RPS3chr11

75116730

-
intron-intronENST00000583517ENST00000529285NLKchr17

26404134

+RPS3chr11

75116730

-
intron-intronENST00000583517ENST00000530164NLKchr17

26404134

+RPS3chr11

75116730

-
intron-intronENST00000583517ENST00000534440NLKchr17

26404134

+RPS3chr11

75116730

-

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 NLK-RPS3


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 NLK-RPS3


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/:26404134/:75116730)
- 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
NLK

Q9UBE8

.
FUNCTION: Serine/threonine-protein kinase that regulates a number of transcription factors with key roles in cell fate determination. Positive effector of the non-canonical Wnt signaling pathway, acting downstream of WNT5A, MAP3K7/TAK1 and HIPK2. Negative regulator of the canonical Wnt/beta-catenin signaling pathway. Binds to and phosphorylates TCF7L2/TCF4 and LEF1, promoting the dissociation of the TCF7L2/LEF1/beta-catenin complex from DNA, as well as the ubiquitination and subsequent proteolysis of LEF1. Together these effects inhibit the transcriptional activation of canonical Wnt/beta-catenin target genes. Negative regulator of the Notch signaling pathway. Binds to and phosphorylates NOTCH1, thereby preventing the formation of a transcriptionally active ternary complex of NOTCH1, RBPJ/RBPSUH and MAML1. Negative regulator of the MYB family of transcription factors. Phosphorylation of MYB leads to its subsequent proteolysis while phosphorylation of MYBL1 and MYBL2 inhibits their interaction with the coactivator CREBBP. Other transcription factors may also be inhibited by direct phosphorylation of CREBBP itself. Acts downstream of IL6 and MAP3K7/TAK1 to phosphorylate STAT3, which is in turn required for activation of NLK by MAP3K7/TAK1. Upon IL1B stimulus, cooperates with ATF5 to activate the transactivation activity of C/EBP subfamily members. Phosphorylates ATF5 but also stabilizes ATF5 protein levels in a kinase-independent manner (PubMed:25512613). {ECO:0000250|UniProtKB:O54949, ECO:0000269|PubMed:12482967, ECO:0000269|PubMed:14960582, ECO:0000269|PubMed:15004007, ECO:0000269|PubMed:15764709, ECO:0000269|PubMed:20061393, ECO:0000269|PubMed:20118921, ECO:0000269|PubMed:20874444, ECO:0000269|PubMed:21454679, ECO:0000269|PubMed:25512613}.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 NLK-RPS3


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 NLK-RPS3


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 NLK-RPS3


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 NLK-RPS3


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