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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:AGRN-IRF3 (FusionGDB2 ID:2999)

Fusion Gene Summary for AGRN-IRF3

check button Fusion gene summary
Fusion gene informationFusion gene name: AGRN-IRF3
Fusion gene ID: 2999
HgeneTgene
Gene symbol

AGRN

IRF3

Gene ID

375790

3661

Gene nameagrininterferon regulatory factor 3
SynonymsAGRIN|CMS8|CMSPPDIIAE7
Cytomap

1p36.33

19q13.33

Type of geneprotein-codingprotein-coding
Descriptionagrinagrin proteoglycaninterferon regulatory factor 3
Modification date2020031520200315
UniProtAcc

O00468

Q14653

Ensembl transtripts involved in fusion geneENST00000477585, ENST00000379370, 
ENST00000309877, ENST00000377135, 
ENST00000377139, ENST00000593922, 
ENST00000596765, ENST00000596822, 
ENST00000597198, ENST00000598808, 
ENST00000599144, ENST00000599223, 
ENST00000599680, ENST00000600022, 
ENST00000600911, ENST00000601291, 
ENST00000442265, 
Fusion gene scores* DoF score14 X 7 X 10=9808 X 5 X 7=280
# samples 189
** MAII scorelog2(18/980*10)=-2.4447848426729
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(9/280*10)=-1.63742992061529
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: AGRN [Title/Abstract] AND IRF3 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointAGRN(970704)-IRF3(50163090), # samples:2
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
HgeneAGRN

GO:0043113

receptor clustering

15340048

TgeneIRF3

GO:0032481

positive regulation of type I interferon production

25636800

TgeneIRF3

GO:0035666

TRIF-dependent toll-like receptor signaling pathway

25636800

TgeneIRF3

GO:0045944

positive regulation of transcription by RNA polymerase II

9660935


check buttonFusion gene breakpoints across AGRN (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 IRF3 (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
ChimerDB4THCATCGA-FK-A3SGAGRNchr1

970704

+IRF3chr19

50163090

-


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Fusion Gene ORF analysis for AGRN-IRF3

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
3UTR-5UTRENST00000477585ENST00000309877AGRNchr1

970704

+IRF3chr19

50163090

-
3UTR-5UTRENST00000477585ENST00000377135AGRNchr1

970704

+IRF3chr19

50163090

-
3UTR-5UTRENST00000477585ENST00000377139AGRNchr1

970704

+IRF3chr19

50163090

-
3UTR-5UTRENST00000477585ENST00000593922AGRNchr1

970704

+IRF3chr19

50163090

-
3UTR-5UTRENST00000477585ENST00000596765AGRNchr1

970704

+IRF3chr19

50163090

-
3UTR-5UTRENST00000477585ENST00000596822AGRNchr1

970704

+IRF3chr19

50163090

-
3UTR-5UTRENST00000477585ENST00000597198AGRNchr1

970704

+IRF3chr19

50163090

-
3UTR-5UTRENST00000477585ENST00000598808AGRNchr1

970704

+IRF3chr19

50163090

-
3UTR-5UTRENST00000477585ENST00000599144AGRNchr1

970704

+IRF3chr19

50163090

-
3UTR-5UTRENST00000477585ENST00000599223AGRNchr1

970704

+IRF3chr19

50163090

-
3UTR-5UTRENST00000477585ENST00000599680AGRNchr1

970704

+IRF3chr19

50163090

-
3UTR-5UTRENST00000477585ENST00000600022AGRNchr1

970704

+IRF3chr19

50163090

-
3UTR-5UTRENST00000477585ENST00000600911AGRNchr1

970704

+IRF3chr19

50163090

-
3UTR-5UTRENST00000477585ENST00000601291AGRNchr1

970704

+IRF3chr19

50163090

-
3UTR-intronENST00000477585ENST00000442265AGRNchr1

970704

+IRF3chr19

50163090

-
5CDS-5UTRENST00000379370ENST00000309877AGRNchr1

970704

+IRF3chr19

50163090

-
5CDS-5UTRENST00000379370ENST00000377135AGRNchr1

970704

+IRF3chr19

50163090

-
5CDS-5UTRENST00000379370ENST00000377139AGRNchr1

970704

+IRF3chr19

50163090

-
5CDS-5UTRENST00000379370ENST00000593922AGRNchr1

970704

+IRF3chr19

50163090

-
5CDS-5UTRENST00000379370ENST00000596765AGRNchr1

970704

+IRF3chr19

50163090

-
5CDS-5UTRENST00000379370ENST00000596822AGRNchr1

970704

+IRF3chr19

50163090

-
5CDS-5UTRENST00000379370ENST00000597198AGRNchr1

970704

+IRF3chr19

50163090

-
5CDS-5UTRENST00000379370ENST00000598808AGRNchr1

970704

+IRF3chr19

50163090

-
5CDS-5UTRENST00000379370ENST00000599144AGRNchr1

970704

+IRF3chr19

50163090

-
5CDS-5UTRENST00000379370ENST00000599223AGRNchr1

970704

+IRF3chr19

50163090

-
5CDS-5UTRENST00000379370ENST00000599680AGRNchr1

970704

+IRF3chr19

50163090

-
5CDS-5UTRENST00000379370ENST00000600022AGRNchr1

970704

+IRF3chr19

50163090

-
5CDS-5UTRENST00000379370ENST00000600911AGRNchr1

970704

+IRF3chr19

50163090

-
5CDS-5UTRENST00000379370ENST00000601291AGRNchr1

970704

+IRF3chr19

50163090

-
5CDS-intronENST00000379370ENST00000442265AGRNchr1

970704

+IRF3chr19

50163090

-

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 AGRN-IRF3


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 AGRN-IRF3


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/:970704/:50163090)
- 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
AGRN

O00468

IRF3

Q14653

FUNCTION: [Isoform 1]: heparan sulfate basal lamina glycoprotein that plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ) and directs key events in postsynaptic differentiation. Component of the AGRN-LRP4 receptor complex that induces the phosphorylation and activation of MUSK. The activation of MUSK in myotubes induces the formation of NMJ by regulating different processes including the transcription of specific genes and the clustering of AChR in the postsynaptic membrane. Calcium ions are required for maximal AChR clustering. AGRN function in neurons is highly regulated by alternative splicing, glycan binding and proteolytic processing. Modulates calcium ion homeostasis in neurons, specifically by inducing an increase in cytoplasmic calcium ions. Functions differentially in the central nervous system (CNS) by inhibiting the alpha(3)-subtype of Na+/K+-ATPase and evoking depolarization at CNS synapses. This secreted isoform forms a bridge, after release from motor neurons, to basal lamina through binding laminin via the NtA domain.; FUNCTION: [Isoform 2]: transmembrane form that is the predominate form in neurons of the brain, induces dendritic filopodia and synapse formation in mature hippocampal neurons in large part due to the attached glycosaminoglycan chains and the action of Rho-family GTPases.; FUNCTION: Isoform 1, isoform 4 and isoform 5: neuron-specific (z+) isoforms that contain C-terminal insertions of 8-19 AA are potent activators of AChR clustering. Isoform 5, agrin (z+8), containing the 8-AA insert, forms a receptor complex in myotubules containing the neuronal AGRN, the muscle-specific kinase MUSK and LRP4, a member of the LDL receptor family. The splicing factors, NOVA1 and NOVA2, regulate AGRN splicing and production of the 'z' isoforms.; FUNCTION: Isoform 3 and isoform 6: lack any 'z' insert, are muscle-specific and may be involved in endothelial cell differentiation.; FUNCTION: [Agrin N-terminal 110 kDa subunit]: is involved in regulation of neurite outgrowth probably due to the presence of the glycosaminoglcan (GAG) side chains of heparan and chondroitin sulfate attached to the Ser/Thr- and Gly/Ser-rich regions. Also involved in modulation of growth factor signaling (By similarity). {ECO:0000250, ECO:0000269|PubMed:19631309, ECO:0000269|PubMed:21969364}.; FUNCTION: [Agrin C-terminal 22 kDa fragment]: this released fragment is important for agrin signaling and to exert a maximal dendritic filopodia-inducing effect. All 'z' splice variants (z+) of this fragment also show an increase in the number of filopodia.FUNCTION: Key transcriptional regulator of type I interferon (IFN)-dependent immune responses which plays a critical role in the innate immune response against DNA and RNA viruses (PubMed:22394562, PubMed:25636800, PubMed:27302953). Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters (PubMed:11846977, PubMed:16846591, PubMed:16979567, PubMed:20049431, PubMed:32972995). Acts as a more potent activator of the IFN-beta (IFNB) gene than the IFN-alpha (IFNA) gene and plays a critical role in both the early and late phases of the IFNA/B gene induction (PubMed:16846591, PubMed:16979567, PubMed:20049431). Found in an inactive form in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, is phosphorylated by IKBKE and TBK1 kinases (PubMed:22394562, PubMed:25636800, PubMed:27302953). This induces a conformational change, leading to its dimerization and nuclear localization and association with CREB binding protein (CREBBP) to form dsRNA-activated factor 1 (DRAF1), a complex which activates the transcription of the type I IFN and ISG genes (PubMed:16154084, PubMed:27302953, PubMed:33440148). Can activate distinct gene expression programs in macrophages and can induce significant apoptosis in primary macrophages (PubMed:16846591). In response to Sendai virus infection, is recruited by TOMM70:HSP90AA1 to mitochondrion and forms an apoptosis complex TOMM70:HSP90AA1:IRF3:BAX inducing apoptosis (PubMed:25609812). Key transcription factor regulating the IFN response during SARS-CoV-2 infection (PubMed:33440148). {ECO:0000269|PubMed:16154084, ECO:0000269|PubMed:22394562, ECO:0000269|PubMed:25609812, ECO:0000269|PubMed:25636800, ECO:0000269|PubMed:27302953, ECO:0000269|PubMed:31413131, ECO:0000269|PubMed:32972995, ECO:0000269|PubMed:33440148, ECO:0000303|PubMed:11846977, ECO:0000303|PubMed:16846591, ECO:0000303|PubMed:16979567, ECO:0000303|PubMed:20049431}.

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 AGRN-IRF3


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 AGRN-IRF3


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 AGRN-IRF3


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 AGRN-IRF3


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