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Center for Computational Systems Medicine
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Fusion Gene and Fusion Protein Summary

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Fusion Amino Acid Sequences (multiple BPs and multiple gene isoforms)

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Fusion Protein Breakpoint Sequences - (for the Screening of the FusionNeoAntigens)

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Potential FusionNeoAntigens in HLA I - (netMHCpan v4.1 + deepHLApan v1.1)

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Potential FusionNeoAntigens in HLA II - (netMHCIIpan v4.1)

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Fusion Breakpoint 14 AA Peptide Structure - (RoseTTAFold)

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D - (Glide)

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Vaccine Design for the FusionNeoAntigens (RNA/protein sequences)

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Potential target of CAR-T therapy development

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Information on the samples that have these potential fusion neoantigens

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Fusion Protein Targeting Drugs - (Manual Curation)

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Fusion Protein Related diseases - (Manual Curation)

Fusion Protein:IRF7-CARS2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: IRF7-CARS2
FusionPDB ID: 40268
FusionGDB2.0 ID: 40268
HgeneTgene
Gene symbol

IRF7

CARS2

Gene ID

3665

79587

Gene nameinterferon regulatory factor 7cysteinyl-tRNA synthetase 2, mitochondrial
SynonymsIMD39|IRF-7|IRF-7H|IRF7A|IRF7B|IRF7C|IRF7HCOXPD27|cysRS
Cytomap

11p15.5

13q34

Type of geneprotein-codingprotein-coding
Descriptioninterferon regulatory factor 7interferon regulatory factor 7G isoforminterferon regulatory factor-7Hprobable cysteine--tRNA ligase, mitochondrialcysteine tRNA ligase 2, mitochondrial (putative)cysteinyl-tRNA synthetase 2, mitochondrial (putative)
Modification date2020031320200313
UniProtAcc

Q92985

Main function of 5'-partner protein: FUNCTION: Key transcriptional regulator of type I interferon (IFN)-dependent immune responses and plays a critical role in the innate immune response against DNA and RNA viruses. 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:17574024, PubMed:32972995). Can efficiently activate both the IFN-beta (IFNB) and the IFN-alpha (IFNA) genes and mediate their induction via both the virus-activated, MyD88-independent pathway and the TLR-activated, MyD88-dependent pathway. Induces transcription of ubiquitin hydrolase USP25 mRNA in response to lipopolysaccharide (LPS) or viral infection in a type I IFN-dependent manner (By similarity). Required during both the early and late phases of the IFN gene induction but is more critical for the late than for the early phase. Exists in an inactive form in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, becomes phosphorylated by IKBKE and TBK1 kinases. This induces a conformational change, leading to its dimerization and nuclear localization where along with other coactivators it can activate transcription of the type I IFN and ISG genes. Can also play a role in regulating adaptive immune responses by inducing PSMB9/LMP2 expression, either directly or through induction of IRF1. Binds to the Q promoter (Qp) of EBV nuclear antigen 1 a (EBNA1) and may play a role in the regulation of EBV latency. Can activate distinct gene expression programs in macrophages and regulate the anti-tumor properties of primary macrophages (By similarity) (PubMed:11073981, PubMed:12374802, PubMed:15361868, PubMed:17404045). {ECO:0000250|UniProtKB:P70434, ECO:0000269|PubMed:11073981, ECO:0000269|PubMed:12374802, ECO:0000269|PubMed:15361868, ECO:0000269|PubMed:17404045, ECO:0000269|PubMed:17574024, ECO:0000269|PubMed:32972995}.

Q9HA77

Main function of 5'-partner protein:
Ensembl transtripts involved in fusion geneENST idsENST00000330243, ENST00000348655, 
ENST00000397566, ENST00000397570, 
ENST00000397574, ENST00000525445, 
ENST00000397562, 
ENST00000535398, 
ENST00000257347, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score3 X 4 X 2=246 X 5 X 3=90
# samples 47
** MAII scorelog2(4/24*10)=0.736965594166206
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
log2(7/90*10)=-0.362570079384708
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: IRF7 [Title/Abstract] AND CARS2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: IRF7 [Title/Abstract] AND CARS2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)IRF7(614478)-CARS2(111293936), # samples:1
Anticipated loss of major functional domain due to fusion event.IRF7-CARS2 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.
IRF7-CARS2 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.
IRF7-CARS2 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.
IRF7-CARS2 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.
IRF7-CARS2 seems lost the major protein functional domain in Hgene partner, which is a transcription factor due to the frame-shifted ORF.
IRF7-CARS2 seems lost the major protein functional domain in Tgene partner, which is a essential gene 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
HgeneIRF7

GO:0002819

regulation of adaptive immune response

17404045

HgeneIRF7

GO:0032727

positive regulation of interferon-alpha production

16127453

HgeneIRF7

GO:0045944

positive regulation of transcription by RNA polymerase II

16127453|17404045

HgeneIRF7

GO:0051607

defense response to virus

21478870



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/chr11:614478/chr13:111293936)
- 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 buttonRetention analysis results 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, are available here.

check buttonFusion gene breakpoints across IRF7 (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 CARS2 (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 Amino Acid Sequences


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)
ENST00000397570IRF7chr11614478-ENST00000257347CARS2chr13111293936-996823244894216
ENST00000397574IRF7chr11614478-ENST00000257347CARS2chr13111293936-996823244894216
ENST00000330243IRF7chr11614478-ENST00000257347CARS2chr13111293936-1052879944297215

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
ENST00000397570ENST00000257347IRF7chr11614478-CARS2chr13111293936-0.57714080.42285913
ENST00000397574ENST00000257347IRF7chr11614478-CARS2chr13111293936-0.57714080.42285913
ENST00000330243ENST00000257347IRF7chr11614478-CARS2chr13111293936-0.606236760.3937633

check button Predicted full-length fusion amino acid sequences. For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among all the predicted ones.

Get the fusion protein sequences from here.

Fusion protein sequence information is available in the fasta format.
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

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Fusion Protein Breakpoint Sequences for IRF7-CARS2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
IRF7chr11614478CARS2chr13111293936823179SRELCWREGPGTDQTEAEAPAAVPPP

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Potential FusionNeoAntigen Information of IRF7-CARS2 in HLA I

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.
IRF7-CARS2_614478_111293936.msa

check button Potential FusionNeoAntigen Information
* We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5)
Fusion geneHchrHbpTgeneTchrTbpHLA IFusionNeoAntigen peptideBinding scoreImmunogenic scoreNeoantigen start (at BP 13)Neoantigen end (at BP 13)
IRF7-CARS2chr11614478chr13111293936823HLA-B41:01REGPGTDQTEA0.99370.8791617
IRF7-CARS2chr11614478chr13111293936823HLA-B50:01REGPGTDQTEA0.99350.8953617
IRF7-CARS2chr11614478chr13111293936823HLA-B50:05REGPGTDQTEA0.99350.8953617
IRF7-CARS2chr11614478chr13111293936823HLA-B50:04REGPGTDQTEA0.99350.8953617

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Potential FusionNeoAntigen Information of IRF7-CARS2 in HLA II

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.

check button Potential FusionNeoAntigen Information
* We used NetMHCIIpan v4.1 (%rank<0.5).
Fusion geneHchrHbpTgeneTchrTbpHLA IIFusionNeoAntigen peptideNeoantigen start (at BP 13)Neoantigen end (at BP 13)

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Fusion breakpoint peptide structures of IRF7-CARS2

check button3D structures of the fusion breakpoint peptide of 14AA sequence that have potential fusion neoantigens
* The minimum length of the amino acid sequence in RoseTTAFold is 14AA. Here, we predicted the 14AA fusion protein breakpoint sequence not the fusion neoantigen peptide, which is shorter than 14 AA.
File nameBPseqHgeneTgeneHchrHbpTchrTbpAAlen
7777REGPGTDQTEAEAPIRF7CARS2chr11614478chr13111293936823

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of IRF7-CARS2

check buttonVirtual screening between 25 HLAs (from PDB) and FusionNeoAntigens
* We used Glide to predict the interaction between HLAs and neoantigens.
HLA allelePDB IDFile nameBPseqDocking scoreGlide score
HLA-B14:023BVN7777REGPGTDQTEAEAP-7.9962-8.1096
HLA-B14:023BVN7777REGPGTDQTEAEAP-5.70842-6.74372
HLA-B52:013W397777REGPGTDQTEAEAP-6.83737-6.95077
HLA-B52:013W397777REGPGTDQTEAEAP-4.4836-5.5189
HLA-A11:014UQ27777REGPGTDQTEAEAP-10.0067-10.1201
HLA-A11:014UQ27777REGPGTDQTEAEAP-9.03915-10.0745
HLA-A24:025HGA7777REGPGTDQTEAEAP-6.56204-6.67544
HLA-A24:025HGA7777REGPGTDQTEAEAP-5.42271-6.45801
HLA-B44:053DX87777REGPGTDQTEAEAP-7.85648-8.89178
HLA-B44:053DX87777REGPGTDQTEAEAP-5.3978-5.5112
HLA-A02:016TDR7777REGPGTDQTEAEAP-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of IRF7-CARS2

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptide sequenceFusionNeoAntigen RNA sequence
IRF7-CARS2chr11614478chr13111293936617REGPGTDQTEAGCAGCTGTCCCACCACCACAGCCACGTGGGAAC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence

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Information of the samples that have these potential fusion neoantigens of IRF7-CARS2

check button These samples were reported as having these fusion breakpoints. For individual breakpoints, we checked the open reading frames considering multiple gene isoforms and chose the in-frame fusion genes only. Then, we made fusion protein sequences and predicted the fusion neoantigens. These fusion-positive samples may have these potential fusion neoantigens.
Cancer typeFusion geneHchrHbpHenstTchrTbpTenstSample
N/AIRF7-CARS2chr11614478ENST00000397570chr13111293936ENST00000257347BE843753

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Potential target of CAR-T therapy development for IRF7-CARS2

check button Predicted 3D structure. We used RoseTTAFold.

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, to provide the retention of the transmembrane domain, we only show the protein feature retention information of those transmembrane features


* Minus value of BPloci means that the break point is located before the CDS.
- In-frame and retained 'Transmembrane'.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

check button Subcellular localization prediction of the transmembrane domain retained fusion proteins
* We used DeepLoc 1.0. The order of the X-axis of the barplot is as follows: Entry_ID, Localization, Type, Nucleus, Cytoplasm, Extracellular, Mitochondrion, Cell_membrane, Endoplasmic_reticulum, Plastid, Golgi.apparatus, Lysosome.Vacuole, Peroxisome. Y-axis is the output score of DeepLoc. Clicking the image will open a new tab with a large image.
HgeneHchrHbpHenstTgeneTchrTbpTenstDeepLoc result

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Related Drugs to IRF7-CARS2

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 IRF7-CARS2

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