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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:IL1R1-IL1R2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: IL1R1-IL1R2
FusionPDB ID: 39461
FusionGDB2.0 ID: 39461
HgeneTgene
Gene symbol

IL1R1

IL1R2

Gene ID

3554

7850

Gene nameinterleukin 1 receptor type 1interleukin 1 receptor type 2
SynonymsCD121A|D2S1473|IL-1R-alpha|IL1R|IL1RA|P80CD121b|CDw121b|IL-1R-2|IL-1RT-2|IL-1RT2|IL1R2c|IL1RB
Cytomap

2q11.2-q12.1

2q11.2

Type of geneprotein-codingprotein-coding
Descriptioninterleukin-1 receptor type 1CD121 antigen-like family member AIL-1R-1IL-1RT-1IL-1RT1interleukin 1 receptor alpha, type Iinterleukin-1 receptor alphainterleukin-1 receptor type Iinterleukin-1 receptor type 2CD121 antigen-like family member BIL-1 type II receptorIL-1R-betaantigen CDw121binterleukin 1 receptor type II variant 3interleukin-1 receptor betainterleukin-1 receptor type IItype II interleukin-1 receptor, beta
Modification date2020031320200313
UniProtAcc

P14778

Main function of 5'-partner protein: FUNCTION: Receptor for IL1A, IL1B and IL1RN. After binding to interleukin-1 associates with the coreceptor IL1RAP to form the high affinity interleukin-1 receptor complex which mediates interleukin-1-dependent activation of NF-kappa-B, MAPK and other pathways. Signaling involves the recruitment of adapter molecules such as TOLLIP, MYD88, and IRAK1 or IRAK2 via the respective TIR domains of the receptor/coreceptor subunits. Binds ligands with comparable affinity and binding of antagonist IL1RN prevents association with IL1RAP to form a signaling complex. Involved in IL1B-mediated costimulation of IFNG production from T-helper 1 (Th1) cells (PubMed:10653850). {ECO:0000269|PubMed:10653850, ECO:0000269|PubMed:10671496}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000233946, ENST00000409288, 
ENST00000409329, ENST00000409929, 
ENST00000410023, ENST00000424272, 
ENST00000409589, 
ENST00000485335, 
ENST00000332549, ENST00000393414, 
ENST00000441002, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score4 X 6 X 6=1445 X 6 X 6=180
# samples 77
** MAII scorelog2(7/144*10)=-1.04064198449735
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(7/180*10)=-1.36257007938471
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: IL1R1 [Title/Abstract] AND IL1R2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: IL1R1 [Title/Abstract] AND IL1R2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)IL1R1(102796334)-IL1R2(102638649), # samples:1
IL1R1(102782741)-IL1R2(102626024), # samples:1
IL1R1(102770477)-IL1R2(102632333), # samples:1
Anticipated loss of major functional domain due to fusion event.IL1R1-IL1R2 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.
IL1R1-IL1R2 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.
IL1R1-IL1R2 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.
IL1R1-IL1R2 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.
* 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
HgeneIL1R1

GO:0032729

positive regulation of interferon-gamma production

10653850

HgeneIL1R1

GO:0070498

interleukin-1-mediated signaling pathway

10383454

HgeneIL1R1

GO:0070555

response to interleukin-1

10383454

HgeneIL1R1

GO:2000556

positive regulation of T-helper 1 cell cytokine production

10653850



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/chr2:102796334/chr2:102638649)
- 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 IL1R1 (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 IL1R2 (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)
ENST00000410023IL1R1chr2102796334-ENST00000332549IL1R2chr2102638649+580451432762027583
ENST00000410023IL1R1chr2102796334-ENST00000393414IL1R2chr2102638649+567751432762027583
ENST00000410023IL1R1chr2102796334-ENST00000441002IL1R2chr2102638649+550051432762027583
ENST00000233946IL1R1chr2102796334-ENST00000332549IL1R2chr2102638649+55684907401791583
ENST00000233946IL1R1chr2102796334-ENST00000393414IL1R2chr2102638649+54414907401791583
ENST00000233946IL1R1chr2102796334-ENST00000441002IL1R2chr2102638649+52644907401791583
ENST00000424272IL1R1chr2102782741-ENST00000332549IL1R2chr2102626024+21788961992025608
ENST00000424272IL1R1chr2102782741-ENST00000393414IL1R2chr2102626024+20518961992025608
ENST00000424272IL1R1chr2102782741-ENST00000441002IL1R2chr2102626024+18748961991719506
ENST00000409929IL1R1chr2102782741-ENST00000332549IL1R2chr2102626024+21788961992025608
ENST00000409929IL1R1chr2102782741-ENST00000393414IL1R2chr2102626024+20518961992025608
ENST00000409929IL1R1chr2102782741-ENST00000441002IL1R2chr2102626024+18748961991719506
ENST00000409329IL1R1chr2102782741-ENST00000332549IL1R2chr2102626024+232410423452171608
ENST00000409329IL1R1chr2102782741-ENST00000393414IL1R2chr2102626024+219710423452171608
ENST00000409329IL1R1chr2102782741-ENST00000441002IL1R2chr2102626024+202010423451865506
ENST00000409288IL1R1chr2102782741-ENST00000332549IL1R2chr2102626024+22559732762102608
ENST00000409288IL1R1chr2102782741-ENST00000393414IL1R2chr2102626024+21289732762102608
ENST00000409288IL1R1chr2102782741-ENST00000441002IL1R2chr2102626024+19519732761796506
ENST00000410023IL1R1chr2102782741-ENST00000332549IL1R2chr2102626024+22559732762102608
ENST00000410023IL1R1chr2102782741-ENST00000393414IL1R2chr2102626024+21289732762102608
ENST00000410023IL1R1chr2102782741-ENST00000441002IL1R2chr2102626024+19519732761796506
ENST00000233946IL1R1chr2102782741-ENST00000332549IL1R2chr2102626024+2019737401866608
ENST00000233946IL1R1chr2102782741-ENST00000393414IL1R2chr2102626024+1892737401866608
ENST00000233946IL1R1chr2102782741-ENST00000441002IL1R2chr2102626024+1715737401560506

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
ENST00000410023ENST00000332549IL1R1chr2102796334-IL1R2chr2102638649+0.0002351670.99976486
ENST00000410023ENST00000393414IL1R1chr2102796334-IL1R2chr2102638649+0.0002497510.9997502
ENST00000410023ENST00000441002IL1R1chr2102796334-IL1R2chr2102638649+0.0002314570.99976856
ENST00000233946ENST00000332549IL1R1chr2102796334-IL1R2chr2102638649+0.0002148350.9997851
ENST00000233946ENST00000393414IL1R1chr2102796334-IL1R2chr2102638649+0.000229330.9997707
ENST00000233946ENST00000441002IL1R1chr2102796334-IL1R2chr2102638649+0.0002080290.99979204
ENST00000424272ENST00000332549IL1R1chr2102782741-IL1R2chr2102626024+0.0003636990.9996363
ENST00000424272ENST00000393414IL1R1chr2102782741-IL1R2chr2102626024+0.0004904770.9995096
ENST00000424272ENST00000441002IL1R1chr2102782741-IL1R2chr2102626024+0.0004256620.99957436
ENST00000409929ENST00000332549IL1R1chr2102782741-IL1R2chr2102626024+0.0003636990.9996363
ENST00000409929ENST00000393414IL1R1chr2102782741-IL1R2chr2102626024+0.0004904770.9995096
ENST00000409929ENST00000441002IL1R1chr2102782741-IL1R2chr2102626024+0.0004256620.99957436
ENST00000409329ENST00000332549IL1R1chr2102782741-IL1R2chr2102626024+0.0004587190.9995413
ENST00000409329ENST00000393414IL1R1chr2102782741-IL1R2chr2102626024+0.000641360.9993586
ENST00000409329ENST00000441002IL1R1chr2102782741-IL1R2chr2102626024+0.0005662650.9994337
ENST00000409288ENST00000332549IL1R1chr2102782741-IL1R2chr2102626024+0.0006327930.9993672
ENST00000409288ENST00000393414IL1R1chr2102782741-IL1R2chr2102626024+0.0008432850.9991567
ENST00000409288ENST00000441002IL1R1chr2102782741-IL1R2chr2102626024+0.0008675070.9991326
ENST00000410023ENST00000332549IL1R1chr2102782741-IL1R2chr2102626024+0.0006327930.9993672
ENST00000410023ENST00000393414IL1R1chr2102782741-IL1R2chr2102626024+0.0008432850.9991567
ENST00000410023ENST00000441002IL1R1chr2102782741-IL1R2chr2102626024+0.0008675070.9991326
ENST00000233946ENST00000332549IL1R1chr2102782741-IL1R2chr2102626024+0.0003444890.9996555
ENST00000233946ENST00000393414IL1R1chr2102782741-IL1R2chr2102626024+0.0004898870.99951017
ENST00000233946ENST00000441002IL1R1chr2102782741-IL1R2chr2102626024+0.0004259680.999574

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 IL1R1-IL1R2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
IL1R1chr2102782741IL1R2chr21026260241042232QYPITRVIEFITLGAARSCRFRGRHY
IL1R1chr2102782741IL1R2chr2102626024737232QYPITRVIEFITLGAARSCRFRGRHY
IL1R1chr2102782741IL1R2chr2102626024896232QYPITRVIEFITLGAARSCRFRGRHY
IL1R1chr2102782741IL1R2chr2102626024973232QYPITRVIEFITLGAARSCRFRGRHY

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Potential FusionNeoAntigen Information of IL1R1-IL1R2 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.
IL1R1-IL1R2_102782741_102626024.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)
IL1R1-IL1R2chr2102782741chr2102626024737HLA-B50:01IEFITLGA0.94480.6529715
IL1R1-IL1R2chr2102782741chr2102626024737HLA-A33:05EFITLGAAR0.98830.594817
IL1R1-IL1R2chr2102782741chr2102626024737HLA-A33:01EFITLGAAR0.98830.594817
IL1R1-IL1R2chr2102782741chr2102626024737HLA-B50:01IEFITLGAA0.12480.6326716
IL1R1-IL1R2chr2102782741chr2102626024737HLA-B57:01ITLGAARSCRF0.99940.96581021
IL1R1-IL1R2chr2102782741chr2102626024737HLA-B15:17ITLGAARSCRF0.99570.81141021
IL1R1-IL1R2chr2102782741chr2102626024737HLA-B57:03ITLGAARSCRF0.99540.97221021
IL1R1-IL1R2chr2102782741chr2102626024737HLA-B50:04IEFITLGA0.94480.6529715
IL1R1-IL1R2chr2102782741chr2102626024737HLA-B50:05IEFITLGA0.94480.6529715
IL1R1-IL1R2chr2102782741chr2102626024737HLA-B50:05IEFITLGAA0.12480.6326716
IL1R1-IL1R2chr2102782741chr2102626024737HLA-B50:04IEFITLGAA0.12480.6326716
IL1R1-IL1R2chr2102782741chr2102626024737HLA-B57:10ITLGAARSCRF0.99940.96581021

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Potential FusionNeoAntigen Information of IL1R1-IL1R2 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.
IL1R1-IL1R2_102782741_102626024.msa

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)
IL1R1-IL1R2chr2102782741chr2102626024737DRB1-1001RVIEFITLGAARSCR520
IL1R1-IL1R2chr2102782741chr2102626024737DRB1-1003RVIEFITLGAARSCR520

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Fusion breakpoint peptide structures of IL1R1-IL1R2

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
10008VIEFITLGAARSCRIL1R1IL1R2chr2102782741chr2102626024737

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of IL1R1-IL1R2

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-B14:023BVN10008VIEFITLGAARSCR-7.9962-8.1096
HLA-B14:023BVN10008VIEFITLGAARSCR-5.70842-6.74372
HLA-B52:013W3910008VIEFITLGAARSCR-6.83737-6.95077
HLA-B52:013W3910008VIEFITLGAARSCR-4.4836-5.5189
HLA-A11:014UQ210008VIEFITLGAARSCR-10.0067-10.1201
HLA-A11:014UQ210008VIEFITLGAARSCR-9.03915-10.0745
HLA-A24:025HGA10008VIEFITLGAARSCR-6.56204-6.67544
HLA-A24:025HGA10008VIEFITLGAARSCR-5.42271-6.45801
HLA-B44:053DX810008VIEFITLGAARSCR-7.85648-8.89178
HLA-B44:053DX810008VIEFITLGAARSCR-5.3978-5.5112
HLA-B35:011A1N10008VIEFITLGAARSCR-6.27422-6.38762
HLA-B35:011A1N10008VIEFITLGAARSCR-5.27424-6.30954
HLA-A02:016TDR10008VIEFITLGAARSCR-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of IL1R1-IL1R2

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
IL1R1-IL1R2chr2102782741chr21026260241021ITLGAARSCRFTTACTCTAGGGGCTGCCAGAAGCTGCCGGTTTC
IL1R1-IL1R2chr2102782741chr2102626024715IEFITLGATAGAATTTATTACTCTAGGGGCTG
IL1R1-IL1R2chr2102782741chr2102626024716IEFITLGAATAGAATTTATTACTCTAGGGGCTGCCA
IL1R1-IL1R2chr2102782741chr2102626024817EFITLGAARAATTTATTACTCTAGGGGCTGCCAGAA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
IL1R1-IL1R2chr2102782741chr2102626024520RVIEFITLGAARSCRGGGTAATAGAATTTATTACTCTAGGGGCTGCCAGAAGCTGCCGGT

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Information of the samples that have these potential fusion neoantigens of IL1R1-IL1R2

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
BRCAIL1R1-IL1R2chr2102782741ENST00000233946chr2102626024ENST00000332549TCGA-BH-A203-01A

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Potential target of CAR-T therapy development for IL1R1-IL1R2

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
HgeneIL1R1chr2:102796334chr2:102638649ENST00000233946-1111337_3561608570.0TransmembraneHelical
HgeneIL1R1chr2:102796334chr2:102638649ENST00000410023-1212337_3561608570.0TransmembraneHelical
TgeneIL1R2chr2:102782741chr2:102626024ENST0000033254919344_3690399.0TransmembraneHelical
TgeneIL1R2chr2:102782741chr2:102626024ENST0000039341419344_3690399.0TransmembraneHelical
TgeneIL1R2chr2:102782741chr2:102626024ENST0000044100206344_3690297.0TransmembraneHelical
TgeneIL1R2chr2:102796334chr2:102638649ENST0000033254949344_3690399.0TransmembraneHelical
TgeneIL1R2chr2:102796334chr2:102638649ENST0000039341449344_3690399.0TransmembraneHelical
TgeneIL1R2chr2:102796334chr2:102638649ENST0000044100236344_3690297.0TransmembraneHelical

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 IL1R1-IL1R2

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 IL1R1-IL1R2

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