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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:PPP1R12A-IRAK3

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PPP1R12A-IRAK3
FusionPDB ID: 67744
FusionGDB2.0 ID: 67744
HgeneTgene
Gene symbol

PPP1R12A

IRAK3

Gene ID

4659

11213

Gene nameprotein phosphatase 1 regulatory subunit 12Ainterleukin 1 receptor associated kinase 3
SynonymsGUBS|M130|MBS|MYPT1ASRT5|IRAKM
Cytomap

12q21.2-q21.31

12q14.3

Type of geneprotein-codingprotein-coding
Descriptionprotein phosphatase 1 regulatory subunit 12Amyosin binding subunitmyosin phosphatase, target subunit 1myosin phosphatase-targeting subunit 1protein phosphatase 1, regulatory (inhibitor) subunit 12Aprotein phosphatase myosin-binding subunitinterleukin-1 receptor-associated kinase 3IL-1 receptor-associated kinase M
Modification date2020032820200313
UniProtAcc.

Q9Y616

Main function of 5'-partner protein: FUNCTION: Inhibits dissociation of IRAK1 and IRAK4 from the Toll-like receptor signaling complex by either inhibiting the phosphorylation of IRAK1 and IRAK4 or stabilizing the receptor complex. {ECO:0000250|UniProtKB:Q8K4B2, ECO:0000269|PubMed:10383454}.
Ensembl transtripts involved in fusion geneENST idsENST00000261207, ENST00000437004, 
ENST00000450142, ENST00000546369, 
ENST00000550107, 
ENST00000457197, 
ENST00000545837, ENST00000261233, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score25 X 22 X 11=60504 X 4 X 4=64
# samples 285
** MAII scorelog2(28/6050*10)=-4.43343641010435
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(5/64*10)=-0.356143810225275
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: PPP1R12A [Title/Abstract] AND IRAK3 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PPP1R12A [Title/Abstract] AND IRAK3 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PPP1R12A(80214553)-IRAK3(66610950), # samples:2
Anticipated loss of major functional domain due to fusion event.PPP1R12A-IRAK3 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.
PPP1R12A-IRAK3 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.
PPP1R12A-IRAK3 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.
PPP1R12A-IRAK3 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.
PPP1R12A-IRAK3 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
PPP1R12A-IRAK3 seems lost the major protein functional domain in Tgene partner, which is a kinase 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
HgenePPP1R12A

GO:0030155

regulation of cell adhesion

20354225

HgenePPP1R12A

GO:0035507

regulation of myosin-light-chain-phosphatase activity

20354225

HgenePPP1R12A

GO:0043086

negative regulation of catalytic activity

19245366

HgenePPP1R12A

GO:0045944

positive regulation of transcription by RNA polymerase II

19245366

TgeneIRAK3

GO:0006468

protein phosphorylation

10383454



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/chr12:80214553/chr12:66610950)
- 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 PPP1R12A (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 IRAK3 (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)
ENST00000546369PPP1R12Achr1280214553-ENST00000261233IRAK3chr1266610950+86469928512194447

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
ENST00000546369ENST00000261233PPP1R12Achr1280214553-IRAK3chr1266610950+0.0016841460.99831593

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 PPP1R12A-IRAK3

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
PPP1R12Achr1280214553IRAK3chr126661095099247KMRKMTRNQKLKQEKKMQCKKHWKRF

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Potential FusionNeoAntigen Information of PPP1R12A-IRAK3 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.
PPP1R12A-IRAK3_80214553_66610950.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)
PPP1R12A-IRAK3chr1280214553chr1266610950992HLA-B44:02QEKKMQCKKHW0.99710.54131223
PPP1R12A-IRAK3chr1280214553chr1266610950992HLA-B44:03QEKKMQCKKHW0.99650.99291223
PPP1R12A-IRAK3chr1280214553chr1266610950992HLA-B44:05QEKKMQCKKHW0.98670.67571223
PPP1R12A-IRAK3chr1280214553chr1266610950992HLA-B44:08QEKKMQCKKHW0.99770.56861223
PPP1R12A-IRAK3chr1280214553chr1266610950992HLA-B44:04QEKKMQCKKHW0.99370.64961223
PPP1R12A-IRAK3chr1280214553chr1266610950992HLA-B44:22QEKKMQCKKHW0.99710.54131223
PPP1R12A-IRAK3chr1280214553chr1266610950992HLA-B44:07QEKKMQCKKHW0.99650.99291223
PPP1R12A-IRAK3chr1280214553chr1266610950992HLA-B44:26QEKKMQCKKHW0.99650.99291223
PPP1R12A-IRAK3chr1280214553chr1266610950992HLA-B44:13QEKKMQCKKHW0.99650.99291223

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Potential FusionNeoAntigen Information of PPP1R12A-IRAK3 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.
PPP1R12A-IRAK3_80214553_66610950.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)
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1103MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1104MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1106MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1135MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1138MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1141MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1141KMRKMTRNQKLKQEK015
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1143MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1144MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1146MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1147MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1148MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1150MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1153MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1154MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1156MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1158MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1159MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1160MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1163MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1176MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1177MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1178MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1184MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1185MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1186MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1188MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1308MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1311MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1316MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1319MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1324MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1336MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1342MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1353MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1361MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1370MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1372MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1376MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1376KMRKMTRNQKLKQEK015
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1384MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1385MRKMTRNQKLKQEKK116
PPP1R12A-IRAK3chr1280214553chr1266610950992DRB1-1396MRKMTRNQKLKQEKK116

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Fusion breakpoint peptide structures of PPP1R12A-IRAK3

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
8060RNQKLKQEKKMQCKPPP1R12AIRAK3chr1280214553chr1266610950992

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PPP1R12A-IRAK3

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-B14:023BVN8060RNQKLKQEKKMQCK-7.15543-7.26883
HLA-B14:023BVN8060RNQKLKQEKKMQCK-4.77435-5.80965
HLA-B52:013W398060RNQKLKQEKKMQCK-6.80875-6.92215
HLA-B52:013W398060RNQKLKQEKKMQCK-4.20386-5.23916
HLA-A11:014UQ28060RNQKLKQEKKMQCK-7.5194-8.5547
HLA-A11:014UQ28060RNQKLKQEKKMQCK-6.9601-7.0735
HLA-A24:025HGA8060RNQKLKQEKKMQCK-7.52403-7.63743
HLA-A24:025HGA8060RNQKLKQEKKMQCK-5.82433-6.85963
HLA-B27:056PYJ8060RNQKLKQEKKMQCK-3.28285-4.31815
HLA-B44:053DX88060RNQKLKQEKKMQCK-5.91172-6.94702
HLA-B44:053DX88060RNQKLKQEKKMQCK-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of PPP1R12A-IRAK3

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
PPP1R12A-IRAK3chr1280214553chr12666109501223QEKKMQCKKHWCAGGAGAAAAAAATGCAGTGTAAGAAGCATTGG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
PPP1R12A-IRAK3chr1280214553chr1266610950015KMRKMTRNQKLKQEKAAGATGAGGAAGATGACTCGGAATCAGAAGCTGAAACAGGAGAAA
PPP1R12A-IRAK3chr1280214553chr1266610950116MRKMTRNQKLKQEKKATGAGGAAGATGACTCGGAATCAGAAGCTGAAACAGGAGAAAAAA

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Information of the samples that have these potential fusion neoantigens of PPP1R12A-IRAK3

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
ESCAPPP1R12A-IRAK3chr1280214553ENST00000546369chr1266610950ENST00000261233TCGA-L5-A8NH

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Potential target of CAR-T therapy development for PPP1R12A-IRAK3

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 PPP1R12A-IRAK3

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 PPP1R12A-IRAK3

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