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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:LONP2-HIRA

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: LONP2-HIRA
FusionPDB ID: 49433
FusionGDB2.0 ID: 49433
HgeneTgene
Gene symbol

LONP2

HIRA

Gene ID

83752

7290

Gene namelon peptidase 2, peroxisomalhistone cell cycle regulator
SynonymsLONP|LONPL|PLON|PSLONDGCR1|TUP1|TUPLE1
Cytomap

16q12.1

22q11.21

Type of geneprotein-codingprotein-coding
Descriptionlon protease homolog 2, peroxisomallon protease 2lon protease-like protein 2peroxisomal LON protease likeperoxisomal Lon protease homolog 2protein HIRADiGeorge critical region gene 1HIR histone cell cycle regulation defective homolog ATUP1-like enhancer of split protein 1histone regulator A
Modification date2020031320200313
UniProtAcc

Q86WA8

Main function of 5'-partner protein: FUNCTION: ATP-dependent serine protease that mediates the selective degradation of misfolded and unassembled polypeptides in the peroxisomal matrix. Necessary for type 2 peroxisome targeting signal (PTS2)-containing protein processing and facilitates peroxisome matrix protein import (By similarity). May indirectly regulate peroxisomal fatty acid beta-oxidation through degradation of the self-processed forms of TYSND1. {ECO:0000255|HAMAP-Rule:MF_03121, ECO:0000269|PubMed:22002062}.

P54198

Main function of 5'-partner protein: FUNCTION: Cooperates with ASF1A to promote replication-independent chromatin assembly. Required for the periodic repression of histone gene transcription during the cell cycle. Required for the formation of senescence-associated heterochromatin foci (SAHF) and efficient senescence-associated cell cycle exit. {ECO:0000269|PubMed:12370293, ECO:0000269|PubMed:14718166, ECO:0000269|PubMed:15621527}.
Ensembl transtripts involved in fusion geneENST idsENST00000285737, ENST00000535754, 
ENST00000564259, 
ENST00000464189, 
ENST00000541063, ENST00000546308, 
ENST00000263208, ENST00000340170, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score10 X 9 X 5=4507 X 6 X 4=168
# samples 117
** MAII scorelog2(11/450*10)=-2.03242147769238
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(7/168*10)=-1.26303440583379
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: LONP2 [Title/Abstract] AND HIRA [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: LONP2 [Title/Abstract] AND HIRA [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)LONP2(48337216)-HIRA(19398301), # samples:3
Anticipated loss of major functional domain due to fusion event.LONP2-HIRA 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.
LONP2-HIRA 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.
LONP2-HIRA 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.
LONP2-HIRA 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
TgeneHIRA

GO:0006336

DNA replication-independent nucleosome assembly

14718166



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/chr16:48337216/chr22:19398301)
- 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 LONP2 (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 HIRA (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)
ENST00000285737LONP2chr1648337216+ENST00000340170HIRAchr2219398301-502618889342831396
ENST00000285737LONP2chr1648337216+ENST00000263208HIRAchr2219398301-564718889349041603
ENST00000535754LONP2chr1648337216+ENST00000340170HIRAchr2219398301-485717195641141352
ENST00000535754LONP2chr1648337216+ENST00000263208HIRAchr2219398301-547817195647351559

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
ENST00000285737ENST00000340170LONP2chr1648337216+HIRAchr2219398301-0.0023645370.9976355
ENST00000285737ENST00000263208LONP2chr1648337216+HIRAchr2219398301-0.0014079770.99859196
ENST00000535754ENST00000340170LONP2chr1648337216+HIRAchr2219398301-0.0023257770.99767417
ENST00000535754ENST00000263208LONP2chr1648337216+HIRAchr2219398301-0.001417840.9985821

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 LONP2-HIRA

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
LONP2chr1648337216HIRAchr22193983011719554EAKLDRSDVTEREGKPIFSVDIHPDG
LONP2chr1648337216HIRAchr22193983011888598EAKLDRSDVTEREGKPIFSVDIHPDG

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Potential FusionNeoAntigen Information of LONP2-HIRA 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.
LONP2-HIRA_48337216_19398301.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)
LONP2-HIRAchr1648337216chr22193983011888HLA-B08:09EGKPIFSV0.99640.62191220
LONP2-HIRAchr1648337216chr22193983011888HLA-B45:01REGKPIFSV0.99820.85121120
LONP2-HIRAchr1648337216chr22193983011888HLA-B50:02REGKPIFSV0.9970.56391120
LONP2-HIRAchr1648337216chr22193983011888HLA-B13:02REGKPIFSV0.99530.64391120
LONP2-HIRAchr1648337216chr22193983011888HLA-B13:01REGKPIFSV0.98760.95431120
LONP2-HIRAchr1648337216chr22193983011888HLA-B18:01TEREGKPIF0.96960.7456918
LONP2-HIRAchr1648337216chr22193983011888HLA-B44:03TEREGKPIF0.96240.8499918
LONP2-HIRAchr1648337216chr22193983011888HLA-B47:01REGKPIFSV0.89380.5891120
LONP2-HIRAchr1648337216chr22193983011888HLA-B41:01REGKPIFSV0.69340.85961120
LONP2-HIRAchr1648337216chr22193983011888HLA-B50:01REGKPIFSV0.35060.66381120
LONP2-HIRAchr1648337216chr22193983011888HLA-B39:13REGKPIFSV0.28740.93761120
LONP2-HIRAchr1648337216chr22193983011888HLA-B15:03TEREGKPIF0.07670.7108918
LONP2-HIRAchr1648337216chr22193983011888HLA-B39:13TEREGKPIF0.04720.8423918
LONP2-HIRAchr1648337216chr22193983011888HLA-B52:01REGKPIFSV0.01030.81151120
LONP2-HIRAchr1648337216chr22193983011888HLA-B40:06REGKPIFSV0.99970.7261120
LONP2-HIRAchr1648337216chr22193983011888HLA-B39:08REGKPIFSV0.53670.79471120
LONP2-HIRAchr1648337216chr22193983011888HLA-B39:08TEREGKPIF0.30490.6888918
LONP2-HIRAchr1648337216chr22193983011888HLA-B73:01EREGKPIFSV0.97150.83891020
LONP2-HIRAchr1648337216chr22193983011888HLA-B51:21EGKPIFSV0.99960.50841220
LONP2-HIRAchr1648337216chr22193983011888HLA-B40:04REGKPIFSV0.99810.741120
LONP2-HIRAchr1648337216chr22193983011888HLA-B18:04TEREGKPIF0.97410.7526918
LONP2-HIRAchr1648337216chr22193983011888HLA-B18:07TEREGKPIF0.9740.6859918
LONP2-HIRAchr1648337216chr22193983011888HLA-B18:05TEREGKPIF0.96960.7456918
LONP2-HIRAchr1648337216chr22193983011888HLA-B18:08TEREGKPIF0.96780.7774918
LONP2-HIRAchr1648337216chr22193983011888HLA-B18:06TEREGKPIF0.96620.7749918
LONP2-HIRAchr1648337216chr22193983011888HLA-B44:26TEREGKPIF0.96240.8499918
LONP2-HIRAchr1648337216chr22193983011888HLA-B44:13TEREGKPIF0.96240.8499918
LONP2-HIRAchr1648337216chr22193983011888HLA-B44:07TEREGKPIF0.96240.8499918
LONP2-HIRAchr1648337216chr22193983011888HLA-B40:04TEREGKPIF0.96220.6643918
LONP2-HIRAchr1648337216chr22193983011888HLA-B18:03TEREGKPIF0.87440.7362918
LONP2-HIRAchr1648337216chr22193983011888HLA-B18:11TEREGKPIF0.76070.7022918
LONP2-HIRAchr1648337216chr22193983011888HLA-B41:03REGKPIFSV0.73450.57571120
LONP2-HIRAchr1648337216chr22193983011888HLA-B15:12TEREGKPIF0.36370.8269918
LONP2-HIRAchr1648337216chr22193983011888HLA-B50:04REGKPIFSV0.35060.66381120
LONP2-HIRAchr1648337216chr22193983011888HLA-B50:05REGKPIFSV0.35060.66381120
LONP2-HIRAchr1648337216chr22193983011888HLA-B39:02REGKPIFSV0.30660.93071120
LONP2-HIRAchr1648337216chr22193983011888HLA-B15:53TEREGKPIF0.25990.8494918
LONP2-HIRAchr1648337216chr22193983011888HLA-B15:54TEREGKPIF0.08960.8045918
LONP2-HIRAchr1648337216chr22193983011888HLA-B39:02TEREGKPIF0.05710.8468918
LONP2-HIRAchr1648337216chr22193983011888HLA-B48:02TEREGKPIF0.04860.6961918
LONP2-HIRAchr1648337216chr22193983011888HLA-B15:68TEREGKPIF0.04570.5491918
LONP2-HIRAchr1648337216chr22193983011888HLA-B15:53VTEREGKPIF0.9580.8459818
LONP2-HIRAchr1648337216chr22193983011888HLA-B18:03DVTEREGKPIF0.9170.5316718

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Potential FusionNeoAntigen Information of LONP2-HIRA 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.
LONP2-HIRA_48337216_19398301.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)
LONP2-HIRAchr1648337216chr22193983011888DRB1-0411REGKPIFSVDIHPDG1126
LONP2-HIRAchr1648337216chr22193983011888DRB1-0417REGKPIFSVDIHPDG1126
LONP2-HIRAchr1648337216chr22193983011888DRB1-0467REGKPIFSVDIHPDG1126
LONP2-HIRAchr1648337216chr22193983011888DRB1-0491REGKPIFSVDIHPDG1126
LONP2-HIRAchr1648337216chr22193983011888DRB1-1457REGKPIFSVDIHPDG1126

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Fusion breakpoint peptide structures of LONP2-HIRA

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
8492SDVTEREGKPIFSVLONP2HIRAchr1648337216chr22193983011888

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of LONP2-HIRA

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-B14:023BVN8492SDVTEREGKPIFSV-7.9962-8.1096
HLA-B14:023BVN8492SDVTEREGKPIFSV-5.70842-6.74372
HLA-B52:013W398492SDVTEREGKPIFSV-6.83737-6.95077
HLA-B52:013W398492SDVTEREGKPIFSV-4.4836-5.5189
HLA-A11:014UQ28492SDVTEREGKPIFSV-10.0067-10.1201
HLA-A11:014UQ28492SDVTEREGKPIFSV-9.03915-10.0745
HLA-A24:025HGA8492SDVTEREGKPIFSV-6.56204-6.67544
HLA-A24:025HGA8492SDVTEREGKPIFSV-5.42271-6.45801
HLA-B44:053DX88492SDVTEREGKPIFSV-7.85648-8.89178
HLA-B44:053DX88492SDVTEREGKPIFSV-5.3978-5.5112
HLA-A02:016TDR8492SDVTEREGKPIFSV-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of LONP2-HIRA

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
LONP2-HIRAchr1648337216chr22193983011020EREGKPIFSVAGAGAGAAGGCAAGCCGATTTTTTCAGTTG
LONP2-HIRAchr1648337216chr22193983011120REGKPIFSVGAGAAGGCAAGCCGATTTTTTCAGTTG
LONP2-HIRAchr1648337216chr22193983011220EGKPIFSVAAGGCAAGCCGATTTTTTCAGTTG
LONP2-HIRAchr1648337216chr2219398301718DVTEREGKPIFATGTGACTGAGAGAGAAGGCAAGCCGATTTTTT
LONP2-HIRAchr1648337216chr2219398301818VTEREGKPIFTGACTGAGAGAGAAGGCAAGCCGATTTTTT
LONP2-HIRAchr1648337216chr2219398301918TEREGKPIFCTGAGAGAGAAGGCAAGCCGATTTTTT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
LONP2-HIRAchr1648337216chr22193983011126REGKPIFSVDIHPDGGAGAAGGCAAGCCGATTTTTTCAGTTGATATTCACCCTGACGGGA

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Information of the samples that have these potential fusion neoantigens of LONP2-HIRA

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
LUADLONP2-HIRAchr1648337216ENST00000285737chr2219398301ENST00000263208TCGA-44-4112-01A

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Potential target of CAR-T therapy development for LONP2-HIRA

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 LONP2-HIRA

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 LONP2-HIRA

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