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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:POLE-HMGCL

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: POLE-HMGCL
FusionPDB ID: 66934
FusionGDB2.0 ID: 66934
HgeneTgene
Gene symbol

POLE

HMGCL

Gene ID

5426

3155

Gene nameDNA polymerase epsilon, catalytic subunit3-hydroxy-3-methylglutaryl-CoA lyase
SynonymsCRCS12|FILS|IMAGEI|POLE1HL
Cytomap

12q24.33

1p36.11

Type of geneprotein-codingprotein-coding
DescriptionDNA polymerase epsilon catalytic subunit ADNA polymerase II subunit ADNA polymerase epsilon catalytic subunit proteinpolymerase (DNA directed), epsilon, catalytic subunitpolymerase (DNA) epsilon, catalytic subunithydroxymethylglutaryl-CoA lyase, mitochondrial3-hydroxy-3-methylglutarate-CoA lyase3-hydroxymethyl-3-methylglutaryl-CoA lyase3-hydroxymethyl-3-methylglutaryl-Coenzyme A lyaseHMG-CoA lyasehydroxymethylglutaricaciduriamitochondrial 3-hydroxy-3-methylg
Modification date2020031320200313
UniProtAcc.

Q8TB92

Main function of 5'-partner protein: FUNCTION: Non-mitochondrial 3-hydroxymethyl-3-methylglutaryl-CoA lyase that catalyzes a cation-dependent cleavage of (S)-3-hydroxy-3-methylglutaryl-CoA into acetyl-CoA and acetoacetate, a key step in ketogenesis, the products of which support energy production in nonhepatic animal tissues. {ECO:0000269|PubMed:22847177, ECO:0000269|PubMed:22865860}.
Ensembl transtripts involved in fusion geneENST idsENST00000320574, ENST00000535270, 
ENST00000434528, 
ENST00000374483, 
ENST00000509389, ENST00000374490, 
ENST00000436439, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score5 X 6 X 3=904 X 4 X 2=32
# samples 64
** MAII scorelog2(6/90*10)=-0.584962500721156
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(4/32*10)=0.321928094887362
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: POLE [Title/Abstract] AND HMGCL [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: POLE [Title/Abstract] AND HMGCL [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)POLE(133225513)-HMGCL(24147086), # samples:1
Anticipated loss of major functional domain due to fusion event.POLE-HMGCL 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.
POLE-HMGCL 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.
POLE-HMGCL 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.
POLE-HMGCL 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
HgenePOLE

GO:0006287

base-excision repair, gap-filling

10559260

TgeneHMGCL

GO:0006629

lipid metabolic process

8027038

TgeneHMGCL

GO:0046951

ketone body biosynthetic process

9200711|22847177|22865860



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/chr12:133225513/chr1:24147086)
- 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 POLE (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 HMGCL (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)
ENST00000320574POLEchr12133225513-ENST00000374490HMGCLchr124147086-568941934451101688
ENST00000320574POLEchr12133225513-ENST00000436439HMGCLchr124147086-547441934448971617
ENST00000535270POLEchr12133225513-ENST00000374490HMGCLchr124147086-557740811349981661
ENST00000535270POLEchr12133225513-ENST00000436439HMGCLchr124147086-536240811347851590

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
ENST00000320574ENST00000374490POLEchr12133225513-HMGCLchr124147086-0.0028379570.9971621
ENST00000320574ENST00000436439POLEchr12133225513-HMGCLchr124147086-0.0026975730.9973024
ENST00000535270ENST00000374490POLEchr12133225513-HMGCLchr124147086-0.0027429560.99725705
ENST00000535270ENST00000436439POLEchr12133225513-HMGCLchr124147086-0.002606550.9973935

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 POLE-HMGCL

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
POLEchr12133225513HMGCLchr12414708640811355QRVAKAEEGASYRKVSTSSMGTLPKR
POLEchr12133225513HMGCLchr12414708641931382QRVAKAEEGASYRKVSTSSMGTLPKR

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Potential FusionNeoAntigen Information of POLE-HMGCL 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.
POLE-HMGCL_133225513_24147086.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)
POLE-HMGCLchr12133225513chr1241470864193HLA-B27:04YRKVSTSSM0.99870.82521120
POLE-HMGCLchr12133225513chr1241470864193HLA-B27:05YRKVSTSSM0.99830.90861120
POLE-HMGCLchr12133225513chr1241470864193HLA-B45:01EEGASYRKV0.99690.7908615
POLE-HMGCLchr12133225513chr1241470864193HLA-B14:01YRKVSTSSM0.98750.72081120
POLE-HMGCLchr12133225513chr1241470864193HLA-B14:02YRKVSTSSM0.98750.72081120
POLE-HMGCLchr12133225513chr1241470864193HLA-B50:02EEGASYRKV0.9870.5545615
POLE-HMGCLchr12133225513chr1241470864193HLA-B39:01YRKVSTSSM0.97780.90171120
POLE-HMGCLchr12133225513chr1241470864193HLA-B44:03EEGASYRKV0.91130.9282615
POLE-HMGCLchr12133225513chr1241470864193HLA-B15:10YRKVSTSSM0.90850.63091120
POLE-HMGCLchr12133225513chr1241470864193HLA-A30:08ASYRKVSTS0.80440.7924918
POLE-HMGCLchr12133225513chr1241470864193HLA-B15:03YRKVSTSSM0.80370.76191120
POLE-HMGCLchr12133225513chr1241470864193HLA-B15:18YRKVSTSSM0.79420.73621120
POLE-HMGCLchr12133225513chr1241470864193HLA-B15:37YRKVSTSSM0.64750.62021120
POLE-HMGCLchr12133225513chr1241470864193HLA-B41:01AEEGASYRKV0.73560.9059515
POLE-HMGCLchr12133225513chr1241470864193HLA-C07:27YRKVSTSSM0.99380.94161120
POLE-HMGCLchr12133225513chr1241470864193HLA-C07:05YRKVSTSSM0.99320.96581120
POLE-HMGCLchr12133225513chr1241470864193HLA-C07:95YRKVSTSSM0.99220.64761120
POLE-HMGCLchr12133225513chr1241470864193HLA-C07:13YRKVSTSSM0.98930.89121120
POLE-HMGCLchr12133225513chr1241470864193HLA-C07:29YRKVSTSSM0.98760.92791120
POLE-HMGCLchr12133225513chr1241470864193HLA-B39:09YRKVSTSSM0.98130.62251120
POLE-HMGCLchr12133225513chr1241470864193HLA-B39:12YRKVSTSSM0.97690.90751120
POLE-HMGCLchr12133225513chr1241470864193HLA-C07:46YRKVSTSSM0.96320.86181120
POLE-HMGCLchr12133225513chr1241470864193HLA-C07:80YRKVSTSSM0.94380.93111120
POLE-HMGCLchr12133225513chr1241470864193HLA-C07:67YRKVSTSSM0.94380.93111120
POLE-HMGCLchr12133225513chr1241470864193HLA-C07:19YRKVSTSSM0.90930.6811120
POLE-HMGCLchr12133225513chr1241470864193HLA-C07:10YRKVSTSSM0.84910.96541120
POLE-HMGCLchr12133225513chr1241470864193HLA-B14:03YRKVSTSSM0.74890.82571120
POLE-HMGCLchr12133225513chr1241470864193HLA-C12:16YRKVSTSSM0.54130.95891120
POLE-HMGCLchr12133225513chr1241470864193HLA-B27:06YRKVSTSSM0.99910.8091120
POLE-HMGCLchr12133225513chr1241470864193HLA-B27:10YRKVSTSSM0.99860.90391120
POLE-HMGCLchr12133225513chr1241470864193HLA-B27:08YRKVSTSSM0.99850.83131120
POLE-HMGCLchr12133225513chr1241470864193HLA-B27:09YRKVSTSSM0.99740.86881120
POLE-HMGCLchr12133225513chr1241470864193HLA-C07:01YRKVSTSSM0.99510.61921120
POLE-HMGCLchr12133225513chr1241470864193HLA-C07:17YRKVSTSSM0.97640.9651120
POLE-HMGCLchr12133225513chr1241470864193HLA-C06:08YRKVSTSSM0.97640.99331120
POLE-HMGCLchr12133225513chr1241470864193HLA-B39:31YRKVSTSSM0.95680.90321120
POLE-HMGCLchr12133225513chr1241470864193HLA-C07:02YRKVSTSSM0.94380.93111120
POLE-HMGCLchr12133225513chr1241470864193HLA-B44:26EEGASYRKV0.91130.9282615
POLE-HMGCLchr12133225513chr1241470864193HLA-B44:13EEGASYRKV0.91130.9282615
POLE-HMGCLchr12133225513chr1241470864193HLA-B44:07EEGASYRKV0.91130.9282615
POLE-HMGCLchr12133225513chr1241470864193HLA-C07:22YRKVSTSSM0.90950.75431120
POLE-HMGCLchr12133225513chr1241470864193HLA-C07:04YRKVSTSSM0.85790.89581120
POLE-HMGCLchr12133225513chr1241470864193HLA-B15:68YRKVSTSSM0.77910.67611120
POLE-HMGCLchr12133225513chr1241470864193HLA-B15:09YRKVSTSSM0.65160.6811120
POLE-HMGCLchr12133225513chr1241470864193HLA-B15:54YRKVSTSSM0.62120.86011120
POLE-HMGCLchr12133225513chr1241470864193HLA-C03:67YRKVSTSSM0.56090.981120
POLE-HMGCLchr12133225513chr1241470864193HLA-A30:01SYRKVSTSS0.50150.85931019
POLE-HMGCLchr12133225513chr1241470864193HLA-C06:02YRKVSTSSM0.4430.9941120
POLE-HMGCLchr12133225513chr1241470864193HLA-C06:17YRKVSTSSM0.4430.9941120
POLE-HMGCLchr12133225513chr1241470864193HLA-C06:06YRKVSTSSM0.33580.98581120
POLE-HMGCLchr12133225513chr1241470864193HLA-C14:03SYRKVSTSSM0.91620.9591020
POLE-HMGCLchr12133225513chr1241470864193HLA-C14:02SYRKVSTSSM0.91620.9591020

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Potential FusionNeoAntigen Information of POLE-HMGCL 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.
POLE-HMGCL_133225513_24147086.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)
POLE-HMGCLchr12133225513chr1241470864193DRB1-0469EGASYRKVSTSSMGT722
POLE-HMGCLchr12133225513chr1241470864193DRB1-0469GASYRKVSTSSMGTL823
POLE-HMGCLchr12133225513chr1241470864193DRB1-0482EGASYRKVSTSSMGT722

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Fusion breakpoint peptide structures of POLE-HMGCL

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
1658EEGASYRKVSTSSMPOLEHMGCLchr12133225513chr1241470864193

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of POLE-HMGCL

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-B14:023BVN1658EEGASYRKVSTSSM-7.9962-8.1096
HLA-B14:023BVN1658EEGASYRKVSTSSM-5.70842-6.74372
HLA-B52:013W391658EEGASYRKVSTSSM-6.83737-6.95077
HLA-B52:013W391658EEGASYRKVSTSSM-4.4836-5.5189
HLA-A11:014UQ21658EEGASYRKVSTSSM-10.0067-10.1201
HLA-A11:014UQ21658EEGASYRKVSTSSM-9.03915-10.0745
HLA-A24:025HGA1658EEGASYRKVSTSSM-6.56204-6.67544
HLA-A24:025HGA1658EEGASYRKVSTSSM-5.42271-6.45801
HLA-B44:053DX81658EEGASYRKVSTSSM-7.85648-8.89178
HLA-B44:053DX81658EEGASYRKVSTSSM-5.3978-5.5112
HLA-A02:016TDR1658EEGASYRKVSTSSM-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of POLE-HMGCL

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
POLE-HMGCLchr12133225513chr1241470861019SYRKVSTSSTATCGCAAGGTCAGCACCTCATCTATG
POLE-HMGCLchr12133225513chr1241470861020SYRKVSTSSMTATCGCAAGGTCAGCACCTCATCTATGGGC
POLE-HMGCLchr12133225513chr1241470861120YRKVSTSSMCGCAAGGTCAGCACCTCATCTATGGGC
POLE-HMGCLchr12133225513chr124147086515AEEGASYRKVGAGGAGGGTGCTTCGTATCGCAAGGTCAGC
POLE-HMGCLchr12133225513chr124147086615EEGASYRKVGAGGGTGCTTCGTATCGCAAGGTCAGC
POLE-HMGCLchr12133225513chr124147086918ASYRKVSTSTCGTATCGCAAGGTCAGCACCTCATCT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
POLE-HMGCLchr12133225513chr124147086722EGASYRKVSTSSMGTGGTGCTTCGTATCGCAAGGTCAGCACCTCATCTATGGGCACTTTA
POLE-HMGCLchr12133225513chr124147086823GASYRKVSTSSMGTLGCTTCGTATCGCAAGGTCAGCACCTCATCTATGGGCACTTTACCA

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Information of the samples that have these potential fusion neoantigens of POLE-HMGCL

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/APOLE-HMGCLchr12133225513ENST00000320574chr124147086ENST00000374490AB209902

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Potential target of CAR-T therapy development for POLE-HMGCL

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 POLE-HMGCL

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 POLE-HMGCL

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