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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:ROR1-PGM1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ROR1-PGM1
FusionPDB ID: 75364
FusionGDB2.0 ID: 75364
HgeneTgene
Gene symbol

ROR1

PGM1

Gene ID

6095

5236

Gene nameRAR related orphan receptor Aphosphoglucomutase 1
SynonymsIDDECA|NR1F1|ROR1|ROR2|ROR3|RZR-ALPHA|RZRACDG1T|GSD14
Cytomap

15q22.2

1p31.3

Type of geneprotein-codingprotein-coding
Descriptionnuclear receptor ROR-alphaROR-alphanuclear receptor RZR-alphanuclear receptor subfamily 1 group F member 1retinoic acid receptor-related orphan receptor alpharetinoid-related orphan receptor alphathyroid hormone nuclear receptor alpha variant 4tranphosphoglucomutase-1PGM 1glucose phosphomutase 1
Modification date2020032220200313
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000371079, ENST00000371080, 
ENST00000482426, ENST00000545203, 
ENST00000371083, ENST00000540265, 
ENST00000483707, ENST00000371084, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score15 X 10 X 7=10508 X 7 X 6=336
# samples 179
** MAII scorelog2(17/1050*10)=-2.62678267641578
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(9/336*10)=-1.90046432644909
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ROR1 [Title/Abstract] AND PGM1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ROR1 [Title/Abstract] AND PGM1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ROR1(64240179)-PGM1(64095095), # samples:1
ROR1(64240179)-PGM1(64114188), # samples:1
Anticipated loss of major functional domain due to fusion event.ROR1-PGM1 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.
ROR1-PGM1 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.
ROR1-PGM1 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.
ROR1-PGM1 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.
ROR1-PGM1 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
ROR1-PGM1 seems lost the major protein functional domain in Hgene partner, which is a kinase due to the frame-shifted ORF.
ROR1-PGM1 seems lost the major protein functional domain in Tgene partner, which is a cell metabolism 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
HgeneROR1

GO:0006355

regulation of transcription, DNA-templated

9328355

HgeneROR1

GO:0030522

intracellular receptor signaling pathway

19965867

HgeneROR1

GO:0036315

cellular response to sterol

19965867

HgeneROR1

GO:0045893

positive regulation of transcription, DNA-templated

7926749

HgeneROR1

GO:0045944

positive regulation of transcription by RNA polymerase II

17545671|19955433

TgenePGM1

GO:0006006

glucose metabolic process

25288802



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/chr1:64240179/chr1:64095095)
- 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 ROR1 (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 PGM1 (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)
ENST00000371080ROR1chr164240179+ENST00000371084PGM1chr164114188+16024873571031224
ENST00000371080ROR1chr164240179+ENST00000540265PGM1chr164114188+15984873571031224
ENST00000371080ROR1chr164240179+ENST00000371083PGM1chr164114188+15784873571031224
ENST00000371079ROR1chr164240179+ENST00000371084PGM1chr164114188+15814663361010224
ENST00000371079ROR1chr164240179+ENST00000540265PGM1chr164114188+15774663361010224
ENST00000371079ROR1chr164240179+ENST00000371083PGM1chr164114188+15574663361010224

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
ENST00000371080ENST00000371084ROR1chr164240179+PGM1chr164114188+0.0029471270.9970529
ENST00000371080ENST00000540265ROR1chr164240179+PGM1chr164114188+0.002951290.9970488
ENST00000371080ENST00000371083ROR1chr164240179+PGM1chr164114188+0.0029480610.99705195
ENST00000371079ENST00000371084ROR1chr164240179+PGM1chr164114188+0.0020512450.9979488
ENST00000371079ENST00000540265ROR1chr164240179+PGM1chr164114188+0.0020255550.99797446
ENST00000371079ENST00000371083ROR1chr164240179+PGM1chr164114188+0.0019434140.9980566

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 ROR1-PGM1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ROR1chr164240179PGM1chr16411418846643AALLLAARGAAAQGSDHIREKDGLWA
ROR1chr164240179PGM1chr16411418848743AALLLAARGAAAQGSDHIREKDGLWA

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Potential FusionNeoAntigen Information of ROR1-PGM1 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.

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)

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Potential FusionNeoAntigen Information of ROR1-PGM1 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.
ROR1-PGM1_64240179_64114188.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)
ROR1-PGM1chr164240179chr164114188466DRB1-0102AALLLAARGAAAQGS015
ROR1-PGM1chr164240179chr164114188466DRB1-0123AALLLAARGAAAQGS015

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Fusion breakpoint peptide structures of ROR1-PGM1

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.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ROR1-PGM1

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

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Vaccine Design for the FusionNeoAntigens of ROR1-PGM1

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

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
ROR1-PGM1chr164240179chr164114188015AALLLAARGAAAQGSCCGCGCTGCTGCTGGCCGCACGCGGGGCTGCTGCCCAAGGTTCTG

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Information of the samples that have these potential fusion neoantigens of ROR1-PGM1

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

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Potential target of CAR-T therapy development for ROR1-PGM1

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 ROR1-PGM1

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 ROR1-PGM1

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