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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:NCOR1-MPRIP

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NCOR1-MPRIP
FusionPDB ID: 57839
FusionGDB2.0 ID: 57839
HgeneTgene
Gene symbol

NCOR1

MPRIP

Gene ID

9611

23164

Gene namenuclear receptor corepressor 1myosin phosphatase Rho interacting protein
SynonymsN-CoR|N-CoR1|PPP1R109|TRAC1|hN-CoRM-RIP|MRIP|RHOIP3|RIP3|p116Rip
Cytomap

17p12-p11.2

17p11.2

Type of geneprotein-codingprotein-coding
Descriptionnuclear receptor corepressor 1protein phosphatase 1, regulatory subunit 109thyroid hormone- and retinoic acid receptor-associated corepressor 1myosin phosphatase Rho-interacting proteinRho interacting protein 3
Modification date2020031320200313
UniProtAcc

O75376

Main function of 5'-partner protein: FUNCTION: Mediates transcriptional repression by certain nuclear receptors (PubMed:20812024). Part of a complex which promotes histone deacetylation and the formation of repressive chromatin structures which may impede the access of basal transcription factors. Participates in the transcriptional repressor activity produced by BCL6. Recruited by ZBTB7A to the androgen response elements/ARE on target genes, negatively regulates androgen receptor signaling and androgen-induced cell proliferation (PubMed:20812024). Mediates the NR1D1-dependent repression and circadian regulation of TSHB expression (By similarity). The NCOR1-HDAC3 complex regulates the circadian expression of the core clock gene ARTNL/BMAL1 and the genes involved in lipid metabolism in the liver (By similarity). {ECO:0000250|UniProtKB:Q60974, ECO:0000269|PubMed:14527417, ECO:0000269|PubMed:20812024}.

Q6WCQ1

Main function of 5'-partner protein: FUNCTION: Targets myosin phosphatase to the actin cytoskeleton. Required for the regulation of the actin cytoskeleton by RhoA and ROCK1. Depletion leads to an increased number of stress fibers in smooth muscle cells through stabilization of actin fibers by phosphorylated myosin. Overexpression of MRIP as well as its F-actin-binding region leads to disassembly of stress fibers in neuronal cells. {ECO:0000250|UniProtKB:P97434, ECO:0000269|PubMed:15545284, ECO:0000269|PubMed:16257966}.
Ensembl transtripts involved in fusion geneENST idsENST00000268712, ENST00000395851, 
ENST00000395848, ENST00000395857, 
ENST00000583226, 
ENST00000395807, 
ENST00000395806, ENST00000341712, 
ENST00000395804, ENST00000395811, 
ENST00000444976, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score30 X 30 X 13=117009 X 7 X 6=378
# samples 339
** MAII scorelog2(33/11700*10)=-5.14789869511231
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(9/378*10)=-2.0703893278914
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: NCOR1 [Title/Abstract] AND MPRIP [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: NCOR1 [Title/Abstract] AND MPRIP [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NCOR1(16075117)-MPRIP(16979024), # samples:1
Anticipated loss of major functional domain due to fusion event.NCOR1-MPRIP 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.
NCOR1-MPRIP 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.
NCOR1-MPRIP 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.
NCOR1-MPRIP 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.
NCOR1-MPRIP seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
NCOR1-MPRIP seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF.
NCOR1-MPRIP seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF.
NCOR1-MPRIP seems lost the major protein functional domain in Tgene partner, which is a essential 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
HgeneNCOR1

GO:0046329

negative regulation of JNK cascade

11931768



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/chr17:16075117/chr17:16979024)
- 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 NCOR1 (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 MPRIP (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)
ENST00000395851NCOR1chr1716075117-ENST00000395811MPRIPchr1716979024+112274792034721150
ENST00000395851NCOR1chr1716075117-ENST00000444976MPRIPchr1716979024+35204792033581112
ENST00000395851NCOR1chr1716075117-ENST00000395804MPRIPchr1716979024+34344792034331138
ENST00000395851NCOR1chr1716075117-ENST00000341712MPRIPchr1716979024+42024792034331137

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
ENST00000395851ENST00000395811NCOR1chr1716075117-MPRIPchr1716979024+0.0005893590.9994106
ENST00000395851ENST00000444976NCOR1chr1716075117-MPRIPchr1716979024+0.0148733090.9851267
ENST00000395851ENST00000395804NCOR1chr1716075117-MPRIPchr1716979024+0.0125161810.98748386
ENST00000395851ENST00000341712NCOR1chr1716075117-MPRIPchr1716979024+0.0061745280.99382544

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 NCOR1-MPRIP

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
NCOR1chr1716075117MPRIPchr1716979024479153LPEGLRASADAKKAKPIYGGWLLLAP

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Potential FusionNeoAntigen Information of NCOR1-MPRIP 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.
NCOR1-MPRIP_16075117_16979024.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)
NCOR1-MPRIPchr1716075117chr1716979024479HLA-B57:01KAKPIYGGW0.99910.98651221
NCOR1-MPRIPchr1716075117chr1716979024479HLA-B58:01KAKPIYGGW0.99780.97481221
NCOR1-MPRIPchr1716075117chr1716979024479HLA-B58:02KAKPIYGGW0.99780.96281221
NCOR1-MPRIPchr1716075117chr1716979024479HLA-B15:16KAKPIYGGW0.99560.87771221
NCOR1-MPRIPchr1716075117chr1716979024479HLA-B15:17KAKPIYGGW0.99420.97051221
NCOR1-MPRIPchr1716075117chr1716979024479HLA-B57:03KAKPIYGGW0.99360.9921221
NCOR1-MPRIPchr1716075117chr1716979024479HLA-A30:08ASADAKKAK0.90570.6972615
NCOR1-MPRIPchr1716075117chr1716979024479HLA-A32:13KAKPIYGGW0.8980.9341221
NCOR1-MPRIPchr1716075117chr1716979024479HLA-B15:02DAKKAKPIY0.80290.8078918
NCOR1-MPRIPchr1716075117chr1716979024479HLA-B57:01KKAKPIYGGW0.99240.97961121
NCOR1-MPRIPchr1716075117chr1716979024479HLA-B15:68AKKAKPIY0.93180.55011018
NCOR1-MPRIPchr1716075117chr1716979024479HLA-B57:10KAKPIYGGW0.99910.98651221
NCOR1-MPRIPchr1716075117chr1716979024479HLA-B58:06KAKPIYGGW0.99780.93231221
NCOR1-MPRIPchr1716075117chr1716979024479HLA-B57:04KAKPIYGGW0.99770.81331221
NCOR1-MPRIPchr1716075117chr1716979024479HLA-A32:01KAKPIYGGW0.98970.96151221
NCOR1-MPRIPchr1716075117chr1716979024479HLA-B15:13KAKPIYGGW0.97080.88641221
NCOR1-MPRIPchr1716075117chr1716979024479HLA-B57:02KAKPIYGGW0.96470.97171221
NCOR1-MPRIPchr1716075117chr1716979024479HLA-B35:24DAKKAKPIY0.9470.7526918
NCOR1-MPRIPchr1716075117chr1716979024479HLA-B15:24KAKPIYGGW0.90350.98071221
NCOR1-MPRIPchr1716075117chr1716979024479HLA-A30:01ASADAKKAK0.89790.8353615
NCOR1-MPRIPchr1716075117chr1716979024479HLA-B35:11DAKKAKPIY0.8330.702918
NCOR1-MPRIPchr1716075117chr1716979024479HLA-B18:04DAKKAKPIY0.68510.7987918
NCOR1-MPRIPchr1716075117chr1716979024479HLA-B15:08DAKKAKPIY0.34410.6315918
NCOR1-MPRIPchr1716075117chr1716979024479HLA-B15:11DAKKAKPIY0.33530.6378918
NCOR1-MPRIPchr1716075117chr1716979024479HLA-B18:07DAKKAKPIY0.31980.6738918
NCOR1-MPRIPchr1716075117chr1716979024479HLA-B35:43DAKKAKPIY0.27280.6376918
NCOR1-MPRIPchr1716075117chr1716979024479HLA-B57:10KKAKPIYGGW0.99240.97961121
NCOR1-MPRIPchr1716075117chr1716979024479HLA-B58:06KKAKPIYGGW0.94520.92281121

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Potential FusionNeoAntigen Information of NCOR1-MPRIP 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.
NCOR1-MPRIP_16075117_16979024.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)
NCOR1-MPRIPchr1716075117chr1716979024479DRB5-0112PEGLRASADAKKAKP116
NCOR1-MPRIPchr1716075117chr1716979024479DRB5-0112LPEGLRASADAKKAK015

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Fusion breakpoint peptide structures of NCOR1-MPRIP

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
578ASADAKKAKPIYGGNCOR1MPRIPchr1716075117chr1716979024479

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of NCOR1-MPRIP

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-B14:023BVN578ASADAKKAKPIYGG-6.66017-6.77357
HLA-B14:023BVN578ASADAKKAKPIYGG-3.48242-4.51772
HLA-B27:093CZF578ASADAKKAKPIYGG10000.110000
HLA-B52:013W39578ASADAKKAKPIYGG-5.06127-5.17467
HLA-B52:013W39578ASADAKKAKPIYGG-4.23673-5.27203
HLA-B18:014JQV578ASADAKKAKPIYGG-3.70535-3.81875
HLA-A11:014UQ2578ASADAKKAKPIYGG-8.9083-9.0217
HLA-A11:014UQ2578ASADAKKAKPIYGG-5.86986-6.90516
HLA-A24:025HGA578ASADAKKAKPIYGG-6.45287-6.56627
HLA-A24:025HGA578ASADAKKAKPIYGG-6.01305-7.04835
HLA-B27:056PYJ578ASADAKKAKPIYGG-4.82238-5.85768
HLA-B27:056PYJ578ASADAKKAKPIYGG-4.78695-4.90035
HLA-B27:036PZ5578ASADAKKAKPIYGG-5.33736-5.45076
HLA-B27:036PZ5578ASADAKKAKPIYGG-2.16924-3.20454
HLA-B44:053DX8578ASADAKKAKPIYGG-5.3498-5.4632
HLA-B44:053DX8578ASADAKKAKPIYGG-3.28888-4.32418
HLA-A02:016TDR578ASADAKKAKPIYGG-2.20851-3.24381

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Vaccine Design for the FusionNeoAntigens of NCOR1-MPRIP

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
NCOR1-MPRIPchr1716075117chr17169790241018AKKAKPIYGCTAAGAAGGCAAAACCCATTTAT
NCOR1-MPRIPchr1716075117chr17169790241121KKAKPIYGGWAAGAAGGCAAAACCCATTTATGGCGGTTGG
NCOR1-MPRIPchr1716075117chr17169790241221KAKPIYGGWAAGGCAAAACCCATTTATGGCGGTTGG
NCOR1-MPRIPchr1716075117chr1716979024615ASADAKKAKGCTTCTGCAGATGCTAAGAAGGCAAAA
NCOR1-MPRIPchr1716075117chr1716979024918DAKKAKPIYGATGCTAAGAAGGCAAAACCCATTTAT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
NCOR1-MPRIPchr1716075117chr1716979024015LPEGLRASADAKKAKCTGCCAGAAGGGCTGAGGGCTTCTGCAGATGCTAAGAAGGCAAAA
NCOR1-MPRIPchr1716075117chr1716979024116PEGLRASADAKKAKPCCAGAAGGGCTGAGGGCTTCTGCAGATGCTAAGAAGGCAAAACCC

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Information of the samples that have these potential fusion neoantigens of NCOR1-MPRIP

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
UCSNCOR1-MPRIPchr1716075117ENST00000395851chr1716979024ENST00000341712TCGA-N8-A4PQ-01A

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Potential target of CAR-T therapy development for NCOR1-MPRIP

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 NCOR1-MPRIP

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 NCOR1-MPRIP

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