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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:PARD3-MTA1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PARD3-MTA1
FusionPDB ID: 62711
FusionGDB2.0 ID: 62711
HgeneTgene
Gene symbol

PARD3

MTA1

Gene ID

56288

9112

Gene namepar-3 family cell polarity regulatormetastasis associated 1
SynonymsASIP|Baz|PAR3|PAR3alpha|PARD-3|PARD3A|PPP1R118|SE2-5L16|SE2-5LT1|SE2-5T2-
Cytomap

10p11.22-p11.21

14q32.33

Type of geneprotein-codingprotein-coding
Descriptionpartitioning defective 3 homologCTCL tumor antigen se2-5PAR3-alphaatypical PKC isotype-specific interacting proteinbazookapar-3 family cell polarity regulator alphapar-3 partitioning defective 3 homologprotein phosphatase 1, regulatory subunit 118metastasis-associated protein MTA1metastasis associated gene 1 protein
Modification date2020032720200313
UniProtAcc.

Q13330

Main function of 5'-partner protein: FUNCTION: Transcriptional coregulator which can act as both a transcriptional corepressor and coactivator. As a part of the histone-deacetylase multiprotein complex (NuRD), regulates transcription of its targets by modifying the acetylation status of the target chromatin and cofactor accessibility to the target DNA. In conjunction with other components of NuRD, acts as a transcriptional corepressor of BRCA1, ESR1, TFF1 and CDKN1A. Acts as a transcriptional coactivator of BCAS3, PAX5 and SUMO2, independent of the NuRD complex. Stimulates the expression of WNT1 by inhibiting the expression of its transcriptional corepressor SIX3. Regulates p53-dependent and -independent DNA repair processes following genotoxic stress. Regulates the stability and function of p53/TP53 by inhibiting its ubiquitination by COP1 and MDM2 thereby regulating the p53-dependent DNA repair. Plays an important role in tumorigenesis, tumor invasion, and metastasis. Involved in the epigenetic regulation of ESR1 expression in breast cancer in a TFAP2C, IFI16 and HDAC4/5/6-dependent manner. Plays a role in the regulation of the circadian clock and is essential for the generation and maintenance of circadian rhythms under constant light and for normal entrainment of behavior to light-dark (LD) cycles. Positively regulates the CLOCK-ARNTL/BMAL1 heterodimer mediated transcriptional activation of its own transcription and the transcription of CRY1. Regulates deacetylation of ARNTL/BMAL1 by regulating SIRT1 expression, resulting in derepressing CRY1-mediated transcription repression. Isoform Short binds to ESR1 and sequesters it in the cytoplasm and enhances its non-genomic responses. With TFCP2L1, promotes establishment and maintenance of pluripotency in embryonic stem cells (ESCs) and inhibits endoderm differentiation (By similarity). {ECO:0000250|UniProtKB:Q8K4B0, ECO:0000269|PubMed:16617102, ECO:0000269|PubMed:17671180, ECO:0000269|PubMed:17922032, ECO:0000269|PubMed:19837670, ECO:0000269|PubMed:21965678, ECO:0000269|PubMed:24413532}.
Ensembl transtripts involved in fusion geneENST idsENST00000340077, ENST00000346874, 
ENST00000350537, ENST00000374773, 
ENST00000374776, ENST00000374788, 
ENST00000374789, ENST00000374790, 
ENST00000374794, ENST00000545260, 
ENST00000545693, ENST00000374768, 
ENST00000466092, ENST00000544292, 
ENST00000435036, ENST00000331320, 
ENST00000405646, ENST00000406191, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score33 X 20 X 14=92406 X 9 X 5=270
# samples 4910
** MAII scorelog2(49/9240*10)=-4.23703919730085
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(10/270*10)=-1.43295940727611
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: PARD3 [Title/Abstract] AND MTA1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PARD3 [Title/Abstract] AND MTA1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PARD3(34985246)-MTA1(105929830), # samples:2
Anticipated loss of major functional domain due to fusion event.PARD3-MTA1 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.
PARD3-MTA1 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.
PARD3-MTA1 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.
PARD3-MTA1 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
TgeneMTA1

GO:0010212

response to ionizing radiation

19805145

TgeneMTA1

GO:1902499

positive regulation of protein autoubiquitination

19805145



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/chr10:34985246/chr14:105929830)
- 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 PARD3 (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 MTA1 (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)
ENST00000545260PARD3chr1034985246-ENST00000331320MTA1chr14105929830+21975521981682494
ENST00000545260PARD3chr1034985246-ENST00000406191MTA1chr14105929830+21615521981646482
ENST00000545260PARD3chr1034985246-ENST00000405646MTA1chr14105929830+21975521981682494
ENST00000545693PARD3chr1034985246-ENST00000331320MTA1chr14105929830+21975521981682494
ENST00000545693PARD3chr1034985246-ENST00000406191MTA1chr14105929830+21615521981646482
ENST00000545693PARD3chr1034985246-ENST00000405646MTA1chr14105929830+21975521981682494
ENST00000350537PARD3chr1034985246-ENST00000331320MTA1chr14105929830+21935481941678494
ENST00000350537PARD3chr1034985246-ENST00000406191MTA1chr14105929830+21575481941642482
ENST00000350537PARD3chr1034985246-ENST00000405646MTA1chr14105929830+21935481941678494
ENST00000346874PARD3chr1034985246-ENST00000331320MTA1chr14105929830+21935481941678494
ENST00000346874PARD3chr1034985246-ENST00000406191MTA1chr14105929830+21575481941642482
ENST00000346874PARD3chr1034985246-ENST00000405646MTA1chr14105929830+21935481941678494
ENST00000374789PARD3chr1034985246-ENST00000331320MTA1chr14105929830+21935481941678494
ENST00000374789PARD3chr1034985246-ENST00000406191MTA1chr14105929830+21575481941642482
ENST00000374789PARD3chr1034985246-ENST00000405646MTA1chr14105929830+21935481941678494
ENST00000374790PARD3chr1034985246-ENST00000331320MTA1chr14105929830+21935481941678494
ENST00000374790PARD3chr1034985246-ENST00000406191MTA1chr14105929830+21575481941642482
ENST00000374790PARD3chr1034985246-ENST00000405646MTA1chr14105929830+21935481941678494
ENST00000374794PARD3chr1034985246-ENST00000331320MTA1chr14105929830+21935481941678494
ENST00000374794PARD3chr1034985246-ENST00000406191MTA1chr14105929830+21575481941642482
ENST00000374794PARD3chr1034985246-ENST00000405646MTA1chr14105929830+21935481941678494
ENST00000374788PARD3chr1034985246-ENST00000331320MTA1chr14105929830+21935481941678494
ENST00000374788PARD3chr1034985246-ENST00000406191MTA1chr14105929830+21575481941642482
ENST00000374788PARD3chr1034985246-ENST00000405646MTA1chr14105929830+21935481941678494
ENST00000374776PARD3chr1034985246-ENST00000331320MTA1chr14105929830+21935481941678494
ENST00000374776PARD3chr1034985246-ENST00000406191MTA1chr14105929830+21575481941642482
ENST00000374776PARD3chr1034985246-ENST00000405646MTA1chr14105929830+21935481941678494
ENST00000340077PARD3chr1034985246-ENST00000331320MTA1chr14105929830+21975521981682494
ENST00000340077PARD3chr1034985246-ENST00000406191MTA1chr14105929830+21615521981646482
ENST00000340077PARD3chr1034985246-ENST00000405646MTA1chr14105929830+21975521981682494
ENST00000374773PARD3chr1034985246-ENST00000331320MTA1chr14105929830+21935481941678494
ENST00000374773PARD3chr1034985246-ENST00000406191MTA1chr14105929830+21575481941642482
ENST00000374773PARD3chr1034985246-ENST00000405646MTA1chr14105929830+21935481941678494

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
ENST00000545260ENST00000331320PARD3chr1034985246-MTA1chr14105929830+0.0231630340.976837
ENST00000545260ENST00000406191PARD3chr1034985246-MTA1chr14105929830+0.0219200120.97808003
ENST00000545260ENST00000405646PARD3chr1034985246-MTA1chr14105929830+0.0231630340.976837
ENST00000545693ENST00000331320PARD3chr1034985246-MTA1chr14105929830+0.0231630340.976837
ENST00000545693ENST00000406191PARD3chr1034985246-MTA1chr14105929830+0.0219200120.97808003
ENST00000545693ENST00000405646PARD3chr1034985246-MTA1chr14105929830+0.0231630340.976837
ENST00000350537ENST00000331320PARD3chr1034985246-MTA1chr14105929830+0.0233048350.9766951
ENST00000350537ENST00000406191PARD3chr1034985246-MTA1chr14105929830+0.0221460520.97785395
ENST00000350537ENST00000405646PARD3chr1034985246-MTA1chr14105929830+0.0233048350.9766951
ENST00000346874ENST00000331320PARD3chr1034985246-MTA1chr14105929830+0.0233048350.9766951
ENST00000346874ENST00000406191PARD3chr1034985246-MTA1chr14105929830+0.0221460520.97785395
ENST00000346874ENST00000405646PARD3chr1034985246-MTA1chr14105929830+0.0233048350.9766951
ENST00000374789ENST00000331320PARD3chr1034985246-MTA1chr14105929830+0.0233048350.9766951
ENST00000374789ENST00000406191PARD3chr1034985246-MTA1chr14105929830+0.0221460520.97785395
ENST00000374789ENST00000405646PARD3chr1034985246-MTA1chr14105929830+0.0233048350.9766951
ENST00000374790ENST00000331320PARD3chr1034985246-MTA1chr14105929830+0.0233048350.9766951
ENST00000374790ENST00000406191PARD3chr1034985246-MTA1chr14105929830+0.0221460520.97785395
ENST00000374790ENST00000405646PARD3chr1034985246-MTA1chr14105929830+0.0233048350.9766951
ENST00000374794ENST00000331320PARD3chr1034985246-MTA1chr14105929830+0.0233048350.9766951
ENST00000374794ENST00000406191PARD3chr1034985246-MTA1chr14105929830+0.0221460520.97785395
ENST00000374794ENST00000405646PARD3chr1034985246-MTA1chr14105929830+0.0233048350.9766951
ENST00000374788ENST00000331320PARD3chr1034985246-MTA1chr14105929830+0.0233048350.9766951
ENST00000374788ENST00000406191PARD3chr1034985246-MTA1chr14105929830+0.0221460520.97785395
ENST00000374788ENST00000405646PARD3chr1034985246-MTA1chr14105929830+0.0233048350.9766951
ENST00000374776ENST00000331320PARD3chr1034985246-MTA1chr14105929830+0.0233048350.9766951
ENST00000374776ENST00000406191PARD3chr1034985246-MTA1chr14105929830+0.0221460520.97785395
ENST00000374776ENST00000405646PARD3chr1034985246-MTA1chr14105929830+0.0233048350.9766951
ENST00000340077ENST00000331320PARD3chr1034985246-MTA1chr14105929830+0.0231630340.976837
ENST00000340077ENST00000406191PARD3chr1034985246-MTA1chr14105929830+0.0219200120.97808003
ENST00000340077ENST00000405646PARD3chr1034985246-MTA1chr14105929830+0.0231630340.976837
ENST00000374773ENST00000331320PARD3chr1034985246-MTA1chr14105929830+0.0233048350.9766951
ENST00000374773ENST00000406191PARD3chr1034985246-MTA1chr14105929830+0.0221460520.97785395
ENST00000374773ENST00000405646PARD3chr1034985246-MTA1chr14105929830+0.0233048350.9766951

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 PARD3-MTA1

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

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Potential FusionNeoAntigen Information of PARD3-MTA1 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 PARD3-MTA1 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.

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)

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Fusion breakpoint peptide structures of PARD3-MTA1

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 PARD3-MTA1

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 PARD3-MTA1

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

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Information of the samples that have these potential fusion neoantigens of PARD3-MTA1

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 PARD3-MTA1

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 PARD3-MTA1

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 PARD3-MTA1

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