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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:ATF6-MNDA

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ATF6-MNDA
FusionPDB ID: 7446
FusionGDB2.0 ID: 7446
HgeneTgene
Gene symbol

ATF6

MNDA

Gene ID

22926

4332

Gene nameactivating transcription factor 6myeloid cell nuclear differentiation antigen
SynonymsACHM7|ATF6APYHIN3
Cytomap

1q23.3

1q23.1

Type of geneprotein-codingprotein-coding
Descriptioncyclic AMP-dependent transcription factor ATF-6 alphacAMP-dependent transcription factor ATF-6 alphamyeloid cell nuclear differentiation antigenepididymis secretory sperm binding protein
Modification date2020031320200313
UniProtAcc

Q99941

Main function of 5'-partner protein: FUNCTION: [Cyclic AMP-dependent transcription factor ATF-6 beta]: Precursor of the transcription factor form (Processed cyclic AMP-dependent transcription factor ATF-6 beta), which is embedded in the endoplasmic reticulum membrane (PubMed:11256944). Endoplasmic reticulum stress promotes processing of this form, releasing the transcription factor form that translocates into the nucleus, where it activates transcription of genes involved in the unfolded protein response (UPR) (PubMed:11256944). {ECO:0000269|PubMed:11256944}.; FUNCTION: [Processed cyclic AMP-dependent transcription factor ATF-6 beta]: Transcription factor that acts in the unfolded protein response (UPR) pathway by activating UPR target genes induced during ER stress (PubMed:11256944). Binds DNA on the 5'-CCAC[GA]-3' half of the ER stress response element (ERSE) (5'-CCAATN(9)CCAC[GA]-3') when NF-Y is bound to ERSE (PubMed:11256944). {ECO:0000269|PubMed:11256944}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000367942, ENST00000476437, 
ENST00000491210, ENST00000368141, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score12 X 10 X 8=9604 X 4 X 4=64
# samples 125
** MAII scorelog2(12/960*10)=-3
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(5/64*10)=-0.356143810225275
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ATF6 [Title/Abstract] AND MNDA [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ATF6 [Title/Abstract] AND MNDA [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ATF6(161789608)-MNDA(158815376), # samples:1
Anticipated loss of major functional domain due to fusion event.ATF6-MNDA 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.
ATF6-MNDA 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.
ATF6-MNDA 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.
ATF6-MNDA 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
HgeneATF6

GO:0043065

positive regulation of apoptotic process

14752510

HgeneATF6

GO:0045944

positive regulation of transcription by RNA polymerase II

14973138

HgeneATF6

GO:1903893

positive regulation of ATF6-mediated unfolded protein response

9837962

HgeneATF6

GO:1990440

positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress

11163209|11256944|16469704



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/chr1:161789608/chr1:158815376)
- 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 ATF6 (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 MNDA (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)
ENST00000367942ATF6chr1161789608+ENST00000368141MNDAchr1158815376+20831162101815601

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
ENST00000367942ENST00000368141ATF6chr1161789608+MNDAchr1158815376+0.0006832170.9993168

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 ATF6-MNDA

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ATF6chr1161789608MNDAchr11588153761162384GTLKRQLDEVVSENQETQAQRQVDAR

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Potential FusionNeoAntigen Information of ATF6-MNDA 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.
ATF6-MNDA_161789608_158815376.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)
ATF6-MNDAchr1161789608chr11588153761162HLA-B50:02SENQETQA0.99910.69361119
ATF6-MNDAchr1161789608chr11588153761162HLA-B45:01SENQETQA0.99640.89991119
ATF6-MNDAchr1161789608chr11588153761162HLA-B41:01SENQETQA0.98440.90931119
ATF6-MNDAchr1161789608chr11588153761162HLA-B50:01SENQETQA0.95520.79031119
ATF6-MNDAchr1161789608chr11588153761162HLA-A33:05ENQETQAQR0.86490.61931221
ATF6-MNDAchr1161789608chr11588153761162HLA-A33:01ENQETQAQR0.86490.61931221
ATF6-MNDAchr1161789608chr11588153761162HLA-A68:05ENQETQAQR0.70060.55181221
ATF6-MNDAchr1161789608chr11588153761162HLA-B50:05SENQETQA0.95520.79031119
ATF6-MNDAchr1161789608chr11588153761162HLA-B50:04SENQETQA0.95520.79031119

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Potential FusionNeoAntigen Information of ATF6-MNDA 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 ATF6-MNDA

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
4837LDEVVSENQETQAQATF6MNDAchr1161789608chr11588153761162

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ATF6-MNDA

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-B14:023BVN4837LDEVVSENQETQAQ-7.15543-7.26883
HLA-B14:023BVN4837LDEVVSENQETQAQ-4.77435-5.80965
HLA-B52:013W394837LDEVVSENQETQAQ-6.80875-6.92215
HLA-B52:013W394837LDEVVSENQETQAQ-4.20386-5.23916
HLA-A11:014UQ24837LDEVVSENQETQAQ-7.5194-8.5547
HLA-A11:014UQ24837LDEVVSENQETQAQ-6.9601-7.0735
HLA-A24:025HGA4837LDEVVSENQETQAQ-7.52403-7.63743
HLA-A24:025HGA4837LDEVVSENQETQAQ-5.82433-6.85963
HLA-B27:056PYJ4837LDEVVSENQETQAQ-3.28285-4.31815
HLA-B44:053DX84837LDEVVSENQETQAQ-5.91172-6.94702
HLA-B44:053DX84837LDEVVSENQETQAQ-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of ATF6-MNDA

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
ATF6-MNDAchr1161789608chr11588153761119SENQETQATCAGAGAATCAGGAAACCCAGGCC
ATF6-MNDAchr1161789608chr11588153761221ENQETQAQRGAGAATCAGGAAACCCAGGCCCAACGG

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 ATF6-MNDA

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
STADATF6-MNDAchr1161789608ENST00000367942chr1158815376ENST00000368141TCGA-BR-8371

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Potential target of CAR-T therapy development for ATF6-MNDA

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 ATF6-MNDA

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 ATF6-MNDA

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