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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:ATF2-CHRNA1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ATF2-CHRNA1
FusionPDB ID: 7409
FusionGDB2.0 ID: 7409
HgeneTgene
Gene symbol

ATF2

CHRNA1

Gene ID

2668

1134

Gene nameglial cell derived neurotrophic factorcholinergic receptor nicotinic alpha 1 subunit
SynonymsATF|ATF1|ATF2|HFB1-GDNF|HSCR3ACHRA|ACHRD|CHRNA|CMS1A|CMS1B|CMS2A|FCCMS|SCCMS
Cytomap

5p13.2

2q31.1

Type of geneprotein-codingprotein-coding
Descriptionglial cell line-derived neurotrophic factorastrocyte-derived trophic factoracetylcholine receptor subunit alphaacetylcholine receptor, nicotinic, alpha 1 (muscle)cholinergic receptor, nicotinic alpha 1cholinergic receptor, nicotinic, alpha 1 (muscle)cholinergic receptor, nicotinic, alpha polypeptide 1 (muscle)muscle nicotin
Modification date2020031420200313
UniProtAcc

P15336

Main function of 5'-partner protein: FUNCTION: Transcriptional activator which regulates the transcription of various genes, including those involved in anti-apoptosis, cell growth, and DNA damage response. Dependent on its binding partner, binds to CRE (cAMP response element) consensus sequences (5'-TGACGTCA-3') or to AP-1 (activator protein 1) consensus sequences (5'-TGACTCA-3'). In the nucleus, contributes to global transcription and the DNA damage response, in addition to specific transcriptional activities that are related to cell development, proliferation and death. In the cytoplasm, interacts with and perturbs HK1- and VDAC1-containing complexes at the mitochondrial outer membrane, thereby impairing mitochondrial membrane potential, inducing mitochondrial leakage and promoting cell death. The phosphorylated form (mediated by ATM) plays a role in the DNA damage response and is involved in the ionizing radiation (IR)-induced S phase checkpoint control and in the recruitment of the MRN complex into the IR-induced foci (IRIF). Exhibits histone acetyltransferase (HAT) activity which specifically acetylates histones H2B and H4 in vitro (PubMed:10821277). In concert with CUL3 and RBX1, promotes the degradation of KAT5 thereby attenuating its ability to acetylate and activate ATM. Can elicit oncogenic or tumor suppressor activities depending on the tissue or cell type. {ECO:0000269|PubMed:10821277, ECO:0000269|PubMed:15916964, ECO:0000269|PubMed:18397884, ECO:0000269|PubMed:22304920}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000487334, ENST00000538946, 
ENST00000392544, ENST00000409437, 
ENST00000426833, ENST00000264110, 
ENST00000345739, ENST00000392543, 
ENST00000409499, ENST00000409635, 
ENST00000409833, ENST00000413123, 
ENST00000261007, ENST00000348749, 
ENST00000409219, ENST00000409323, 
ENST00000409542, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score12 X 11 X 9=11884 X 3 X 3=36
# samples 134
** MAII scorelog2(13/1188*10)=-3.19195130777231
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(4/36*10)=0.15200309344505
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: ATF2 [Title/Abstract] AND CHRNA1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ATF2 [Title/Abstract] AND CHRNA1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ATF2(175945388)-CHRNA1(175624361), # samples:1
Anticipated loss of major functional domain due to fusion event.ATF2-CHRNA1 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.
ATF2-CHRNA1 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.
ATF2-CHRNA1 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.
ATF2-CHRNA1 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.
ATF2-CHRNA1 seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF.
ATF2-CHRNA1 seems lost the major protein functional domain in Hgene partner, which is a transcription factor due to the frame-shifted ORF.
ATF2-CHRNA1 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
ATF2-CHRNA1 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target 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
HgeneATF2

GO:0001755

neural crest cell migration

15242795

HgeneATF2

GO:0008284

positive regulation of cell proliferation

22897442

HgeneATF2

GO:0031175

neuron projection development

15242795

HgeneATF2

GO:0032770

positive regulation of monooxygenase activity

12358785

HgeneATF2

GO:0043524

negative regulation of neuron apoptotic process

8493557

HgeneATF2

GO:0045944

positive regulation of transcription by RNA polymerase II

12358785

HgeneATF2

GO:0048255

mRNA stabilization

12358785

HgeneATF2

GO:0051584

regulation of dopamine uptake involved in synaptic transmission

8493557

HgeneATF2

GO:0072107

positive regulation of ureteric bud formation

8657307

HgeneATF2

GO:0090190

positive regulation of branching involved in ureteric bud morphogenesis

8657307|17229286

HgeneATF2

GO:2001240

negative regulation of extrinsic apoptotic signaling pathway in absence of ligand

10921886



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/chr2:175945388/chr2:175624361)
- 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 ATF2 (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 CHRNA1 (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)
ENST00000345739ATF2chr2175945388-ENST00000348749CHRNA1chr2175624361-335614933762823815
ENST00000345739ATF2chr2175945388-ENST00000261007CHRNA1chr2175624361-336314933762898840
ENST00000345739ATF2chr2175945388-ENST00000409219CHRNA1chr2175624361-289814933762583735
ENST00000345739ATF2chr2175945388-ENST00000409542CHRNA1chr2175624361-289214933762577733
ENST00000345739ATF2chr2175945388-ENST00000409323CHRNA1chr2175624361-297614933762259627
ENST00000264110ATF2chr2175945388-ENST00000348749CHRNA1chr2175624361-345315902992920873
ENST00000264110ATF2chr2175945388-ENST00000261007CHRNA1chr2175624361-346015902992995898
ENST00000264110ATF2chr2175945388-ENST00000409219CHRNA1chr2175624361-299515902992680793
ENST00000264110ATF2chr2175945388-ENST00000409542CHRNA1chr2175624361-298915902992674791
ENST00000264110ATF2chr2175945388-ENST00000409323CHRNA1chr2175624361-307315902992356685
ENST00000409635ATF2chr2175945388-ENST00000348749CHRNA1chr2175624361-341615534362883815
ENST00000409635ATF2chr2175945388-ENST00000261007CHRNA1chr2175624361-342315534362958840
ENST00000409635ATF2chr2175945388-ENST00000409219CHRNA1chr2175624361-295815534362643735
ENST00000409635ATF2chr2175945388-ENST00000409542CHRNA1chr2175624361-295215534362637733
ENST00000409635ATF2chr2175945388-ENST00000409323CHRNA1chr2175624361-303615534362319627
ENST00000392543ATF2chr2175945388-ENST00000348749CHRNA1chr2175624361-23334702621800512
ENST00000392543ATF2chr2175945388-ENST00000261007CHRNA1chr2175624361-23404702621875537
ENST00000392543ATF2chr2175945388-ENST00000409219CHRNA1chr2175624361-18754702621560432
ENST00000392543ATF2chr2175945388-ENST00000409542CHRNA1chr2175624361-18694702621554430
ENST00000392543ATF2chr2175945388-ENST00000409323CHRNA1chr2175624361-19534702621236324
ENST00000409499ATF2chr2175945388-ENST00000348749CHRNA1chr2175624361-23334702621800512
ENST00000409499ATF2chr2175945388-ENST00000261007CHRNA1chr2175624361-23404702621875537
ENST00000409499ATF2chr2175945388-ENST00000409219CHRNA1chr2175624361-18754702621560432
ENST00000409499ATF2chr2175945388-ENST00000409542CHRNA1chr2175624361-18694702621554430
ENST00000409499ATF2chr2175945388-ENST00000409323CHRNA1chr2175624361-19534702621236324

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
ENST00000345739ENST00000348749ATF2chr2175945388-CHRNA1chr2175624361-0.001445090.9985549
ENST00000345739ENST00000261007ATF2chr2175945388-CHRNA1chr2175624361-0.0011804490.99881953
ENST00000345739ENST00000409219ATF2chr2175945388-CHRNA1chr2175624361-0.0026945390.9973054
ENST00000345739ENST00000409542ATF2chr2175945388-CHRNA1chr2175624361-0.0025497460.9974503
ENST00000345739ENST00000409323ATF2chr2175945388-CHRNA1chr2175624361-0.0031905660.9968094
ENST00000264110ENST00000348749ATF2chr2175945388-CHRNA1chr2175624361-0.0007808220.9992192
ENST00000264110ENST00000261007ATF2chr2175945388-CHRNA1chr2175624361-0.0006597440.99934024
ENST00000264110ENST00000409219ATF2chr2175945388-CHRNA1chr2175624361-0.0015373840.9984627
ENST00000264110ENST00000409542ATF2chr2175945388-CHRNA1chr2175624361-0.0016070160.998393
ENST00000264110ENST00000409323ATF2chr2175945388-CHRNA1chr2175624361-0.0029097980.9970902
ENST00000409635ENST00000348749ATF2chr2175945388-CHRNA1chr2175624361-0.0014331850.9985668
ENST00000409635ENST00000261007ATF2chr2175945388-CHRNA1chr2175624361-0.0011892930.99881077
ENST00000409635ENST00000409219ATF2chr2175945388-CHRNA1chr2175624361-0.0026550590.9973449
ENST00000409635ENST00000409542ATF2chr2175945388-CHRNA1chr2175624361-0.0025154760.99748445
ENST00000409635ENST00000409323ATF2chr2175945388-CHRNA1chr2175624361-0.0032100740.9967899
ENST00000392543ENST00000348749ATF2chr2175945388-CHRNA1chr2175624361-0.0012828970.99871707
ENST00000392543ENST00000261007ATF2chr2175945388-CHRNA1chr2175624361-0.0011400770.9988599
ENST00000392543ENST00000409219ATF2chr2175945388-CHRNA1chr2175624361-0.0018854320.9981146
ENST00000392543ENST00000409542ATF2chr2175945388-CHRNA1chr2175624361-0.0031739760.99682605
ENST00000392543ENST00000409323ATF2chr2175945388-CHRNA1chr2175624361-0.0013703210.9986297
ENST00000409499ENST00000348749ATF2chr2175945388-CHRNA1chr2175624361-0.0012828970.99871707
ENST00000409499ENST00000261007ATF2chr2175945388-CHRNA1chr2175624361-0.0011400770.9988599
ENST00000409499ENST00000409219ATF2chr2175945388-CHRNA1chr2175624361-0.0018854320.9981146
ENST00000409499ENST00000409542ATF2chr2175945388-CHRNA1chr2175624361-0.0031739760.99682605
ENST00000409499ENST00000409323ATF2chr2175945388-CHRNA1chr2175624361-0.0013703210.9986297

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 ATF2-CHRNA1

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 ATF2-CHRNA1 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 ATF2-CHRNA1 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 ATF2-CHRNA1

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 ATF2-CHRNA1

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 ATF2-CHRNA1

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 ATF2-CHRNA1

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 ATF2-CHRNA1

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
TgeneCHRNA1chr2:175945388chr2:175624361ENST00000261007010256_2800483.0TransmembraneNote=Helical
TgeneCHRNA1chr2:175945388chr2:175624361ENST00000261007010288_3060483.0TransmembraneNote=Helical
TgeneCHRNA1chr2:175945388chr2:175624361ENST00000261007010322_3410483.0TransmembraneNote=Helical
TgeneCHRNA1chr2:175945388chr2:175624361ENST00000261007010454_4720483.0TransmembraneNote=Helical
TgeneCHRNA1chr2:175945388chr2:175624361ENST0000034874909256_2800458.0TransmembraneNote=Helical
TgeneCHRNA1chr2:175945388chr2:175624361ENST0000034874909288_3060458.0TransmembraneNote=Helical
TgeneCHRNA1chr2:175945388chr2:175624361ENST0000034874909322_3410458.0TransmembraneNote=Helical
TgeneCHRNA1chr2:175945388chr2:175624361ENST0000034874909454_4720458.0TransmembraneNote=Helical

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 ATF2-CHRNA1

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 ATF2-CHRNA1

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
HgeneATF2C0006826Malignant Neoplasms1CTD_human
HgeneATF2C0027651Neoplasms1CTD_human
HgeneATF2C0086692Benign Neoplasm1CTD_human
HgeneATF2C0235874Disease Exacerbation1CTD_human