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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:CPD-AATF

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CPD-AATF
FusionPDB ID: 18919
FusionGDB2.0 ID: 18919
HgeneTgene
Gene symbol

CPD

AATF

Gene ID

9455

26574

Gene namehomer scaffold protein 2apoptosis antagonizing transcription factor
SynonymsACPD|CPD|DFNA68|HOMER-2|VESL-2BFR2|CHE-1|CHE1|DED
Cytomap

15q25.2

17q12

Type of geneprotein-codingprotein-coding
Descriptionhomer protein homolog 2cupidinhomer homolog 2homer homolog 3homer scaffolding protein 2homer, neuronal immediate early gene, 2protein AATFrb-binding protein Che-1
Modification date2020031320200313
UniProtAcc

O75976

Main function of 5'-partner protein:

Q9NY61

Main function of 5'-partner protein: FUNCTION: May function as a general inhibitor of the histone deacetylase HDAC1. Binding to the pocket region of RB1 may displace HDAC1 from RB1/E2F complexes, leading to activation of E2F target genes and cell cycle progression. Conversely, displacement of HDAC1 from SP1 bound to the CDKN1A promoter leads to increased expression of this CDK inhibitor and blocks cell cycle progression. Also antagonizes PAWR mediated induction of aberrant amyloid peptide production in Alzheimer disease (presenile and senile dementia), although the molecular basis for this phenomenon has not been described to date. {ECO:0000269|PubMed:12450794, ECO:0000269|PubMed:12847090, ECO:0000269|PubMed:14627703, ECO:0000269|PubMed:15207272}.
Ensembl transtripts involved in fusion geneENST idsENST00000225719, ENST00000543464, 
ENST00000584051, 
ENST00000590321, 
ENST00000225402, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score26 X 16 X 10=416026 X 13 X 11=3718
# samples 2628
** MAII scorelog2(26/4160*10)=-4
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(28/3718*10)=-3.73102803797452
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: CPD [Title/Abstract] AND AATF [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CPD [Title/Abstract] AND AATF [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CPD(28748001)-AATF(35376304), # samples:3
Anticipated loss of major functional domain due to fusion event.CPD-AATF 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.
CPD-AATF 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.
CPD-AATF 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.
CPD-AATF 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
TgeneAATF

GO:0032929

negative regulation of superoxide anion generation

15207272

TgeneAATF

GO:0045944

positive regulation of transcription by RNA polymerase II

18049476

TgeneAATF

GO:2000378

negative regulation of reactive oxygen species metabolic process

15207272



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/chr17:28748001/chr17:35376304)
- 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 CPD (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 AATF (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)
ENST00000225719CPDchr1728748001+ENST00000225402AATFchr1735376304+17051213761497473
ENST00000543464CPDchr1728748001+ENST00000225402AATFchr1735376304+12907984021082226
ENST00000225719CPDchr1728748001+ENST00000225402AATFchr1735376303+17051213761497473
ENST00000543464CPDchr1728748001+ENST00000225402AATFchr1735376303+12907984021082226
ENST00000225719CPDchr1728748000+ENST00000225402AATFchr1735376303+17051213761497473
ENST00000543464CPDchr1728748000+ENST00000225402AATFchr1735376303+12907984021082226

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
ENST00000225719ENST00000225402CPDchr1728748001+AATFchr1735376304+0.0071604960.99283946
ENST00000543464ENST00000225402CPDchr1728748001+AATFchr1735376304+0.0013606430.9986394
ENST00000225719ENST00000225402CPDchr1728748001+AATFchr1735376303+0.0071604960.99283946
ENST00000543464ENST00000225402CPDchr1728748001+AATFchr1735376303+0.0013606430.9986394
ENST00000225719ENST00000225402CPDchr1728748000+AATFchr1735376303+0.0071604960.99283946
ENST00000543464ENST00000225402CPDchr1728748000+AATFchr1735376303+0.0013606430.9986394

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 CPD-AATF

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CPDchr1728748000AATFchr17353763031213379ENNRESLITLIEKLLRELIERKTSSL
CPDchr1728748000AATFchr1735376303798132ENNRESLITLIEKLLRELIERKTSSL
CPDchr1728748001AATFchr17353763031213379ENNRESLITLIEKLLRELIERKTSSL
CPDchr1728748001AATFchr1735376303798132ENNRESLITLIEKLLRELIERKTSSL
CPDchr1728748001AATFchr17353763041213379ENNRESLITLIEKLLRELIERKTSSL
CPDchr1728748001AATFchr1735376304798132ENNRESLITLIEKLLRELIERKTSSL

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Potential FusionNeoAntigen Information of CPD-AATF 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.
CPD-AATF_28748000_35376303.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)
CPD-AATFchr1728748000chr17353763031213HLA-A02:22SLITLIEKL0.99460.6455514
CPD-AATFchr1728748000chr17353763031213HLA-A02:13SLITLIEKL0.99420.6792514
CPD-AATFchr1728748000chr17353763031213HLA-A02:27SLITLIEKL0.99410.6025514
CPD-AATFchr1728748000chr17353763031213HLA-A02:67SLITLIEKL0.99290.6614514
CPD-AATFchr1728748000chr17353763031213HLA-A02:24SLITLIEKL0.99290.6614514
CPD-AATFchr1728748000chr17353763031213HLA-A02:30SLITLIEKL0.99290.6614514
CPD-AATFchr1728748000chr17353763031213HLA-A02:60SLITLIEKL0.99250.6815514
CPD-AATFchr1728748000chr17353763031213HLA-A02:11SLITLIEKL0.99250.6869514
CPD-AATFchr1728748000chr17353763031213HLA-A02:04SLITLIEKL0.99120.5964514
CPD-AATFchr1728748000chr17353763031213HLA-A74:09KLLRELIER0.99110.59441221
CPD-AATFchr1728748000chr17353763031213HLA-A74:03KLLRELIER0.99110.59441221
CPD-AATFchr1728748000chr17353763031213HLA-A74:11KLLRELIER0.99110.59441221
CPD-AATFchr1728748000chr17353763031213HLA-A02:21SLITLIEKL0.9910.7916514
CPD-AATFchr1728748000chr17353763031213HLA-A02:38SLITLIEKL0.98460.5713514
CPD-AATFchr1728748000chr17353763031213HLA-A02:35SLITLIEKL0.97640.6833514
CPD-AATFchr1728748000chr17353763031213HLA-A02:29SLITLIEKL0.97120.6635514
CPD-AATFchr1728748000chr17353763031213HLA-A02:20SLITLIEKL0.93850.662514
CPD-AATFchr1728748000chr17353763031213HLA-A31:02KLLRELIER0.91410.51591221
CPD-AATFchr1728748000chr17353763031213HLA-B13:01SLITLIEKL0.08520.8411514
CPD-AATFchr1728748000chr17353763031213HLA-A02:13TLIEKLLREL0.99730.6003818
CPD-AATFchr1728748000chr17353763031213HLA-A02:38TLIEKLLREL0.99380.6583818
CPD-AATFchr1728748000chr17353763031213HLA-A02:21TLIEKLLREL0.9920.5177818
CPD-AATFchr1728748000chr17353763031213HLA-A74:03KLLRELIERK0.91750.50761222
CPD-AATFchr1728748000chr17353763031213HLA-A74:11KLLRELIERK0.91750.50761222
CPD-AATFchr1728748000chr17353763031213HLA-A74:09KLLRELIERK0.91750.50761222
CPD-AATFchr1728748000chr17353763031213HLA-A02:07SLITLIEKL0.99360.6882514
CPD-AATFchr1728748000chr17353763031213HLA-A02:01SLITLIEKL0.99290.6614514
CPD-AATFchr1728748000chr17353763031213HLA-B18:03IEKLLREL0.99550.8151018
CPD-AATFchr1728748000chr17353763031213HLA-A02:03SLITLIEKL0.99420.7658514
CPD-AATFchr1728748000chr17353763031213HLA-A74:01KLLRELIER0.99110.59441221
CPD-AATFchr1728748000chr17353763031213HLA-A02:06SLITLIEKL0.9910.7916514
CPD-AATFchr1728748000chr17353763031213HLA-A02:14SLITLIEKL0.99090.7275514
CPD-AATFchr1728748000chr17353763031213HLA-B15:73SLITLIEKL0.9020.6968514
CPD-AATFchr1728748000chr17353763031213HLA-B15:30SLITLIEKL0.81020.6543514
CPD-AATFchr1728748000chr17353763031213HLA-C17:01SLITLIEKL0.45140.876514
CPD-AATFchr1728748000chr17353763031213HLA-A02:03TLIEKLLREL0.99880.5692818
CPD-AATFchr1728748000chr17353763031213HLA-A02:06TLIEKLLREL0.9920.5177818
CPD-AATFchr1728748000chr17353763031213HLA-A74:01KLLRELIERK0.91750.50761222
CPD-AATFchr1728748000chr17353763031213HLA-B40:04RESLITLIEKL0.99930.6341314

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Potential FusionNeoAntigen Information of CPD-AATF 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.
CPD-AATF_28748000_35376303.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)
CPD-AATFchr1728748000chr17353763031213DRB1-1113RESLITLIEKLLREL318
CPD-AATFchr1728748000chr17353763031213DRB1-1134RESLITLIEKLLREL318
CPD-AATFchr1728748000chr17353763031213DRB1-1344RESLITLIEKLLREL318
CPD-AATFchr1728748000chr17353763031213DRB1-1417RESLITLIEKLLREL318
CPD-AATFchr1728748000chr17353763031213DRB1-1523NRESLITLIEKLLRE217

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Fusion breakpoint peptide structures of CPD-AATF

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
5130LITLIEKLLRELIECPDAATFchr1728748000chr17353763031213

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CPD-AATF

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-B14:023BVN5130LITLIEKLLRELIE-7.9962-8.1096
HLA-B14:023BVN5130LITLIEKLLRELIE-5.70842-6.74372
HLA-B52:013W395130LITLIEKLLRELIE-6.83737-6.95077
HLA-B52:013W395130LITLIEKLLRELIE-4.4836-5.5189
HLA-A11:014UQ25130LITLIEKLLRELIE-10.0067-10.1201
HLA-A11:014UQ25130LITLIEKLLRELIE-9.03915-10.0745
HLA-A24:025HGA5130LITLIEKLLRELIE-6.56204-6.67544
HLA-A24:025HGA5130LITLIEKLLRELIE-5.42271-6.45801
HLA-B44:053DX85130LITLIEKLLRELIE-7.85648-8.89178
HLA-B44:053DX85130LITLIEKLLRELIE-5.3978-5.5112
HLA-A02:016TDR5130LITLIEKLLRELIE-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of CPD-AATF

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
CPD-AATFchr1728748000chr17353763031018IEKLLRELATTGAAAAGCTCCTTCGAGAACTC
CPD-AATFchr1728748000chr17353763031221KLLRELIERAAGCTCCTTCGAGAACTCATAGAACGG
CPD-AATFchr1728748000chr17353763031222KLLRELIERKAAGCTCCTTCGAGAACTCATAGAACGGAAG
CPD-AATFchr1728748000chr1735376303314RESLITLIEKLCGTGAGTCTTTGATCACATTGATTGAAAAGCTC
CPD-AATFchr1728748000chr1735376303514SLITLIEKLTCTTTGATCACATTGATTGAAAAGCTC
CPD-AATFchr1728748000chr1735376303818TLIEKLLRELACATTGATTGAAAAGCTCCTTCGAGAACTC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
CPD-AATFchr1728748000chr1735376303217NRESLITLIEKLLREAATCGTGAGTCTTTGATCACATTGATTGAAAAGCTCCTTCGAGAA
CPD-AATFchr1728748000chr1735376303318RESLITLIEKLLRELCGTGAGTCTTTGATCACATTGATTGAAAAGCTCCTTCGAGAACTC

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Information of the samples that have these potential fusion neoantigens of CPD-AATF

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
BRCACPD-AATFchr1728748000ENST00000225719chr1735376303ENST00000225402TCGA-A2-A1FW-01A

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Potential target of CAR-T therapy development for CPD-AATF

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 CPD-AATF

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 CPD-AATF

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