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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:ACLY-TAF15

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ACLY-TAF15
FusionPDB ID: 1332
FusionGDB2.0 ID: 1332
HgeneTgene
Gene symbol

ACLY

TAF15

Gene ID

47

8148

Gene nameATP citrate lyaseTATA-box binding protein associated factor 15
SynonymsACL|ATPCL|CLATPNpl3|RBP56|TAF2N|TAFII68
Cytomap

17q21.2

17q12

Type of geneprotein-codingprotein-coding
DescriptionATP-citrate synthaseATP-citrate (pro-S-)-lyasecitrate cleavage enzymeTATA-binding protein-associated factor 2NRBP56/CSMF fusionTAF15 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 68kDaTATA box binding protein (TBP)-associated factor, RNA polymerase II, N, 68kD (RNA-binding protein 56)TATA box-bin
Modification date2020031320200313
UniProtAcc

P53396

Main function of 5'-partner protein: FUNCTION: Catalyzes the cleavage of citrate into oxaloacetate and acetyl-CoA, the latter serving as common substrate for de novo cholesterol and fatty acid synthesis. {ECO:0000269|PubMed:10653665, ECO:0000269|PubMed:1371749, ECO:0000269|PubMed:19286649, ECO:0000269|PubMed:23932781, ECO:0000269|PubMed:9116495}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000393896, ENST00000590151, 
ENST00000352035, ENST00000353196, 
ENST00000537919, ENST00000588779, 
ENST00000311979, ENST00000588240, 
ENST00000592237, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score11 X 14 X 6=92416 X 11 X 11=1936
# samples 1316
** MAII scorelog2(13/924*10)=-2.8293812283876
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(16/1936*10)=-3.59693514238723
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ACLY [Title/Abstract] AND TAF15 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ACLY [Title/Abstract] AND TAF15 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ACLY(40054002)-TAF15(34163136), # samples:2
Anticipated loss of major functional domain due to fusion event.ACLY-TAF15 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.
ACLY-TAF15 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.
ACLY-TAF15 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.
ACLY-TAF15 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.
ACLY-TAF15 seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
ACLY-TAF15 seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF.
ACLY-TAF15 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
HgeneACLY

GO:0006085

acetyl-CoA biosynthetic process

1371749

HgeneACLY

GO:0006101

citrate metabolic process

1371749

HgeneACLY

GO:0006107

oxaloacetate metabolic process

1371749

HgeneACLY

GO:0008610

lipid biosynthetic process

23932781

TgeneTAF15

GO:0048255

mRNA stabilization

27378374



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/chr17:40054002/chr17:34163136)
- 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 ACLY (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 TAF15 (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)
ENST00000352035ACLYchr1740054002-ENST00000588240TAF15chr1734163136+296315601312665844
ENST00000352035ACLYchr1740054002-ENST00000592237TAF15chr1734163136+264215601312509792
ENST00000352035ACLYchr1740054002-ENST00000311979TAF15chr1734163136+295515601312665844
ENST00000353196ACLYchr1740054002-ENST00000588240TAF15chr1734163136+299515921632697844
ENST00000353196ACLYchr1740054002-ENST00000592237TAF15chr1734163136+267415921632541792
ENST00000353196ACLYchr1740054002-ENST00000311979TAF15chr1734163136+298715921632697844
ENST00000537919ACLYchr1740054002-ENST00000588240TAF15chr1734163136+21767731271878583
ENST00000537919ACLYchr1740054002-ENST00000592237TAF15chr1734163136+18557731271722531
ENST00000537919ACLYchr1740054002-ENST00000311979TAF15chr1734163136+21687731271878583

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
ENST00000352035ENST00000588240ACLYchr1740054002-TAF15chr1734163136+0.0012224240.99877757
ENST00000352035ENST00000592237ACLYchr1740054002-TAF15chr1734163136+0.0010551950.9989448
ENST00000352035ENST00000311979ACLYchr1740054002-TAF15chr1734163136+0.001237030.99876297
ENST00000353196ENST00000588240ACLYchr1740054002-TAF15chr1734163136+0.00120410.99879587
ENST00000353196ENST00000592237ACLYchr1740054002-TAF15chr1734163136+0.0010231320.99897695
ENST00000353196ENST00000311979ACLYchr1740054002-TAF15chr1734163136+0.0012185650.9987814
ENST00000537919ENST00000588240ACLYchr1740054002-TAF15chr1734163136+0.0018684030.9981316
ENST00000537919ENST00000592237ACLYchr1740054002-TAF15chr1734163136+0.0011362450.9988638
ENST00000537919ENST00000311979ACLYchr1740054002-TAF15chr1734163136+0.0019280470.9980719

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 ACLY-TAF15

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ACLYchr1740054002TAF15chr17341631361560476VAPAKKAKPAMPQDSESDNSDNNTIF
ACLYchr1740054002TAF15chr17341631361560580SFATRRPEFMRGGGSGGGRRGRGGYR
ACLYchr1740054002TAF15chr17341631361560702SGDRSGGGYGGDRSGGGYGGDRGGGY
ACLYchr1740054002TAF15chr17341631361560723RGGGYGGDRGGGYGGDRGGGYGGDRG
ACLYchr1740054002TAF15chr17341631361560738DRGGGYGGDRGGYGGDRGGGYGGDRG
ACLYchr1740054002TAF15chr17341631361592476VAPAKKAKPAMPQDSESDNSDNNTIF
ACLYchr1740054002TAF15chr17341631361592580SFATRRPEFMRGGGSGGGRRGRGGYR
ACLYchr1740054002TAF15chr17341631361592702SGDRSGGGYGGDRSGGGYGGDRGGGY
ACLYchr1740054002TAF15chr17341631361592723RGGGYGGDRGGGYGGDRGGGYGGDRG
ACLYchr1740054002TAF15chr17341631361592738DRGGGYGGDRGGYGGDRGGGYGGDRG
ACLYchr1740054002TAF15chr1734163136773215VAPAKKAKPAMPQDSESDNSDNNTIF
ACLYchr1740054002TAF15chr1734163136773319SFATRRPEFMRGGGSGGGRRGRGGYR
ACLYchr1740054002TAF15chr1734163136773441SGDRSGGGYGGDRSGGGYGGDRGGGY
ACLYchr1740054002TAF15chr1734163136773462RGGGYGGDRGGGYGGDRGGGYGGDRG
ACLYchr1740054002TAF15chr1734163136773477DRGGGYGGDRGGYGGDRGGGYGGDRG

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Potential FusionNeoAntigen Information of ACLY-TAF15 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 ACLY-TAF15 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.
ACLY-TAF15_40054002_34163136.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)
ACLY-TAF15chr1740054002chr17341631361560DRB3-0101RGGYGGDRGGGYGGD924
ACLY-TAF15chr1740054002chr17341631361560DRB3-0104RGGYGGDRGGGYGGD924
ACLY-TAF15chr1740054002chr17341631361560DRB3-0105RGGYGGDRGGGYGGD924
ACLY-TAF15chr1740054002chr17341631361560DRB3-0108RGGYGGDRGGGYGGD924
ACLY-TAF15chr1740054002chr17341631361560DRB3-0109RGGYGGDRGGGYGGD924
ACLY-TAF15chr1740054002chr17341631361560DRB3-0111RGGYGGDRGGGYGGD924
ACLY-TAF15chr1740054002chr17341631361560DRB3-0112RGGYGGDRGGGYGGD924
ACLY-TAF15chr1740054002chr17341631361560DRB3-0113RGGYGGDRGGGYGGD924

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Fusion breakpoint peptide structures of ACLY-TAF15

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 ACLY-TAF15

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 ACLY-TAF15

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
ACLY-TAF15chr1740054002chr1734163136924RGGYGGDRGGGYGGDCCATGCCACAAGATTCAGAATCTGATAATTCAGATAACAACACAA

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Information of the samples that have these potential fusion neoantigens of ACLY-TAF15

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 ACLY-TAF15

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 ACLY-TAF15

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 ACLY-TAF15

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