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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:ACSL6-CDS2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ACSL6-CDS2
FusionPDB ID: 1520
FusionGDB2.0 ID: 1520
HgeneTgene
Gene symbol

ACSL6

CDS2

Gene ID

23305

8760

Gene nameacyl-CoA synthetase long chain family member 6CDP-diacylglycerol synthase 2
SynonymsACS2|FACL6|LACS 6|LACS2|LACS5-
Cytomap

5q31.1

20p12.3

Type of geneprotein-codingprotein-coding
Descriptionlong-chain-fatty-acid--CoA ligase 6arachidonate--CoA ligasefatty-acid-Coenzyme A ligase, long-chain 6long fatty acyl-CoA synthetase 2phosphatidate cytidylyltransferase 2CDP-DAG synthase 2CDP-DG synthase 2CDP-DG synthetase 2CDP-diacylglycerol synthase (phosphatidate cytidylyltransferase) 2CDP-diglyceride diphosphorylase 2CDP-diglyceride pyrophosphorylase 2CDP-diglyceride synthase
Modification date2020031320200327
UniProtAcc

Q9UKU0

Main function of 5'-partner protein: FUNCTION: Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoA for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:22633490, PubMed:24269233). Plays an important role in fatty acid metabolism in brain and the acyl-CoAs produced may be utilized exclusively for the synthesis of the brain lipid. {ECO:0000269|PubMed:22633490, ECO:0000269|PubMed:24269233}.

O95674

Main function of 5'-partner protein: FUNCTION: Catalyzes the conversion of phosphatidic acid (PA) to CDP-diacylglycerol (CDP-DAG), an essential intermediate in the synthesis of phosphatidylglycerol, cardiolipin and phosphatidylinositol (PubMed:25375833). Exhibits specificity for the nature of the acyl chains at the sn-1 and sn-2 positions in the substrate, PA and the preferred acyl chain composition is 1-stearoyl-2-arachidonoyl-sn-phosphatidic acid (PubMed:25375833). Plays an important role in regulating the growth and maturation of lipid droplets which are storage organelles at the center of lipid and energy homeostasis (PubMed:26946540, PubMed:31548309). {ECO:0000269|PubMed:25375833, ECO:0000269|PubMed:26946540, ECO:0000269|PubMed:31548309}.
Ensembl transtripts involved in fusion geneENST idsENST00000296869, ENST00000357096, 
ENST00000379240, ENST00000379244, 
ENST00000379246, ENST00000379249, 
ENST00000379255, ENST00000379264, 
ENST00000379272, ENST00000431707, 
ENST00000543479, ENST00000544770, 
ENST00000477640, 
ENST00000379062, 
ENST00000379070, ENST00000535100, 
ENST00000460006, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score5 X 4 X 3=6010 X 11 X 7=770
# samples 413
** MAII scorelog2(4/60*10)=-0.584962500721156
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(13/770*10)=-2.56634682255381
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ACSL6 [Title/Abstract] AND CDS2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ACSL6 [Title/Abstract] AND CDS2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ACSL6(131307243)-CDS2(5154169), # samples:1
Anticipated loss of major functional domain due to fusion event.ACSL6-CDS2 seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
ACSL6-CDS2 seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF.
ACSL6-CDS2 seems lost the major protein functional domain in Tgene partner, which is a cell metabolism 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
HgeneACSL6

GO:0001676

long-chain fatty acid metabolic process

24269233



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/chr5:131307243/chr20:5154169)
- 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 ACSL6 (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 CDS2 (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)
ENST00000379249ACSL6chr5131307243-ENST00000460006CDS2chr205154169+10437150332783926
ENST00000379264ACSL6chr5131307243-ENST00000460006CDS2chr205154169+104771543432823926
ENST00000379272ACSL6chr5131307243-ENST00000460006CDS2chr205154169+10482154832828941
ENST00000296869ACSL6chr5131307243-ENST00000460006CDS2chr205154169+104281494512774907
ENST00000379246ACSL6chr5131307243-ENST00000460006CDS2chr205154169+1049215581662838890
ENST00000357096ACSL6chr5131307243-ENST00000460006CDS2chr205154169+10068113402414804
ENST00000431707ACSL6chr5131307243-ENST00000460006CDS2chr205154169+102591325172605862

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
ENST00000379249ENST00000460006ACSL6chr5131307243-CDS2chr205154169+0.0001949740.99980503
ENST00000379264ENST00000460006ACSL6chr5131307243-CDS2chr205154169+0.0001957850.9998042
ENST00000379272ENST00000460006ACSL6chr5131307243-CDS2chr205154169+0.0001910680.99980897
ENST00000296869ENST00000460006ACSL6chr5131307243-CDS2chr205154169+0.0001939550.9998061
ENST00000379246ENST00000460006ACSL6chr5131307243-CDS2chr205154169+0.0004781110.99952185
ENST00000357096ENST00000460006ACSL6chr5131307243-CDS2chr205154169+0.0002971730.99970275
ENST00000431707ENST00000460006ACSL6chr5131307243-CDS2chr205154169+0.0002190660.99978095

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 ACSL6-CDS2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ACSL6chr5131307243CDS2chr2051541691134378TVLGFLRAALGCQESESEAKVDGETA
ACSL6chr5131307243CDS2chr2051541691325436TVLGFLRAALGCQESESEAKVDGETA
ACSL6chr5131307243CDS2chr2051541691494481TVLGFLRAALGCQESESEAKVDGETA
ACSL6chr5131307243CDS2chr2051541691503500TVLGFLRAALGCQESESEAKVDGETA
ACSL6chr5131307243CDS2chr2051541691543500TVLGFLRAALGCQESESEAKVDGETA
ACSL6chr5131307243CDS2chr2051541691548515TVLGFLRAALGCQESESEAKVDGETA
ACSL6chr5131307243CDS2chr2051541691558464TVLGFLRAALGCQESESEAKVDGETA

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Potential FusionNeoAntigen Information of ACSL6-CDS2 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.
ACSL6-CDS2_131307243_5154169.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)
ACSL6-CDS2chr5131307243chr2051541691494HLA-B45:01QESESEAKV0.99780.77641221
ACSL6-CDS2chr5131307243chr2051541691494HLA-B50:02QESESEAKV0.99710.77071221
ACSL6-CDS2chr5131307243chr2051541691494HLA-B44:03QESESEAKV0.81150.97511221
ACSL6-CDS2chr5131307243chr2051541691494HLA-B50:01QESESEAKV0.47190.851221
ACSL6-CDS2chr5131307243chr2051541691494HLA-B41:01QESESEAKV0.46480.90811221
ACSL6-CDS2chr5131307243chr2051541691494HLA-B39:13QESESEAKV0.06250.95661221
ACSL6-CDS2chr5131307243chr2051541691494HLA-B40:06QESESEAKV0.99730.79461221
ACSL6-CDS2chr5131307243chr2051541691494HLA-B44:10QESESEAKV0.94340.57281221
ACSL6-CDS2chr5131307243chr2051541691494HLA-B44:09QESESEAKV0.8750.51861221
ACSL6-CDS2chr5131307243chr2051541691494HLA-B39:08QESESEAKV0.46460.90251221
ACSL6-CDS2chr5131307243chr2051541691494HLA-B40:04QESESEAKV0.98160.80051221
ACSL6-CDS2chr5131307243chr2051541691494HLA-B44:26QESESEAKV0.81150.97511221
ACSL6-CDS2chr5131307243chr2051541691494HLA-B44:07QESESEAKV0.81150.97511221
ACSL6-CDS2chr5131307243chr2051541691494HLA-B44:13QESESEAKV0.81150.97511221
ACSL6-CDS2chr5131307243chr2051541691494HLA-B41:03QESESEAKV0.66240.6071221
ACSL6-CDS2chr5131307243chr2051541691494HLA-B50:04QESESEAKV0.47190.851221
ACSL6-CDS2chr5131307243chr2051541691494HLA-B50:05QESESEAKV0.47190.851221

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Potential FusionNeoAntigen Information of ACSL6-CDS2 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 ACSL6-CDS2

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
7666RAALGCQESESEAKACSL6CDS2chr5131307243chr2051541691494

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ACSL6-CDS2

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-B14:023BVN7666RAALGCQESESEAK-7.15543-7.26883
HLA-B14:023BVN7666RAALGCQESESEAK-4.77435-5.80965
HLA-B52:013W397666RAALGCQESESEAK-6.80875-6.92215
HLA-B52:013W397666RAALGCQESESEAK-4.20386-5.23916
HLA-A11:014UQ27666RAALGCQESESEAK-7.5194-8.5547
HLA-A11:014UQ27666RAALGCQESESEAK-6.9601-7.0735
HLA-A24:025HGA7666RAALGCQESESEAK-7.52403-7.63743
HLA-A24:025HGA7666RAALGCQESESEAK-5.82433-6.85963
HLA-B27:056PYJ7666RAALGCQESESEAK-3.28285-4.31815
HLA-B44:053DX87666RAALGCQESESEAK-5.91172-6.94702
HLA-B44:053DX87666RAALGCQESESEAK-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of ACSL6-CDS2

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
ACSL6-CDS2chr5131307243chr2051541691221QESESEAKVCAGGAGTCAGAGTCAGAAGCAAAGGTA

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 ACSL6-CDS2

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
PRADACSL6-CDS2chr5131307243ENST00000296869chr205154169ENST00000460006TCGA-ZG-A9LZ-01A

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Potential target of CAR-T therapy development for ACSL6-CDS2

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
HgeneACSL6chr5:131307243chr20:5154169ENST00000296869-142125_45478723.0TransmembraneHelical%3B Signal-anchor for type III membrane protein
HgeneACSL6chr5:131307243chr20:5154169ENST00000357096-121925_45378623.0TransmembraneHelical%3B Signal-anchor for type III membrane protein
HgeneACSL6chr5:131307243chr20:5154169ENST00000379240-142125_45453698.0TransmembraneHelical%3B Signal-anchor for type III membrane protein
HgeneACSL6chr5:131307243chr20:5154169ENST00000379244-142125_45453698.0TransmembraneHelical%3B Signal-anchor for type III membrane protein
HgeneACSL6chr5:131307243chr20:5154169ENST00000379246-142125_45464709.0TransmembraneHelical%3B Signal-anchor for type III membrane protein
HgeneACSL6chr5:131307243chr20:5154169ENST00000379249-142125_45453668.0TransmembraneHelical%3B Signal-anchor for type III membrane protein
HgeneACSL6chr5:131307243chr20:5154169ENST00000379255-132025_45378623.0TransmembraneHelical%3B Signal-anchor for type III membrane protein
HgeneACSL6chr5:131307243chr20:5154169ENST00000379264-142125_45478723.0TransmembraneHelical%3B Signal-anchor for type III membrane protein
HgeneACSL6chr5:131307243chr20:5154169ENST00000379272-152225_45468713.0TransmembraneHelical%3B Signal-anchor for type III membrane protein
HgeneACSL6chr5:131307243chr20:5154169ENST00000543479-142125_45453698.0TransmembraneHelical%3B Signal-anchor for type III membrane protein
TgeneCDS2chr5:131307243chr20:5154169ENST00000460006013132_1520446.0TransmembraneHelical
TgeneCDS2chr5:131307243chr20:5154169ENST00000460006013166_1860446.0TransmembraneHelical
TgeneCDS2chr5:131307243chr20:5154169ENST00000460006013213_2330446.0TransmembraneHelical
TgeneCDS2chr5:131307243chr20:5154169ENST00000460006013262_2820446.0TransmembraneHelical
TgeneCDS2chr5:131307243chr20:5154169ENST00000460006013340_3600446.0TransmembraneHelical
TgeneCDS2chr5:131307243chr20:5154169ENST0000046000601379_990446.0TransmembraneHelical

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 ACSL6-CDS2

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 ACSL6-CDS2

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