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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:ACSL5-VTI1A

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ACSL5-VTI1A
FusionPDB ID: 1518
FusionGDB2.0 ID: 1518
HgeneTgene
Gene symbol

ACSL5

VTI1A

Gene ID

51703

143187

Gene nameacyl-CoA synthetase long chain family member 5vesicle transport through interaction with t-SNAREs 1A
SynonymsACS2|ACS5|FACL5MMDS3|MVti1|VTI1RP2|Vti1-rp2
Cytomap

10q25.2

10q25.2

Type of geneprotein-codingprotein-coding
Descriptionlong-chain-fatty-acid--CoA ligase 5FACL5 for fatty acid coenzyme A ligase 5LACS 5arachidonate--CoA ligasefatty acid coenzyme A ligase 5fatty-acid-Coenzyme A ligase, long-chain 5long-chain acyl-CoA synthetase 5long-chain fatty acid coenzyme A ligasevesicle transport through interaction with t-SNAREs homolog 1ASNARE Vti1a-beta proteinvesicle transport v-SNARE protein Vti1-like 2
Modification date2020031320200313
UniProtAcc

Q9ULC5

Main function of 5'-partner protein: FUNCTION: Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoAs for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:17681178, PubMed:24269233, PubMed:22633490). ACSL5 may activate fatty acids from exogenous sources for the synthesis of triacylglycerol destined for intracellular storage (By similarity). Utilizes a wide range of saturated fatty acids with a preference for C16-C18 unsaturated fatty acids (By similarity). It was suggested that it may also stimulate fatty acid oxidation (By similarity). At the villus tip of the crypt-villus axis of the small intestine may sensitize epithelial cells to apoptosis specifically triggered by the death ligand TRAIL. May have a role in the survival of glioma cells. {ECO:0000250, ECO:0000269|PubMed:17681178, ECO:0000269|PubMed:18806831, ECO:0000269|PubMed:19459852, ECO:0000269|PubMed:22633490, ECO:0000269|PubMed:24269233}.

Q96AJ9

Main function of 5'-partner protein: FUNCTION: V-SNARE that mediates vesicle transport pathways through interactions with t-SNAREs on the target membrane. These interactions are proposed to mediate aspects of the specificity of vesicle trafficking and to promote fusion of the lipid bilayers. Involved in vesicular transport from the late endosomes to the trans-Golgi network. Along with VAMP7, involved in an non-conventional RAB1-dependent traffic route to the cell surface used by KCNIP1 and KCND2. May be involved in increased cytokine secretion associated with cellular senescence. {ECO:0000269|PubMed:18195106, ECO:0000269|PubMed:19138172}.
Ensembl transtripts involved in fusion geneENST idsENST00000479936, ENST00000354273, 
ENST00000354655, ENST00000356116, 
ENST00000393081, ENST00000433418, 
ENST00000369410, 
ENST00000393077, 
ENST00000432306, ENST00000483122, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 6 X 5=18017 X 15 X 10=2550
# samples 624
** MAII scorelog2(6/180*10)=-1.58496250072116
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(24/2550*10)=-3.4093909361377
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ACSL5 [Title/Abstract] AND VTI1A [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ACSL5 [Title/Abstract] AND VTI1A [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)VTI1A(114224416)-ACSL5(114154676), # samples:2
ACSL5(114164564)-VTI1A(114286845), # samples:1
Anticipated loss of major functional domain due to fusion event.
* 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
HgeneACSL5

GO:0001676

long-chain fatty acid metabolic process

24269233

TgeneVTI1A

GO:0042147

retrograde transport, endosome to Golgi

15215310|18195106



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/chr10:114224416/chr10:114154676)
- 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 ACSL5 (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 VTI1A (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)
ENST00000354655ACSL5chr10114164564+ENST00000432306VTI1Achr10114286845+20717132541060268
ENST00000354655ACSL5chr10114164564+ENST00000393077VTI1Achr10114286845+44647132541102282
ENST00000393081ACSL5chr10114164564+ENST00000432306VTI1Achr10114286845+20977392801086268
ENST00000393081ACSL5chr10114164564+ENST00000393077VTI1Achr10114286845+44907392801128282
ENST00000433418ACSL5chr10114164564+ENST00000432306VTI1Achr10114286845+2070712491059336
ENST00000433418ACSL5chr10114164564+ENST00000393077VTI1Achr10114286845+4463712491101350
ENST00000356116ACSL5chr10114164564+ENST00000432306VTI1Achr10114286845+2070712491059336
ENST00000356116ACSL5chr10114164564+ENST00000393077VTI1Achr10114286845+4463712491101350
ENST00000354273ACSL5chr10114164564+ENST00000432306VTI1Achr10114286845+2069711481058336
ENST00000354273ACSL5chr10114164564+ENST00000393077VTI1Achr10114286845+4462711481100350

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
ENST00000354655ENST00000432306ACSL5chr10114164564+VTI1Achr10114286845+0.0005533910.9994466
ENST00000354655ENST00000393077ACSL5chr10114164564+VTI1Achr10114286845+0.000337050.999663
ENST00000393081ENST00000432306ACSL5chr10114164564+VTI1Achr10114286845+0.0007232910.9992767
ENST00000393081ENST00000393077ACSL5chr10114164564+VTI1Achr10114286845+0.0004695050.99953055
ENST00000433418ENST00000432306ACSL5chr10114164564+VTI1Achr10114286845+0.0017366450.9982634
ENST00000433418ENST00000393077ACSL5chr10114164564+VTI1Achr10114286845+0.0010297040.99897027
ENST00000356116ENST00000432306ACSL5chr10114164564+VTI1Achr10114286845+0.0017366450.9982634
ENST00000356116ENST00000393077ACSL5chr10114164564+VTI1Achr10114286845+0.0010297040.99897027
ENST00000354273ENST00000432306ACSL5chr10114164564+VTI1Achr10114286845+0.0017491820.9982508
ENST00000354273ENST00000393077ACSL5chr10114164564+VTI1Achr10114286845+0.0010352170.9989648

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 ACSL5-VTI1A

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 ACSL5-VTI1A 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 ACSL5-VTI1A 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 ACSL5-VTI1A

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 ACSL5-VTI1A

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 ACSL5-VTI1A

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 ACSL5-VTI1A

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 ACSL5-VTI1A

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
HgeneACSL5chr10:114164564chr10:114286845ENST00000354273+52112_32144684.0TransmembraneHelical%3B Signal-anchor for type III membrane protein
HgeneACSL5chr10:114164564chr10:114286845ENST00000354655+52112_32144684.0TransmembraneHelical%3B Signal-anchor for type III membrane protein
HgeneACSL5chr10:114164564chr10:114286845ENST00000356116+52112_32200740.0TransmembraneHelical%3B Signal-anchor for type III membrane protein
HgeneACSL5chr10:114164564chr10:114286845ENST00000393081+52112_32144684.0TransmembraneHelical%3B Signal-anchor for type III membrane protein
HgeneACSL5chr10:114164564chr10:114286845ENST00000433418+52012_32144660.0TransmembraneHelical%3B Signal-anchor for type III membrane protein
TgeneVTI1Achr10:114164564chr10:114286845ENST0000039307728193_2130218.0TransmembraneHelical
TgeneVTI1Achr10:114164564chr10:114286845ENST0000043230628193_2130204.0TransmembraneHelical

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 ACSL5-VTI1A

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 ACSL5-VTI1A

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
HgeneACSL5C0003865Arthritis, Adjuvant-Induced1CTD_human
HgeneACSL5C0971858Arthritis, Collagen-Induced1CTD_human
HgeneACSL5C0993582Arthritis, Experimental1CTD_human
TgeneVTI1AC0001418Adenocarcinoma1CTD_human
TgeneVTI1AC0009402Colorectal Carcinoma1CTD_human
TgeneVTI1AC0009404Colorectal Neoplasms1CTD_human
TgeneVTI1AC0205641Adenocarcinoma, Basal Cell1CTD_human
TgeneVTI1AC0205642Adenocarcinoma, Oxyphilic1CTD_human
TgeneVTI1AC0205643Carcinoma, Cribriform1CTD_human
TgeneVTI1AC0205644Carcinoma, Granular Cell1CTD_human
TgeneVTI1AC0205645Adenocarcinoma, Tubular1CTD_human