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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:ARL3-ACO1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ARL3-ACO1
FusionPDB ID: 6597
FusionGDB2.0 ID: 6597
HgeneTgene
Gene symbol

ARL3

ACO1

Gene ID

403

48

Gene nameADP ribosylation factor like GTPase 3aconitase 1
SynonymsARFL3|JBTS35|RP83ACONS|HEL60|IREB1|IREBP|IREBP1|IRP1
Cytomap

10q24.32

9p21.1

Type of geneprotein-codingprotein-coding
DescriptionADP-ribosylation factor-like protein 3ADP-ribosylation factor-like 3ARF-like 3cytoplasmic aconitate hydrataseaconitase 1, solubleaconitate hydratase, cytoplasmiccitrate hydro-lyasecytoplasmic aconitasecytosplasmic aconitaseepididymis luminal protein 60epididymis secretory sperm binding proteinferritin repressor proteiniron
Modification date2020031520200313
UniProtAcc

P36405

Main function of 5'-partner protein: FUNCTION: Small GTP-binding protein which cycles between an inactive GDP-bound and an active GTP-bound form, and the rate of cycling is regulated by guanine nucleotide exchange factors (GEF) and GTPase-activating proteins (GAP) (PubMed:16525022, PubMed:18588884). Required for normal cytokinesis and cilia signaling (PubMed:22085962). Requires assistance from GTPase-activating proteins (GAPs) like RP2 and PDE6D, in order to cycle between inactive GDP-bound and active GTP-bound forms. Required for targeting proteins to the cilium, including myristoylated NPHP3 and prenylated INPP5E (PubMed:30269812). Targets NPHP3 to the ciliary membrane by releasing myristoylated NPHP3 from UNC119B cargo adapter into the cilium (PubMed:22085962). Required for PKD1:PKD2 complex targeting from the trans-Golgi network to the cilium (By similarity). {ECO:0000250|UniProtKB:Q9WUL7, ECO:0000269|PubMed:16525022, ECO:0000269|PubMed:18588884, ECO:0000269|PubMed:22085962}.

P21399

Main function of 5'-partner protein: FUNCTION: Iron sensor. Binds a 4Fe-4S cluster and functions as aconitase when cellular iron levels are high. Functions as mRNA binding protein that regulates uptake, sequestration and utilization of iron when cellular iron levels are low. Binds to iron-responsive elements (IRES) in target mRNA species when iron levels are low. Binding of a 4Fe-4S cluster precludes RNA binding. {ECO:0000269|PubMed:1946430, ECO:0000269|PubMed:23891004, ECO:0000269|PubMed:8041788}.; FUNCTION: Catalyzes the isomerization of citrate to isocitrate via cis-aconitate. {ECO:0000250}.
Ensembl transtripts involved in fusion geneENST idsENST00000260746, ENST00000309951, 
ENST00000379923, ENST00000541043, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score3 X 3 X 2=189 X 12 X 5=540
# samples 312
** MAII scorelog2(3/18*10)=0.736965594166206
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
log2(12/540*10)=-2.16992500144231
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ARL3 [Title/Abstract] AND ACO1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ARL3 [Title/Abstract] AND ACO1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ACO1(32436395)-ARL3(104445758), # samples:2
ARL3(104445573)-ACO1(32440463), # samples:1
Anticipated loss of major functional domain due to fusion event.ACO1-ARL3 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.
ACO1-ARL3 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.
ARL3-ACO1 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.
ARL3-ACO1 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.
ARL3-ACO1 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.
ARL3-ACO1 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
HgeneARL3

GO:0007264

small GTPase mediated signal transduction

22085962

TgeneACO1

GO:0006101

citrate metabolic process

8041788|16527810

TgeneACO1

GO:0010040

response to iron(II) ion

8041788



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/chr10:32436395/chr9:104445758)
- 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 ARL3 (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 ACO1 (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)
ENST00000260746ARL3chr10104445573-ENST00000541043ACO1chr932440463+17776331321055307
ENST00000260746ARL3chr10104445573-ENST00000379923ACO1chr932440463+17816331321055307
ENST00000260746ARL3chr10104445573-ENST00000309951ACO1chr932440463+57146331321055307

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
ENST00000260746ENST00000541043ARL3chr10104445573-ACO1chr932440463+0.0030724370.99692756
ENST00000260746ENST00000379923ARL3chr10104445573-ACO1chr932440463+0.0030585120.9969415
ENST00000260746ENST00000309951ARL3chr10104445573-ACO1chr932440463+0.0005903960.99940956

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 ARL3-ACO1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ARL3chr10104445573ACO1chr932440463633166QIQSCSALTGEGVQLDVFDAAERYQQ

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Potential FusionNeoAntigen Information of ARL3-ACO1 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.
ARL3-ACO1_104445573_32440463.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)
ARL3-ACO1chr10104445573chr932440463633HLA-A02:22ALTGEGVQL0.9760.6157615
ARL3-ACO1chr10104445573chr932440463633HLA-A02:30ALTGEGVQL0.94820.6034615
ARL3-ACO1chr10104445573chr932440463633HLA-A02:24ALTGEGVQL0.94820.6034615
ARL3-ACO1chr10104445573chr932440463633HLA-A02:67ALTGEGVQL0.94820.6034615
ARL3-ACO1chr10104445573chr932440463633HLA-A02:60ALTGEGVQL0.94560.6298615
ARL3-ACO1chr10104445573chr932440463633HLA-A02:11ALTGEGVQL0.94290.6261615
ARL3-ACO1chr10104445573chr932440463633HLA-A02:27ALTGEGVQL0.94110.7144615
ARL3-ACO1chr10104445573chr932440463633HLA-A02:38ALTGEGVQL0.93420.7714615
ARL3-ACO1chr10104445573chr932440463633HLA-A02:13ALTGEGVQL0.9310.7797615
ARL3-ACO1chr10104445573chr932440463633HLA-A02:16ALTGEGVQL0.92010.5226615
ARL3-ACO1chr10104445573chr932440463633HLA-A02:04ALTGEGVQL0.88270.7977615
ARL3-ACO1chr10104445573chr932440463633HLA-A02:17ALTGEGVQL0.8430.7336615
ARL3-ACO1chr10104445573chr932440463633HLA-A02:19ALTGEGVQL0.80840.7088615
ARL3-ACO1chr10104445573chr932440463633HLA-A02:29ALTGEGVQL0.79460.6056615
ARL3-ACO1chr10104445573chr932440463633HLA-A02:20ALTGEGVQL0.77550.6139615
ARL3-ACO1chr10104445573chr932440463633HLA-A02:35ALTGEGVQL0.76060.6124615
ARL3-ACO1chr10104445573chr932440463633HLA-A02:02ALTGEGVQL0.97650.519615
ARL3-ACO1chr10104445573chr932440463633HLA-A02:05ALTGEGVQL0.9590.609615
ARL3-ACO1chr10104445573chr932440463633HLA-A02:01ALTGEGVQL0.94820.6034615
ARL3-ACO1chr10104445573chr932440463633HLA-A02:03ALTGEGVQL0.95620.6909615
ARL3-ACO1chr10104445573chr932440463633HLA-A02:14ALTGEGVQL0.92270.6914615
ARL3-ACO1chr10104445573chr932440463633HLA-B15:73ALTGEGVQL0.58320.9688615
ARL3-ACO1chr10104445573chr932440463633HLA-B15:30ALTGEGVQL0.49610.9687615
ARL3-ACO1chr10104445573chr932440463633HLA-B40:21ALTGEGVQL0.02650.6785615
ARL3-ACO1chr10104445573chr932440463633HLA-B35:13SALTGEGVQL0.85540.8554515

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Potential FusionNeoAntigen Information of ARL3-ACO1 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.
ARL3-ACO1_104445573_32440463.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)
ARL3-ACO1chr10104445573chr932440463633DRB5-0103GVQLDVFDAAERYQQ1126
ARL3-ACO1chr10104445573chr932440463633DRB5-0106GVQLDVFDAAERYQQ1126
ARL3-ACO1chr10104445573chr932440463633DRB5-0106EGVQLDVFDAAERYQ1025
ARL3-ACO1chr10104445573chr932440463633DRB5-0106GEGVQLDVFDAAERY924
ARL3-ACO1chr10104445573chr932440463633DRB5-0111GVQLDVFDAAERYQQ1126
ARL3-ACO1chr10104445573chr932440463633DRB5-0111EGVQLDVFDAAERYQ1025
ARL3-ACO1chr10104445573chr932440463633DRB5-0202GVQLDVFDAAERYQQ1126
ARL3-ACO1chr10104445573chr932440463633DRB5-0202EGVQLDVFDAAERYQ1025
ARL3-ACO1chr10104445573chr932440463633DRB5-0202GEGVQLDVFDAAERY924
ARL3-ACO1chr10104445573chr932440463633DRB5-0203GVQLDVFDAAERYQQ1126
ARL3-ACO1chr10104445573chr932440463633DRB5-0203EGVQLDVFDAAERYQ1025
ARL3-ACO1chr10104445573chr932440463633DRB5-0204GVQLDVFDAAERYQQ1126
ARL3-ACO1chr10104445573chr932440463633DRB5-0204EGVQLDVFDAAERYQ1025
ARL3-ACO1chr10104445573chr932440463633DRB5-0204GEGVQLDVFDAAERY924
ARL3-ACO1chr10104445573chr932440463633DRB5-0205GVQLDVFDAAERYQQ1126
ARL3-ACO1chr10104445573chr932440463633DRB5-0205EGVQLDVFDAAERYQ1025
ARL3-ACO1chr10104445573chr932440463633DRB5-0205GEGVQLDVFDAAERY924

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Fusion breakpoint peptide structures of ARL3-ACO1

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
414ALTGEGVQLDVFDAARL3ACO1chr10104445573chr932440463633

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ARL3-ACO1

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-B14:023BVN414ALTGEGVQLDVFDA-7.15543-7.26883
HLA-B14:023BVN414ALTGEGVQLDVFDA-4.77435-5.80965
HLA-B52:013W39414ALTGEGVQLDVFDA-6.80875-6.92215
HLA-B52:013W39414ALTGEGVQLDVFDA-4.20386-5.23916
HLA-A11:014UQ2414ALTGEGVQLDVFDA-7.5194-8.5547
HLA-A11:014UQ2414ALTGEGVQLDVFDA-6.9601-7.0735
HLA-A24:025HGA414ALTGEGVQLDVFDA-7.52403-7.63743
HLA-A24:025HGA414ALTGEGVQLDVFDA-5.82433-6.85963
HLA-B27:056PYJ414ALTGEGVQLDVFDA-3.28285-4.31815
HLA-B44:053DX8414ALTGEGVQLDVFDA-5.91172-6.94702
HLA-B44:053DX8414ALTGEGVQLDVFDA-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of ARL3-ACO1

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
ARL3-ACO1chr10104445573chr932440463515SALTGEGVQLGCTCTCACAGGAGAGGGCGTTCAGCTTGAT
ARL3-ACO1chr10104445573chr932440463615ALTGEGVQLCTCACAGGAGAGGGCGTTCAGCTTGAT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
ARL3-ACO1chr10104445573chr9324404631025EGVQLDVFDAAERYQGGCGTTCAGCTTGATGTGTTTGATGCTGCTGAGCGGTACCAGCAG
ARL3-ACO1chr10104445573chr9324404631126GVQLDVFDAAERYQQGTTCAGCTTGATGTGTTTGATGCTGCTGAGCGGTACCAGCAGGCA
ARL3-ACO1chr10104445573chr932440463924GEGVQLDVFDAAERYGAGGGCGTTCAGCTTGATGTGTTTGATGCTGCTGAGCGGTACCAG

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Information of the samples that have these potential fusion neoantigens of ARL3-ACO1

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
UCECARL3-ACO1chr10104445573ENST00000260746chr932440463ENST00000309951TCGA-D1-A175-01A

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Potential target of CAR-T therapy development for ARL3-ACO1

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 ARL3-ACO1

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 ARL3-ACO1

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