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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:CLN6-ARL6IP5

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CLN6-ARL6IP5
FusionPDB ID: 17237
FusionGDB2.0 ID: 17237
HgeneTgene
Gene symbol

CLN6

ARL6IP5

Gene ID

54982

10550

Gene nameCLN6 transmembrane ER proteinADP ribosylation factor like GTPase 6 interacting protein 5
SynonymsCLN4A|HsT18960|nclfDERP11|GTRAP3-18|HSPC127|JWA|PRAF3|Yip6b|addicsin|hp22|jmx
Cytomap

15q23

3p14.1

Type of geneprotein-codingprotein-coding
Descriptionceroid-lipofuscinosis neuronal protein 6ceroid-lipofuscinosis neuronal 6 late infantileceroid-lipofuscinosis, neuronal 6, late infantilePRA1 family protein 3ADP-ribosylation factor GTPase 6 interacting protein 5ADP-ribosylation factor-like 6 interacting protein 5ADP-ribosylation factor-like protein 6-interacting protein 5ADP-ribosylation-like factor 6 interacting protein 5ARL-6-inter
Modification date2020032820200313
UniProtAcc

Q9NWW5

Main function of 5'-partner protein:

O75915

Main function of 5'-partner protein: FUNCTION: Regulates intracellular concentrations of taurine and glutamate. Negatively modulates SLC1A1/EAAC1 glutamate transport activity by decreasing its affinity for glutamate in a PKC activity-dependent manner. Plays a role in the retention of SLC1A1/EAAC1 in the endoplasmic reticulum. {ECO:0000250|UniProtKB:Q8R5J9, ECO:0000250|UniProtKB:Q9ES40}.
Ensembl transtripts involved in fusion geneENST idsENST00000249806, ENST00000538696, 
ENST00000564752, ENST00000566347, 
ENST00000418702, ENST00000565471, 
ENST00000569336, 
ENST00000273258, 
ENST00000478935, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score12 X 7 X 9=7568 X 7 X 3=168
# samples 128
** MAII scorelog2(12/756*10)=-2.65535182861255
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(8/168*10)=-1.0703893278914
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: CLN6 [Title/Abstract] AND ARL6IP5 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CLN6 [Title/Abstract] AND ARL6IP5 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CLN6(68510874)-ARL6IP5(69150990), # samples:1
Anticipated loss of major functional domain due to fusion event.CLN6-ARL6IP5 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.
CLN6-ARL6IP5 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.
CLN6-ARL6IP5 seems lost the major protein functional domain in Tgene partner, which is a tumor suppressor 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
TgeneARL6IP5

GO:0008631

intrinsic apoptotic signaling pathway in response to oxidative stress

18387645



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/chr15:68510874/chr3:69150990)
- 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 CLN6 (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 ARL6IP5 (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)
ENST00000418702CLN6chr1568510874-ENST00000273258ARL6IP5chr369150990+2105284186674162
ENST00000418702CLN6chr1568510874-ENST00000478935ARL6IP5chr369150990+15302843012100

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
ENST00000418702ENST00000273258CLN6chr1568510874-ARL6IP5chr369150990+0.0095913760.99040866
ENST00000418702ENST00000478935CLN6chr1568510874-ARL6IP5chr369150990+0.60450350.39549646

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 CLN6-ARL6IP5

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CLN6chr1568510874ARL6IP5chr36915099028433RTGFWTLGVPLPWFLSPFNMILGGIV

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Potential FusionNeoAntigen Information of CLN6-ARL6IP5 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.
CLN6-ARL6IP5_68510874_69150990.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)
CLN6-ARL6IP5chr1568510874chr369150990284HLA-B35:05LPWFLSPF0.99580.67451018
CLN6-ARL6IP5chr1568510874chr369150990284HLA-A02:17TLGVPLPWFL0.83090.7447515
CLN6-ARL6IP5chr1568510874chr369150990284HLA-B51:02LPWFLSPFNMI0.95530.59691021
CLN6-ARL6IP5chr1568510874chr369150990284HLA-B78:01VPLPWFLSP0.92940.6155817
CLN6-ARL6IP5chr1568510874chr369150990284HLA-B35:17LPWFLSPF0.99580.81171018
CLN6-ARL6IP5chr1568510874chr369150990284HLA-B35:30LPWFLSPF0.99580.81171018
CLN6-ARL6IP5chr1568510874chr369150990284HLA-B78:02VPLPWFLSP0.90920.6264817
CLN6-ARL6IP5chr1568510874chr369150990284HLA-B51:21VPLPWFLSP0.75370.5105817
CLN6-ARL6IP5chr1568510874chr369150990284HLA-B35:17VPLPWFLSPF0.99230.6173818
CLN6-ARL6IP5chr1568510874chr369150990284HLA-B35:30VPLPWFLSPF0.99230.6173818
CLN6-ARL6IP5chr1568510874chr369150990284HLA-B51:09LPWFLSPFNMI0.97420.57051021

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Potential FusionNeoAntigen Information of CLN6-ARL6IP5 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 CLN6-ARL6IP5

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
5039LGVPLPWFLSPFNMCLN6ARL6IP5chr1568510874chr369150990284

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CLN6-ARL6IP5

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-B14:023BVN5039LGVPLPWFLSPFNM-6.01316-6.12656
HLA-B14:023BVN5039LGVPLPWFLSPFNM-3.92858-4.96388
HLA-B52:013W395039LGVPLPWFLSPFNM-5.92102-6.95632
HLA-B52:013W395039LGVPLPWFLSPFNM-4.84472-4.95812
HLA-A24:025HGA5039LGVPLPWFLSPFNM-8.26357-9.29887
HLA-A24:025HGA5039LGVPLPWFLSPFNM-7.03366-7.14706
HLA-B44:053DX85039LGVPLPWFLSPFNM-6.13971-6.25311
HLA-B44:053DX85039LGVPLPWFLSPFNM-5.20728-6.24258
HLA-A02:016TDR5039LGVPLPWFLSPFNM-5.28864-5.40204

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Vaccine Design for the FusionNeoAntigens of CLN6-ARL6IP5

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
CLN6-ARL6IP5chr1568510874chr3691509901018LPWFLSPFATTGCCATGGTTTCTGAGTCCCTT
CLN6-ARL6IP5chr1568510874chr3691509901021LPWFLSPFNMIATTGCCATGGTTTCTGAGTCCCTTCAACATGAT
CLN6-ARL6IP5chr1568510874chr369150990515TLGVPLPWFLGACTTTGGGCGTCCCATTGCCATGGTTTCT
CLN6-ARL6IP5chr1568510874chr369150990817VPLPWFLSPCGTCCCATTGCCATGGTTTCTGAGTCC
CLN6-ARL6IP5chr1568510874chr369150990818VPLPWFLSPFCGTCCCATTGCCATGGTTTCTGAGTCCCTT

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 CLN6-ARL6IP5

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
STADCLN6-ARL6IP5chr1568510874ENST00000418702chr369150990ENST00000273258TCGA-BR-8683-01A

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Potential target of CAR-T therapy development for CLN6-ARL6IP5

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
TgeneARL6IP5chr15:68510874chr3:69150990ENST0000027325803115_1350189.0TransmembraneHelical
TgeneARL6IP5chr15:68510874chr3:69150990ENST000002732580357_770189.0TransmembraneHelical
TgeneARL6IP5chr15:68510874chr3:69150990ENST000002732580394_1140189.0TransmembraneHelical

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 CLN6-ARL6IP5

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 CLN6-ARL6IP5

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