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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:CLCN5-PAGE1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CLCN5-PAGE1
FusionPDB ID: 17002
FusionGDB2.0 ID: 17002
HgeneTgene
Gene symbol

CLCN5

PAGE1

Gene ID

1184

8712

Gene namechloride voltage-gated channel 5PAGE family member 1
SynonymsCLC5|CLCK2|ClC-5|DENTS|NPHL1|NPHL2|XLRH|XRN|hCIC-K2AL5|CT16.3|GAGE-9|GAGEB1|PAGE-1
Cytomap

Xp11.23

Xp11.23

Type of geneprotein-codingprotein-coding
DescriptionH(+)/Cl(-) exchange transporter 5chloride channel, voltage-sensitive 5chloride transporter ClC-5voltage-gated chloride ion channel CLCN5P antigen family member 1G antigen 9G antigen family B member 1G antigen, family B, 1 (prostate associated)P antigen family, member 1 (prostate associated)prostate associated gene 1prostate-associated gene 1 protein
Modification date2020031320200313
UniProtAcc

P51795

Main function of 5'-partner protein: FUNCTION: Proton-coupled chloride transporter. Functions as antiport system and exchanges chloride ions against protons. Important for normal acidification of the endosome lumen. May play an important role in renal tubular function.
.
Ensembl transtripts involved in fusion geneENST idsENST00000376088, ENST00000376091, 
ENST00000482218, ENST00000307367, 
ENST00000376108, 
ENST00000376150, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 4 X 4=963 X 3 X 3=27
# samples 63
** MAII scorelog2(6/96*10)=-0.678071905112638
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(3/27*10)=0.15200309344505
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: CLCN5 [Title/Abstract] AND PAGE1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CLCN5 [Title/Abstract] AND PAGE1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CLCN5(49689924)-PAGE1(49455977), # samples:3
Anticipated loss of major functional domain due to fusion event.CLCN5-PAGE1 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.
CLCN5-PAGE1 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


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/chrX:49689924/chrX:49455977)
- 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 CLCN5 (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 PAGE1 (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)
ENST00000376088CLCN5chrX49689924+ENST00000376150PAGE1chrX49455977-1023657593931112
ENST00000376091CLCN5chrX49689924+ENST00000376150PAGE1chrX49455977-714348284622112
ENST00000482218CLCN5chrX49689924+ENST00000376150PAGE1chrX49455977-589223159497112

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
ENST00000376088ENST00000376150CLCN5chrX49689924+PAGE1chrX49455977-0.0956694260.90433055
ENST00000376091ENST00000376150CLCN5chrX49689924+PAGE1chrX49455977-0.066975390.93302464
ENST00000482218ENST00000376150CLCN5chrX49689924+PAGE1chrX49455977-0.054903780.94509625

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 CLCN5-PAGE1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CLCN5chrX49689924PAGE1chrX4945597722321SVGEDRIKMAMWQGQEPEADSQELVQ
CLCN5chrX49689924PAGE1chrX4945597722363CLRNEEQMKLPAEGPEPEADSQEQVH
CLCN5chrX49689924PAGE1chrX4945597734821SVGEDRIKMAMWQGQEPEADSQELVQ
CLCN5chrX49689924PAGE1chrX4945597734863CLRNEEQMKLPAEGPEPEADSQEQVH
CLCN5chrX49689924PAGE1chrX4945597765721SVGEDRIKMAMWQGQEPEADSQELVQ
CLCN5chrX49689924PAGE1chrX4945597765763CLRNEEQMKLPAEGPEPEADSQEQVH

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Potential FusionNeoAntigen Information of CLCN5-PAGE1 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.
CLCN5-PAGE1_49689924_49455977.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)
CLCN5-PAGE1chrX49689924chrX49455977657HLA-B50:02AEGPEPEA0.99990.8091119
CLCN5-PAGE1chrX49689924chrX49455977657HLA-B45:01AEGPEPEA0.99980.96151119
CLCN5-PAGE1chrX49689924chrX49455977657HLA-B41:01AEGPEPEA0.97350.95341119
CLCN5-PAGE1chrX49689924chrX49455977657HLA-B56:01LPAEGPEPEA0.97470.6213919
CLCN5-PAGE1chrX49689924chrX49455977657HLA-B54:01LPAEGPEPEA0.9960.8729919
CLCN5-PAGE1chrX49689924chrX49455977657HLA-B55:02LPAEGPEPEA0.97460.6565919
CLCN5-PAGE1chrX49689924chrX49455977657HLA-B56:05LPAEGPEPEA0.79550.8071919
CLCN5-PAGE1chrX49689924chrX49455977657HLA-B78:02LPAEGPEPEA0.61150.8928919

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Potential FusionNeoAntigen Information of CLCN5-PAGE1 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 CLCN5-PAGE1

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
7412QMKLPAEGPEPEADCLCN5PAGE1chrX49689924chrX49455977657

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CLCN5-PAGE1

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-B14:023BVN7412QMKLPAEGPEPEAD-7.9962-8.1096
HLA-B14:023BVN7412QMKLPAEGPEPEAD-5.70842-6.74372
HLA-B52:013W397412QMKLPAEGPEPEAD-6.83737-6.95077
HLA-B52:013W397412QMKLPAEGPEPEAD-4.4836-5.5189
HLA-A11:014UQ27412QMKLPAEGPEPEAD-10.0067-10.1201
HLA-A11:014UQ27412QMKLPAEGPEPEAD-9.03915-10.0745
HLA-A24:025HGA7412QMKLPAEGPEPEAD-6.56204-6.67544
HLA-A24:025HGA7412QMKLPAEGPEPEAD-5.42271-6.45801
HLA-B44:053DX87412QMKLPAEGPEPEAD-7.85648-8.89178
HLA-B44:053DX87412QMKLPAEGPEPEAD-5.3978-5.5112
HLA-A02:016TDR7412QMKLPAEGPEPEAD-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of CLCN5-PAGE1

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
CLCN5-PAGE1chrX49689924chrX494559771119AEGPEPEAGGCAGGGGCAGGAGCCTGAAGCTG
CLCN5-PAGE1chrX49689924chrX49455977919LPAEGPEPEACCATGTGGCAGGGGCAGGAGCCTGAAGCTG

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 CLCN5-PAGE1

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
STADCLCN5-PAGE1chrX49689924ENST00000376088chrX49455977ENST00000376150TCGA-VQ-AA6J-01A

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Potential target of CAR-T therapy development for CLCN5-PAGE1

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 CLCN5-PAGE1

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 CLCN5-PAGE1

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