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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:CLSTN1-CTNNBIP1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CLSTN1-CTNNBIP1
FusionPDB ID: 17342
FusionGDB2.0 ID: 17342
HgeneTgene
Gene symbol

CLSTN1

CTNNBIP1

Gene ID

22883

56998

Gene namecalsyntenin 1catenin beta interacting protein 1
SynonymsALC-ALPHA|CDHR12|CST-1|CSTN1|PIK3CD|XB31alpha|alcalpha1|alcalpha2ICAT
Cytomap

1p36.22

1p36.22

Type of geneprotein-codingprotein-coding
Descriptioncalsyntenin-1alcadein-alphaalzheimer-related cadherin-like proteincadherin-related family member 12non-classical cadherin XB31alphabeta-catenin-interacting protein 1beta-catenin-interacting protein ICATinhibitor of beta-catenin and Tcf-4
Modification date2020031320200313
UniProtAcc

O94985

Main function of 5'-partner protein: FUNCTION: Induces KLC1 association with vesicles and functions as a cargo in axonal anterograde transport. Complex formation with APBA2 and APP, stabilizes APP metabolism and enhances APBA2-mediated suppression of beta-APP40 secretion, due to the retardation of intracellular APP maturation. In complex with APBA2 and C99, a C-terminal APP fragment, abolishes C99 interaction with PSEN1 and thus APP C99 cleavage by gamma-secretase, most probably through stabilization of the direct interaction between APBA2 and APP. The intracellular fragment AlcICD suppresses APBB1-dependent transactivation stimulated by APP C-terminal intracellular fragment (AICD), most probably by competing with AICD for APBB1-binding. May modulate calcium-mediated postsynaptic signals (By similarity). {ECO:0000250, ECO:0000269|PubMed:12972431}.

Q9NSA3

Main function of 5'-partner protein: FUNCTION: Prevents the interaction between CTNNB1 and TCF family members, and acts as negative regulator of the Wnt signaling pathway. {ECO:0000269|PubMed:12408824}.
Ensembl transtripts involved in fusion geneENST idsENST00000361311, ENST00000377288, 
ENST00000377298, ENST00000477264, 
ENST00000377256, ENST00000377258, 
ENST00000377263, ENST00000400904, 
ENST00000537447, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score12 X 15 X 7=12607 X 7 X 9=441
# samples 2013
** MAII scorelog2(20/1260*10)=-2.65535182861255
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(13/441*10)=-1.76226703252907
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: CLSTN1 [Title/Abstract] AND CTNNBIP1 [Title/Abstract] AND fusion [Title/Abstract]

Recurrent chimeric fusion RNAs in non-cancer tissues and cells (pmid: 26837576)
Recurrent chimeric fusion RNAs in non-cancer tissues and cells (pmid: 26837576)
Fusion neoantigen context

PubMed: CLSTN1 [Title/Abstract] AND CTNNBIP1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CTNNBIP1(9931244)-CLSTN1(9833452), # samples:6
CLSTN1(9833330)-CTNNBIP1(9910834), # samples:2
CLSTN1(9809519)-CTNNBIP1(9910834), # samples:2
Anticipated loss of major functional domain due to fusion event.CLSTN1-CTNNBIP1 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.
CLSTN1-CTNNBIP1 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.
CLSTN1-CTNNBIP1 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.
CLSTN1-CTNNBIP1 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.
CLSTN1-CTNNBIP1 seems lost the major protein functional domain in Tgene partner, which is a tumor suppressor due to the frame-shifted ORF.
CTNNBIP1-CLSTN1 seems lost the major protein functional domain in Hgene 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
TgeneCTNNBIP1

GO:0032091

negative regulation of protein binding

12408825|18287330



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/chr1:9931244/chr1:9833452)
- 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 CLSTN1 (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 CTNNBIP1 (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)
ENST00000377298CLSTN1chr19809518-ENST00000377263CTNNBIP1chr19910834-427917785681836422
ENST00000361311CLSTN1chr19809518-ENST00000377263CTNNBIP1chr19910834-37071206261264412
ENST00000377288CLSTN1chr19809518-ENST00000377263CTNNBIP1chr19910834-427917785681836422
ENST00000377298CLSTN1chr19809519-ENST00000377263CTNNBIP1chr19910834-427917785681836422
ENST00000361311CLSTN1chr19809519-ENST00000377263CTNNBIP1chr19910834-37071206261264412
ENST00000377288CLSTN1chr19809519-ENST00000377263CTNNBIP1chr19910834-427917785681836422

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
ENST00000377298ENST00000377263CLSTN1chr19809518-CTNNBIP1chr19910834-0.0009227650.9990772
ENST00000361311ENST00000377263CLSTN1chr19809518-CTNNBIP1chr19910834-0.0018044240.9981956
ENST00000377288ENST00000377263CLSTN1chr19809518-CTNNBIP1chr19910834-0.0009227650.9990772
ENST00000377298ENST00000377263CLSTN1chr19809519-CTNNBIP1chr19910834-0.0009227650.9990772
ENST00000361311ENST00000377263CLSTN1chr19809519-CTNNBIP1chr19910834-0.0018044240.9981956
ENST00000377288ENST00000377263CLSTN1chr19809519-CTNNBIP1chr19910834-0.0009227650.9990772

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 CLSTN1-CTNNBIP1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CLSTN1chr19809518CTNNBIP1chr19910834120631PERAAQRHGGGGGGSSLDPRSSPRRG
CLSTN1chr19809518CTNNBIP1chr19910834177831PERAAQRHGGGGGGSSLDPRSSPRRG
CLSTN1chr19809519CTNNBIP1chr19910834120631PERAAQRHGGGGGGSSLDPRSSPRRG
CLSTN1chr19809519CTNNBIP1chr19910834177831PERAAQRHGGGGGGSSLDPRSSPRRG

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Potential FusionNeoAntigen Information of CLSTN1-CTNNBIP1 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.
CLSTN1-CTNNBIP1_9809518_9910834.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)
CLSTN1-CTNNBIP1chr19809518chr199108341206HLA-B07:10RHGGGGGGSSL0.98460.645617

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Potential FusionNeoAntigen Information of CLSTN1-CTNNBIP1 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 CLSTN1-CTNNBIP1

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
7909RHGGGGGGSSLDPRCLSTN1CTNNBIP1chr19809518chr199108341206

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CLSTN1-CTNNBIP1

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-B14:023BVN7909RHGGGGGGSSLDPR-4.80459-4.91799
HLA-B14:023BVN7909RHGGGGGGSSLDPR-4.16605-5.20135
HLA-B52:013W397909RHGGGGGGSSLDPR-6.48086-6.59426
HLA-B52:013W397909RHGGGGGGSSLDPR-5.62696-6.66226
HLA-A11:014UQ27909RHGGGGGGSSLDPR-9.41651-9.52991
HLA-A24:025HGA7909RHGGGGGGSSLDPR-8.42614-8.53954
HLA-A24:025HGA7909RHGGGGGGSSLDPR-5.8265-6.8618
HLA-B27:056PYJ7909RHGGGGGGSSLDPR-4.47497-4.58837
HLA-B44:053DX87909RHGGGGGGSSLDPR-5.6919-5.8053
HLA-B44:053DX87909RHGGGGGGSSLDPR-3.86336-4.89866
HLA-A02:016TDR7909RHGGGGGGSSLDPR-4.55202-4.66542

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Vaccine Design for the FusionNeoAntigens of CLSTN1-CTNNBIP1

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
CLSTN1-CTNNBIP1chr19809518chr19910834617RHGGGGGGSSLAGTCCCTCCACCGGCTCTGTGGTGCAGAGGACG

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 CLSTN1-CTNNBIP1

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
LUADCLSTN1-CTNNBIP1chr19809518ENST00000361311chr19910834ENST00000377263TCGA-55-8616

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Potential target of CAR-T therapy development for CLSTN1-CTNNBIP1

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 CLSTN1-CTNNBIP1

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 CLSTN1-CTNNBIP1

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