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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:CLASP2-GLB1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CLASP2-GLB1
FusionPDB ID: 16943
FusionGDB2.0 ID: 16943
HgeneTgene
Gene symbol

CLASP2

GLB1

Gene ID

23122

2720

Gene namecytoplasmic linker associated protein 2galactosidase beta 1
Synonyms-EBP|ELNR1|MPS4B
Cytomap

3p22.3

3p22.3

Type of geneprotein-codingprotein-coding
DescriptionCLIP-associating protein 2CLIP-associating protein CLASP2multiple asters (Mast)-like homolog 2protein Orbit homolog 2beta-galactosidaseacid beta-galactosidaseelastin binding proteinelastin receptor 1, 67kDalactase
Modification date2020031320200313
UniProtAcc

O75122

Main function of 5'-partner protein: FUNCTION: Microtubule plus-end tracking protein that promotes the stabilization of dynamic microtubules (PubMed:26003921). Involved in the nucleation of noncentrosomal microtubules originating from the trans-Golgi network (TGN). Required for the polarization of the cytoplasmic microtubule arrays in migrating cells towards the leading edge of the cell. May act at the cell cortex to enhance the frequency of rescue of depolymerizing microtubules by attaching their plus-ends to cortical platforms composed of ERC1 and PHLDB2 (PubMed:16824950). This cortical microtubule stabilizing activity is regulated at least in part by phosphatidylinositol 3-kinase signaling. Also performs a similar stabilizing function at the kinetochore which is essential for the bipolar alignment of chromosomes on the mitotic spindle (PubMed:16866869, PubMed:16914514). Acts as a mediator of ERBB2-dependent stabilization of microtubules at the cell cortex. {ECO:0000269|PubMed:11290329, ECO:0000269|PubMed:15631994, ECO:0000269|PubMed:16824950, ECO:0000269|PubMed:16866869, ECO:0000269|PubMed:16914514, ECO:0000269|PubMed:17543864, ECO:0000269|PubMed:20937854, ECO:0000269|PubMed:26003921}.

Q8NCI6

Main function of 5'-partner protein:
Ensembl transtripts involved in fusion geneENST idsENST00000313350, ENST00000333778, 
ENST00000359576, ENST00000399362, 
ENST00000461133, ENST00000468888, 
ENST00000480013, ENST00000487200, 
ENST00000307312, ENST00000482896, 
ENST00000539981, 
ENST00000307377, 
ENST00000399402, ENST00000445488, 
ENST00000497796, ENST00000307363, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score9 X 9 X 6=4869 X 9 X 5=405
# samples 99
** MAII scorelog2(9/486*10)=-2.43295940727611
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(9/405*10)=-2.16992500144231
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: CLASP2 [Title/Abstract] AND GLB1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CLASP2 [Title/Abstract] AND GLB1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CLASP2(33673784)-GLB1(33114205), # samples:1
Anticipated loss of major functional domain due to fusion event.CLASP2-GLB1 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.
CLASP2-GLB1 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
TgeneGLB1

GO:0044262

cellular carbohydrate metabolic process

11927518



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/chr3:33673784/chr3:33114205)
- 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 CLASP2 (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 GLB1 (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)
ENST00000468888CLASP2chr333673784-ENST00000307363GLB1chr333114205-338899252950981
ENST00000399362CLASP2chr333673784-ENST00000307363GLB1chr333114205-369212962913254987
ENST00000359576CLASP2chr333673784-ENST00000307363GLB1chr333114205-369212962913254987
ENST00000480013CLASP2chr333673784-ENST00000307363GLB1chr333114205-30916952752653792
ENST00000461133CLASP2chr333673784-ENST00000307363GLB1chr333114205-2755359232317764
ENST00000313350CLASP2chr333673784-ENST00000307363GLB1chr333114205-28344381772396739
ENST00000487200CLASP2chr333673784-ENST00000307363GLB1chr333114205-28454491882407739
ENST00000333778CLASP2chr333673784-ENST00000307363GLB1chr333114205-28954992262457743

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
ENST00000468888ENST00000307363CLASP2chr333673784-GLB1chr333114205-0.0004728910.9995271
ENST00000399362ENST00000307363CLASP2chr333673784-GLB1chr333114205-0.0005389580.999461
ENST00000359576ENST00000307363CLASP2chr333673784-GLB1chr333114205-0.0005389580.999461
ENST00000480013ENST00000307363CLASP2chr333673784-GLB1chr333114205-0.0031114160.9968886
ENST00000461133ENST00000307363CLASP2chr333673784-GLB1chr333114205-0.0025606030.9974394
ENST00000313350ENST00000307363CLASP2chr333673784-GLB1chr333114205-0.0021544740.99784553
ENST00000487200ENST00000307363CLASP2chr333673784-GLB1chr333114205-0.0021034750.99789655
ENST00000333778ENST00000307363CLASP2chr333673784-GLB1chr333114205-0.0016003890.99839956

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 CLASP2-GLB1

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 CLASP2-GLB1 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 CLASP2-GLB1 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 CLASP2-GLB1

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 CLASP2-GLB1

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 CLASP2-GLB1

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 CLASP2-GLB1

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 CLASP2-GLB1

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 CLASP2-GLB1

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 CLASP2-GLB1

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