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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:GNB1L-CTSC

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: GNB1L-CTSC
FusionPDB ID: 33679
FusionGDB2.0 ID: 33679
HgeneTgene
Gene symbol

GNB1L

CTSC

Gene ID

54584

1075

Gene nameG protein subunit beta 1 likecathepsin C
SynonymsDGCRK3|FKSG1|GY2|WDR14|WDVCFCPPI|DPP-I|DPP1|DPPI|HMS|JP|JPD|PALS|PDON1|PLS
Cytomap

22q11.21

11q14.2

Type of geneprotein-codingprotein-coding
Descriptionguanine nucleotide-binding protein subunit beta-like protein 1G-protein beta subunit-like proteinWD repeat-containing protein 14WD40 repeat-containing protein deleted in VCFSg protein subunit beta-like protein 1guanine nucleotide binding protein (G pdipeptidyl peptidase 1cathepsin Jdipeptidyl transferasedipeptidyl-peptidase I
Modification date2020031320200313
UniProtAcc

Q9BYB4

Main function of 5'-partner protein:

P53634

Main function of 5'-partner protein: FUNCTION: Thiol protease. Has dipeptidylpeptidase activity. Active against a broad range of dipeptide substrates composed of both polar and hydrophobic amino acids. Proline cannot occupy the P1 position and arginine cannot occupy the P2 position of the substrate. Can act as both an exopeptidase and endopeptidase. Activates serine proteases such as elastase, cathepsin G and granzymes A and B. Can also activate neuraminidase and factor XIII. {ECO:0000269|PubMed:1586157}.
Ensembl transtripts involved in fusion geneENST idsENST00000329517, ENST00000403325, 
ENST00000460402, ENST00000405009, 
ENST00000393301, ENST00000524463, 
ENST00000529974, ENST00000227266, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score8 X 5 X 5=2006 X 4 X 4=96
# samples 86
** MAII scorelog2(8/200*10)=-1.32192809488736
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(6/96*10)=-0.678071905112638
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: GNB1L [Title/Abstract] AND CTSC [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: GNB1L [Title/Abstract] AND CTSC [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)GNB1L(19789524)-CTSC(88033813), # samples:1
Anticipated loss of major functional domain due to fusion event.GNB1L-CTSC 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.
GNB1L-CTSC 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.
GNB1L-CTSC 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.
GNB1L-CTSC 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.
GNB1L-CTSC seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
GNB1L-CTSC seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target 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
TgeneCTSC

GO:0006508

proteolysis

8811434



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/chr22:19789524/chr11:88033813)
- 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 GNB1L (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 CTSC (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)
ENST00000403325GNB1Lchr2219789524-ENST00000227266CTSCchr1188033813-231811538961903335

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
ENST00000403325ENST00000227266GNB1Lchr2219789524-CTSCchr1188033813-0.07734320.9226568

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 GNB1L-CTSC

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
GNB1Lchr2219789524CTSCchr1188033813115385RWLSGAWTGSRPCRPKPAPLTAEIQQ

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Potential FusionNeoAntigen Information of GNB1L-CTSC 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.
GNB1L-CTSC_19789524_88033813.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)
GNB1L-CTSCchr2219789524chr11880338131153HLA-B07:02RPCRPKPAPL0.99950.50011020
GNB1L-CTSCchr2219789524chr11880338131153HLA-B07:10RPCRPKPAPL0.99950.5261020
GNB1L-CTSCchr2219789524chr11880338131153HLA-B08:01RPCRPKPAPL0.97030.50881020
GNB1L-CTSCchr2219789524chr11880338131153HLA-B56:01CRPKPAPLTA0.92370.55351222
GNB1L-CTSCchr2219789524chr11880338131153HLA-B07:02RPCRPKPAPLT0.99970.54171021
GNB1L-CTSCchr2219789524chr11880338131153HLA-B07:12RPCRPKPAPL0.99290.63271020
GNB1L-CTSCchr2219789524chr11880338131153HLA-B42:02RPCRPKPAPL0.98030.51481020
GNB1L-CTSCchr2219789524chr11880338131153HLA-B42:01RPCRPKPAPL0.97440.5061020
GNB1L-CTSCchr2219789524chr11880338131153HLA-B54:01CRPKPAPLTA0.95880.74551222
GNB1L-CTSCchr2219789524chr11880338131153HLA-B07:04RPCRPKPAPLT0.99590.57191021
GNB1L-CTSCchr2219789524chr11880338131153HLA-B07:22RPCRPKPAPL0.99950.50011020
GNB1L-CTSCchr2219789524chr11880338131153HLA-B55:02CRPKPAPLTA0.9850.54591222
GNB1L-CTSCchr2219789524chr11880338131153HLA-B08:18RPCRPKPAPL0.97030.50881020
GNB1L-CTSCchr2219789524chr11880338131153HLA-B67:01RPCRPKPAPL0.77310.73651020
GNB1L-CTSCchr2219789524chr11880338131153HLA-B07:22RPCRPKPAPLT0.99970.54171021

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Potential FusionNeoAntigen Information of GNB1L-CTSC 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 GNB1L-CTSC

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
10550WTGSRPCRPKPAPLGNB1LCTSCchr2219789524chr11880338131153

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of GNB1L-CTSC

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-B14:023BVN10550WTGSRPCRPKPAPL-8.80752-8.92092
HLA-B14:023BVN10550WTGSRPCRPKPAPL-6.22944-7.26474
HLA-B52:013W3910550WTGSRPCRPKPAPL-5.86746-5.98086
HLA-B52:013W3910550WTGSRPCRPKPAPL-5.4484-6.4837
HLA-A11:014UQ210550WTGSRPCRPKPAPL-11.1453-11.2587
HLA-A11:014UQ210550WTGSRPCRPKPAPL-9.83303-10.8683
HLA-A24:025HGA10550WTGSRPCRPKPAPL-8.82492-8.93832
HLA-A24:025HGA10550WTGSRPCRPKPAPL-5.24336-6.27866
HLA-B44:053DX810550WTGSRPCRPKPAPL-7.83487-7.94827
HLA-B44:053DX810550WTGSRPCRPKPAPL-4.78129-5.81659
HLA-A02:016TDR10550WTGSRPCRPKPAPL-5.19167-5.30507
HLA-A02:016TDR10550WTGSRPCRPKPAPL-0.129251-1.16455

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Vaccine Design for the FusionNeoAntigens of GNB1L-CTSC

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
GNB1L-CTSCchr2219789524chr11880338131020RPCRPKPAPLGCCCTGCAGGCCCAAACCTGCACCACTGAC
GNB1L-CTSCchr2219789524chr11880338131021RPCRPKPAPLTGCCCTGCAGGCCCAAACCTGCACCACTGACTGC
GNB1L-CTSCchr2219789524chr11880338131222CRPKPAPLTACAGGCCCAAACCTGCACCACTGACTGCTGA

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 GNB1L-CTSC

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
LUSCGNB1L-CTSCchr2219789524ENST00000403325chr1188033813ENST00000227266TCGA-66-2727-01A

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Potential target of CAR-T therapy development for GNB1L-CTSC

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 GNB1L-CTSC

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 GNB1L-CTSC

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