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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:CTRB1-KLK10

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CTRB1-KLK10
FusionPDB ID: 20430
FusionGDB2.0 ID: 20430
HgeneTgene
Gene symbol

CTRB1

KLK10

Gene ID

1504

5655

Gene namechymotrypsinogen B1kallikrein related peptidase 10
SynonymsCTRBNES1|PRSSL1
Cytomap

16q23.1

19q13.41

Type of geneprotein-codingprotein-coding
Descriptionchymotrypsinogen Bkallikrein-10breast normal epithelial cell associated serine proteasekallikrein 10 protein 1kallikrein 10 protein 12kallikrein 10 protein 13kallikrein 10 protein 2kallikrein 10 protein 3kallikrein 10 protein 4kallikrein 10 protein 5kallikrein 10
Modification date2020031320200313
UniProtAcc

P17538

Main function of 5'-partner protein:

O43240

Main function of 5'-partner protein: FUNCTION: Has a tumor-suppressor role for NES1 in breast and prostate cancer.
Ensembl transtripts involved in fusion geneENST idsENST00000361017, ENST00000309958, 
ENST00000358789, ENST00000391805, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score5 X 3 X 2=307 X 6 X 3=126
# samples 48
** MAII scorelog2(4/30*10)=0.415037499278844
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
log2(8/126*10)=-0.655351828612554
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: CTRB1 [Title/Abstract] AND KLK10 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CTRB1 [Title/Abstract] AND KLK10 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CTRB1(75258086)-KLK10(51518208), # samples:2
CTRB1(75257526)-KLK10(51518208), # samples:2
Anticipated loss of major functional domain due to fusion event.CTRB1-KLK10 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.
CTRB1-KLK10 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.
CTRB1-KLK10 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


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/chr16:75258086/chr19:51518208)
- 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 CTRB1 (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 KLK10 (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)
ENST00000361017CTRB1chr1675258086+ENST00000391805KLK10chr1951518208-28466388802293
ENST00000361017CTRB1chr1675258086+ENST00000358789KLK10chr1951518208-13216388790260

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
ENST00000361017ENST00000391805CTRB1chr1675258086+KLK10chr1951518208-0.0036734220.9963265
ENST00000361017ENST00000358789CTRB1chr1675258086+KLK10chr1951518208-0.0073880670.99261194

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 CTRB1-KLK10

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CTRB1chr1675258086KLK10chr195151820863859WQVSLQDKTGFHFCGGSLISEDWVVT

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Potential FusionNeoAntigen Information of CTRB1-KLK10 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.
CTRB1-KLK10_75258086_51518208.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)
CTRB1-KLK10chr1675258086chr1951518208638HLA-B39:01FHFCGGSL0.99670.97281018
CTRB1-KLK10chr1675258086chr1951518208638HLA-B39:24FHFCGGSL0.99590.76771018
CTRB1-KLK10chr1675258086chr1951518208638HLA-B39:06FHFCGGSL0.99090.92821018
CTRB1-KLK10chr1675258086chr1951518208638HLA-B15:10FHFCGGSL0.99070.62831018
CTRB1-KLK10chr1675258086chr1951518208638HLA-B15:37FHFCGGSL0.94690.69731018
CTRB1-KLK10chr1675258086chr1951518208638HLA-B39:01FHFCGGSLI0.99860.97931019
CTRB1-KLK10chr1675258086chr1951518208638HLA-B39:24FHFCGGSLI0.99810.74841019
CTRB1-KLK10chr1675258086chr1951518208638HLA-B39:06FHFCGGSLI0.99780.95971019
CTRB1-KLK10chr1675258086chr1951518208638HLA-B38:02FHFCGGSLI0.99760.99111019
CTRB1-KLK10chr1675258086chr1951518208638HLA-B38:01FHFCGGSLI0.99760.99061019
CTRB1-KLK10chr1675258086chr1951518208638HLA-B15:10FHFCGGSLI0.97440.65871019
CTRB1-KLK10chr1675258086chr1951518208638HLA-B15:37FHFCGGSLI0.72770.73311019
CTRB1-KLK10chr1675258086chr1951518208638HLA-B39:09FHFCGGSL0.99760.87281018
CTRB1-KLK10chr1675258086chr1951518208638HLA-B39:05FHFCGGSL0.99140.96841018
CTRB1-KLK10chr1675258086chr1951518208638HLA-B39:09FHFCGGSLI0.99880.88441019
CTRB1-KLK10chr1675258086chr1951518208638HLA-B39:05FHFCGGSLI0.99710.97581019
CTRB1-KLK10chr1675258086chr1951518208638HLA-B39:31FHFCGGSL0.99750.97351018
CTRB1-KLK10chr1675258086chr1951518208638HLA-B15:09FHFCGGSL0.97170.94041018
CTRB1-KLK10chr1675258086chr1951518208638HLA-B39:11FHFCGGSL0.61670.94831018
CTRB1-KLK10chr1675258086chr1951518208638HLA-B39:31FHFCGGSLI0.99880.97931019
CTRB1-KLK10chr1675258086chr1951518208638HLA-B38:05FHFCGGSLI0.99760.99061019
CTRB1-KLK10chr1675258086chr1951518208638HLA-B15:09FHFCGGSLI0.98540.96521019
CTRB1-KLK10chr1675258086chr1951518208638HLA-B39:11FHFCGGSLI0.64070.95431019

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Potential FusionNeoAntigen Information of CTRB1-KLK10 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 CTRB1-KLK10

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
1192DKTGFHFCGGSLISCTRB1KLK10chr1675258086chr1951518208638

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CTRB1-KLK10

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-B14:023BVN1192DKTGFHFCGGSLIS-7.15543-7.26883
HLA-B14:023BVN1192DKTGFHFCGGSLIS-4.77435-5.80965
HLA-B52:013W391192DKTGFHFCGGSLIS-6.80875-6.92215
HLA-B52:013W391192DKTGFHFCGGSLIS-4.20386-5.23916
HLA-A11:014UQ21192DKTGFHFCGGSLIS-7.5194-8.5547
HLA-A11:014UQ21192DKTGFHFCGGSLIS-6.9601-7.0735
HLA-A24:025HGA1192DKTGFHFCGGSLIS-7.52403-7.63743
HLA-A24:025HGA1192DKTGFHFCGGSLIS-5.82433-6.85963
HLA-B27:056PYJ1192DKTGFHFCGGSLIS-3.28285-4.31815
HLA-B44:053DX81192DKTGFHFCGGSLIS-5.91172-6.94702
HLA-B44:053DX81192DKTGFHFCGGSLIS-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of CTRB1-KLK10

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
CTRB1-KLK10chr1675258086chr19515182081018FHFCGGSLTCCTGCATGAGTGACTCTGGAGGC
CTRB1-KLK10chr1675258086chr19515182081019FHFCGGSLITCCTGCATGAGTGACTCTGGAGGCCCC

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 CTRB1-KLK10

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
PAADCTRB1-KLK10chr1675258086ENST00000361017chr1951518208ENST00000358789TCGA-F2-7273

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Potential target of CAR-T therapy development for CTRB1-KLK10

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 CTRB1-KLK10

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 CTRB1-KLK10

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