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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:NXF1-KLK10

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NXF1-KLK10
FusionPDB ID: 61203
FusionGDB2.0 ID: 61203
HgeneTgene
Gene symbol

NXF1

KLK10

Gene ID

10482

5655

Gene namenuclear RNA export factor 1kallikrein related peptidase 10
SynonymsMEX67|TAPNES1|PRSSL1
Cytomap

11q12.3

19q13.41

Type of geneprotein-codingprotein-coding
Descriptionnuclear RNA export factor 1mRNA export factor TAPtip associating proteintip-associated proteinkallikrein-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.

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 idsENST00000294172, ENST00000532297, 
ENST00000439713, ENST00000531131, 
ENST00000531709, ENST00000533048, 
ENST00000309958, ENST00000358789, 
ENST00000391805, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score10 X 13 X 7=9107 X 6 X 3=126
# samples 128
** MAII scorelog2(12/910*10)=-2.92283213947754
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
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: NXF1 [Title/Abstract] AND KLK10 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: NXF1 [Title/Abstract] AND KLK10 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NXF1(62567848)-KLK10(51520546), # samples:1
Anticipated loss of major functional domain due to fusion event.NXF1-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.
NXF1-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.
NXF1-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.
NXF1-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.
NXF1-KLK10 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
NXF1-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
HgeneNXF1

GO:0006406

mRNA export from nucleus

19165146|28984244



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/chr11:62567848/chr19:51520546)
- 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 NXF1 (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)
ENST00000532297NXF1chr1162567848-ENST00000309958KLK10chr1951520546-445016466301853407
ENST00000532297NXF1chr1162567848-ENST00000391805KLK10chr1951520546-444416466301853407
ENST00000532297NXF1chr1162567848-ENST00000358789KLK10chr1951520546-291916466301853407

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
ENST00000532297ENST00000309958NXF1chr1162567848-KLK10chr1951520546-0.0046906880.9953093
ENST00000532297ENST00000391805NXF1chr1162567848-KLK10chr1951520546-0.0046719450.99532807
ENST00000532297ENST00000358789NXF1chr1162567848-KLK10chr1951520546-0.0081638050.99183613

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 NXF1-KLK10

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
NXF1chr1162567848KLK10chr19515205461646338SLCDTFRDQSTYISRRGGAAPPKRHA

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Potential FusionNeoAntigen Information of NXF1-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.
NXF1-KLK10_62567848_51520546.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)
NXF1-KLK10chr1162567848chr19515205461646HLA-A31:02TFRDQSTYISR0.99440.503415
NXF1-KLK10chr1162567848chr19515205461646HLA-B73:01FRDQSTYIS0.83960.5692514

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Potential FusionNeoAntigen Information of NXF1-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.
NXF1-KLK10_62567848_51520546.msa

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)
NXF1-KLK10chr1162567848chr19515205461646DRB1-0103QSTYISRRGGAAPPK823
NXF1-KLK10chr1162567848chr19515205461646DRB1-0103DQSTYISRRGGAAPP722
NXF1-KLK10chr1162567848chr19515205461646DRB1-0103STYISRRGGAAPPKR924
NXF1-KLK10chr1162567848chr19515205461646DRB1-0802QSTYISRRGGAAPPK823
NXF1-KLK10chr1162567848chr19515205461646DRB1-0809QSTYISRRGGAAPPK823
NXF1-KLK10chr1162567848chr19515205461646DRB1-0813QSTYISRRGGAAPPK823
NXF1-KLK10chr1162567848chr19515205461646DRB1-0815QSTYISRRGGAAPPK823
NXF1-KLK10chr1162567848chr19515205461646DRB1-0821QSTYISRRGGAAPPK823
NXF1-KLK10chr1162567848chr19515205461646DRB1-0830QSTYISRRGGAAPPK823
NXF1-KLK10chr1162567848chr19515205461646DRB1-1130QSTYISRRGGAAPPK823
NXF1-KLK10chr1162567848chr19515205461646DRB1-1367QSTYISRRGGAAPPK823
NXF1-KLK10chr1162567848chr19515205461646DRB5-0103QSTYISRRGGAAPPK823

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Fusion breakpoint peptide structures of NXF1-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
7746RDQSTYISRRGGAANXF1KLK10chr1162567848chr19515205461646

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of NXF1-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-B14:023BVN7746RDQSTYISRRGGAA-7.9962-8.1096
HLA-B14:023BVN7746RDQSTYISRRGGAA-5.70842-6.74372
HLA-B52:013W397746RDQSTYISRRGGAA-6.83737-6.95077
HLA-B52:013W397746RDQSTYISRRGGAA-4.4836-5.5189
HLA-A11:014UQ27746RDQSTYISRRGGAA-10.0067-10.1201
HLA-A11:014UQ27746RDQSTYISRRGGAA-9.03915-10.0745
HLA-A24:025HGA7746RDQSTYISRRGGAA-6.56204-6.67544
HLA-A24:025HGA7746RDQSTYISRRGGAA-5.42271-6.45801
HLA-B44:053DX87746RDQSTYISRRGGAA-7.85648-8.89178
HLA-B44:053DX87746RDQSTYISRRGGAA-5.3978-5.5112
HLA-A02:016TDR7746RDQSTYISRRGGAA-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of NXF1-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
NXF1-KLK10chr1162567848chr1951520546415TFRDQSTYISRCTTCCGAGACCAGTCCACCTACATCAGCCGCAG
NXF1-KLK10chr1162567848chr1951520546514FRDQSTYISCCGAGACCAGTCCACCTACATCAGCCG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
NXF1-KLK10chr1162567848chr1951520546722DQSTYISRRGGAAPPCCAGTCCACCTACATCAGCCGCAGAGGCGGCGCTGCTCCCCCAAA
NXF1-KLK10chr1162567848chr1951520546823QSTYISRRGGAAPPKGTCCACCTACATCAGCCGCAGAGGCGGCGCTGCTCCCCCAAAACG
NXF1-KLK10chr1162567848chr1951520546924STYISRRGGAAPPKRCACCTACATCAGCCGCAGAGGCGGCGCTGCTCCCCCAAAACGACA

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Information of the samples that have these potential fusion neoantigens of NXF1-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
OVNXF1-KLK10chr1162567848ENST00000532297chr1951520546ENST00000309958TCGA-24-1546

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Potential target of CAR-T therapy development for NXF1-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 NXF1-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 NXF1-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