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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:GXYLT2-NEK3

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: GXYLT2-NEK3
FusionPDB ID: 35416
FusionGDB2.0 ID: 35416
HgeneTgene
Gene symbol

GXYLT2

NEK3

Gene ID

727936

4752

Gene nameglucoside xylosyltransferase 2NIMA related kinase 3
SynonymsGLT8D4HSPK36
Cytomap

3p13

13q14.3

Type of geneprotein-codingprotein-coding
Descriptionglucoside xylosyltransferase 2glycosyltransferase 8 domain containing 4glycosyltransferase 8 domain-containing protein 4serine/threonine-protein kinase Nek3HSPK 36NIMA (never in mitosis gene a)-related kinase 3glycogen synthase A kinasehydroxyalkyl-protein kinasenever in mitosis A-related kinase 3nimA-related protein kinase 3phosphorylase B kinase kinase
Modification date2020031320200313
UniProtAcc

A0PJZ3

Main function of 5'-partner protein: FUNCTION: Glycosyltransferase which elongates the O-linked glucose attached to EGF-like repeats in the extracellular domain of Notch proteins by catalyzing the addition of xylose. {ECO:0000269|PubMed:19940119}.

P51956

Main function of 5'-partner protein: FUNCTION: Protein kinase which influences neuronal morphogenesis and polarity through effects on microtubules. Regulates microtubule acetylation in neurons. Contributes to prolactin-mediated phosphorylation of PXN and VAV2. Implicated in prolactin-mediated cytoskeletal reorganization and motility of breast cancer cells through mechanisms involving RAC1 activation and phosphorylation of PXN and VAV2. {ECO:0000269|PubMed:15618286, ECO:0000269|PubMed:17297458}.
Ensembl transtripts involved in fusion geneENST idsENST00000389617, ENST00000339406, 
ENST00000378101, ENST00000400357, 
ENST00000452082, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score7 X 5 X 5=1751 X 1 X 1=1
# samples 71
** MAII scorelog2(7/175*10)=-1.32192809488736
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(1/1*10)=3.32192809488736
Fusion gene context

PubMed: GXYLT2 [Title/Abstract] AND NEK3 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: GXYLT2 [Title/Abstract] AND NEK3 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NEK3(52722550)-GXYLT2(73006380), # samples:3
GXYLT2(72971486)-NEK3(52719026), # samples:2
Anticipated loss of major functional domain due to fusion event.NEK3-GXYLT2 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.
NEK3-GXYLT2 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.
GXYLT2-NEK3 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.
GXYLT2-NEK3 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.
GXYLT2-NEK3 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.
GXYLT2-NEK3 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
HgeneGXYLT2

GO:0016266

O-glycan processing

19940119



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/chr3:52722550/chr13:73006380)
- 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 GXYLT2 (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 NEK3 (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)
ENST00000389617GXYLT2chr372971486+ENST00000378101NEK3chr1352719026-2178761801678532
ENST00000389617GXYLT2chr372971486+ENST00000339406NEK3chr1352719026-2178761801678532
ENST00000389617GXYLT2chr372971486+ENST00000452082NEK3chr1352719026-2119761801627515
ENST00000389617GXYLT2chr372971486+ENST00000400357NEK3chr1352719026-2119761801627515

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
ENST00000389617ENST00000378101GXYLT2chr372971486+NEK3chr1352719026-0.0032793460.9967206
ENST00000389617ENST00000339406GXYLT2chr372971486+NEK3chr1352719026-0.0032793460.9967206
ENST00000389617ENST00000452082GXYLT2chr372971486+NEK3chr1352719026-0.0037101280.99628985
ENST00000389617ENST00000400357GXYLT2chr372971486+NEK3chr1352719026-0.0037101280.99628985

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 GXYLT2-NEK3

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
GXYLT2chr372971486NEK3chr1352719026761222QEWKKLFKPCAAQRLFLPFQANSWKN

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Potential FusionNeoAntigen Information of GXYLT2-NEK3 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.
GXYLT2-NEK3_72971486_52719026.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)
GXYLT2-NEK3chr372971486chr1352719026761HLA-B27:07QRLFLPFQA0.99960.58541221
GXYLT2-NEK3chr372971486chr1352719026761HLA-B27:05QRLFLPFQA0.99940.53361221
GXYLT2-NEK3chr372971486chr1352719026761HLA-B39:06QRLFLPFQA0.99680.87171221
GXYLT2-NEK3chr372971486chr1352719026761HLA-A31:02LFKPCAAQR0.91670.8397514
GXYLT2-NEK3chr372971486chr1352719026761HLA-A31:06LFKPCAAQR0.90650.5663514
GXYLT2-NEK3chr372971486chr1352719026761HLA-A74:03KLFKPCAAQR0.99610.7904414
GXYLT2-NEK3chr372971486chr1352719026761HLA-A74:11KLFKPCAAQR0.99610.7904414
GXYLT2-NEK3chr372971486chr1352719026761HLA-A74:09KLFKPCAAQR0.99610.7904414
GXYLT2-NEK3chr372971486chr1352719026761HLA-A31:06KLFKPCAAQR0.99210.5217414
GXYLT2-NEK3chr372971486chr1352719026761HLA-A31:02KLFKPCAAQR0.97990.8058414
GXYLT2-NEK3chr372971486chr1352719026761HLA-A31:02KKLFKPCAAQR0.98920.836314
GXYLT2-NEK3chr372971486chr1352719026761HLA-B15:07AQRLFLPF0.99920.62021119
GXYLT2-NEK3chr372971486chr1352719026761HLA-B15:04AQRLFLPF0.99860.80491119
GXYLT2-NEK3chr372971486chr1352719026761HLA-B27:14QRLFLPFQA0.99950.57541221
GXYLT2-NEK3chr372971486chr1352719026761HLA-B73:01QRLFLPFQA0.9980.80551221
GXYLT2-NEK3chr372971486chr1352719026761HLA-A31:01LFKPCAAQR0.97520.7986514
GXYLT2-NEK3chr372971486chr1352719026761HLA-B27:03QRLFLPFQA0.96940.57131221
GXYLT2-NEK3chr372971486chr1352719026761HLA-C07:13FKPCAAQRL0.52020.9023615
GXYLT2-NEK3chr372971486chr1352719026761HLA-C07:29FKPCAAQRL0.49280.911615
GXYLT2-NEK3chr372971486chr1352719026761HLA-A31:01KLFKPCAAQR0.99590.7777414
GXYLT2-NEK3chr372971486chr1352719026761HLA-B27:14AQRLFLPFQA0.95620.57981121
GXYLT2-NEK3chr372971486chr1352719026761HLA-B73:01AQRLFLPFQA0.92320.84061121
GXYLT2-NEK3chr372971486chr1352719026761HLA-A31:01KKLFKPCAAQR0.99260.822314
GXYLT2-NEK3chr372971486chr1352719026761HLA-B15:35AQRLFLPF0.99920.80541119
GXYLT2-NEK3chr372971486chr1352719026761HLA-B15:68AQRLFLPF0.99870.54931119
GXYLT2-NEK3chr372971486chr1352719026761HLA-B27:09QRLFLPFQA0.99950.53231221
GXYLT2-NEK3chr372971486chr1352719026761HLA-B27:10QRLFLPFQA0.99940.63361221
GXYLT2-NEK3chr372971486chr1352719026761HLA-B27:06QRLFLPFQA0.99930.57431221
GXYLT2-NEK3chr372971486chr1352719026761HLA-A74:01KLFKPCAAQR0.99610.7904414

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Potential FusionNeoAntigen Information of GXYLT2-NEK3 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.
GXYLT2-NEK3_72971486_52719026.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)
GXYLT2-NEK3chr372971486chr1352719026761DRB1-0103KKLFKPCAAQRLFLP318

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Fusion breakpoint peptide structures of GXYLT2-NEK3

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
2432FKPCAAQRLFLPFQGXYLT2NEK3chr372971486chr1352719026761

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of GXYLT2-NEK3

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-B14:023BVN2432FKPCAAQRLFLPFQ-7.15543-7.26883
HLA-B14:023BVN2432FKPCAAQRLFLPFQ-4.77435-5.80965
HLA-B52:013W392432FKPCAAQRLFLPFQ-6.80875-6.92215
HLA-B52:013W392432FKPCAAQRLFLPFQ-4.20386-5.23916
HLA-A11:014UQ22432FKPCAAQRLFLPFQ-7.5194-8.5547
HLA-A11:014UQ22432FKPCAAQRLFLPFQ-6.9601-7.0735
HLA-A24:025HGA2432FKPCAAQRLFLPFQ-7.52403-7.63743
HLA-A24:025HGA2432FKPCAAQRLFLPFQ-5.82433-6.85963
HLA-B27:056PYJ2432FKPCAAQRLFLPFQ-3.28285-4.31815
HLA-B44:053DX82432FKPCAAQRLFLPFQ-5.91172-6.94702
HLA-B44:053DX82432FKPCAAQRLFLPFQ-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of GXYLT2-NEK3

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
GXYLT2-NEK3chr372971486chr13527190261119AQRLFLPFCTTCCGTTTCAGGCAAATAGTTGG
GXYLT2-NEK3chr372971486chr13527190261121AQRLFLPFQACTTCCGTTTCAGGCAAATAGTTGGAAAAAT
GXYLT2-NEK3chr372971486chr13527190261221QRLFLPFQACCGTTTCAGGCAAATAGTTGGAAAAAT
GXYLT2-NEK3chr372971486chr1352719026314KKLFKPCAAQRCCCTGTGCTGCCCAGAGACTCTTTCTTCCGTTT
GXYLT2-NEK3chr372971486chr1352719026414KLFKPCAAQRTGTGCTGCCCAGAGACTCTTTCTTCCGTTT
GXYLT2-NEK3chr372971486chr1352719026514LFKPCAAQRGCTGCCCAGAGACTCTTTCTTCCGTTT
GXYLT2-NEK3chr372971486chr1352719026615FKPCAAQRLGCCCAGAGACTCTTTCTTCCGTTTCAG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
GXYLT2-NEK3chr372971486chr1352719026318KKLFKPCAAQRLFLPCCCTGTGCTGCCCAGAGACTCTTTCTTCCGTTTCAGGCAAATAGT

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Information of the samples that have these potential fusion neoantigens of GXYLT2-NEK3

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
SKCMGXYLT2-NEK3chr372971486ENST00000389617chr1352719026ENST00000339406TCGA-EB-A44R-06A

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Potential target of CAR-T therapy development for GXYLT2-NEK3

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
HgeneGXYLT2chr3:72971486chr13:52719026ENST00000389617+375_25200444.0TransmembraneHelical%3B Signal-anchor for type II membrane protein

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 GXYLT2-NEK3

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 GXYLT2-NEK3

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