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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:NFATC2-DOK5

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NFATC2-DOK5
FusionPDB ID: 58789
FusionGDB2.0 ID: 58789
HgeneTgene
Gene symbol

NFATC2

DOK5

Gene ID

4773

55816

Gene namenuclear factor of activated T cells 2docking protein 5
SynonymsNFAT1|NFATPC20orf180|IRS-6|IRS6
Cytomap

20q13.2

20q13.2

Type of geneprotein-codingprotein-coding
Descriptionnuclear factor of activated T-cells, cytoplasmic 2NF-ATc2NFAT pre-existing subunitNFAT transcription complex, preexisting componentT cell transcription factor NFAT1nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2nuclear factdocking protein 5downstream of tyrosine kinase 5insulin receptor substrate 6
Modification date2020032920200320
UniProtAcc

Q8NCF5

Main function of 5'-partner protein: FUNCTION: In T-helper 2 (Th2) cells, regulates the magnitude of NFAT-driven transcription of a specific subset of cytokine genes, including IL3, IL4, IL5 and IL13, but not IL2. Recruits PRMT1 to the IL4 promoter; this leads to enhancement of histone H4 'Arg-3'-methylation and facilitates subsequent histone acetylation at the IL4 locus, thus promotes robust cytokine expression (By similarity). Down-regulates formation of poly-SUMO chains by UBE2I/UBC9 (By similarity). {ECO:0000250}.

Q9P104

Main function of 5'-partner protein: FUNCTION: DOK proteins are enzymatically inert adaptor or scaffolding proteins. They provide a docking platform for the assembly of multimolecular signaling complexes. DOK5 functions in RET-mediated neurite outgrowth and plays a positive role in activation of the MAP kinase pathway. Putative link with downstream effectors of RET in neuronal differentiation.
Ensembl transtripts involved in fusion geneENST idsENST00000371564, ENST00000396009, 
ENST00000414705, ENST00000609507, 
ENST00000609943, ENST00000610033, 
ENST00000395939, ENST00000491469, 
ENST00000262593, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score9 X 9 X 5=40511 X 9 X 8=792
# samples 812
** MAII scorelog2(8/405*10)=-2.33985000288462
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(12/792*10)=-2.72246602447109
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: NFATC2 [Title/Abstract] AND DOK5 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: NFATC2 [Title/Abstract] AND DOK5 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NFATC2(50133323)-DOK5(53171472), # samples:2
Anticipated loss of major functional domain due to fusion event.NFATC2-DOK5 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.
NFATC2-DOK5 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.
NFATC2-DOK5 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.
NFATC2-DOK5 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.
NFATC2-DOK5 seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF.
NFATC2-DOK5 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
NFATC2-DOK5 seems lost the major protein functional domain in Hgene partner, which is a transcription factor due to the frame-shifted ORF.
NFATC2-DOK5 seems lost the major protein functional domain in Hgene 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
HgeneNFATC2

GO:0016477

cell migration

21871017

HgeneNFATC2

GO:0045893

positive regulation of transcription, DNA-templated

15790681

HgeneNFATC2

GO:1905064

negative regulation of vascular smooth muscle cell differentiation

23853098



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/chr20:50133323/chr20:53171472)
- 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 NFATC2 (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 DOK5 (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)
ENST00000396009NFATC2chr2050133323-ENST00000262593DOK5chr2053171472+309915522112406731
ENST00000609943NFATC2chr2050133323-ENST00000262593DOK5chr2053171472+302114742022328708
ENST00000610033NFATC2chr2050133323-ENST00000262593DOK5chr2053171472+258510383631892509
ENST00000609507NFATC2chr2050133323-ENST00000262593DOK5chr2053171472+25079602341814526

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
ENST00000396009ENST00000262593NFATC2chr2050133323-DOK5chr2053171472+0.0146426690.98535734
ENST00000609943ENST00000262593NFATC2chr2050133323-DOK5chr2053171472+0.0183914580.98160857
ENST00000610033ENST00000262593NFATC2chr2050133323-DOK5chr2053171472+0.0339680540.96603197
ENST00000609507ENST00000262593NFATC2chr2050133323-DOK5chr2053171472+0.0278495230.9721505

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 NFATC2-DOK5

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
NFATC2chr2050133323DOK5chr20531714721038224GAVKAPTGGHPVVQIYQRCWLVFKKA
NFATC2chr2050133323DOK5chr20531714721474423GAVKAPTGGHPVVQIYQRCWLVFKKA
NFATC2chr2050133323DOK5chr20531714721552446GAVKAPTGGHPVVQIYQRCWLVFKKA

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Potential FusionNeoAntigen Information of NFATC2-DOK5 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.
NFATC2-DOK5_50133323_53171472.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)
NFATC2-DOK5chr2050133323chr20531714721552HLA-B15:18GHPVVQIY0.94970.5161816
NFATC2-DOK5chr2050133323chr20531714721552HLA-B57:01VVQIYQRCW0.99510.95021120
NFATC2-DOK5chr2050133323chr20531714721552HLA-B15:25GGHPVVQIY0.98890.8661716
NFATC2-DOK5chr2050133323chr20531714721552HLA-B58:02VVQIYQRCW0.98120.87231120
NFATC2-DOK5chr2050133323chr20531714721552HLA-B58:01VVQIYQRCW0.97540.89421120
NFATC2-DOK5chr2050133323chr20531714721552HLA-B15:01GGHPVVQIY0.96990.8152716
NFATC2-DOK5chr2050133323chr20531714721552HLA-A32:13VVQIYQRCW0.8120.95841120
NFATC2-DOK5chr2050133323chr20531714721552HLA-B15:03GGHPVVQIY0.7760.6524716
NFATC2-DOK5chr2050133323chr20531714721552HLA-B15:05GGHPVVQIY0.96610.7457716
NFATC2-DOK5chr2050133323chr20531714721552HLA-B15:07GGHPVVQIY0.9530.6664716
NFATC2-DOK5chr2050133323chr20531714721552HLA-C07:19GGHPVVQIY0.69960.7461716
NFATC2-DOK5chr2050133323chr20531714721552HLA-B15:04GGHPVVQIY0.68070.8309716
NFATC2-DOK5chr2050133323chr20531714721552HLA-C15:04GGHPVVQIY0.67570.9209716
NFATC2-DOK5chr2050133323chr20531714721552HLA-C12:12GGHPVVQIY0.13190.9239716
NFATC2-DOK5chr2050133323chr20531714721552HLA-B44:06HPVVQIYQRCW0.92910.518920
NFATC2-DOK5chr2050133323chr20531714721552HLA-B57:10VVQIYQRCW0.99510.95021120
NFATC2-DOK5chr2050133323chr20531714721552HLA-B15:39GGHPVVQIY0.98730.7559716
NFATC2-DOK5chr2050133323chr20531714721552HLA-B57:04VVQIYQRCW0.98550.6511120
NFATC2-DOK5chr2050133323chr20531714721552HLA-B58:06VVQIYQRCW0.9820.81911120
NFATC2-DOK5chr2050133323chr20531714721552HLA-B15:135GGHPVVQIY0.97120.8356716
NFATC2-DOK5chr2050133323chr20531714721552HLA-B15:34GGHPVVQIY0.96990.8152716
NFATC2-DOK5chr2050133323chr20531714721552HLA-B15:33GGHPVVQIY0.96990.8152716
NFATC2-DOK5chr2050133323chr20531714721552HLA-B15:125GGHPVVQIY0.96990.8152716
NFATC2-DOK5chr2050133323chr20531714721552HLA-B15:27GGHPVVQIY0.9690.8466716
NFATC2-DOK5chr2050133323chr20531714721552HLA-B15:20GGHPVVQIY0.96410.8051716
NFATC2-DOK5chr2050133323chr20531714721552HLA-B15:50GGHPVVQIY0.95780.9319716
NFATC2-DOK5chr2050133323chr20531714721552HLA-B35:28GGHPVVQIY0.95480.8175716
NFATC2-DOK5chr2050133323chr20531714721552HLA-B15:35GGHPVVQIY0.91290.8365716
NFATC2-DOK5chr2050133323chr20531714721552HLA-C03:02GGHPVVQIY0.8340.9491716
NFATC2-DOK5chr2050133323chr20531714721552HLA-B15:12GGHPVVQIY0.80910.8254716
NFATC2-DOK5chr2050133323chr20531714721552HLA-C15:09GGHPVVQIY0.67570.9209716
NFATC2-DOK5chr2050133323chr20531714721552HLA-B15:54GGHPVVQIY0.63430.7363716
NFATC2-DOK5chr2050133323chr20531714721552HLA-C12:02GGHPVVQIY0.42330.9634716
NFATC2-DOK5chr2050133323chr20531714721552HLA-B15:68GGHPVVQIY0.36750.5706716
NFATC2-DOK5chr2050133323chr20531714721552HLA-C16:04GGHPVVQIY0.14540.9792716
NFATC2-DOK5chr2050133323chr20531714721552HLA-C02:02GGHPVVQIY0.04320.9811716
NFATC2-DOK5chr2050133323chr20531714721552HLA-C02:10GGHPVVQIY0.04320.9811716

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Potential FusionNeoAntigen Information of NFATC2-DOK5 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 NFATC2-DOK5

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
9357TGGHPVVQIYQRCWNFATC2DOK5chr2050133323chr20531714721552

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of NFATC2-DOK5

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-B14:023BVN9357TGGHPVVQIYQRCW-7.9962-8.1096
HLA-B14:023BVN9357TGGHPVVQIYQRCW-5.70842-6.74372
HLA-B52:013W399357TGGHPVVQIYQRCW-6.83737-6.95077
HLA-B52:013W399357TGGHPVVQIYQRCW-4.4836-5.5189
HLA-A11:014UQ29357TGGHPVVQIYQRCW-10.0067-10.1201
HLA-A11:014UQ29357TGGHPVVQIYQRCW-9.03915-10.0745
HLA-A24:025HGA9357TGGHPVVQIYQRCW-6.56204-6.67544
HLA-A24:025HGA9357TGGHPVVQIYQRCW-5.42271-6.45801
HLA-B44:053DX89357TGGHPVVQIYQRCW-7.85648-8.89178
HLA-B44:053DX89357TGGHPVVQIYQRCW-5.3978-5.5112
HLA-A02:016TDR9357TGGHPVVQIYQRCW-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of NFATC2-DOK5

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
NFATC2-DOK5chr2050133323chr20531714721120VVQIYQRCWGTTCAGATTTATCAGCGATGCTGGTTA
NFATC2-DOK5chr2050133323chr2053171472716GGHPVVQIYGGCCACCCTGTGGTTCAGATTTATCAG
NFATC2-DOK5chr2050133323chr2053171472816GHPVVQIYCACCCTGTGGTTCAGATTTATCAG
NFATC2-DOK5chr2050133323chr2053171472920HPVVQIYQRCWCCTGTGGTTCAGATTTATCAGCGATGCTGGTTA

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 NFATC2-DOK5

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
SKCMNFATC2-DOK5chr2050133323ENST00000396009chr2053171472ENST00000262593TCGA-EE-A2MH-06A

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Potential target of CAR-T therapy development for NFATC2-DOK5

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 NFATC2-DOK5

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 NFATC2-DOK5

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
HgeneNFATC2C0011860Diabetes Mellitus, Non-Insulin-Dependent1CTD_human
HgeneNFATC2C0020542Pulmonary Hypertension1CTD_human
HgeneNFATC2C0027765nervous system disorder1CTD_human