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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:NFATC2IP-HS3ST4

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NFATC2IP-HS3ST4
FusionPDB ID: 58794
FusionGDB2.0 ID: 58794
HgeneTgene
Gene symbol

NFATC2IP

HS3ST4

Gene ID

84901

9951

Gene namenuclear factor of activated T cells 2 interacting proteinheparan sulfate-glucosamine 3-sulfotransferase 4
SynonymsESC2|NIP45|RAD603-OST-4|30ST4|3OST4|h3-OST-4
Cytomap

16p11.2

16p12.1

Type of geneprotein-codingprotein-coding
DescriptionNFATC2-interacting protein45 kDa NF-AT-interacting protein45 kDa NFAT-interacting proteinnuclear factor of activated T-cells, cytoplasmic 2-interacting proteinnuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2 interacting proteiheparan sulfate glucosamine 3-O-sulfotransferase 4heparan sulfate (glucosamine) 3-O-sulfotransferase 4heparan sulfate 3-O-sulfotransferase 4heparan sulfate D-glucosaminyl 3-O-sulfotransferase 4
Modification date2020031320200313
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}.

Q9Y661

Main function of 5'-partner protein: FUNCTION: Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) to catalyze the transfer of a sulfo group to an N-unsubstituted glucosamine linked to a 2-O-sulfo iduronic acid unit on heparan sulfate. Unlike 3-OST-1, does not convert non-anticoagulant heparan sulfate to anticoagulant heparan sulfate (By similarity). {ECO:0000250}.
Ensembl transtripts involved in fusion geneENST idsENST00000320805, ENST00000564978, 
ENST00000568148, ENST00000562977, 
ENST00000475436, ENST00000331351, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 5 X 3=9011 X 8 X 5=440
# samples 613
** MAII scorelog2(6/90*10)=-0.584962500721156
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(13/440*10)=-1.7589919004962
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: NFATC2IP [Title/Abstract] AND HS3ST4 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: NFATC2IP [Title/Abstract] AND HS3ST4 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NFATC2IP(28970421)-HS3ST4(26146933), # samples:3
Anticipated loss of major functional domain due to fusion event.NFATC2IP-HS3ST4 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.
NFATC2IP-HS3ST4 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.
NFATC2IP-HS3ST4 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.
NFATC2IP-HS3ST4 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


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/chr16:28970421/chr16:26146933)
- 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 NFATC2IP (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 HS3ST4 (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)
ENST00000564978NFATC2IPchr1628970421+ENST00000331351HS3ST4chr1626146933+2433356363992209
ENST00000320805NFATC2IPchr1628970421+ENST00000331351HS3ST4chr1626146933+32531176751247390
ENST00000568148NFATC2IPchr1628970421+ENST00000331351HS3ST4chr1626146933+26595825891218209

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
ENST00000564978ENST00000331351NFATC2IPchr1628970421+HS3ST4chr1626146933+0.0056007020.99439925
ENST00000320805ENST00000331351NFATC2IPchr1628970421+HS3ST4chr1626146933+0.006087560.99391246
ENST00000568148ENST00000331351NFATC2IPchr1628970421+HS3ST4chr1626146933+0.0057156170.99428433

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 NFATC2IP-HS3ST4

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
NFATC2IPchr1628970421HS3ST4chr16261469331176363RVQGKEKHQTLEVSLSRKCDAQDFGW

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Potential FusionNeoAntigen Information of NFATC2IP-HS3ST4 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.
NFATC2IP-HS3ST4_28970421_26146933.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)
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-B39:01HQTLEVSL0.99340.888715
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-B39:13HQTLEVSL0.97580.8513715
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-B39:01KHQTLEVSL0.99890.7511615
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-B39:13KHQTLEVSL0.99830.7352615
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-B38:02KHQTLEVSL0.99820.8879615
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-B39:06KHQTLEVSL0.9980.6072615
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-B38:01KHQTLEVSL0.99790.8839615
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-B14:02KHQTLEVSL0.98330.6363615
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-B14:01KHQTLEVSL0.98330.6363615
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-A74:03QTLEVSLSR0.95520.5008817
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-A74:11QTLEVSLSR0.95520.5008817
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-A74:09QTLEVSLSR0.95520.5008817
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-B50:01LEVSLSRKC0.01250.56181019
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-B39:01EKHQTLEVSL0.9970.6864515
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-B38:02EKHQTLEVSL0.99410.8121515
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-B38:01EKHQTLEVSL0.9940.7822515
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-B39:09HQTLEVSL0.99430.5618715
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-B39:05HQTLEVSL0.980.8631715
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-B39:08HQTLEVSL0.97940.8727715
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-B39:12KHQTLEVSL0.99870.7539615
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-B39:05KHQTLEVSL0.99830.7238615
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-C07:13KHQTLEVSL0.8950.8768615
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-B39:08KHQTLEVSL0.78070.7004615
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-B14:03KHQTLEVSL0.60730.6304615
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-B39:12EKHQTLEVSL0.99610.6912515
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-B39:05EKHQTLEVSL0.98860.65515
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-B39:02HQTLEVSL0.99430.8588715
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-B39:31HQTLEVSL0.99320.8886715
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-B39:11HQTLEVSL0.9770.8761715
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-B15:09HQTLEVSL0.90920.6868715
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-B39:31KHQTLEVSL0.9990.7518615
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-B39:02KHQTLEVSL0.99890.741615
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-B38:05KHQTLEVSL0.99790.8839615
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-B15:09KHQTLEVSL0.96950.5593615
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-A74:01QTLEVSLSR0.95520.5008817
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-B39:11KHQTLEVSL0.85640.6461615
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-C07:04KHQTLEVSL0.75810.9087615
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-B50:05LEVSLSRKC0.01250.56181019
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-B50:04LEVSLSRKC0.01250.56181019
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-B39:31EKHQTLEVSL0.9970.6868515
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-B38:05EKHQTLEVSL0.9940.7822515
NFATC2IP-HS3ST4chr1628970421chr16261469331176HLA-B39:11EKHQTLEVSL0.9240.576515

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Potential FusionNeoAntigen Information of NFATC2IP-HS3ST4 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 NFATC2IP-HS3ST4

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
4278KHQTLEVSLSRKCDNFATC2IPHS3ST4chr1628970421chr16261469331176

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of NFATC2IP-HS3ST4

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-B14:023BVN4278KHQTLEVSLSRKCD-7.15543-7.26883
HLA-B14:023BVN4278KHQTLEVSLSRKCD-4.77435-5.80965
HLA-B52:013W394278KHQTLEVSLSRKCD-6.80875-6.92215
HLA-B52:013W394278KHQTLEVSLSRKCD-4.20386-5.23916
HLA-A11:014UQ24278KHQTLEVSLSRKCD-7.5194-8.5547
HLA-A11:014UQ24278KHQTLEVSLSRKCD-6.9601-7.0735
HLA-A24:025HGA4278KHQTLEVSLSRKCD-7.52403-7.63743
HLA-A24:025HGA4278KHQTLEVSLSRKCD-5.82433-6.85963
HLA-B27:056PYJ4278KHQTLEVSLSRKCD-3.28285-4.31815
HLA-B44:053DX84278KHQTLEVSLSRKCD-5.91172-6.94702
HLA-B44:053DX84278KHQTLEVSLSRKCD-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of NFATC2IP-HS3ST4

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
NFATC2IP-HS3ST4chr1628970421chr16261469331019LEVSLSRKCCTGTCTCGAAAATGTGATGCCCAAGAC
NFATC2IP-HS3ST4chr1628970421chr1626146933515EKHQTLEVSLACACTGGAAGTCTCACTGTCTCGAAAATGT
NFATC2IP-HS3ST4chr1628970421chr1626146933615KHQTLEVSLCTGGAAGTCTCACTGTCTCGAAAATGT
NFATC2IP-HS3ST4chr1628970421chr1626146933715HQTLEVSLGAAGTCTCACTGTCTCGAAAATGT
NFATC2IP-HS3ST4chr1628970421chr1626146933817QTLEVSLSRGTCTCACTGTCTCGAAAATGTGATGCC

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 NFATC2IP-HS3ST4

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
BRCANFATC2IP-HS3ST4chr1628970421ENST00000320805chr1626146933ENST00000331351TCGA-D8-A27M-01A

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Potential target of CAR-T therapy development for NFATC2IP-HS3ST4

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 NFATC2IP-HS3ST4

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 NFATC2IP-HS3ST4

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