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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:NFIC-SPATA33

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NFIC-SPATA33
FusionPDB ID: 58925
FusionGDB2.0 ID: 58925
HgeneTgene
Gene symbol

NFIC

SPATA33

Gene ID

4782

124045

Gene namenuclear factor I Cspermatogenesis associated 33
SynonymsCTF|CTF5|NF-I|NFIC16orf55
Cytomap

19p13.3

16q24.3

Type of geneprotein-codingprotein-coding
Descriptionnuclear factor 1 C-typeCCAAT-box-binding transcription factorNF-I/CNF1-CTGGCA-binding proteinnuclear factor I/C (CCAAT-binding transcription factor)spermatogenesis-associated protein 33
Modification date2020031320200313
UniProtAcc

P08651

Main function of 5'-partner protein: FUNCTION: Recognizes and binds the palindromic sequence 5'-TTGGCNNNNNGCCAA-3' present in viral and cellular promoters and in the origin of replication of adenovirus type 2. These proteins are individually capable of activating transcription and replication.

Q96N06

Main function of 5'-partner protein:
Ensembl transtripts involved in fusion geneENST idsENST00000346156, ENST00000395111, 
ENST00000586919, ENST00000589123, 
ENST00000341919, ENST00000443272, 
ENST00000588839, ENST00000590282, 
ENST00000566857, ENST00000568929, 
ENST00000579310, ENST00000301031, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score30 X 20 X 13=78003 X 1 X 3=9
# samples 363
** MAII scorelog2(36/7800*10)=-4.4374053123073
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(3/9*10)=1.73696559416621
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: NFIC [Title/Abstract] AND SPATA33 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: NFIC [Title/Abstract] AND SPATA33 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NFIC(3359683)-SPATA33(89735694), # samples:1
Anticipated loss of major functional domain due to fusion event.NFIC-SPATA33 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.
NFIC-SPATA33 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.
NFIC-SPATA33 seems lost the major protein functional domain in Hgene partner, which is a transcription factor 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
HgeneNFIC

GO:0000122

negative regulation of transcription by RNA polymerase II

19706729

HgeneNFIC

GO:0045944

positive regulation of transcription by RNA polymerase II

1524678|19706729



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/chr19:3359683/chr16:89735694)
- 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 NFIC (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 SPATA33 (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)
ENST00000589123NFICchr193359683+ENST00000301031SPATA33chr1689735694+21051231212310300
ENST00000346156NFICchr193359683+ENST00000301031SPATA33chr1689735694+2050681157255300
ENST00000395111NFICchr193359683+ENST00000301031SPATA33chr1689735694+2021391128226300
ENST00000586919NFICchr193359683+ENST00000301031SPATA33chr1689735694+198531092190300

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
ENST00000589123ENST00000301031NFICchr193359683+SPATA33chr1689735694+0.84378520.1562148
ENST00000346156ENST00000301031NFICchr193359683+SPATA33chr1689735694+0.933500470.066499546
ENST00000395111ENST00000301031NFICchr193359683+SPATA33chr1689735694+0.97680880.023191275
ENST00000586919ENST00000301031NFICchr193359683+SPATA33chr1689735694+0.98089210.019107908

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 NFIC-SPATA33

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
NFICchr193359683SPATA33chr168973569412316ALGKAGPNGNGERAAASHRVGRAWCT
NFICchr193359683SPATA33chr168973569412379RPGAPSLRAREKGATASHRVGRAWCT
NFICchr193359683SPATA33chr1689735694316ALGKAGPNGNGERAAASHRVGRAWCT
NFICchr193359683SPATA33chr1689735694379RPGAPSLRAREKGATASHRVGRAWCT
NFICchr193359683SPATA33chr16897356943916ALGKAGPNGNGERAAASHRVGRAWCT
NFICchr193359683SPATA33chr16897356943979RPGAPSLRAREKGATASHRVGRAWCT
NFICchr193359683SPATA33chr16897356946816ALGKAGPNGNGERAAASHRVGRAWCT
NFICchr193359683SPATA33chr16897356946879RPGAPSLRAREKGATASHRVGRAWCT

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Potential FusionNeoAntigen Information of NFIC-SPATA33 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.
NFIC-SPATA33_3359683_89735694.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)
NFIC-SPATA33chr193359683chr168973569468HLA-B39:06ERAAASHRV0.99770.81151120
NFIC-SPATA33chr193359683chr168973569468HLA-B14:02ERAAASHRV0.99720.73451120
NFIC-SPATA33chr193359683chr168973569468HLA-B14:01ERAAASHRV0.99720.73451120
NFIC-SPATA33chr193359683chr168973569468HLA-B73:01ERAAASHRV0.99140.70091120
NFIC-SPATA33chr193359683chr168973569468HLA-B39:12ERAAASHRV0.98910.73061120
NFIC-SPATA33chr193359683chr168973569468HLA-B39:31ERAAASHRV0.99030.73171120
NFIC-SPATA33chr193359683chr168973569468HLA-C06:08ERAAASHRV0.69420.96531120
NFIC-SPATA33chr193359683chr168973569468HLA-C06:02ERAAASHRV0.00470.97931120
NFIC-SPATA33chr193359683chr168973569468HLA-C06:17ERAAASHRV0.00470.97931120
NFIC-SPATA33chr193359683chr168973569468HLA-B55:02GPNGNGERAA0.6960.5711515

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Potential FusionNeoAntigen Information of NFIC-SPATA33 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 NFIC-SPATA33

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
6824PNGNGERAAASHRVNFICSPATA33chr193359683chr168973569468

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of NFIC-SPATA33

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-B14:023BVN6824PNGNGERAAASHRV-7.9962-8.1096
HLA-B14:023BVN6824PNGNGERAAASHRV-5.70842-6.74372
HLA-B52:013W396824PNGNGERAAASHRV-6.83737-6.95077
HLA-B52:013W396824PNGNGERAAASHRV-4.4836-5.5189
HLA-A11:014UQ26824PNGNGERAAASHRV-10.0067-10.1201
HLA-A11:014UQ26824PNGNGERAAASHRV-9.03915-10.0745
HLA-A24:025HGA6824PNGNGERAAASHRV-6.56204-6.67544
HLA-A24:025HGA6824PNGNGERAAASHRV-5.42271-6.45801
HLA-B44:053DX86824PNGNGERAAASHRV-7.85648-8.89178
HLA-B44:053DX86824PNGNGERAAASHRV-5.3978-5.5112
HLA-A02:016TDR6824PNGNGERAAASHRV-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of NFIC-SPATA33

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
NFIC-SPATA33chr193359683chr16897356941120ERAAASHRVGCCATGAGAAACCTGATGTAAAGCAAA
NFIC-SPATA33chr193359683chr1689735694515GPNGNGERAATCGCCTCCTCGCAGCAGCGCCATGAGAAAC

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 NFIC-SPATA33

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
ACCNFIC-SPATA33chr193359683ENST00000346156chr1689735694ENST00000301031TCGA-OR-A5K2-01A

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Potential target of CAR-T therapy development for NFIC-SPATA33

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 NFIC-SPATA33

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 NFIC-SPATA33

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