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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:TBCD-NFIC

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TBCD-NFIC
FusionPDB ID: 89476
FusionGDB2.0 ID: 89476
HgeneTgene
Gene symbol

TBCD

NFIC

Gene ID

6904

4782

Gene nametubulin folding cofactor Dnuclear factor I C
SynonymsPEBAT|SSD-1|tfcDCTF|CTF5|NF-I|NFI
Cytomap

17q25.3

19p13.3

Type of geneprotein-codingprotein-coding
Descriptiontubulin-specific chaperone Dbeta-tubulin cofactor Dnuclear factor 1 C-typeCCAAT-box-binding transcription factorNF-I/CNF1-CTGGCA-binding proteinnuclear factor I/C (CCAAT-binding transcription factor)
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.
Ensembl transtripts involved in fusion geneENST idsENST00000576691, ENST00000355528, 
ENST00000539345, ENST00000397466, 
ENST00000341919, ENST00000346156, 
ENST00000395111, ENST00000443272, 
ENST00000586919, ENST00000589123, 
ENST00000590282, ENST00000588839, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score20 X 23 X 13=598024 X 21 X 9=4536
# samples 2727
** MAII scorelog2(27/5980*10)=-4.46911417203464
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(27/4536*10)=-4.0703893278914
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

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

Fusion neoantigen context

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

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TBCD(80899359)-NFIC(3381709), # samples:1
Anticipated loss of major functional domain due to fusion event.TBCD-NFIC 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.
TBCD-NFIC 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.
TBCD-NFIC 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.
TBCD-NFIC 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
HgeneTBCD

GO:0006457

protein folding

20740604

HgeneTBCD

GO:0007021

tubulin complex assembly

28158450

HgeneTBCD

GO:0007023

post-chaperonin tubulin folding pathway

11847227

HgeneTBCD

GO:0031115

negative regulation of microtubule polymerization

10831612|20740604

TgeneNFIC

GO:0000122

negative regulation of transcription by RNA polymerase II

19706729

TgeneNFIC

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/chr17:80899359/chr19:3381709)
- 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 TBCD (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 NFIC (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)
ENST00000355528TBCDchr1780899359+ENST00000589123NFICchr193381709+11639369413051901686
ENST00000355528TBCDchr1780899359+ENST00000346156NFICchr193381709+5801369413049111593
ENST00000355528TBCDchr1780899359+ENST00000395111NFICchr193381709+5410369413049831617
ENST00000355528TBCDchr1780899359+ENST00000586919NFICchr193381709+4912369413049111594
ENST00000355528TBCDchr1780899359+ENST00000341919NFICchr193381709+5149369413049501606
ENST00000355528TBCDchr1780899359+ENST00000590282NFICchr193381709+5168369413049831617
ENST00000355528TBCDchr1780899359+ENST00000443272NFICchr193381709+5329369413051901686
ENST00000539345TBCDchr1780899359+ENST00000589123NFICchr193381709+1165937143652101724
ENST00000539345TBCDchr1780899359+ENST00000346156NFICchr193381709+582137143649311631
ENST00000539345TBCDchr1780899359+ENST00000395111NFICchr193381709+543037143650031655
ENST00000539345TBCDchr1780899359+ENST00000586919NFICchr193381709+493237143649311631
ENST00000539345TBCDchr1780899359+ENST00000341919NFICchr193381709+516937143649701644
ENST00000539345TBCDchr1780899359+ENST00000590282NFICchr193381709+518837143650031655
ENST00000539345TBCDchr1780899359+ENST00000443272NFICchr193381709+534937143652101724

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
ENST00000355528ENST00000589123TBCDchr1780899359+NFICchr193381709+0.0008986820.9991014
ENST00000355528ENST00000346156TBCDchr1780899359+NFICchr193381709+0.0027772950.99722266
ENST00000355528ENST00000395111TBCDchr1780899359+NFICchr193381709+0.0024801360.9975198
ENST00000355528ENST00000586919TBCDchr1780899359+NFICchr193381709+0.0028952830.9971047
ENST00000355528ENST00000341919TBCDchr1780899359+NFICchr193381709+0.0026981470.9973018
ENST00000355528ENST00000590282TBCDchr1780899359+NFICchr193381709+0.0025426180.99745744
ENST00000355528ENST00000443272TBCDchr1780899359+NFICchr193381709+0.0034361860.99656385
ENST00000539345ENST00000589123TBCDchr1780899359+NFICchr193381709+0.0004332050.99956673
ENST00000539345ENST00000346156TBCDchr1780899359+NFICchr193381709+0.0027519790.997248
ENST00000539345ENST00000395111TBCDchr1780899359+NFICchr193381709+0.0024005570.9975994
ENST00000539345ENST00000586919TBCDchr1780899359+NFICchr193381709+0.002827610.9971724
ENST00000539345ENST00000341919TBCDchr1780899359+NFICchr193381709+0.0020530070.99794704
ENST00000539345ENST00000590282TBCDchr1780899359+NFICchr193381709+0.0024532070.99754673
ENST00000539345ENST00000443272TBCDchr1780899359+NFICchr193381709+0.0018911060.99810886

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 TBCD-NFIC

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
TBCDchr1780899359NFICchr19338170936941187CDLLGVPRPQLVPQDEFHPFIEALLP
TBCDchr1780899359NFICchr19338170937141225CDLLGVPRPQLVPQDEFHPFIEALLP

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Potential FusionNeoAntigen Information of TBCD-NFIC 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.
TBCD-NFIC_80899359_3381709.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)
TBCD-NFICchr1780899359chr1933817093694HLA-B35:01VPQDEFHPF0.99690.95941120
TBCD-NFICchr1780899359chr1933817093694HLA-B35:08VPQDEFHPF0.99320.95311120
TBCD-NFICchr1780899359chr1933817093694HLA-B35:05VPQDEFHPF0.99210.83151120
TBCD-NFICchr1780899359chr1933817093694HLA-B15:02VPQDEFHPF0.98160.9711120
TBCD-NFICchr1780899359chr1933817093694HLA-B35:03VPQDEFHPF0.96230.95751120
TBCD-NFICchr1780899359chr1933817093694HLA-B35:02VPQDEFHPF0.82720.98261120
TBCD-NFICchr1780899359chr1933817093694HLA-B35:04VPQDEFHPF0.82720.98261120
TBCD-NFICchr1780899359chr1933817093694HLA-B35:08LVPQDEFHPF0.98190.9641020
TBCD-NFICchr1780899359chr1933817093694HLA-B35:05LVPQDEFHPF0.97720.8661020
TBCD-NFICchr1780899359chr1933817093694HLA-B07:02RPQLVPQDEF0.97580.5044717
TBCD-NFICchr1780899359chr1933817093694HLA-B35:01LVPQDEFHPF0.9650.96981020
TBCD-NFICchr1780899359chr1933817093694HLA-B53:01LVPQDEFHPF0.91910.61351020
TBCD-NFICchr1780899359chr1933817093694HLA-B35:08RPQLVPQDEF0.85130.8776717
TBCD-NFICchr1780899359chr1933817093694HLA-B82:01RPQLVPQDEF0.41910.5116717
TBCD-NFICchr1780899359chr1933817093694HLA-B13:01RPQLVPQDEF0.15830.9423717
TBCD-NFICchr1780899359chr1933817093694HLA-B15:31VPQDEFHPF0.99640.95751120
TBCD-NFICchr1780899359chr1933817093694HLA-B35:12VPQDEFHPF0.82720.98261120
TBCD-NFICchr1780899359chr1933817093694HLA-B07:12VPQDEFHPF0.81550.67971120
TBCD-NFICchr1780899359chr1933817093694HLA-B78:01VPQDEFHPF0.70290.56611120
TBCD-NFICchr1780899359chr1933817093694HLA-B42:02VPQDEFHPF0.48360.70531120
TBCD-NFICchr1780899359chr1933817093694HLA-B39:10VPQDEFHPF0.44160.9531120
TBCD-NFICchr1780899359chr1933817093694HLA-B42:01VPQDEFHPF0.41180.69721120
TBCD-NFICchr1780899359chr1933817093694HLA-B07:12RPQLVPQDEF0.97080.6707717
TBCD-NFICchr1780899359chr1933817093694HLA-B42:02RPQLVPQDEF0.60980.7835717
TBCD-NFICchr1780899359chr1933817093694HLA-B42:01RPQLVPQDEF0.54280.778717
TBCD-NFICchr1780899359chr1933817093694HLA-B35:77VPQDEFHPF0.99690.95941120
TBCD-NFICchr1780899359chr1933817093694HLA-B35:23VPQDEFHPF0.99670.96291120
TBCD-NFICchr1780899359chr1933817093694HLA-B35:20VPQDEFHPF0.9960.97871120
TBCD-NFICchr1780899359chr1933817093694HLA-B35:17VPQDEFHPF0.99350.92051120
TBCD-NFICchr1780899359chr1933817093694HLA-B35:30VPQDEFHPF0.99350.92051120
TBCD-NFICchr1780899359chr1933817093694HLA-B35:24VPQDEFHPF0.99220.97441120
TBCD-NFICchr1780899359chr1933817093694HLA-B35:11VPQDEFHPF0.98580.96371120
TBCD-NFICchr1780899359chr1933817093694HLA-B53:02VPQDEFHPF0.96390.58211120
TBCD-NFICchr1780899359chr1933817093694HLA-B07:09VPRPQLVPQ0.96190.6458514
TBCD-NFICchr1780899359chr1933817093694HLA-B35:13VPQDEFHPF0.94630.961120
TBCD-NFICchr1780899359chr1933817093694HLA-B15:13VPQDEFHPF0.90670.78571120
TBCD-NFICchr1780899359chr1933817093694HLA-B35:09VPQDEFHPF0.82720.98261120
TBCD-NFICchr1780899359chr1933817093694HLA-B18:04VPQDEFHPF0.78710.96711120
TBCD-NFICchr1780899359chr1933817093694HLA-B78:02VPQDEFHPF0.7770.72011120
TBCD-NFICchr1780899359chr1933817093694HLA-B18:07VPQDEFHPF0.60090.95231120
TBCD-NFICchr1780899359chr1933817093694HLA-B18:03VPQDEFHPF0.50120.95891120
TBCD-NFICchr1780899359chr1933817093694HLA-B18:08VPQDEFHPF0.48930.95511120
TBCD-NFICchr1780899359chr1933817093694HLA-B67:01VPQDEFHPF0.46120.88071120
TBCD-NFICchr1780899359chr1933817093694HLA-B15:08VPQDEFHPF0.41940.94511120
TBCD-NFICchr1780899359chr1933817093694HLA-B35:43VPQDEFHPF0.40610.94741120
TBCD-NFICchr1780899359chr1933817093694HLA-B15:11VPQDEFHPF0.40520.94671120
TBCD-NFICchr1780899359chr1933817093694HLA-B35:30LVPQDEFHPF0.98050.94091020
TBCD-NFICchr1780899359chr1933817093694HLA-B35:17LVPQDEFHPF0.98050.94091020
TBCD-NFICchr1780899359chr1933817093694HLA-B07:22RPQLVPQDEF0.97580.5044717
TBCD-NFICchr1780899359chr1933817093694HLA-B35:23LVPQDEFHPF0.96840.97091020
TBCD-NFICchr1780899359chr1933817093694HLA-B35:77LVPQDEFHPF0.9650.96981020
TBCD-NFICchr1780899359chr1933817093694HLA-B35:24LVPQDEFHPF0.93350.97641020
TBCD-NFICchr1780899359chr1933817093694HLA-B53:02LVPQDEFHPF0.86530.7461020
TBCD-NFICchr1780899359chr1933817093694HLA-B55:04RPQLVPQDEF0.52170.5852717
TBCD-NFICchr1780899359chr1933817093694HLA-B82:02RPQLVPQDEF0.41910.5116717

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Potential FusionNeoAntigen Information of TBCD-NFIC 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.
TBCD-NFIC_80899359_3381709.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)
TBCD-NFICchr1780899359chr1933817093694DRB1-1529VPQDEFHPFIEALLP1126

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Fusion breakpoint peptide structures of TBCD-NFIC

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
6955PRPQLVPQDEFHPFTBCDNFICchr1780899359chr1933817093694

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

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-B14:023BVN6955PRPQLVPQDEFHPF-7.15543-7.26883
HLA-B14:023BVN6955PRPQLVPQDEFHPF-4.77435-5.80965
HLA-B52:013W396955PRPQLVPQDEFHPF-6.80875-6.92215
HLA-B52:013W396955PRPQLVPQDEFHPF-4.20386-5.23916
HLA-A11:014UQ26955PRPQLVPQDEFHPF-7.5194-8.5547
HLA-A11:014UQ26955PRPQLVPQDEFHPF-6.9601-7.0735
HLA-A24:025HGA6955PRPQLVPQDEFHPF-7.52403-7.63743
HLA-A24:025HGA6955PRPQLVPQDEFHPF-5.82433-6.85963
HLA-B27:056PYJ6955PRPQLVPQDEFHPF-3.28285-4.31815
HLA-B44:053DX86955PRPQLVPQDEFHPF-5.91172-6.94702
HLA-B44:053DX86955PRPQLVPQDEFHPF-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of TBCD-NFIC

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
TBCD-NFICchr1780899359chr1933817091020LVPQDEFHPFGTGCCCCAGGATGAGTTCCACCCGTTCATC
TBCD-NFICchr1780899359chr1933817091120VPQDEFHPFCCCCAGGATGAGTTCCACCCGTTCATC
TBCD-NFICchr1780899359chr193381709514VPRPQLVPQCCCAGGCCCCAGCTGGTGCCCCAGGAT
TBCD-NFICchr1780899359chr193381709717RPQLVPQDEFCCCCAGCTGGTGCCCCAGGATGAGTTCCAC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
TBCD-NFICchr1780899359chr1933817091126VPQDEFHPFIEALLPCCCCAGGATGAGTTCCACCCGTTCATCGAGGCCCTGCTGCCTCAC

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Information of the samples that have these potential fusion neoantigens of TBCD-NFIC

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
BRCATBCD-NFICchr1780899359ENST00000355528chr193381709ENST00000341919TCGA-AN-A0AM

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

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 TBCD-NFIC

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 TBCD-NFIC

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