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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-NFIX

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TBCD-NFIX
FusionPDB ID: 89477
FusionGDB2.0 ID: 89477
HgeneTgene
Gene symbol

TBCD

NFIX

Gene ID

6904

4784

Gene nametubulin folding cofactor Dnuclear factor I X
SynonymsPEBAT|SSD-1|tfcDCTF|MRSHSS|NF-I/X|NF1-X|NF1A|SOTOS2
Cytomap

17q25.3

19p13.13

Type of geneprotein-codingprotein-coding
Descriptiontubulin-specific chaperone Dbeta-tubulin cofactor Dnuclear factor 1 X-typeCCAAT-box-binding transcription factorTGGCA-binding proteinnuclear factor 1/X
Modification date2020031320200329
UniProtAcc.

Q14938

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, 
ENST00000360105, ENST00000397661, 
ENST00000585575, ENST00000587760, 
ENST00000592199, ENST00000358552, 
ENST00000587260, ENST00000588228, 
ENST00000588680, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score20 X 23 X 13=598022 X 13 X 10=2860
# samples 2726
** MAII scorelog2(27/5980*10)=-4.46911417203464
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(26/2860*10)=-3.4594316186373
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

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

Fusion neoantigen context

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

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TBCD(80899359)-NFIX(13135835), # samples:3
Anticipated loss of major functional domain due to fusion event.TBCD-NFIX 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-NFIX 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-NFIX 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-NFIX 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

TgeneNFIX

GO:0000122

negative regulation of transcription by RNA polymerase II

19706729

TgeneNFIX

GO:0045944

positive regulation of transcription by RNA polymerase II

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/chr19:13135835)
- 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 NFIX (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+ENST00000397661NFIXchr1913135835+6580369413049921620
ENST00000355528TBCDchr1780899359+ENST00000592199NFIXchr1913135835+5176369413051751682
ENST00000355528TBCDchr1780899359+ENST00000587760NFIXchr1913135835+5137369413049921620
ENST00000355528TBCDchr1780899359+ENST00000585575NFIXchr1913135835+5176369413051751682
ENST00000355528TBCDchr1780899359+ENST00000360105NFIXchr1913135835+9052369413048691579
ENST00000539345TBCDchr1780899359+ENST00000397661NFIXchr1913135835+660037143650121658
ENST00000539345TBCDchr1780899359+ENST00000592199NFIXchr1913135835+519637143651951719
ENST00000539345TBCDchr1780899359+ENST00000587760NFIXchr1913135835+515737143650121658
ENST00000539345TBCDchr1780899359+ENST00000585575NFIXchr1913135835+519637143651951719
ENST00000539345TBCDchr1780899359+ENST00000360105NFIXchr1913135835+907237143648891617
ENST00000355528TBCDchr1780899359+ENST00000397661NFIXchr1913135834+6580369413049921620
ENST00000355528TBCDchr1780899359+ENST00000592199NFIXchr1913135834+5176369413051751682
ENST00000355528TBCDchr1780899359+ENST00000587760NFIXchr1913135834+5137369413049921620
ENST00000355528TBCDchr1780899359+ENST00000585575NFIXchr1913135834+5176369413051751682
ENST00000355528TBCDchr1780899359+ENST00000360105NFIXchr1913135834+9052369413048691579
ENST00000539345TBCDchr1780899359+ENST00000397661NFIXchr1913135834+660037143650121658
ENST00000539345TBCDchr1780899359+ENST00000592199NFIXchr1913135834+519637143651951719
ENST00000539345TBCDchr1780899359+ENST00000587760NFIXchr1913135834+515737143650121658
ENST00000539345TBCDchr1780899359+ENST00000585575NFIXchr1913135834+519637143651951719
ENST00000539345TBCDchr1780899359+ENST00000360105NFIXchr1913135834+907237143648891617

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
ENST00000355528ENST00000397661TBCDchr1780899359+NFIXchr1913135835+0.0023224560.9976775
ENST00000355528ENST00000592199TBCDchr1780899359+NFIXchr1913135835+0.0021602410.9978397
ENST00000355528ENST00000587760TBCDchr1780899359+NFIXchr1913135835+0.002799680.99720037
ENST00000355528ENST00000585575TBCDchr1780899359+NFIXchr1913135835+0.0021602410.9978397
ENST00000355528ENST00000360105TBCDchr1780899359+NFIXchr1913135835+0.0010117940.9989882
ENST00000539345ENST00000397661TBCDchr1780899359+NFIXchr1913135835+0.0018703820.99812967
ENST00000539345ENST00000592199TBCDchr1780899359+NFIXchr1913135835+0.0019211380.9980788
ENST00000539345ENST00000587760TBCDchr1780899359+NFIXchr1913135835+0.0022355260.99776447
ENST00000539345ENST00000585575TBCDchr1780899359+NFIXchr1913135835+0.0019211380.9980788
ENST00000539345ENST00000360105TBCDchr1780899359+NFIXchr1913135835+0.000894580.9991054
ENST00000355528ENST00000397661TBCDchr1780899359+NFIXchr1913135834+0.0023224560.9976775
ENST00000355528ENST00000592199TBCDchr1780899359+NFIXchr1913135834+0.0021602410.9978397
ENST00000355528ENST00000587760TBCDchr1780899359+NFIXchr1913135834+0.002799680.99720037
ENST00000355528ENST00000585575TBCDchr1780899359+NFIXchr1913135834+0.0021602410.9978397
ENST00000355528ENST00000360105TBCDchr1780899359+NFIXchr1913135834+0.0010117940.9989882
ENST00000539345ENST00000397661TBCDchr1780899359+NFIXchr1913135834+0.0018703820.99812967
ENST00000539345ENST00000592199TBCDchr1780899359+NFIXchr1913135834+0.0019211380.9980788
ENST00000539345ENST00000587760TBCDchr1780899359+NFIXchr1913135834+0.0022355260.99776447
ENST00000539345ENST00000585575TBCDchr1780899359+NFIXchr1913135834+0.0019211380.9980788
ENST00000539345ENST00000360105TBCDchr1780899359+NFIXchr1913135834+0.000894580.9991054

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-NFIX

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
TBCDchr1780899359NFIXchr191313583436941187CDLLGVPRPQLVPQDEFHPFIEALLP
TBCDchr1780899359NFIXchr191313583437141225CDLLGVPRPQLVPQDEFHPFIEALLP
TBCDchr1780899359NFIXchr191313583536941187CDLLGVPRPQLVPQDEFHPFIEALLP
TBCDchr1780899359NFIXchr191313583537141225CDLLGVPRPQLVPQDEFHPFIEALLP

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Potential FusionNeoAntigen Information of TBCD-NFIX 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.

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)

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Potential FusionNeoAntigen Information of TBCD-NFIX 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 TBCD-NFIX

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.

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

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

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Vaccine Design for the FusionNeoAntigens of TBCD-NFIX

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

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 TBCD-NFIX

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

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

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-NFIX

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-NFIX

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