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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:TRUB2-KCNT1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TRUB2-KCNT1
FusionPDB ID: 94468
FusionGDB2.0 ID: 94468
HgeneTgene
Gene symbol

TRUB2

KCNT1

Gene ID

26995

57582

Gene nameTruB pseudouridine synthase family member 2potassium sodium-activated channel subfamily T member 1
SynonymsCLONE24922EIEE14|ENFL5|KCa4.1|SLACK|Slo2.2|bA100C15.2
Cytomap

9q34.11

9q34.3

Type of geneprotein-codingprotein-coding
Descriptionmitochondrial mRNA pseudouridine synthase TRUB2TruB pseudouridine (psi) synthase family member 2TruB pseudouridine (psi) synthase homolog 2probable tRNA pseudouridine synthase 2potassium channel subfamily T member 1Sequence like a calcium-activated K+ channelpotassium channel, sodium activated subfamily T, member 1potassium channel, subfamily T, member 1
Modification date2020031320200313
UniProtAcc.

Q5JUK3

Main function of 5'-partner protein: FUNCTION: Outwardly rectifying potassium channel subunit that may coassemble with other Slo-type channel subunits. Activated by high intracellular sodium or chloride levels. Activated upon stimulation of G-protein coupled receptors, such as CHRM1 and GRIA1. May be regulated by calcium in the absence of sodium ions (in vitro) (By similarity). {ECO:0000250}.
Ensembl transtripts involved in fusion geneENST idsENST00000460320, ENST00000372890, 
ENST00000546104, 
ENST00000263604, 
ENST00000298480, ENST00000371757, 
ENST00000486577, ENST00000487664, 
ENST00000488444, ENST00000490355, 
ENST00000491806, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 6 X 3=1082 X 4 X 2=16
# samples 74
** MAII scorelog2(7/108*10)=-0.625604485218502
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(4/16*10)=1.32192809488736
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: TRUB2 [Title/Abstract] AND KCNT1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: TRUB2 [Title/Abstract] AND KCNT1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TRUB2(131083878)-KCNT1(138641944), # samples:3
Anticipated loss of major functional domain due to fusion event.TRUB2-KCNT1 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.
TRUB2-KCNT1 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.
TRUB2-KCNT1 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
TRUB2-KCNT1 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target 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


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/chr9:131083878/chr9:138641944)
- 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 TRUB2 (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 KCNT1 (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)
ENST00000546104TRUB2chr9131083878-ENST00000298480KCNT1chr9138641944+499749554740111154
ENST00000546104TRUB2chr9131083878-ENST00000487664KCNT1chr9138641944+500649554740201157
ENST00000546104TRUB2chr9131083878-ENST00000371757KCNT1chr9138641944+489149554739481133
ENST00000546104TRUB2chr9131083878-ENST00000486577KCNT1chr9138641944+400049554739991151
ENST00000546104TRUB2chr9131083878-ENST00000491806KCNT1chr9138641944+400949554740051152
ENST00000546104TRUB2chr9131083878-ENST00000488444KCNT1chr9138641944+400949554740051152
ENST00000546104TRUB2chr9131083878-ENST00000490355KCNT1chr9138641944+400649554740021151
ENST00000546104TRUB2chr9131083878-ENST00000263604KCNT1chr9138641944+497649554739901147
ENST00000546104TRUB2chr9131083877-ENST00000298480KCNT1chr9138641943+499749554740111154
ENST00000546104TRUB2chr9131083877-ENST00000487664KCNT1chr9138641943+500649554740201157
ENST00000546104TRUB2chr9131083877-ENST00000371757KCNT1chr9138641943+489149554739481133
ENST00000546104TRUB2chr9131083877-ENST00000486577KCNT1chr9138641943+400049554739991151
ENST00000546104TRUB2chr9131083877-ENST00000491806KCNT1chr9138641943+400949554740051152
ENST00000546104TRUB2chr9131083877-ENST00000488444KCNT1chr9138641943+400949554740051152
ENST00000546104TRUB2chr9131083877-ENST00000490355KCNT1chr9138641943+400649554740021151
ENST00000546104TRUB2chr9131083877-ENST00000263604KCNT1chr9138641943+497649554739901147

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
ENST00000546104ENST00000298480TRUB2chr9131083878-KCNT1chr9138641944+0.005879140.9941209
ENST00000546104ENST00000487664TRUB2chr9131083878-KCNT1chr9138641944+0.0063143830.99368566
ENST00000546104ENST00000371757TRUB2chr9131083878-KCNT1chr9138641944+0.0083375450.9916625
ENST00000546104ENST00000486577TRUB2chr9131083878-KCNT1chr9138641944+0.0086635850.99133635
ENST00000546104ENST00000491806TRUB2chr9131083878-KCNT1chr9138641944+0.0073258820.9926742
ENST00000546104ENST00000488444TRUB2chr9131083878-KCNT1chr9138641944+0.0073258820.9926742
ENST00000546104ENST00000490355TRUB2chr9131083878-KCNT1chr9138641944+0.0077656710.99223435
ENST00000546104ENST00000263604TRUB2chr9131083878-KCNT1chr9138641944+0.0064532270.9935468
ENST00000546104ENST00000298480TRUB2chr9131083877-KCNT1chr9138641943+0.005879140.9941209
ENST00000546104ENST00000487664TRUB2chr9131083877-KCNT1chr9138641943+0.0063143830.99368566
ENST00000546104ENST00000371757TRUB2chr9131083877-KCNT1chr9138641943+0.0083375450.9916625
ENST00000546104ENST00000486577TRUB2chr9131083877-KCNT1chr9138641943+0.0086635850.99133635
ENST00000546104ENST00000491806TRUB2chr9131083877-KCNT1chr9138641943+0.0073258820.9926742
ENST00000546104ENST00000488444TRUB2chr9131083877-KCNT1chr9138641943+0.0073258820.9926742
ENST00000546104ENST00000490355TRUB2chr9131083877-KCNT1chr9138641943+0.0077656710.99223435
ENST00000546104ENST00000263604TRUB2chr9131083877-KCNT1chr9138641943+0.0064532270.9935468

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 TRUB2-KCNT1

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

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Potential FusionNeoAntigen Information of TRUB2-KCNT1 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 TRUB2-KCNT1 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 TRUB2-KCNT1

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 TRUB2-KCNT1

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 TRUB2-KCNT1

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 TRUB2-KCNT1

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 TRUB2-KCNT1

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
TgeneKCNT1chr9:131083877chr9:138641943ENST00000263604131282_30201231.0IntramembranePore-forming
TgeneKCNT1chr9:131083877chr9:138641943ENST00000298480132282_30201257.0IntramembranePore-forming
TgeneKCNT1chr9:131083877chr9:138641943ENST00000371757131282_30201236.0IntramembranePore-forming
TgeneKCNT1chr9:131083878chr9:138641944ENST00000263604131282_30201231.0IntramembranePore-forming
TgeneKCNT1chr9:131083878chr9:138641944ENST00000298480132282_30201257.0IntramembranePore-forming
TgeneKCNT1chr9:131083878chr9:138641944ENST00000371757131282_30201236.0IntramembranePore-forming
TgeneKCNT1chr9:131083877chr9:138641943ENST00000263604131156_17601231.0TransmembraneHelical%3B Name%3DSegment S2
TgeneKCNT1chr9:131083877chr9:138641943ENST00000263604131188_20801231.0TransmembraneHelical%3B Name%3DSegment S3
TgeneKCNT1chr9:131083877chr9:138641943ENST00000263604131214_22601231.0TransmembraneHelical%3B Name%3DSegment S4
TgeneKCNT1chr9:131083877chr9:138641943ENST00000263604131252_27201231.0TransmembraneHelical%3B Name%3DSegment S5
TgeneKCNT1chr9:131083877chr9:138641943ENST00000263604131305_32501231.0TransmembraneHelical%3B Name%3DSegment S6
TgeneKCNT1chr9:131083877chr9:138641943ENST0000026360413198_11801231.0TransmembraneHelical%3B Name%3DSegment S1
TgeneKCNT1chr9:131083877chr9:138641943ENST00000298480132156_17601257.0TransmembraneHelical%3B Name%3DSegment S2
TgeneKCNT1chr9:131083877chr9:138641943ENST00000298480132188_20801257.0TransmembraneHelical%3B Name%3DSegment S3
TgeneKCNT1chr9:131083877chr9:138641943ENST00000298480132214_22601257.0TransmembraneHelical%3B Name%3DSegment S4
TgeneKCNT1chr9:131083877chr9:138641943ENST00000298480132252_27201257.0TransmembraneHelical%3B Name%3DSegment S5
TgeneKCNT1chr9:131083877chr9:138641943ENST00000298480132305_32501257.0TransmembraneHelical%3B Name%3DSegment S6
TgeneKCNT1chr9:131083877chr9:138641943ENST0000029848013298_11801257.0TransmembraneHelical%3B Name%3DSegment S1
TgeneKCNT1chr9:131083877chr9:138641943ENST00000371757131156_17601236.0TransmembraneHelical%3B Name%3DSegment S2
TgeneKCNT1chr9:131083877chr9:138641943ENST00000371757131188_20801236.0TransmembraneHelical%3B Name%3DSegment S3
TgeneKCNT1chr9:131083877chr9:138641943ENST00000371757131214_22601236.0TransmembraneHelical%3B Name%3DSegment S4
TgeneKCNT1chr9:131083877chr9:138641943ENST00000371757131252_27201236.0TransmembraneHelical%3B Name%3DSegment S5
TgeneKCNT1chr9:131083877chr9:138641943ENST00000371757131305_32501236.0TransmembraneHelical%3B Name%3DSegment S6
TgeneKCNT1chr9:131083877chr9:138641943ENST0000037175713198_11801236.0TransmembraneHelical%3B Name%3DSegment S1
TgeneKCNT1chr9:131083878chr9:138641944ENST00000263604131156_17601231.0TransmembraneHelical%3B Name%3DSegment S2
TgeneKCNT1chr9:131083878chr9:138641944ENST00000263604131188_20801231.0TransmembraneHelical%3B Name%3DSegment S3
TgeneKCNT1chr9:131083878chr9:138641944ENST00000263604131214_22601231.0TransmembraneHelical%3B Name%3DSegment S4
TgeneKCNT1chr9:131083878chr9:138641944ENST00000263604131252_27201231.0TransmembraneHelical%3B Name%3DSegment S5
TgeneKCNT1chr9:131083878chr9:138641944ENST00000263604131305_32501231.0TransmembraneHelical%3B Name%3DSegment S6
TgeneKCNT1chr9:131083878chr9:138641944ENST0000026360413198_11801231.0TransmembraneHelical%3B Name%3DSegment S1
TgeneKCNT1chr9:131083878chr9:138641944ENST00000298480132156_17601257.0TransmembraneHelical%3B Name%3DSegment S2
TgeneKCNT1chr9:131083878chr9:138641944ENST00000298480132188_20801257.0TransmembraneHelical%3B Name%3DSegment S3
TgeneKCNT1chr9:131083878chr9:138641944ENST00000298480132214_22601257.0TransmembraneHelical%3B Name%3DSegment S4
TgeneKCNT1chr9:131083878chr9:138641944ENST00000298480132252_27201257.0TransmembraneHelical%3B Name%3DSegment S5
TgeneKCNT1chr9:131083878chr9:138641944ENST00000298480132305_32501257.0TransmembraneHelical%3B Name%3DSegment S6
TgeneKCNT1chr9:131083878chr9:138641944ENST0000029848013298_11801257.0TransmembraneHelical%3B Name%3DSegment S1
TgeneKCNT1chr9:131083878chr9:138641944ENST00000371757131156_17601236.0TransmembraneHelical%3B Name%3DSegment S2
TgeneKCNT1chr9:131083878chr9:138641944ENST00000371757131188_20801236.0TransmembraneHelical%3B Name%3DSegment S3
TgeneKCNT1chr9:131083878chr9:138641944ENST00000371757131214_22601236.0TransmembraneHelical%3B Name%3DSegment S4
TgeneKCNT1chr9:131083878chr9:138641944ENST00000371757131252_27201236.0TransmembraneHelical%3B Name%3DSegment S5
TgeneKCNT1chr9:131083878chr9:138641944ENST00000371757131305_32501236.0TransmembraneHelical%3B Name%3DSegment S6
TgeneKCNT1chr9:131083878chr9:138641944ENST0000037175713198_11801236.0TransmembraneHelical%3B Name%3DSegment S1

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 TRUB2-KCNT1

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 TRUB2-KCNT1

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