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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:NAA25-TBX5

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NAA25-TBX5
FusionPDB ID: 56976
FusionGDB2.0 ID: 56976
HgeneTgene
Gene symbol

NAA25

TBX5

Gene ID

80018

6910

Gene nameN-alpha-acetyltransferase 25, NatB auxiliary subunitT-box transcription factor 5
SynonymsC12orf30|MDM20|NAP1HOS
Cytomap

12q24.13

12q24.21

Type of geneprotein-codingprotein-coding
DescriptionN-alpha-acetyltransferase 25, NatB auxiliary subunitN-terminal acetyltransferase B complex subunit NAA25mitochondrial distribution and morphology 20natB complex subunit MDM20T-box transcription factor TBX5T-box 5T-box protein 5
Modification date2020031320200313
UniProtAcc

Q14CX7

Main function of 5'-partner protein: FUNCTION: Non-catalytic subunit of the NatB complex which catalyzes acetylation of the N-terminal methionine residues of peptides beginning with Met-Asp-Glu. May play a role in normal cell-cycle progression. {ECO:0000269|PubMed:18570629}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000261745, ENST00000526441, 
ENST00000552726, ENST00000349716, 
ENST00000310346, ENST00000405440, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score10 X 14 X 8=11202 X 2 X 2=8
# samples 142
** MAII scorelog2(14/1120*10)=-3
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(2/8*10)=1.32192809488736
Fusion gene context

PubMed: NAA25 [Title/Abstract] AND TBX5 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: NAA25 [Title/Abstract] AND TBX5 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NAA25(112518864)-TBX5(114793911), # samples:3
Anticipated loss of major functional domain due to fusion event.NAA25-TBX5 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.
NAA25-TBX5 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.
NAA25-TBX5 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.
NAA25-TBX5 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.
NAA25-TBX5 seems lost the major protein functional domain in Tgene partner, which is a transcription factor due to the frame-shifted ORF.
NAA25-TBX5 seems lost the major protein functional domain in Tgene partner, which is a tumor suppressor 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
TgeneTBX5

GO:0007267

cell-cell signaling

11161571

TgeneTBX5

GO:0007507

heart development

15138308

TgeneTBX5

GO:0008285

negative regulation of cell proliferation

11161571|12237100

TgeneTBX5

GO:0030336

negative regulation of cell migration

15138308

TgeneTBX5

GO:0045893

positive regulation of transcription, DNA-templated

11431700|12499378|12845333|16332960|27035640

TgeneTBX5

GO:0045944

positive regulation of transcription by RNA polymerase II

29174768

TgeneTBX5

GO:0051891

positive regulation of cardioblast differentiation

11431700

TgeneTBX5

GO:0060039

pericardium development

15138308

TgeneTBX5

GO:0060044

negative regulation of cardiac muscle cell proliferation

11161571



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/chr12:112518864/chr12:114793911)
- 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 NAA25 (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 TBX5 (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)
ENST00000261745NAA25chr12112518864-ENST00000310346TBX5chr12114793911-290272657923288
ENST00000261745NAA25chr12112518864-ENST00000405440TBX5chr12114793911-145272657923288

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
ENST00000261745ENST00000310346NAA25chr12112518864-TBX5chr12114793911-0.007099990.9929
ENST00000261745ENST00000405440NAA25chr12112518864-TBX5chr12114793911-0.0223943220.97760576

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 NAA25-TBX5

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
NAA25chr12112518864TBX5chr12114793911726222NPYYFWSVMSLIMQRKNVPPQTIPIR

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Potential FusionNeoAntigen Information of NAA25-TBX5 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.
NAA25-TBX5_112518864_114793911.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)
NAA25-TBX5chr12112518864chr12114793911726HLA-A30:08SVMSLIMQR0.89740.5252615
NAA25-TBX5chr12112518864chr12114793911726HLA-A30:01SVMSLIMQR0.90780.7564615
NAA25-TBX5chr12112518864chr12114793911726HLA-A30:01SVMSLIMQRK0.97260.6872616

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Potential FusionNeoAntigen Information of NAA25-TBX5 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 NAA25-TBX5

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
9159SVMSLIMQRKNVPPNAA25TBX5chr12112518864chr12114793911726

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of NAA25-TBX5

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-B14:023BVN9159SVMSLIMQRKNVPP-7.15543-7.26883
HLA-B14:023BVN9159SVMSLIMQRKNVPP-4.77435-5.80965
HLA-B52:013W399159SVMSLIMQRKNVPP-6.80875-6.92215
HLA-B52:013W399159SVMSLIMQRKNVPP-4.20386-5.23916
HLA-A11:014UQ29159SVMSLIMQRKNVPP-7.5194-8.5547
HLA-A11:014UQ29159SVMSLIMQRKNVPP-6.9601-7.0735
HLA-A24:025HGA9159SVMSLIMQRKNVPP-7.52403-7.63743
HLA-A24:025HGA9159SVMSLIMQRKNVPP-5.82433-6.85963
HLA-B27:056PYJ9159SVMSLIMQRKNVPP-3.28285-4.31815
HLA-B44:053DX89159SVMSLIMQRKNVPP-5.91172-6.94702
HLA-B44:053DX89159SVMSLIMQRKNVPP-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of NAA25-TBX5

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
NAA25-TBX5chr12112518864chr12114793911615SVMSLIMQRGTGATGAGCTTAATTATGCAAAGGAAG
NAA25-TBX5chr12112518864chr12114793911616SVMSLIMQRKGTGATGAGCTTAATTATGCAAAGGAAGAAT

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 NAA25-TBX5

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
BRCANAA25-TBX5chr12112518864ENST00000261745chr12114793911ENST00000310346TCGA-A2-A04U-01A

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Potential target of CAR-T therapy development for NAA25-TBX5

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 NAA25-TBX5

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 NAA25-TBX5

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