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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:HOXB3-MAPT

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: HOXB3-MAPT
FusionPDB ID: 37429
FusionGDB2.0 ID: 37429
HgeneTgene
Gene symbol

HOXB3

MAPT

Gene ID

3213

4137

Gene namehomeobox B3microtubule associated protein tau
SynonymsHOX2|HOX2G|Hox-2.7DDPAC|FTDP-17|MAPTL|MSTD|MTBT1|MTBT2|PPND|PPP1R103|TAU
Cytomap

17q21.32

17q21.31

Type of geneprotein-codingprotein-coding
Descriptionhomeobox protein Hox-B3homeo box 2Ghomeobox protein Hox-2.7homeobox protein Hox-2Gmicrotubule-associated protein tauG protein beta1/gamma2 subunit-interacting factor 1PHF-tauneurofibrillary tangle proteinpaired helical filament-tauprotein phosphatase 1, regulatory subunit 103
Modification date2020031320200329
UniProtAcc

P14651

Main function of 5'-partner protein: FUNCTION: Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.

P10636

Main function of 5'-partner protein: FUNCTION: Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). The C-terminus binds axonal microtubules while the N-terminus binds neural plasma membrane components, suggesting that tau functions as a linker protein between both (PubMed:21985311, PubMed:32961270). Axonal polarity is predetermined by TAU/MAPT localization (in the neuronal cell) in the domain of the cell body defined by the centrosome. The short isoforms allow plasticity of the cytoskeleton whereas the longer isoforms may preferentially play a role in its stabilization. {ECO:0000269|PubMed:21985311, ECO:0000269|PubMed:32961270}.
Ensembl transtripts involved in fusion geneENST idsENST00000465120, ENST00000490677, 
ENST00000311626, ENST00000460160, 
ENST00000485909, ENST00000489475, 
ENST00000498678, ENST00000470495, 
ENST00000472863, ENST00000476342, 
ENST00000552000, 
ENST00000334239, 
ENST00000415613, ENST00000420682, 
ENST00000431008, ENST00000446361, 
ENST00000570299, ENST00000571987, 
ENST00000574436, ENST00000576518, 
ENST00000262410, ENST00000340799, 
ENST00000344290, ENST00000347967, 
ENST00000351559, ENST00000535772, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score9 X 6 X 6=3245 X 7 X 4=140
# samples 105
** MAII scorelog2(10/324*10)=-1.6959938131099
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(5/140*10)=-1.48542682717024
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: HOXB3 [Title/Abstract] AND MAPT [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: HOXB3 [Title/Abstract] AND MAPT [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)HOXB3(46651199)-MAPT(44068826), # samples:2
Anticipated loss of major functional domain due to fusion event.HOXB3-MAPT 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.
HOXB3-MAPT 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.
HOXB3-MAPT 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.
HOXB3-MAPT 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.
HOXB3-MAPT 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
HgeneHOXB3

GO:0045944

positive regulation of transcription by RNA polymerase II

9556594

TgeneMAPT

GO:0000226

microtubule cytoskeleton organization

1057175

TgeneMAPT

GO:0031116

positive regulation of microtubule polymerization

1421571|7706316

TgeneMAPT

GO:0045773

positive regulation of axon extension

1389180

TgeneMAPT

GO:0050848

regulation of calcium-mediated signaling

18272392

TgeneMAPT

GO:0097435

supramolecular fiber organization

15654759



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/chr17:46651199/chr17:44068826)
- 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 HOXB3 (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 MAPT (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)
ENST00000490677HOXB3chr1746651199-ENST00000535772MAPTchr1744068826+5154187142990282
ENST00000490677HOXB3chr1746651199-ENST00000344290MAPTchr1744068826+53011871421137331
ENST00000490677HOXB3chr1746651199-ENST00000351559MAPTchr1744068826+52471871421083313
ENST00000490677HOXB3chr1746651199-ENST00000347967MAPTchr1744068826+5154187142990282
ENST00000490677HOXB3chr1746651199-ENST00000262410MAPTchr1744068826+52471871421083313
ENST00000490677HOXB3chr1746651199-ENST00000340799MAPTchr1744068826+52471871421083313

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
ENST00000490677ENST00000535772HOXB3chr1746651199-MAPTchr1744068826+0.0058603860.9941397
ENST00000490677ENST00000344290HOXB3chr1746651199-MAPTchr1744068826+0.0031126170.9968874
ENST00000490677ENST00000351559HOXB3chr1746651199-MAPTchr1744068826+0.0026969980.997303
ENST00000490677ENST00000347967HOXB3chr1746651199-MAPTchr1744068826+0.0058603860.9941397
ENST00000490677ENST00000262410HOXB3chr1746651199-MAPTchr1744068826+0.0026969980.997303
ENST00000490677ENST00000340799HOXB3chr1746651199-MAPTchr1744068826+0.0026969980.997303

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 HOXB3-MAPT

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
HOXB3chr1746651199MAPTchr174406882618715SAEFGREEARGAKGADGKTKIATPRG

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Potential FusionNeoAntigen Information of HOXB3-MAPT 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.
HOXB3-MAPT_46651199_44068826.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)
HOXB3-MAPTchr1746651199chr1744068826187HLA-B45:01EEARGAKGA0.98780.9024615
HOXB3-MAPTchr1746651199chr1744068826187HLA-B50:02EEARGAKGA0.95310.7158615
HOXB3-MAPTchr1746651199chr1744068826187HLA-B41:01EEARGAKGA0.31630.931615
HOXB3-MAPTchr1746651199chr1744068826187HLA-B45:01REEARGAKGA0.88340.8932515
HOXB3-MAPTchr1746651199chr1744068826187HLA-B41:01REEARGAKGA0.74660.9145515

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Potential FusionNeoAntigen Information of HOXB3-MAPT 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.
HOXB3-MAPT_46651199_44068826.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)
HOXB3-MAPTchr1746651199chr1744068826187DRB1-0103SAEFGREEARGAKGA015
HOXB3-MAPTchr1746651199chr1744068826187DRB1-0109SAEFGREEARGAKGA015
HOXB3-MAPTchr1746651199chr1744068826187DRB1-0115SAEFGREEARGAKGA015

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Fusion breakpoint peptide structures of HOXB3-MAPT

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
1632EEARGAKGADGKTKHOXB3MAPTchr1746651199chr1744068826187

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of HOXB3-MAPT

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-B14:023BVN1632EEARGAKGADGKTK-7.24289-7.35629
HLA-B14:023BVN1632EEARGAKGADGKTK-6.44411-7.47941
HLA-B52:013W391632EEARGAKGADGKTK-6.85231-6.96571
HLA-B52:013W391632EEARGAKGADGKTK-5.09533-6.13063
HLA-A11:014UQ21632EEARGAKGADGKTK-8.61576-8.72916
HLA-A24:025HGA1632EEARGAKGADGKTK-6.80714-7.84244
HLA-A24:025HGA1632EEARGAKGADGKTK-6.33574-6.44914
HLA-B44:053DX81632EEARGAKGADGKTK-7.01739-7.13079
HLA-B44:053DX81632EEARGAKGADGKTK-3.37818-4.41348

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Vaccine Design for the FusionNeoAntigens of HOXB3-MAPT

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
HOXB3-MAPTchr1746651199chr1744068826515REEARGAKGACGAGAGGAGGCGAGAGGCGCAAAGGGGGCT
HOXB3-MAPTchr1746651199chr1744068826615EEARGAKGAGAGGAGGCGAGAGGCGCAAAGGGGGCT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
HOXB3-MAPTchr1746651199chr1744068826015SAEFGREEARGAKGATCTGCAGAGTTCGGGCGAGAGGAGGCGAGAGGCGCAAAGGGGGCT

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Information of the samples that have these potential fusion neoantigens of HOXB3-MAPT

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
BLCAHOXB3-MAPTchr1746651199ENST00000490677chr1744068826ENST00000262410TCGA-HQ-A2OF-01A

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Potential target of CAR-T therapy development for HOXB3-MAPT

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 HOXB3-MAPT

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 HOXB3-MAPT

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