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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:KIF13A-TPMT

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: KIF13A-TPMT
FusionPDB ID: 42538
FusionGDB2.0 ID: 42538
HgeneTgene
Gene symbol

KIF13A

TPMT

Gene ID

63971

7172

Gene namekinesin family member 13Athiopurine S-methyltransferase
SynonymsRBKIN|bA500C11.2TPMTD
Cytomap

6p22.3

6p22.3

Type of geneprotein-codingprotein-coding
Descriptionkinesin-like protein KIF13Ahomolog of mouse KIF13A mannose-6-phosphate receptor transporterkinesin-like protein RBKINthiopurine S-methyltransferaseS-adenosyl-L-methionine:thiopurine S-methyltransferase
Modification date2020031320200315
UniProtAcc

Q9H1H9

Main function of 5'-partner protein: FUNCTION: Plus end-directed microtubule-dependent motor protein involved in intracellular transport and regulating various processes such as mannose-6-phosphate receptor (M6PR) transport to the plasma membrane, endosomal sorting during melanosome biogenesis and cytokinesis. Mediates the transport of M6PR-containing vesicles from trans-Golgi network to the plasma membrane via direct interaction with the AP-1 complex. During melanosome maturation, required for delivering melanogenic enzymes from recycling endosomes to nascent melanosomes by creating peripheral recycling endosomal subdomains in melanocytes. Also required for the abcission step in cytokinesis: mediates translocation of ZFYVE26, and possibly TTC19, to the midbody during cytokinesis. {ECO:0000269|PubMed:19841138, ECO:0000269|PubMed:20208530}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000259711, ENST00000378814, 
ENST00000378816, ENST00000378826, 
ENST00000378843, ENST00000502704, 
ENST00000503342, 
ENST00000309983, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score14 X 12 X 9=15126 X 3 X 5=90
# samples 178
** MAII scorelog2(17/1512*10)=-3.15285148808337
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(8/90*10)=-0.169925001442312
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: KIF13A [Title/Abstract] AND TPMT [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: KIF13A [Title/Abstract] AND TPMT [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)KIF13A(17987285)-TPMT(18134120), # samples:2
KIF13A(17987285)-TPMT(18149402), # samples:2
TPMT(18148054)-KIF13A(17794935), # samples:1
Anticipated loss of major functional domain due to fusion event.KIF13A-TPMT 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.
KIF13A-TPMT 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.
TPMT-KIF13A seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
TPMT-KIF13A seems lost the major protein functional domain in Tgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
TPMT-KIF13A seems lost the major protein functional domain in Tgene partner, which is a essential gene 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
TgeneTPMT

GO:0017144

drug metabolic process

657528|18484748



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/chr6:17987285/chr6:18134120)
- 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 KIF13A (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 TPMT (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)
ENST00000378814KIF13Achr617987285-ENST00000309983TPMTchr618134120-27471460389129
ENST00000259711KIF13Achr617987285-ENST00000309983TPMTchr618134120-2853252106495129
ENST00000378843KIF13Achr617987285-ENST00000309983TPMTchr618134120-276516418407129
ENST00000378826KIF13Achr617987285-ENST00000309983TPMTchr618134120-276616519408129
ENST00000378816KIF13Achr617987285-ENST00000309983TPMTchr618134120-2852251105494129
ENST00000502704KIF13Achr617987285-ENST00000309983TPMTchr618134120-2907306160549129

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
ENST00000378814ENST00000309983KIF13Achr617987285-TPMTchr618134120-0.0061704510.99382955
ENST00000259711ENST00000309983KIF13Achr617987285-TPMTchr618134120-0.0050219390.994978
ENST00000378843ENST00000309983KIF13Achr617987285-TPMTchr618134120-0.0133751950.98662484
ENST00000378826ENST00000309983KIF13Achr617987285-TPMTchr618134120-0.0149932550.98500675
ENST00000378816ENST00000309983KIF13Achr617987285-TPMTchr618134120-0.0053291340.9946708
ENST00000502704ENST00000309983KIF13Achr617987285-TPMTchr618134120-0.0039776370.9960224

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 KIF13A-TPMT

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
KIF13Achr617987285TPMTchr61813412014648VLHPPPSNTKQGESYADTMFSLLGKK
KIF13Achr617987285TPMTchr61813412016448VLHPPPSNTKQGESYADTMFSLLGKK
KIF13Achr617987285TPMTchr61813412016548VLHPPPSNTKQGESYADTMFSLLGKK
KIF13Achr617987285TPMTchr61813412025148VLHPPPSNTKQGESYADTMFSLLGKK
KIF13Achr617987285TPMTchr61813412025248VLHPPPSNTKQGESYADTMFSLLGKK
KIF13Achr617987285TPMTchr61813412030648VLHPPPSNTKQGESYADTMFSLLGKK

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Potential FusionNeoAntigen Information of KIF13A-TPMT 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.
KIF13A-TPMT_17987285_18134120.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)
KIF13A-TPMTchr617987285chr618134120252HLA-B44:03GESYADTMF0.97410.91791120
KIF13A-TPMTchr617987285chr618134120252HLA-B44:26GESYADTMF0.97410.91791120
KIF13A-TPMTchr617987285chr618134120252HLA-B44:13GESYADTMF0.97410.91791120
KIF13A-TPMTchr617987285chr618134120252HLA-B44:07GESYADTMF0.97410.91791120
KIF13A-TPMTchr617987285chr618134120252HLA-B40:04GESYADTMF0.95290.65571120
KIF13A-TPMTchr617987285chr618134120252HLA-B18:11GESYADTMF0.73190.7941120
KIF13A-TPMTchr617987285chr618134120252HLA-B41:03GESYADTMF0.22510.51661120
KIF13A-TPMTchr617987285chr618134120252HLA-B15:53GESYADTMF0.15070.6791120
KIF13A-TPMTchr617987285chr618134120252HLA-A69:01ESYADTMFSL0.99210.5731222
KIF13A-TPMTchr617987285chr618134120252HLA-B40:04GESYADTMFSL0.99870.7411122

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Potential FusionNeoAntigen Information of KIF13A-TPMT 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 KIF13A-TPMT

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
8870SNTKQGESYADTMFKIF13ATPMTchr617987285chr618134120252

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of KIF13A-TPMT

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-B14:023BVN8870SNTKQGESYADTMF-6.60553-6.71893
HLA-B14:023BVN8870SNTKQGESYADTMF-3.25382-4.28912
HLA-B52:013W398870SNTKQGESYADTMF-5.90011-6.01351
HLA-B52:013W398870SNTKQGESYADTMF-5.4415-6.4768
HLA-B18:014JQV8870SNTKQGESYADTMF-2.23313-2.34653
HLA-A11:014UQ28870SNTKQGESYADTMF-6.31705-6.43045
HLA-A11:014UQ28870SNTKQGESYADTMF-4.25402-5.28932
HLA-A24:025HGA8870SNTKQGESYADTMF-7.95591-8.06931
HLA-A24:025HGA8870SNTKQGESYADTMF-6.24522-7.28052
HLA-B27:056PYJ8870SNTKQGESYADTMF-3.83335-4.86865
HLA-B44:053DX88870SNTKQGESYADTMF-6.2025-6.3159
HLA-B44:053DX88870SNTKQGESYADTMF-5.27651-6.31181
HLA-A02:016TDR8870SNTKQGESYADTMF-6.48102-6.59442

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Vaccine Design for the FusionNeoAntigens of KIF13A-TPMT

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
KIF13A-TPMTchr617987285chr6181341201120GESYADTMFAGAAAGCTATGCAGATACAATGTTTTC
KIF13A-TPMTchr617987285chr6181341201122GESYADTMFSLAGAAAGCTATGCAGATACAATGTTTTCCCTCCT
KIF13A-TPMTchr617987285chr6181341201222ESYADTMFSLAAGCTATGCAGATACAATGTTTTCCCTCCT

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 KIF13A-TPMT

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
BRCAKIF13A-TPMTchr617987285ENST00000259711chr618134120ENST00000309983TCGA-A2-A0CX-01A

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Potential target of CAR-T therapy development for KIF13A-TPMT

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 KIF13A-TPMT

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 KIF13A-TPMT

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