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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:MKLN1-ST7

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: MKLN1-ST7
FusionPDB ID: 54092
FusionGDB2.0 ID: 54092
HgeneTgene
Gene symbol

MKLN1

ST7

Gene ID

4289

93655

Gene namemuskelin 1ST7 overlapping transcript 3
SynonymsTWA2NCRNA00026|ST7|ST7OT3
Cytomap

7q32.3

7q31.2

Type of geneprotein-codingncRNA
Descriptionmuskelinmuskelin 1, intracellular mediator containing kelch motifsST7 overlapping transcript 3 (non-coding RNA)ST7 overlapping transcript 3 (non-protein coding)suppression of tumorigenicity 7
Modification date2020031320200313
UniProtAcc

Q9UL63

Main function of 5'-partner protein: FUNCTION: Component of the CTLH E3 ubiquitin-protein ligase complex that selectively accepts ubiquitin from UBE2H and mediates ubiquitination and subsequent proteasomal degradation of the transcription factor HBP1 (PubMed:29911972). Required for internalization of the GABA receptor GABRA1 from the cell membrane via endosomes and subsequent GABRA1 degradation (By similarity). Acts as a mediator of cell spreading and cytoskeletal responses to the extracellular matrix component THBS1 (PubMed:18710924). {ECO:0000250|UniProtKB:O89050, ECO:0000269|PubMed:18710924, ECO:0000269|PubMed:29911972}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000352689, ENST00000421797, 
ENST00000429546, ENST00000498778, 
ENST00000393443, ENST00000393444, 
ENST00000393447, ENST00000487459, 
ENST00000465133, ENST00000265437, 
ENST00000323984, ENST00000393446, 
ENST00000393449, ENST00000393451, 
ENST00000422922, ENST00000432298, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score15 X 15 X 7=157513 X 10 X 8=1040
# samples 1614
** MAII scorelog2(16/1575*10)=-3.29920801838728
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(14/1040*10)=-2.89308479608349
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: MKLN1 [Title/Abstract] AND ST7 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: MKLN1 [Title/Abstract] AND ST7 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MKLN1(131084192)-ST7(116829375), # samples:1
Anticipated loss of major functional domain due to fusion event.MKLN1-ST7 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.
MKLN1-ST7 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.
MKLN1-ST7 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.
MKLN1-ST7 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


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/chr7:131084192/chr7:116829375)
- 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 MKLN1 (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 ST7 (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)
ENST00000421797MKLN1chr7131084192+ENST00000393446ST7chr7116829375+16418392051401398
ENST00000421797MKLN1chr7131084192+ENST00000265437ST7chr7116829375+24468392051518437
ENST00000421797MKLN1chr7131084192+ENST00000393451ST7chr7116829375+17418392051494429
ENST00000421797MKLN1chr7131084192+ENST00000393449ST7chr7116829375+17268392051479424
ENST00000421797MKLN1chr7131084192+ENST00000323984ST7chr7116829375+17418392051494429
ENST00000421797MKLN1chr7131084192+ENST00000432298ST7chr7116829375+17418392051494429
ENST00000421797MKLN1chr7131084192+ENST00000422922ST7chr7116829375+17418392051494429
ENST00000352689MKLN1chr7131084192+ENST00000393446ST7chr7116829375+154574311305434
ENST00000352689MKLN1chr7131084192+ENST00000265437ST7chr7116829375+235074311422473
ENST00000352689MKLN1chr7131084192+ENST00000393451ST7chr7116829375+164574311398465
ENST00000352689MKLN1chr7131084192+ENST00000393449ST7chr7116829375+163074311383460
ENST00000352689MKLN1chr7131084192+ENST00000323984ST7chr7116829375+164574311398465
ENST00000352689MKLN1chr7131084192+ENST00000432298ST7chr7116829375+164574311398465
ENST00000352689MKLN1chr7131084192+ENST00000422922ST7chr7116829375+164574311398465

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
ENST00000421797ENST00000393446MKLN1chr7131084192+ST7chr7116829375+0.0011679380.99883205
ENST00000421797ENST00000265437MKLN1chr7131084192+ST7chr7116829375+0.0014670630.9985329
ENST00000421797ENST00000393451MKLN1chr7131084192+ST7chr7116829375+0.0011673680.99883264
ENST00000421797ENST00000393449MKLN1chr7131084192+ST7chr7116829375+0.001166950.998833
ENST00000421797ENST00000323984MKLN1chr7131084192+ST7chr7116829375+0.0011673680.99883264
ENST00000421797ENST00000432298MKLN1chr7131084192+ST7chr7116829375+0.0011673680.99883264
ENST00000421797ENST00000422922MKLN1chr7131084192+ST7chr7116829375+0.0011673680.99883264
ENST00000352689ENST00000393446MKLN1chr7131084192+ST7chr7116829375+0.0016359150.99836403
ENST00000352689ENST00000265437MKLN1chr7131084192+ST7chr7116829375+0.0022400980.99775994
ENST00000352689ENST00000393451MKLN1chr7131084192+ST7chr7116829375+0.0015613640.99843866
ENST00000352689ENST00000393449MKLN1chr7131084192+ST7chr7116829375+0.0017974990.99820244
ENST00000352689ENST00000323984MKLN1chr7131084192+ST7chr7116829375+0.0015613640.99843866
ENST00000352689ENST00000432298MKLN1chr7131084192+ST7chr7116829375+0.0015613640.99843866
ENST00000352689ENST00000422922MKLN1chr7131084192+ST7chr7116829375+0.0015613640.99843866

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 MKLN1-ST7

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
MKLN1chr7131084192ST7chr7116829375743247FDACEELIEKAVNDISLPKSATICYT
MKLN1chr7131084192ST7chr7116829375839211FDACEELIEKAVNDISLPKSATICYT

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Potential FusionNeoAntigen Information of MKLN1-ST7 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.
MKLN1-ST7_131084192_116829375.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)
MKLN1-ST7chr7131084192chr7116829375743HLA-B39:01EKAVNDISL0.99630.8755817
MKLN1-ST7chr7131084192chr7116829375743HLA-B38:02EKAVNDISL0.99090.913817
MKLN1-ST7chr7131084192chr7116829375743HLA-A30:08AVNDISLPK0.97830.70641019
MKLN1-ST7chr7131084192chr7116829375743HLA-B15:10EKAVNDISL0.92910.5265817
MKLN1-ST7chr7131084192chr7116829375743HLA-B15:37EKAVNDISL0.60020.5423817
MKLN1-ST7chr7131084192chr7116829375743HLA-A30:08KAVNDISLPK0.99560.6596919
MKLN1-ST7chr7131084192chr7116829375743HLA-B39:05EKAVNDISL0.99320.8474817
MKLN1-ST7chr7131084192chr7116829375743HLA-B40:06NDISLPKSA0.98880.60241221
MKLN1-ST7chr7131084192chr7116829375743HLA-B14:03EKAVNDISL0.48350.7436817
MKLN1-ST7chr7131084192chr7116829375743HLA-B39:31EKAVNDISL0.99660.8754817
MKLN1-ST7chr7131084192chr7116829375743HLA-A30:01AVNDISLPK0.97360.83831019
MKLN1-ST7chr7131084192chr7116829375743HLA-B39:11EKAVNDISL0.57040.6479817
MKLN1-ST7chr7131084192chr7116829375743HLA-A30:01KAVNDISLPK0.99560.8125919

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Potential FusionNeoAntigen Information of MKLN1-ST7 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.
MKLN1-ST7_131084192_116829375.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)
MKLN1-ST7chr7131084192chr7116829375743DRB1-0451EELIEKAVNDISLPK419
MKLN1-ST7chr7131084192chr7116829375743DRB1-0470EELIEKAVNDISLPK419
MKLN1-ST7chr7131084192chr7116829375743DRB4-0101EELIEKAVNDISLPK419
MKLN1-ST7chr7131084192chr7116829375743DRB4-0101CEELIEKAVNDISLP318
MKLN1-ST7chr7131084192chr7116829375743DRB4-0101ELIEKAVNDISLPKS520
MKLN1-ST7chr7131084192chr7116829375743DRB4-0103EELIEKAVNDISLPK419
MKLN1-ST7chr7131084192chr7116829375743DRB4-0103CEELIEKAVNDISLP318
MKLN1-ST7chr7131084192chr7116829375743DRB4-0103ELIEKAVNDISLPKS520
MKLN1-ST7chr7131084192chr7116829375743DRB4-0104EELIEKAVNDISLPK419
MKLN1-ST7chr7131084192chr7116829375743DRB4-0104CEELIEKAVNDISLP318
MKLN1-ST7chr7131084192chr7116829375743DRB4-0106EELIEKAVNDISLPK419
MKLN1-ST7chr7131084192chr7116829375743DRB4-0106CEELIEKAVNDISLP318
MKLN1-ST7chr7131084192chr7116829375743DRB4-0106ELIEKAVNDISLPKS520
MKLN1-ST7chr7131084192chr7116829375743DRB4-0107EELIEKAVNDISLPK419
MKLN1-ST7chr7131084192chr7116829375743DRB4-0107CEELIEKAVNDISLP318
MKLN1-ST7chr7131084192chr7116829375743DRB4-0107ELIEKAVNDISLPKS520
MKLN1-ST7chr7131084192chr7116829375743DRB4-0108EELIEKAVNDISLPK419
MKLN1-ST7chr7131084192chr7116829375743DRB4-0108CEELIEKAVNDISLP318
MKLN1-ST7chr7131084192chr7116829375743DRB4-0108ELIEKAVNDISLPKS520

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Fusion breakpoint peptide structures of MKLN1-ST7

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
5087LIEKAVNDISLPKSMKLN1ST7chr7131084192chr7116829375743

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of MKLN1-ST7

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-B14:023BVN5087LIEKAVNDISLPKS-7.9962-8.1096
HLA-B14:023BVN5087LIEKAVNDISLPKS-5.70842-6.74372
HLA-B52:013W395087LIEKAVNDISLPKS-6.83737-6.95077
HLA-B52:013W395087LIEKAVNDISLPKS-4.4836-5.5189
HLA-A11:014UQ25087LIEKAVNDISLPKS-10.0067-10.1201
HLA-A11:014UQ25087LIEKAVNDISLPKS-9.03915-10.0745
HLA-A24:025HGA5087LIEKAVNDISLPKS-6.56204-6.67544
HLA-A24:025HGA5087LIEKAVNDISLPKS-5.42271-6.45801
HLA-B44:053DX85087LIEKAVNDISLPKS-7.85648-8.89178
HLA-B44:053DX85087LIEKAVNDISLPKS-5.3978-5.5112
HLA-A02:016TDR5087LIEKAVNDISLPKS-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of MKLN1-ST7

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
MKLN1-ST7chr7131084192chr71168293751019AVNDISLPKCTGTAAATGATATAAGCTTACCAAAGT
MKLN1-ST7chr7131084192chr71168293751221NDISLPKSAATGATATAAGCTTACCAAAGTCAGCAA
MKLN1-ST7chr7131084192chr7116829375817EKAVNDISLAAAAGGCTGTAAATGATATAAGCTTAC
MKLN1-ST7chr7131084192chr7116829375919KAVNDISLPKAGGCTGTAAATGATATAAGCTTACCAAAGT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
MKLN1-ST7chr7131084192chr7116829375318CEELIEKAVNDISLPGCGAAGAGTTGATTGAAAAGGCTGTAAATGATATAAGCTTACCAA
MKLN1-ST7chr7131084192chr7116829375419EELIEKAVNDISLPKAAGAGTTGATTGAAAAGGCTGTAAATGATATAAGCTTACCAAAGT
MKLN1-ST7chr7131084192chr7116829375520ELIEKAVNDISLPKSAGTTGATTGAAAAGGCTGTAAATGATATAAGCTTACCAAAGTCAG

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Information of the samples that have these potential fusion neoantigens of MKLN1-ST7

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
COADMKLN1-ST7chr7131084192ENST00000352689chr7116829375ENST00000265437TCGA-AA-3521-01A

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Potential target of CAR-T therapy development for MKLN1-ST7

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
TgeneST7chr7:131084192chr7:116829375ENST00000265437916512_5320586.0TransmembraneHelical
TgeneST7chr7:131084192chr7:116829375ENST00000393443916512_5320500.0TransmembraneHelical
TgeneST7chr7:131084192chr7:116829375ENST00000393451815512_5320555.0TransmembraneHelical

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 MKLN1-ST7

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 MKLN1-ST7

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