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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:MYO1C-SMTNL2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: MYO1C-SMTNL2
FusionPDB ID: 56638
FusionGDB2.0 ID: 56638
HgeneTgene
Gene symbol

MYO1C

SMTNL2

Gene ID

4643

342527

Gene namemyosin IEsmoothelin like 2
SynonymsFSGS6|HuncM-IC|MYO1C-
Cytomap

15q22.2

17p13.2

Type of geneprotein-codingprotein-coding
Descriptionunconventional myosin-IeMYO1E variant proteinmyosin-ICunconventional myosin 1Esmoothelin-like protein 2
Modification date2020031320200313
UniProtAcc

O00159

Main function of 5'-partner protein: FUNCTION: Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Their highly divergent tails are presumed to bind to membranous compartments, which would be moved relative to actin filaments. Involved in glucose transporter recycling in response to insulin by regulating movement of intracellular GLUT4-containing vesicles to the plasma membrane. Component of the hair cell's (the sensory cells of the inner ear) adaptation-motor complex. Acts as a mediator of adaptation of mechanoelectrical transduction in stereocilia of vestibular hair cells. Binds phosphoinositides and links the actin cytoskeleton to cellular membranes. {ECO:0000269|PubMed:24636949}.; FUNCTION: Isoform 3 is involved in regulation of transcription. Associated with transcriptional active ribosomal genes. Appears to cooperate with the WICH chromatin-remodeling complex to facilitate transcription. Necessary for the formation of the first phosphodiester bond during transcription initiation (By similarity). {ECO:0000250}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000359786, ENST00000361007, 
ENST00000438665, ENST00000545534, 
ENST00000575158, ENST00000573198, 
ENST00000338859, ENST00000389313, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 8 X 5=2403 X 3 X 3=27
# samples 73
** MAII scorelog2(7/240*10)=-1.77760757866355
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(3/27*10)=0.15200309344505
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: MYO1C [Title/Abstract] AND SMTNL2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: MYO1C [Title/Abstract] AND SMTNL2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MYO1C(1381910)-SMTNL2(4510656), # samples:2
Anticipated loss of major functional domain due to fusion event.MYO1C-SMTNL2 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.
MYO1C-SMTNL2 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.
MYO1C-SMTNL2 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.
MYO1C-SMTNL2 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.
MYO1C-SMTNL2 seems lost the major protein functional domain in Hgene partner, which is a epigenetic 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


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/chr17:1381910/chr17:4510656)
- 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 MYO1C (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 SMTNL2 (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)
ENST00000575158MYO1Cchr171381910-ENST00000389313SMTNL2chr174510656+223812841501301383
ENST00000359786MYO1Cchr171381704-ENST00000338859SMTNL2chr174510656+257916202771746489
ENST00000438665MYO1Cchr171381704-ENST00000338859SMTNL2chr174510656+24201461401587515
ENST00000361007MYO1Cchr171381704-ENST00000338859SMTNL2chr174510656+22581299821425447
ENST00000545534MYO1Cchr171381704-ENST00000338859SMTNL2chr174510656+242514662431592449

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
ENST00000575158ENST00000389313MYO1Cchr171381910-SMTNL2chr174510656+0.0033418970.9966581
ENST00000359786ENST00000338859MYO1Cchr171381704-SMTNL2chr174510656+0.0050548420.9949451
ENST00000438665ENST00000338859MYO1Cchr171381704-SMTNL2chr174510656+0.0030470150.996953
ENST00000361007ENST00000338859MYO1Cchr171381704-SMTNL2chr174510656+0.0024998220.9975001
ENST00000545534ENST00000338859MYO1Cchr171381704-SMTNL2chr174510656+0.0017081240.9982919

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 MYO1C-SMTNL2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
MYO1Cchr171381704SMTNL2chr1745106561299405LLDIYGFEVFQHNRNLANCERLIEVE
MYO1Cchr171381704SMTNL2chr1745106561461473LLDIYGFEVFQHNRNLANCERLIEVE
MYO1Cchr171381704SMTNL2chr1745106561466407LLDIYGFEVFQHNRNLANCERLIEVE
MYO1Cchr171381704SMTNL2chr1745106561620447LLDIYGFEVFQHNRNLANCERLIEVE

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Potential FusionNeoAntigen Information of MYO1C-SMTNL2 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.
MYO1C-SMTNL2_1381704_4510656.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)
MYO1C-SMTNL2chr171381704chr1745106561620HLA-A31:02GFEVFQHNR0.95090.6524514
MYO1C-SMTNL2chr171381704chr1745106561620HLA-C03:08EVFQHNRNL0.89670.8874716
MYO1C-SMTNL2chr171381704chr1745106561620HLA-C12:04EVFQHNRNL0.32960.9886716
MYO1C-SMTNL2chr171381704chr1745106561620HLA-C06:03EVFQHNRNL0.32470.9915716
MYO1C-SMTNL2chr171381704chr1745106561620HLA-C14:02VFQHNRNL0.82830.9613816
MYO1C-SMTNL2chr171381704chr1745106561620HLA-C14:03VFQHNRNL0.82830.9613816
MYO1C-SMTNL2chr171381704chr1745106561620HLA-A25:01EVFQHNRNL0.99580.8489716
MYO1C-SMTNL2chr171381704chr1745106561620HLA-A69:01EVFQHNRNL0.96220.687716
MYO1C-SMTNL2chr171381704chr1745106561620HLA-B08:12EVFQHNRNL0.78220.5555716
MYO1C-SMTNL2chr171381704chr1745106561620HLA-C06:08EVFQHNRNL0.55160.9725716
MYO1C-SMTNL2chr171381704chr1745106561620HLA-C06:17EVFQHNRNL0.32380.9879716
MYO1C-SMTNL2chr171381704chr1745106561620HLA-C06:02EVFQHNRNL0.32380.9879716

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Potential FusionNeoAntigen Information of MYO1C-SMTNL2 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.
MYO1C-SMTNL2_1381704_4510656.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)
MYO1C-SMTNL2chr171381704chr1745106561620DRB1-1182IYGFEVFQHNRNLAN318
MYO1C-SMTNL2chr171381704chr1745106561620DRB1-1376GFEVFQHNRNLANCE520
MYO1C-SMTNL2chr171381704chr1745106561620DRB1-1376IYGFEVFQHNRNLAN318
MYO1C-SMTNL2chr171381704chr1745106561620DRB1-1424IYGFEVFQHNRNLAN318
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0202FEVFQHNRNLANCER621
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0202GFEVFQHNRNLANCE520
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0202EVFQHNRNLANCERL722
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0205FEVFQHNRNLANCER621
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0205GFEVFQHNRNLANCE520
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0205EVFQHNRNLANCERL722
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0210FEVFQHNRNLANCER621
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0210GFEVFQHNRNLANCE520
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0210EVFQHNRNLANCERL722
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0211FEVFQHNRNLANCER621
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0211GFEVFQHNRNLANCE520
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0211EVFQHNRNLANCERL722
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0212FEVFQHNRNLANCER621
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0212GFEVFQHNRNLANCE520
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0212EVFQHNRNLANCERL722
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0213FEVFQHNRNLANCER621
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0213GFEVFQHNRNLANCE520
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0213EVFQHNRNLANCERL722
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0215FEVFQHNRNLANCER621
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0215GFEVFQHNRNLANCE520
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0215EVFQHNRNLANCERL722
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0217FEVFQHNRNLANCER621
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0217GFEVFQHNRNLANCE520
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0217EVFQHNRNLANCERL722
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0218FEVFQHNRNLANCER621
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0218GFEVFQHNRNLANCE520
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0218EVFQHNRNLANCERL722
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0219FEVFQHNRNLANCER621
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0219GFEVFQHNRNLANCE520
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0219EVFQHNRNLANCERL722
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0220FEVFQHNRNLANCER621
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0220GFEVFQHNRNLANCE520
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0220EVFQHNRNLANCERL722
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0222FEVFQHNRNLANCER621
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0222GFEVFQHNRNLANCE520
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0222EVFQHNRNLANCERL722
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0223FEVFQHNRNLANCER621
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0223GFEVFQHNRNLANCE520
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0223EVFQHNRNLANCERL722
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0225FEVFQHNRNLANCER621
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0225GFEVFQHNRNLANCE520
MYO1C-SMTNL2chr171381704chr1745106561620DRB3-0225EVFQHNRNLANCERL722

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Fusion breakpoint peptide structures of MYO1C-SMTNL2

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
2352FEVFQHNRNLANCEMYO1CSMTNL2chr171381704chr1745106561620

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of MYO1C-SMTNL2

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-B14:023BVN2352FEVFQHNRNLANCE-8.85616-8.96956
HLA-B14:023BVN2352FEVFQHNRNLANCE-5.66423-6.69953
HLA-B52:013W392352FEVFQHNRNLANCE-6.49489-6.60829
HLA-B52:013W392352FEVFQHNRNLANCE-3.99785-5.03315
HLA-A11:014UQ22352FEVFQHNRNLANCE-4.90759-5.94289
HLA-A24:025HGA2352FEVFQHNRNLANCE-7.27887-7.39227
HLA-A24:025HGA2352FEVFQHNRNLANCE-7.11524-8.15054
HLA-B27:056PYJ2352FEVFQHNRNLANCE-6.11615-6.22955
HLA-B27:056PYJ2352FEVFQHNRNLANCE-4.78818-5.82348
HLA-B44:053DX82352FEVFQHNRNLANCE-7.22602-7.33942
HLA-B44:053DX82352FEVFQHNRNLANCE-4.86671-5.90201

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Vaccine Design for the FusionNeoAntigens of MYO1C-SMTNL2

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
MYO1C-SMTNL2chr171381704chr174510656514GFEVFQHNRCTTTGAAGTGTTTCAGCATAACAGGAA
MYO1C-SMTNL2chr171381704chr174510656716EVFQHNRNLAGTGTTTCAGCATAACAGGAATCTGGC
MYO1C-SMTNL2chr171381704chr174510656816VFQHNRNLGTTTCAGCATAACAGGAATCTGGC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
MYO1C-SMTNL2chr171381704chr174510656318IYGFEVFQHNRNLANTTATGGCTTTGAAGTGTTTCAGCATAACAGGAATCTGGCCAACTG
MYO1C-SMTNL2chr171381704chr174510656520GFEVFQHNRNLANCECTTTGAAGTGTTTCAGCATAACAGGAATCTGGCCAACTGTGAGCG
MYO1C-SMTNL2chr171381704chr174510656621FEVFQHNRNLANCERTGAAGTGTTTCAGCATAACAGGAATCTGGCCAACTGTGAGCGCCT
MYO1C-SMTNL2chr171381704chr174510656722EVFQHNRNLANCERLAGTGTTTCAGCATAACAGGAATCTGGCCAACTGTGAGCGCCTCAT

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Information of the samples that have these potential fusion neoantigens of MYO1C-SMTNL2

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
UCECMYO1C-SMTNL2chr171381704ENST00000359786chr174510656ENST00000338859TCGA-AJ-A3BD-01A

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Potential target of CAR-T therapy development for MYO1C-SMTNL2

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 MYO1C-SMTNL2

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 MYO1C-SMTNL2

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