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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:MYSM1-MIS18A

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: MYSM1-MIS18A
FusionPDB ID: 56863
FusionGDB2.0 ID: 56863
HgeneTgene
Gene symbol

MYSM1

MIS18A

Gene ID

114803

54069

Gene nameMyb like, SWIRM and MPN domains 1MIS18 kinetochore protein A
Synonyms2A-DUB|2ADUB|BMFS4B28|C21orf45|C21orf46|FASP1|MIS18alpha|hMis18alpha
Cytomap

1p32.1

21q22.11

Type of geneprotein-codingprotein-coding
Descriptionhistone H2A deubiquitinase MYSM1myb-like, SWIRM and MPN domain-containing protein 1protein Mis18-alphaFAPP1-associated protein 1MIS18 kinetochore protein homolog A
Modification date2020032020200313
UniProtAcc

Q5VVJ2

Main function of 5'-partner protein: FUNCTION: Metalloprotease with deubiquitinase activity that plays important regulator roles in hematopoietic stem cell function, blood cell production and immune response (PubMed:24062447, PubMed:26220525, PubMed:28115216). Participates in the normal programming of B-cell responses to antigen after the maturation process (By similarity). Within the cytoplasm, plays critical roles in the repression of innate immunity and autoimmunity (PubMed:33086059). Removes 'Lys-63'-linked polyubiquitins from TRAF3 and TRAF6 complexes (By similarity). Attenuates NOD2-mediated inflammation and tissue injury by promoting 'Lys-63'-linked deubiquitination of RIPK2 component (By similarity). Suppresses the CGAS-STING1 signaling pathway by cleaving STING1 'Lys-63'-linked ubiquitin chains (PubMed:33086059). In the nucleus, acts as a hematopoietic transcription regulator derepressing a range of genes essential for normal stem cell differentiation including EBF1 and PAX5 in B-cells, ID2 in NK-cell progenitor or FLT3 in dendritic cell precursors (PubMed:24062447). Deubiquitinates monoubiquitinated histone H2A, a specific tag for epigenetic transcriptional repression, leading to dissociation of histone H1 from the nucleosome (PubMed:17707232). {ECO:0000250|UniProtKB:Q69Z66, ECO:0000269|PubMed:17707232, ECO:0000269|PubMed:22169041, ECO:0000269|PubMed:24062447, ECO:0000269|PubMed:26220525, ECO:0000269|PubMed:28115216, ECO:0000269|PubMed:33086059}.

Q9NYP9

Main function of 5'-partner protein: FUNCTION: Required for recruitment of CENPA to centromeres and normal chromosome segregation during mitosis. {ECO:0000269|PubMed:17199038}.
Ensembl transtripts involved in fusion geneENST idsENST00000472487, ENST00000493821, 
ENST00000486363, ENST00000290130, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score9 X 11 X 6=5944 X 3 X 3=36
# samples 114
** MAII scorelog2(11/594*10)=-2.43295940727611
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(4/36*10)=0.15200309344505
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: MYSM1 [Title/Abstract] AND MIS18A [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: MYSM1 [Title/Abstract] AND MIS18A [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MYSM1(59155897)-MIS18A(33642840), # samples:1
Anticipated loss of major functional domain due to fusion event.MYSM1-MIS18A 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.
MYSM1-MIS18A 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/chr1:59155897/chr21:33642840)
- 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 MYSM1 (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 MIS18A (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)
ENST00000472487MYSM1chr159155897-ENST00000290130MIS18Achr2133642840-147936040660206

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
ENST00000472487ENST00000290130MYSM1chr159155897-MIS18Achr2133642840-0.001382560.9986174

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 MYSM1-MIS18A

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
MYSM1chr159155897MIS18Achr2133642840360107KYMKSLQKTAKIIVLETLCCAGCSLN

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Potential FusionNeoAntigen Information of MYSM1-MIS18A 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.
MYSM1-MIS18A_59155897_33642840.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)
MYSM1-MIS18Achr159155897chr2133642840360HLA-B39:24AKIIVLETL0.99750.7317918
MYSM1-MIS18Achr159155897chr2133642840360HLA-B39:01QKTAKIIVL0.99740.7657615
MYSM1-MIS18Achr159155897chr2133642840360HLA-B14:01QKTAKIIVL0.99480.5265615
MYSM1-MIS18Achr159155897chr2133642840360HLA-B14:02QKTAKIIVL0.99480.5265615
MYSM1-MIS18Achr159155897chr2133642840360HLA-B39:13QKTAKIIVL0.99320.8076615
MYSM1-MIS18Achr159155897chr2133642840360HLA-B39:13AKIIVLETL0.980.9812918
MYSM1-MIS18Achr159155897chr2133642840360HLA-B13:02LQKTAKIIV0.45820.6518514
MYSM1-MIS18Achr159155897chr2133642840360HLA-B52:01LQKTAKIIV0.03450.8675514
MYSM1-MIS18Achr159155897chr2133642840360HLA-B57:03KTAKIIVLETL0.99930.992718
MYSM1-MIS18Achr159155897chr2133642840360HLA-C15:06KTAKIIVL0.99990.8616715
MYSM1-MIS18Achr159155897chr2133642840360HLA-B39:09QKTAKIIVL0.99820.5287615
MYSM1-MIS18Achr159155897chr2133642840360HLA-B39:09AKIIVLETL0.99690.8335918
MYSM1-MIS18Achr159155897chr2133642840360HLA-B39:12QKTAKIIVL0.99680.7695615
MYSM1-MIS18Achr159155897chr2133642840360HLA-B39:05QKTAKIIVL0.99190.7423615
MYSM1-MIS18Achr159155897chr2133642840360HLA-B15:04LQKTAKIIV0.81480.8638514
MYSM1-MIS18Achr159155897chr2133642840360HLA-B14:03QKTAKIIVL0.63620.5979615
MYSM1-MIS18Achr159155897chr2133642840360HLA-B15:04LQKTAKIIVL0.97910.8651515
MYSM1-MIS18Achr159155897chr2133642840360HLA-C15:02KTAKIIVL0.99990.8073715
MYSM1-MIS18Achr159155897chr2133642840360HLA-C15:05KTAKIIVL0.99990.8421715
MYSM1-MIS18Achr159155897chr2133642840360HLA-C16:02KTAKIIVL0.99970.9714715
MYSM1-MIS18Achr159155897chr2133642840360HLA-B39:02QKTAKIIVL0.99750.8098615
MYSM1-MIS18Achr159155897chr2133642840360HLA-B39:31QKTAKIIVL0.99750.7666615
MYSM1-MIS18Achr159155897chr2133642840360HLA-B39:02AKIIVLETL0.99690.9815918
MYSM1-MIS18Achr159155897chr2133642840360HLA-B15:09QKTAKIIVL0.83660.5828615
MYSM1-MIS18Achr159155897chr2133642840360HLA-B48:02AKIIVLETL0.62270.8914918
MYSM1-MIS18Achr159155897chr2133642840360HLA-B15:68AKIIVLETL0.1420.743918

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Potential FusionNeoAntigen Information of MYSM1-MIS18A 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.
MYSM1-MIS18A_59155897_33642840.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)
MYSM1-MIS18Achr159155897chr2133642840360DRB1-1401MKSLQKTAKIIVLET217
MYSM1-MIS18Achr159155897chr2133642840360DRB1-1401YMKSLQKTAKIIVLE116
MYSM1-MIS18Achr159155897chr2133642840360DRB1-1426MKSLQKTAKIIVLET217
MYSM1-MIS18Achr159155897chr2133642840360DRB1-1426YMKSLQKTAKIIVLE116
MYSM1-MIS18Achr159155897chr2133642840360DRB1-1428MKSLQKTAKIIVLET217
MYSM1-MIS18Achr159155897chr2133642840360DRB1-1435MKSLQKTAKIIVLET217
MYSM1-MIS18Achr159155897chr2133642840360DRB1-1438MKSLQKTAKIIVLET217
MYSM1-MIS18Achr159155897chr2133642840360DRB1-1438YMKSLQKTAKIIVLE116
MYSM1-MIS18Achr159155897chr2133642840360DRB1-1454MKSLQKTAKIIVLET217
MYSM1-MIS18Achr159155897chr2133642840360DRB1-1454YMKSLQKTAKIIVLE116
MYSM1-MIS18Achr159155897chr2133642840360DRB1-1458MKSLQKTAKIIVLET217
MYSM1-MIS18Achr159155897chr2133642840360DRB1-1458YMKSLQKTAKIIVLE116
MYSM1-MIS18Achr159155897chr2133642840360DRB1-1460MKSLQKTAKIIVLET217
MYSM1-MIS18Achr159155897chr2133642840360DRB1-1460YMKSLQKTAKIIVLE116
MYSM1-MIS18Achr159155897chr2133642840360DRB1-1471MKSLQKTAKIIVLET217
MYSM1-MIS18Achr159155897chr2133642840360DRB1-1475MKSLQKTAKIIVLET217
MYSM1-MIS18Achr159155897chr2133642840360DRB1-1486MKSLQKTAKIIVLET217
MYSM1-MIS18Achr159155897chr2133642840360DRB1-1486YMKSLQKTAKIIVLE116
MYSM1-MIS18Achr159155897chr2133642840360DRB1-1487MKSLQKTAKIIVLET217
MYSM1-MIS18Achr159155897chr2133642840360DRB1-1487YMKSLQKTAKIIVLE116
MYSM1-MIS18Achr159155897chr2133642840360DRB1-1488MKSLQKTAKIIVLET217
MYSM1-MIS18Achr159155897chr2133642840360DRB1-1488YMKSLQKTAKIIVLE116
MYSM1-MIS18Achr159155897chr2133642840360DRB1-1490MKSLQKTAKIIVLET217
MYSM1-MIS18Achr159155897chr2133642840360DRB1-1490YMKSLQKTAKIIVLE116
MYSM1-MIS18Achr159155897chr2133642840360DRB1-1497MKSLQKTAKIIVLET217
MYSM1-MIS18Achr159155897chr2133642840360DRB1-1497YMKSLQKTAKIIVLE116
MYSM1-MIS18Achr159155897chr2133642840360DRB1-1499MKSLQKTAKIIVLET217
MYSM1-MIS18Achr159155897chr2133642840360DRB1-1499YMKSLQKTAKIIVLE116

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Fusion breakpoint peptide structures of MYSM1-MIS18A

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
7363QKTAKIIVLETLCCMYSM1MIS18Achr159155897chr2133642840360

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of MYSM1-MIS18A

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-B14:023BVN7363QKTAKIIVLETLCC-6.6779-6.7897
HLA-B14:023BVN7363QKTAKIIVLETLCC-3.28788-4.33098
HLA-B52:013W397363QKTAKIIVLETLCC-7.60207-7.71387
HLA-B52:013W397363QKTAKIIVLETLCC-5.07484-6.11794
HLA-A24:025HGA7363QKTAKIIVLETLCC-6.91423-7.02603
HLA-A24:025HGA7363QKTAKIIVLETLCC-4.89502-5.93812
HLA-B27:056PYJ7363QKTAKIIVLETLCC-4.17707-5.22017
HLA-B44:053DX87363QKTAKIIVLETLCC-6.19701-6.30881
HLA-B44:053DX87363QKTAKIIVLETLCC-5.18733-6.23043

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Vaccine Design for the FusionNeoAntigens of MYSM1-MIS18A

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
MYSM1-MIS18Achr159155897chr2133642840514LQKTAKIIVTCTGCAGAAAACAGCAAAAATCATCGT
MYSM1-MIS18Achr159155897chr2133642840515LQKTAKIIVLTCTGCAGAAAACAGCAAAAATCATCGTCCT
MYSM1-MIS18Achr159155897chr2133642840615QKTAKIIVLGCAGAAAACAGCAAAAATCATCGTCCT
MYSM1-MIS18Achr159155897chr2133642840715KTAKIIVLGAAAACAGCAAAAATCATCGTCCT
MYSM1-MIS18Achr159155897chr2133642840718KTAKIIVLETLGAAAACAGCAAAAATCATCGTCCTTGAGACTTT
MYSM1-MIS18Achr159155897chr2133642840918AKIIVLETLAGCAAAAATCATCGTCCTTGAGACTTT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
MYSM1-MIS18Achr159155897chr2133642840116YMKSLQKTAKIIVLEATACATGAAGAGTCTGCAGAAAACAGCAAAAATCATCGTCCTTGA
MYSM1-MIS18Achr159155897chr2133642840217MKSLQKTAKIIVLETCATGAAGAGTCTGCAGAAAACAGCAAAAATCATCGTCCTTGAGAC

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Information of the samples that have these potential fusion neoantigens of MYSM1-MIS18A

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
STADMYSM1-MIS18Achr159155897ENST00000472487chr2133642840ENST00000290130TCGA-CD-A48C

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Potential target of CAR-T therapy development for MYSM1-MIS18A

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 MYSM1-MIS18A

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 MYSM1-MIS18A

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