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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:MTUS1-ASAH1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: MTUS1-ASAH1
FusionPDB ID: 55932
FusionGDB2.0 ID: 55932
HgeneTgene
Gene symbol

MTUS1

ASAH1

Gene ID

57509

427

Gene namemicrotubule associated scaffold protein 1N-acylsphingosine amidohydrolase 1
SynonymsATBP|ATIP|ATIP3|ICIS|MP44|MTSG1AC|ACDase|ASAH|PHP|PHP32|SMAPME
Cytomap

8p22

8p22

Type of geneprotein-codingprotein-coding
Descriptionmicrotubule-associated tumor suppressor 1AT2 receptor-binding proteinAT2 receptor-interacting proteinAT2R binding proteinangiotensin-II type 2 receptor-interacting proteinerythroid differentiation-relatedmicrotubule associated tumor suppressor 1mitacid ceramidaseN-acylethanolamine hydrolase ASAH1N-acylsphingosine amidohydrolase (acid ceramidase) 1acid CDaseacylsphingosine deacylaseputative 32 kDa heart protein
Modification date2020031320200313
UniProtAcc

Q9ULD2

Main function of 5'-partner protein: FUNCTION: Cooperates with AGTR2 to inhibit ERK2 activation and cell proliferation. May be required for AGTR2 cell surface expression. Together with PTPN6, induces UBE2V2 expression upon angiotensin-II stimulation. Isoform 1 inhibits breast cancer cell proliferation, delays the progression of mitosis by prolonging metaphase and reduces tumor growth. {ECO:0000269|PubMed:12692079, ECO:0000269|PubMed:19794912}.

Q13510

Main function of 5'-partner protein: FUNCTION: Lysosomal ceramidase that hydrolyzes sphingolipid ceramides into sphingosine and free fatty acids at acidic pH (PubMed:10610716, PubMed:7744740, PubMed:15655246, PubMed:11451951). Ceramides, sphingosine, and its phosphorylated form sphingosine-1-phosphate are bioactive lipids that mediate cellular signaling pathways regulating several biological processes including cell proliferation, apoptosis and differentiation (PubMed:10610716). Has a higher catalytic efficiency towards C12-ceramides versus other ceramides (PubMed:7744740, PubMed:15655246). Also catalyzes the reverse reaction allowing the synthesis of ceramides from fatty acids and sphingosine (PubMed:12764132, PubMed:12815059). For the reverse synthetic reaction, the natural sphingosine D-erythro isomer is more efficiently utilized as a substrate compared to D-erythro-dihydrosphingosine and D-erythro-phytosphingosine, while the fatty acids with chain lengths of 12 or 14 carbons are the most efficiently used (PubMed:12764132). Has also an N-acylethanolamine hydrolase activity (PubMed:15655246). By regulating the levels of ceramides, sphingosine and sphingosine-1-phosphate in the epidermis, mediates the calcium-induced differentiation of epidermal keratinocytes (PubMed:17713573). Also indirectly regulates tumor necrosis factor/TNF-induced apoptosis (By similarity). By regulating the intracellular balance between ceramides and sphingosine, in adrenocortical cells, probably also acts as a regulator of steroidogenesis (PubMed:22261821). {ECO:0000250|UniProtKB:Q9WV54, ECO:0000269|PubMed:10610716, ECO:0000269|PubMed:11451951, ECO:0000269|PubMed:12764132, ECO:0000269|PubMed:12815059, ECO:0000269|PubMed:15655246, ECO:0000269|PubMed:17713573, ECO:0000269|PubMed:22261821, ECO:0000269|PubMed:7744740, ECO:0000303|PubMed:10610716}.; FUNCTION: [Isoform 2]: May directly regulate steroidogenesis by binding the nuclear receptor NR5A1 and negatively regulating its transcriptional activity. {ECO:0000305|PubMed:22927646}.
Ensembl transtripts involved in fusion geneENST idsENST00000262102, ENST00000381862, 
ENST00000381869, ENST00000519263, 
ENST00000297488, ENST00000381861, 
ENST00000400046, ENST00000518713, 
ENST00000544260, 
ENST00000520051, 
ENST00000262097, ENST00000314146, 
ENST00000381733, ENST00000417108, 
ENST00000520781, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score12 X 13 X 5=78013 X 10 X 8=1040
# samples 1516
** MAII scorelog2(15/780*10)=-2.37851162325373
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(16/1040*10)=-2.70043971814109
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: MTUS1 [Title/Abstract] AND ASAH1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: MTUS1 [Title/Abstract] AND ASAH1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MTUS1(17601113)-ASAH1(17920739), # samples:3
Anticipated loss of major functional domain due to fusion event.MTUS1-ASAH1 seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted ORF.
MTUS1-ASAH1 seems lost the major protein functional domain in Tgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
MTUS1-ASAH1 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target 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
TgeneASAH1

GO:0046512

sphingosine biosynthetic process

12815059

TgeneASAH1

GO:0046513

ceramide biosynthetic process

12764132|12815059

TgeneASAH1

GO:0046514

ceramide catabolic process

12815059



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/chr8:17601113/chr8:17920739)
- 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 MTUS1 (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 ASAH1 (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)
ENST00000519263MTUS1chr817601113-ENST00000262097ASAH1chr817920739-4301246117431911005
ENST00000519263MTUS1chr817601113-ENST00000381733ASAH1chr817920739-4300246117431911005
ENST00000519263MTUS1chr817601113-ENST00000417108ASAH1chr817920739-4274246117431911005
ENST00000519263MTUS1chr817601113-ENST00000520781ASAH1chr817920739-4274246117431911005
ENST00000519263MTUS1chr817601113-ENST00000314146ASAH1chr817920739-3528246117431911005
ENST00000519263MTUS1chr817601112-ENST00000262097ASAH1chr817920739-4301246117431911005
ENST00000519263MTUS1chr817601112-ENST00000381733ASAH1chr817920739-4300246117431911005
ENST00000519263MTUS1chr817601112-ENST00000417108ASAH1chr817920739-4274246117431911005
ENST00000519263MTUS1chr817601112-ENST00000520781ASAH1chr817920739-4274246117431911005
ENST00000519263MTUS1chr817601112-ENST00000314146ASAH1chr817920739-3528246117431911005

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
ENST00000519263ENST00000262097MTUS1chr817601113-ASAH1chr817920739-0.0001689470.9998311
ENST00000519263ENST00000381733MTUS1chr817601113-ASAH1chr817920739-0.0001694710.9998305
ENST00000519263ENST00000417108MTUS1chr817601113-ASAH1chr817920739-0.0001647130.99983525
ENST00000519263ENST00000520781MTUS1chr817601113-ASAH1chr817920739-0.0001647130.99983525
ENST00000519263ENST00000314146MTUS1chr817601113-ASAH1chr817920739-0.0003130950.99968696
ENST00000519263ENST00000262097MTUS1chr817601112-ASAH1chr817920739-0.0001689470.9998311
ENST00000519263ENST00000381733MTUS1chr817601112-ASAH1chr817920739-0.0001694710.9998305
ENST00000519263ENST00000417108MTUS1chr817601112-ASAH1chr817920739-0.0001647130.99983525
ENST00000519263ENST00000520781MTUS1chr817601112-ASAH1chr817920739-0.0001647130.99983525
ENST00000519263ENST00000314146MTUS1chr817601112-ASAH1chr817920739-0.0003130950.99968696

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 MTUS1-ASAH1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
MTUS1chr817601112ASAH1chr8179207392461762AVSPQRIRRVSSSGHLIHGRNMDFGV
MTUS1chr817601113ASAH1chr8179207392461762AVSPQRIRRVSSSGHLIHGRNMDFGV

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Potential FusionNeoAntigen Information of MTUS1-ASAH1 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.
MTUS1-ASAH1_17601112_17920739.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)
MTUS1-ASAH1chr817601112chr8179207392461HLA-B27:04RRVSSSGHL0.99910.8029716
MTUS1-ASAH1chr817601112chr8179207392461HLA-B27:05RRVSSSGHL0.9990.732716
MTUS1-ASAH1chr817601112chr8179207392461HLA-B15:16RVSSSGHLI0.94990.6665817
MTUS1-ASAH1chr817601112chr8179207392461HLA-A74:09SSGHLIHGR0.94420.59231120
MTUS1-ASAH1chr817601112chr8179207392461HLA-A74:11SSGHLIHGR0.94420.59231120
MTUS1-ASAH1chr817601112chr8179207392461HLA-A74:03SSGHLIHGR0.94420.59231120
MTUS1-ASAH1chr817601112chr8179207392461HLA-A30:08RVSSSGHLI0.92950.7299817
MTUS1-ASAH1chr817601112chr8179207392461HLA-A32:13RVSSSGHLI0.89990.9003817
MTUS1-ASAH1chr817601112chr8179207392461HLA-A31:02SSGHLIHGR0.8710.57471120
MTUS1-ASAH1chr817601112chr8179207392461HLA-B13:02RVSSSGHLI0.03190.5462817
MTUS1-ASAH1chr817601112chr8179207392461HLA-B07:10RRVSSSGHL0.02570.6526716
MTUS1-ASAH1chr817601112chr8179207392461HLA-B13:01RVSSSGHLI0.02240.7315817
MTUS1-ASAH1chr817601112chr8179207392461HLA-A31:06SSSGHLIHGR0.96890.50541020
MTUS1-ASAH1chr817601112chr8179207392461HLA-A31:02SSSGHLIHGR0.95630.62971020
MTUS1-ASAH1chr817601112chr8179207392461HLA-B27:14RRVSSSGHL0.99910.6437716
MTUS1-ASAH1chr817601112chr8179207392461HLA-C15:06RVSSSGHLI0.99070.9401817
MTUS1-ASAH1chr817601112chr8179207392461HLA-C07:95RRVSSSGHL0.99050.6108716
MTUS1-ASAH1chr817601112chr8179207392461HLA-C07:05RRVSSSGHL0.98240.8254716
MTUS1-ASAH1chr817601112chr8179207392461HLA-C07:27RRVSSSGHL0.96290.8577716
MTUS1-ASAH1chr817601112chr8179207392461HLA-A31:01SSGHLIHGR0.96210.52241120
MTUS1-ASAH1chr817601112chr8179207392461HLA-B27:03RRVSSSGHL0.95160.765716
MTUS1-ASAH1chr817601112chr8179207392461HLA-C07:46RRVSSSGHL0.83670.8244716
MTUS1-ASAH1chr817601112chr8179207392461HLA-C12:16RRVSSSGHL0.00790.9568716
MTUS1-ASAH1chr817601112chr8179207392461HLA-A31:01SSSGHLIHGR0.98280.57451020
MTUS1-ASAH1chr817601112chr8179207392461HLA-B27:10RRVSSSGHL0.99920.8877716
MTUS1-ASAH1chr817601112chr8179207392461HLA-B27:08RRVSSSGHL0.9990.6192716
MTUS1-ASAH1chr817601112chr8179207392461HLA-B27:06RRVSSSGHL0.99870.7382716
MTUS1-ASAH1chr817601112chr8179207392461HLA-B27:09RRVSSSGHL0.99750.688716
MTUS1-ASAH1chr817601112chr8179207392461HLA-C07:01RRVSSSGHL0.99370.6339716
MTUS1-ASAH1chr817601112chr8179207392461HLA-C15:02RVSSSGHLI0.99310.8372817
MTUS1-ASAH1chr817601112chr8179207392461HLA-C15:05RVSSSGHLI0.99150.8771817
MTUS1-ASAH1chr817601112chr8179207392461HLA-A32:01RVSSSGHLI0.97550.8622817
MTUS1-ASAH1chr817601112chr8179207392461HLA-A74:01SSGHLIHGR0.94420.59231120
MTUS1-ASAH1chr817601112chr8179207392461HLA-A30:01RVSSSGHLI0.93280.8996817
MTUS1-ASAH1chr817601112chr8179207392461HLA-C06:08RRVSSSGHL0.80280.9627716
MTUS1-ASAH1chr817601112chr8179207392461HLA-C07:22RRVSSSGHL0.77230.6472716
MTUS1-ASAH1chr817601112chr8179207392461HLA-B27:06RRVSSSGHLI0.99940.6445717
MTUS1-ASAH1chr817601112chr8179207392461HLA-B27:09RRVSSSGHLI0.9990.6074717

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Potential FusionNeoAntigen Information of MTUS1-ASAH1 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 MTUS1-ASAH1

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
3960IRRVSSSGHLIHGRMTUS1ASAH1chr817601112chr8179207392461

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of MTUS1-ASAH1

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-B14:023BVN3960IRRVSSSGHLIHGR-6.53507-6.53507
HLA-A24:025HGA3960IRRVSSSGHLIHGR-6.46398-6.46398
HLA-B27:056PYJ3960IRRVSSSGHLIHGR-3.42521-3.42521

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Vaccine Design for the FusionNeoAntigens of MTUS1-ASAH1

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
MTUS1-ASAH1chr817601112chr8179207391020SSSGHLIHGRCCAGTTCTGGTCATCTAATACATGGGAGAA
MTUS1-ASAH1chr817601112chr8179207391120SSGHLIHGRGTTCTGGTCATCTAATACATGGGAGAA
MTUS1-ASAH1chr817601112chr817920739716RRVSSSGHLGGCGTGTGTCCAGTTCTGGTCATCTAA
MTUS1-ASAH1chr817601112chr817920739717RRVSSSGHLIGGCGTGTGTCCAGTTCTGGTCATCTAATAC
MTUS1-ASAH1chr817601112chr817920739817RVSSSGHLIGTGTGTCCAGTTCTGGTCATCTAATAC

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 MTUS1-ASAH1

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
STADMTUS1-ASAH1chr817601112ENST00000519263chr817920739ENST00000262097TCGA-HU-A4GF

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Potential target of CAR-T therapy development for MTUS1-ASAH1

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 MTUS1-ASAH1

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 MTUS1-ASAH1

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