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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:ASAH1-WWOX

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ASAH1-WWOX
FusionPDB ID: 6947
FusionGDB2.0 ID: 6947
HgeneTgene
Gene symbol

ASAH1

WWOX

Gene ID

427

51741

Gene nameN-acylsphingosine amidohydrolase 1WW domain containing oxidoreductase
SynonymsAC|ACDase|ASAH|PHP|PHP32|SMAPMED16S432E|EIEE28|FOR|FRA16D|HHCMA56|PRO0128|SCAR12|SDR41C1|WOX1
Cytomap

8p22

16q23.1-q23.2

Type of geneprotein-codingprotein-coding
Descriptionacid ceramidaseN-acylethanolamine hydrolase ASAH1N-acylsphingosine amidohydrolase (acid ceramidase) 1acid CDaseacylsphingosine deacylaseputative 32 kDa heart proteinWW domain-containing oxidoreductaseWW domain-containing protein WWOXfragile site FRA16D oxidoreductaseshort chain dehydrogenase/reductase family 41C member 1
Modification date2020031320200313
UniProtAcc

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 idsENST00000262097, ENST00000381733, 
ENST00000417108, ENST00000520781, 
ENST00000314146, ENST00000520051, 
ENST00000355860, ENST00000408984, 
ENST00000565791, ENST00000569818, 
ENST00000402655, ENST00000406884, 
ENST00000566780, ENST00000539474, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score15 X 16 X 7=168030 X 23 X 10=6900
# samples 1636
** MAII scorelog2(16/1680*10)=-3.39231742277876
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(36/6900*10)=-4.26052755022322
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

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

Fusion neoantigen context

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

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ASAH1(17927301)-WWOX(79245505), # samples:1
Anticipated loss of major functional domain due to fusion event.ASAH1-WWOX 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.
ASAH1-WWOX 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.
ASAH1-WWOX 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.
ASAH1-WWOX 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.
ASAH1-WWOX seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
ASAH1-WWOX seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
ASAH1-WWOX seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
ASAH1-WWOX seems lost the major protein functional domain in Tgene partner, which is a tumor suppressor 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
HgeneASAH1

GO:0046512

sphingosine biosynthetic process

12815059

HgeneASAH1

GO:0046513

ceramide biosynthetic process

12764132|12815059

HgeneASAH1

GO:0046514

ceramide catabolic process

12815059

TgeneWWOX

GO:0030178

negative regulation of Wnt signaling pathway

19465938

TgeneWWOX

GO:0071560

cellular response to transforming growth factor beta stimulus

19366691



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/chr8:17927301/chr16:79245505)
- 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 ASAH1 (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 WWOX (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)
ENST00000262097ASAH1chr817927301-ENST00000539474WWOXchr1679245505+167561515803262
ENST00000381733ASAH1chr817927301-ENST00000539474WWOXchr1679245505+15785185706233
ENST00000417108ASAH1chr817927301-ENST00000539474WWOXchr1679245505+139933921527168
ENST00000520781ASAH1chr817927301-ENST00000539474WWOXchr1679245505+167561515803262

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
ENST00000262097ENST00000539474ASAH1chr817927301-WWOXchr1679245505+0.0250162260.97498375
ENST00000381733ENST00000539474ASAH1chr817927301-WWOXchr1679245505+0.112233930.88776606
ENST00000417108ENST00000539474ASAH1chr817927301-WWOXchr1679245505+0.0199213550.9800787
ENST00000520781ENST00000539474ASAH1chr817927301-WWOXchr1679245505+0.0250162260.97498375

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 ASAH1-WWOX

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ASAH1chr817927301WWOXchr1679245505339106PSGKIMQVVDEKLQQGAATTVYCAAV
ASAH1chr817927301WWOXchr1679245505518171PSGKIMQVVDEKLQQGAATTVYCAAV
ASAH1chr817927301WWOXchr1679245505615200PSGKIMQVVDEKLQQGAATTVYCAAV

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Potential FusionNeoAntigen Information of ASAH1-WWOX 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.
ASAH1-WWOX_17927301_79245505.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)
ASAH1-WWOXchr817927301chr1679245505615HLA-B45:01DEKLQQGAA0.99350.9454918
ASAH1-WWOXchr817927301chr1679245505615HLA-B50:02DEKLQQGAA0.96370.8096918
ASAH1-WWOXchr817927301chr1679245505615HLA-A02:13KLQQGAATTV0.99220.84831121
ASAH1-WWOXchr817927301chr1679245505615HLA-A02:27KLQQGAATTV0.98060.80841121
ASAH1-WWOXchr817927301chr1679245505615HLA-B13:02KLQQGAATTV0.19570.97691121
ASAH1-WWOXchr817927301chr1679245505615HLA-B15:01KLQQGAATTVY0.99990.88361122
ASAH1-WWOXchr817927301chr1679245505615HLA-B15:25KLQQGAATTVY0.99390.93291122
ASAH1-WWOXchr817927301chr1679245505615HLA-A80:01KLQQGAATTVY0.95710.54211122
ASAH1-WWOXchr817927301chr1679245505615HLA-B15:07KLQQGAATTVY0.99940.69431122
ASAH1-WWOXchr817927301chr1679245505615HLA-B15:05KLQQGAATTVY0.96070.87981122
ASAH1-WWOXchr817927301chr1679245505615HLA-B15:135KLQQGAATTVY0.99990.89291122
ASAH1-WWOXchr817927301chr1679245505615HLA-B15:33KLQQGAATTVY0.99990.88361122
ASAH1-WWOXchr817927301chr1679245505615HLA-B15:125KLQQGAATTVY0.99990.88361122
ASAH1-WWOXchr817927301chr1679245505615HLA-B15:34KLQQGAATTVY0.99990.88361122
ASAH1-WWOXchr817927301chr1679245505615HLA-B15:50KLQQGAATTVY0.99990.8591122
ASAH1-WWOXchr817927301chr1679245505615HLA-B15:27KLQQGAATTVY0.99990.88141122
ASAH1-WWOXchr817927301chr1679245505615HLA-B15:12KLQQGAATTVY0.99970.89311122
ASAH1-WWOXchr817927301chr1679245505615HLA-B15:35KLQQGAATTVY0.99930.76281122
ASAH1-WWOXchr817927301chr1679245505615HLA-B15:53KLQQGAATTVY0.99810.86571122
ASAH1-WWOXchr817927301chr1679245505615HLA-B15:39KLQQGAATTVY0.99550.8821122
ASAH1-WWOXchr817927301chr1679245505615HLA-B15:20KLQQGAATTVY0.96110.92321122
ASAH1-WWOXchr817927301chr1679245505615HLA-B35:28KLQQGAATTVY0.94820.94941122

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Potential FusionNeoAntigen Information of ASAH1-WWOX 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.
ASAH1-WWOX_17927301_79245505.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)
ASAH1-WWOXchr817927301chr1679245505615DRB1-1410SGKIMQVVDEKLQQG116
ASAH1-WWOXchr817927301chr1679245505615DRB1-1410PSGKIMQVVDEKLQQ015
ASAH1-WWOXchr817927301chr1679245505615DRB1-1503SGKIMQVVDEKLQQG116
ASAH1-WWOXchr817927301chr1679245505615DRB1-1523SGKIMQVVDEKLQQG116
ASAH1-WWOXchr817927301chr1679245505615DRB1-1525SGKIMQVVDEKLQQG116
ASAH1-WWOXchr817927301chr1679245505615DRB1-1615SGKIMQVVDEKLQQG116

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Fusion breakpoint peptide structures of ASAH1-WWOX

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
7641QVVDEKLQQGAATTASAH1WWOXchr817927301chr1679245505615

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

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-B14:023BVN7641QVVDEKLQQGAATT-7.15543-7.26883
HLA-B14:023BVN7641QVVDEKLQQGAATT-4.77435-5.80965
HLA-B52:013W397641QVVDEKLQQGAATT-6.80875-6.92215
HLA-B52:013W397641QVVDEKLQQGAATT-4.20386-5.23916
HLA-A11:014UQ27641QVVDEKLQQGAATT-7.5194-8.5547
HLA-A11:014UQ27641QVVDEKLQQGAATT-6.9601-7.0735
HLA-A24:025HGA7641QVVDEKLQQGAATT-7.52403-7.63743
HLA-A24:025HGA7641QVVDEKLQQGAATT-5.82433-6.85963
HLA-B27:056PYJ7641QVVDEKLQQGAATT-3.28285-4.31815
HLA-B44:053DX87641QVVDEKLQQGAATT-5.91172-6.94702
HLA-B44:053DX87641QVVDEKLQQGAATT-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of ASAH1-WWOX

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
ASAH1-WWOXchr817927301chr16792455051121KLQQGAATTVAAATTGCAACAGGGAGCTGCCACCACCGTG
ASAH1-WWOXchr817927301chr16792455051122KLQQGAATTVYAAATTGCAACAGGGAGCTGCCACCACCGTGTAC
ASAH1-WWOXchr817927301chr1679245505918DEKLQQGAAGATGAAAAATTGCAACAGGGAGCTGCC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
ASAH1-WWOXchr817927301chr1679245505015PSGKIMQVVDEKLQQCCAAGTGGAAAAATTATGCAGGTGGTGGATGAAAAATTGCAACAG
ASAH1-WWOXchr817927301chr1679245505116SGKIMQVVDEKLQQGAGTGGAAAAATTATGCAGGTGGTGGATGAAAAATTGCAACAGGGA

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Information of the samples that have these potential fusion neoantigens of ASAH1-WWOX

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
LUSCASAH1-WWOXchr817927301ENST00000262097chr1679245505ENST00000539474TCGA-56-6545-01A

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

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 ASAH1-WWOX

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 ASAH1-WWOX

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