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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:ACER2-C8orf37

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ACER2-C8orf37
FusionPDB ID: 1283
FusionGDB2.0 ID: 1283
HgeneTgene
Gene symbol

ACER2

C8orf37

Gene ID

340485

157657

Gene namealkaline ceramidase 2chromosome 8 open reading frame 37
SynonymsALKCDase2|ASAH3LBBS21|CORD16|FAP418|MOT25|RP64|smalltalk
Cytomap

9p22.1

8q22.1

Type of geneprotein-codingprotein-coding
Descriptionalkaline ceramidase 2alkCDase 2alkaline CDase 2ceramide hydrolasehaCER2protein C8orf37Bardet-Biedl syndrome 21
Modification date2020031320200313
UniProtAcc

Q5QJU3

Main function of 5'-partner protein: FUNCTION: Golgi ceramidase that catalyzes the hydrolysis of ceramides into sphingoid bases like sphingosine and free fatty acids at alkaline pH (PubMed:16940153, PubMed:18945876, PubMed:20207939, PubMed:20089856). 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:20207939). Has a better catalytic efficiency towards unsaturated long-chain ceramides, including C18:1-, C20:1- and C24:1-ceramides (PubMed:16940153, PubMed:18945876, PubMed:20207939, PubMed:20089856). Saturated long-chain ceramides and unsaturated very long-chain ceramides are also good substrates, whereas saturated very long-chain ceramides and short-chain ceramides are poor substrates (PubMed:20089856). Also hydrolyzes dihydroceramides to produce dihydrosphingosine (PubMed:20207939, PubMed:20628055). It is the ceramidase that controls the levels of circulating sphingosine-1-phosphate and dihydrosphingosine-1-phosphate in plasma through their production by hematopoietic cells (By similarity). Regulates cell proliferation, autophagy and apoptosis by the production of sphingosine and sphingosine-1-phosphate (PubMed:16940153, PubMed:26943039, PubMed:28294157, PubMed:29229990). As part of a p53/TP53-dependent pathway, promotes for instance autophagy and apoptosis in response to DNA damage (PubMed:26943039, PubMed:28294157, PubMed:29229990). Through the production of sphingosine, may also regulate the function of the Golgi complex and regulate the glycosylation of proteins (PubMed:18945876). {ECO:0000250|UniProtKB:Q8VD53, ECO:0000269|PubMed:16940153, ECO:0000269|PubMed:18945876, ECO:0000269|PubMed:20089856, ECO:0000269|PubMed:20207939, ECO:0000269|PubMed:20628055, ECO:0000269|PubMed:26943039, ECO:0000269|PubMed:28294157, ECO:0000269|PubMed:29229990, ECO:0000303|PubMed:20207939}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000340967, ENST00000380376, 
ENST00000286688, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score3 X 3 X 2=181 X 1 X 1=1
# samples 31
** MAII scorelog2(3/18*10)=0.736965594166206
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
log2(1/1*10)=3.32192809488736
Fusion gene context

PubMed: ACER2 [Title/Abstract] AND C8orf37 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ACER2 [Title/Abstract] AND C8orf37 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ACER2(19435082)-C8orf37(96276002), # samples:2
Anticipated loss of major functional domain due to fusion event.ACER2-C8orf37 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.
ACER2-C8orf37 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
HgeneACER2

GO:0001953

negative regulation of cell-matrix adhesion

18945876

HgeneACER2

GO:0006974

cellular response to DNA damage stimulus

26943039

HgeneACER2

GO:0008284

positive regulation of cell proliferation

16940153

HgeneACER2

GO:0032526

response to retinoic acid

18945876

HgeneACER2

GO:0033629

negative regulation of cell adhesion mediated by integrin

18945876

HgeneACER2

GO:0046512

sphingosine biosynthetic process

16940153|20089856|20628055



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/chr9:19435082/chr8:96276002)
- 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 ACER2 (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 C8orf37 (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)
ENST00000380376ACER2chr919435082+ENST00000286688C8orf37chr896276002-3828661771129350
ENST00000340967ACER2chr919435082+ENST00000286688C8orf37chr896276002-36965292997331

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
ENST00000380376ENST00000286688ACER2chr919435082+C8orf37chr896276002-0.0009500060.99904996
ENST00000340967ENST00000286688ACER2chr919435082+C8orf37chr896276002-0.0008509930.99914896

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 ACER2-C8orf37

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ACER2chr919435082C8orf37chr896276002529173TLGVPCTALLIAELKRSTETFKKEDD
ACER2chr919435082C8orf37chr896276002661192TLGVPCTALLIAELKRSTETFKKEDD

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Potential FusionNeoAntigen Information of ACER2-C8orf37 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.
ACER2-C8orf37_19435082_96276002.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)
ACER2-C8orf37chr919435082chr896276002529HLA-B45:01AELKRSTET0.98420.96721120
ACER2-C8orf37chr919435082chr896276002529HLA-B50:02AELKRSTET0.98160.77821120
ACER2-C8orf37chr919435082chr896276002529HLA-B15:01ELKRSTETF0.98060.88341221
ACER2-C8orf37chr919435082chr896276002529HLA-B08:01ELKRSTETF0.96110.70291221
ACER2-C8orf37chr919435082chr896276002529HLA-B15:02ELKRSTETF0.88250.9471221
ACER2-C8orf37chr919435082chr896276002529HLA-B41:01AELKRSTET0.4160.97311120
ACER2-C8orf37chr919435082chr896276002529HLA-B50:01AELKRSTET0.17710.79791120
ACER2-C8orf37chr919435082chr896276002529HLA-A32:13ELKRSTETF0.14920.94081221
ACER2-C8orf37chr919435082chr896276002529HLA-B44:03AELKRSTETF0.99940.98331121
ACER2-C8orf37chr919435082chr896276002529HLA-B47:01AELKRSTETF0.99820.56151121
ACER2-C8orf37chr919435082chr896276002529HLA-B15:01AELKRSTETF0.99090.89221121
ACER2-C8orf37chr919435082chr896276002529HLA-B40:06AELKRSTET0.9880.68791120
ACER2-C8orf37chr919435082chr896276002529HLA-B15:07ELKRSTETF0.96680.66351221
ACER2-C8orf37chr919435082chr896276002529HLA-B15:21ELKRSTETF0.88250.91641221
ACER2-C8orf37chr919435082chr896276002529HLA-B15:31ELKRSTETF0.53650.89941221
ACER2-C8orf37chr919435082chr896276002529HLA-B15:07AELKRSTETF0.98940.69261121
ACER2-C8orf37chr919435082chr896276002529HLA-B44:10AELKRSTETF0.98470.58471121
ACER2-C8orf37chr919435082chr896276002529HLA-B15:34ELKRSTETF0.98060.88341221
ACER2-C8orf37chr919435082chr896276002529HLA-B15:33ELKRSTETF0.98060.88341221
ACER2-C8orf37chr919435082chr896276002529HLA-B15:125ELKRSTETF0.98060.88341221
ACER2-C8orf37chr919435082chr896276002529HLA-B15:135ELKRSTETF0.97880.88341221
ACER2-C8orf37chr919435082chr896276002529HLA-B15:27ELKRSTETF0.97820.88631221
ACER2-C8orf37chr919435082chr896276002529HLA-B15:11ELKRSTETF0.97790.8271221
ACER2-C8orf37chr919435082chr896276002529HLA-B15:08ELKRSTETF0.97670.83651221
ACER2-C8orf37chr919435082chr896276002529HLA-B35:43ELKRSTETF0.9730.83591221
ACER2-C8orf37chr919435082chr896276002529HLA-B15:35ELKRSTETF0.96630.86071221
ACER2-C8orf37chr919435082chr896276002529HLA-B15:24ELKRSTETF0.96390.87581221
ACER2-C8orf37chr919435082chr896276002529HLA-B08:18ELKRSTETF0.96110.70291221
ACER2-C8orf37chr919435082chr896276002529HLA-A25:01ELKRSTETF0.95650.91121221
ACER2-C8orf37chr919435082chr896276002529HLA-B15:53ELKRSTETF0.94220.85721221
ACER2-C8orf37chr919435082chr896276002529HLA-B15:50ELKRSTETF0.88660.8971221
ACER2-C8orf37chr919435082chr896276002529HLA-B15:12ELKRSTETF0.77080.87391221
ACER2-C8orf37chr919435082chr896276002529HLA-B15:13ELKRSTETF0.71430.61491221
ACER2-C8orf37chr919435082chr896276002529HLA-B08:12ELKRSTETF0.680.85621221
ACER2-C8orf37chr919435082chr896276002529HLA-B35:20ELKRSTETF0.49530.95631221
ACER2-C8orf37chr919435082chr896276002529HLA-B15:30ELKRSTETF0.4920.82471221
ACER2-C8orf37chr919435082chr896276002529HLA-B15:20ELKRSTETF0.40930.94491221
ACER2-C8orf37chr919435082chr896276002529HLA-B50:05AELKRSTET0.17710.79791120
ACER2-C8orf37chr919435082chr896276002529HLA-B50:04AELKRSTET0.17710.79791120
ACER2-C8orf37chr919435082chr896276002529HLA-B44:26AELKRSTETF0.99940.98331121
ACER2-C8orf37chr919435082chr896276002529HLA-B44:13AELKRSTETF0.99940.98331121
ACER2-C8orf37chr919435082chr896276002529HLA-B44:07AELKRSTETF0.99940.98331121
ACER2-C8orf37chr919435082chr896276002529HLA-B15:54AELKRSTETF0.99490.8351121
ACER2-C8orf37chr919435082chr896276002529HLA-B15:35AELKRSTETF0.99230.88391121
ACER2-C8orf37chr919435082chr896276002529HLA-B15:27AELKRSTETF0.99180.91411121
ACER2-C8orf37chr919435082chr896276002529HLA-B15:135AELKRSTETF0.99110.88931121
ACER2-C8orf37chr919435082chr896276002529HLA-B15:125AELKRSTETF0.99090.89221121
ACER2-C8orf37chr919435082chr896276002529HLA-B15:33AELKRSTETF0.99090.89221121
ACER2-C8orf37chr919435082chr896276002529HLA-B15:34AELKRSTETF0.99090.89221121
ACER2-C8orf37chr919435082chr896276002529HLA-B40:04AELKRSTETF0.9890.72311121
ACER2-C8orf37chr919435082chr896276002529HLA-B15:50AELKRSTETF0.98890.93041121
ACER2-C8orf37chr919435082chr896276002529HLA-B15:53AELKRSTETF0.98830.87161121
ACER2-C8orf37chr919435082chr896276002529HLA-B15:24AELKRSTETF0.98270.90071121
ACER2-C8orf37chr919435082chr896276002529HLA-B15:12AELKRSTETF0.96110.87451121
ACER2-C8orf37chr919435082chr896276002529HLA-B48:02AELKRSTETF0.94140.94591121
ACER2-C8orf37chr919435082chr896276002529HLA-B41:03AELKRSTETF0.83550.71591121

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Potential FusionNeoAntigen Information of ACER2-C8orf37 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.
ACER2-C8orf37_19435082_96276002.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)
ACER2-C8orf37chr919435082chr896276002529DRB1-0822ALLIAELKRSTETFK722
ACER2-C8orf37chr919435082chr896276002529DRB1-1358ALLIAELKRSTETFK722
ACER2-C8orf37chr919435082chr896276002529DRB1-1358TALLIAELKRSTETF621

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Fusion breakpoint peptide structures of ACER2-C8orf37

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
9232TALLIAELKRSTETACER2C8orf37chr919435082chr896276002529

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ACER2-C8orf37

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-B14:023BVN9232TALLIAELKRSTET-7.9962-8.1096
HLA-B14:023BVN9232TALLIAELKRSTET-5.70842-6.74372
HLA-B52:013W399232TALLIAELKRSTET-6.83737-6.95077
HLA-B52:013W399232TALLIAELKRSTET-4.4836-5.5189
HLA-A11:014UQ29232TALLIAELKRSTET-10.0067-10.1201
HLA-A11:014UQ29232TALLIAELKRSTET-9.03915-10.0745
HLA-A24:025HGA9232TALLIAELKRSTET-6.56204-6.67544
HLA-A24:025HGA9232TALLIAELKRSTET-5.42271-6.45801
HLA-B44:053DX89232TALLIAELKRSTET-7.85648-8.89178
HLA-B44:053DX89232TALLIAELKRSTET-5.3978-5.5112
HLA-A02:016TDR9232TALLIAELKRSTET-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of ACER2-C8orf37

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
ACER2-C8orf37chr919435082chr8962760021120AELKRSTETAAAGAGATCAACAGAAACATTTAAAAA
ACER2-C8orf37chr919435082chr8962760021121AELKRSTETFAAAGAGATCAACAGAAACATTTAAAAAAGA
ACER2-C8orf37chr919435082chr8962760021221ELKRSTETFGAGATCAACAGAAACATTTAAAAAAGA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
ACER2-C8orf37chr919435082chr896276002621TALLIAELKRSTETFGCTCATCGCAGAGCTAAAGAGATCAACAGAAACATTTAAAAAAGA
ACER2-C8orf37chr919435082chr896276002722ALLIAELKRSTETFKCATCGCAGAGCTAAAGAGATCAACAGAAACATTTAAAAAAGAAGA

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Information of the samples that have these potential fusion neoantigens of ACER2-C8orf37

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
PRADACER2-C8orf37chr919435082ENST00000340967chr896276002ENST00000286688TCGA-EJ-A7NF-01A

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Potential target of CAR-T therapy development for ACER2-C8orf37

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
HgeneACER2chr9:19435082chr8:96276002ENST00000340967+46125_142167276.0TransmembraneHelical
HgeneACER2chr9:19435082chr8:96276002ENST00000340967+46144_164167276.0TransmembraneHelical
HgeneACER2chr9:19435082chr8:96276002ENST00000340967+4633_53167276.0TransmembraneHelical
HgeneACER2chr9:19435082chr8:96276002ENST00000340967+4663_83167276.0TransmembraneHelical
HgeneACER2chr9:19435082chr8:96276002ENST00000340967+4687_107167276.0TransmembraneHelical
HgeneACER2chr9:19435082chr8:96276002ENST00000380376+4533_53118141.0TransmembraneHelical
HgeneACER2chr9:19435082chr8:96276002ENST00000380376+4563_83118141.0TransmembraneHelical
HgeneACER2chr9:19435082chr8:96276002ENST00000380376+4587_107118141.0TransmembraneHelical

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 ACER2-C8orf37

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 ACER2-C8orf37

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