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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:DAGLA-MS4A10

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: DAGLA-MS4A10
FusionPDB ID: 21287
FusionGDB2.0 ID: 21287
HgeneTgene
Gene symbol

DAGLA

MS4A10

Gene ID

747

341116

Gene namediacylglycerol lipase alphamembrane spanning 4-domains A10
SynonymsC11orf11|DAGL(ALPHA)|DAGLALPHA|NSDDRCD20L7|MS4A9
Cytomap

11q12.2

11q12.2

Type of geneprotein-codingprotein-coding
Descriptionsn1-specific diacylglycerol lipase alphaDGL-alphaneural stem cell-derived dendrite regulatormembrane-spanning 4-domains subfamily A member 10CD20 antigen-like 7membrane-spanning 4-domains, subfamily A, member 10
Modification date2020031320200313
UniProtAcc

Q9Y4D2

Main function of 5'-partner protein: FUNCTION: Serine hydrolase that hydrolyzes arachidonic acid-esterified diacylglycerols (DAGs) to produce the principal endocannabinoid, 2-arachidonoylglycerol (2-AG) (PubMed:14610053, PubMed:26668358, PubMed:23502535). Preferentially hydrolyzes sn-1 fatty acids from diacylglycerols (DAG) that contain arachidonic acid (AA) esterified at the sn-2 position to biosynthesize 2-AG (PubMed:14610053, PubMed:26668358, PubMed:23502535). Has negligible activity against other lipids including monoacylglycerols and phospholipids (PubMed:14610053). Plays a key role in regulating 2-AG signaling in the central nervous system (CNS). Regulates 2-AG involved in retrograde suppression at central synapses. Supports axonal growth during development and adult neurogenesis. Plays a role for eCB signaling in the physiological regulation of anxiety and depressive behaviors. Regulates also neuroinflammatory responses in the brain, in particular, LPS-induced microglial activation (By similarity). {ECO:0000250|UniProtKB:Q6WQJ1, ECO:0000269|PubMed:14610053, ECO:0000269|PubMed:23502535, ECO:0000269|PubMed:26668358}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000257215, ENST00000308287, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score7 X 6 X 5=2101 X 1 X 1=1
# samples 81
** MAII scorelog2(8/210*10)=-1.39231742277876
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(1/1*10)=3.32192809488736
Fusion gene context

PubMed: DAGLA [Title/Abstract] AND MS4A10 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: DAGLA [Title/Abstract] AND MS4A10 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)DAGLA(61502474)-MS4A10(60561445), # samples:1
Anticipated loss of major functional domain due to fusion event.
* 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
HgeneDAGLA

GO:0019369

arachidonic acid metabolic process

14610053

HgeneDAGLA

GO:0042136

neurotransmitter biosynthetic process

14610053

HgeneDAGLA

GO:0046340

diacylglycerol catabolic process

14610053



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/chr11:61502474/chr11:60561445)
- 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 DAGLA (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 MS4A10 (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)
ENST00000257215DAGLAchr1161502474-ENST00000308287MS4A10chr1160561445+308412441161687523

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
ENST00000257215ENST00000308287DAGLAchr1161502474-MS4A10chr1160561445+0.0081284060.9918716

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 DAGLA-MS4A10

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
DAGLAchr1161502474MS4A10chr11605614451244376TAVDIVYTSCHDAKMLCLMTNLISLF

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Potential FusionNeoAntigen Information of DAGLA-MS4A10 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.
DAGLA-MS4A10_61502474_60561445.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)
DAGLA-MS4A10chr1161502474chr11605614451244HLA-B39:01CHDAKMLCL0.99730.8929918
DAGLA-MS4A10chr1161502474chr11605614451244HLA-B38:02CHDAKMLCL0.99460.9575918
DAGLA-MS4A10chr1161502474chr11605614451244HLA-B38:01CHDAKMLCL0.99410.9515918
DAGLA-MS4A10chr1161502474chr11605614451244HLA-B39:12CHDAKMLCL0.99710.9044918
DAGLA-MS4A10chr1161502474chr11605614451244HLA-B39:09CHDAKMLCL0.99690.5922918
DAGLA-MS4A10chr1161502474chr11605614451244HLA-B39:05CHDAKMLCL0.99430.8719918
DAGLA-MS4A10chr1161502474chr11605614451244HLA-B14:03CHDAKMLCL0.32540.7857918
DAGLA-MS4A10chr1161502474chr11605614451244HLA-B38:05CHDAKMLCL0.99410.9515918
DAGLA-MS4A10chr1161502474chr11605614451244HLA-C18:01CHDAKMLCL0.90480.9449918
DAGLA-MS4A10chr1161502474chr11605614451244HLA-B39:11CHDAKMLCL0.87230.8215918
DAGLA-MS4A10chr1161502474chr11605614451244HLA-B39:11SCHDAKMLCL0.6560.7548818

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Potential FusionNeoAntigen Information of DAGLA-MS4A10 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 DAGLA-MS4A10

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
10835YTSCHDAKMLCLMTDAGLAMS4A10chr1161502474chr11605614451244

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of DAGLA-MS4A10

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-B14:023BVN10835YTSCHDAKMLCLMT-7.9962-8.1096
HLA-B14:023BVN10835YTSCHDAKMLCLMT-5.70842-6.74372
HLA-B52:013W3910835YTSCHDAKMLCLMT-6.83737-6.95077
HLA-B52:013W3910835YTSCHDAKMLCLMT-4.4836-5.5189
HLA-A11:014UQ210835YTSCHDAKMLCLMT-10.0067-10.1201
HLA-A11:014UQ210835YTSCHDAKMLCLMT-9.03915-10.0745
HLA-A24:025HGA10835YTSCHDAKMLCLMT-6.56204-6.67544
HLA-A24:025HGA10835YTSCHDAKMLCLMT-5.42271-6.45801
HLA-B44:053DX810835YTSCHDAKMLCLMT-7.85648-8.89178
HLA-B44:053DX810835YTSCHDAKMLCLMT-5.3978-5.5112
HLA-A02:016TDR10835YTSCHDAKMLCLMT-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of DAGLA-MS4A10

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
DAGLA-MS4A10chr1161502474chr1160561445818SCHDAKMLCLTCCTGCCATGATGCGAAGATGTTGTGCCTG
DAGLA-MS4A10chr1161502474chr1160561445918CHDAKMLCLTGCCATGATGCGAAGATGTTGTGCCTG

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 DAGLA-MS4A10

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
HNSCDAGLA-MS4A10chr1161502474ENST00000257215chr1160561445ENST00000308287TCGA-QK-A6VB-01A

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Potential target of CAR-T therapy development for DAGLA-MS4A10

check button Predicted 3D structure. We used RoseTTAFold.
132_DAGLA-MS4A10_c102e_pred.pdb


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
HgeneDAGLAchr11:61502474chr11:60561445ENST00000257215-1020102_1223761043.0TransmembraneHelical
HgeneDAGLAchr11:61502474chr11:60561445ENST00000257215-1020137_1573761043.0TransmembraneHelical
HgeneDAGLAchr11:61502474chr11:60561445ENST00000257215-102023_433761043.0TransmembraneHelical
HgeneDAGLAchr11:61502474chr11:60561445ENST00000257215-102061_813761043.0TransmembraneHelical
TgeneMS4A10chr11:61502474chr11:60561445ENST0000030828738122_1420268.0TransmembraneHelical
TgeneMS4A10chr11:61502474chr11:60561445ENST0000030828738172_1920268.0TransmembraneHelical

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
DAGLAchr1161502474ENST00000257215MS4A10chr1160561445ENST00000308287

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Related Drugs to DAGLA-MS4A10

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 DAGLA-MS4A10

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