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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:CARM1-PLA2G4C

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CARM1-PLA2G4C
FusionPDB ID: 13061
FusionGDB2.0 ID: 13061
HgeneTgene
Gene symbol

CARM1

PLA2G4C

Gene ID

10498

8605

Gene namecoactivator associated arginine methyltransferase 1phospholipase A2 group IVC
SynonymsPRMT4CPLA2-gamma
Cytomap

19p13.2

19q13.33

Type of geneprotein-codingprotein-coding
Descriptionhistone-arginine methyltransferase CARM1protein arginine N-methyltransferase 4cytosolic phospholipase A2 gammaphospholipase A2, group IVC (cytosolic, calcium-independent)
Modification date2020031320200313
UniProtAcc

Q86X55

Main function of 5'-partner protein: FUNCTION: Methylates (mono- and asymmetric dimethylation) the guanidino nitrogens of arginyl residues in several proteins involved in DNA packaging, transcription regulation, pre-mRNA splicing, and mRNA stability. Recruited to promoters upon gene activation together with histone acetyltransferases from EP300/P300 and p160 families, methylates histone H3 at 'Arg-17' (H3R17me), forming mainly asymmetric dimethylarginine (H3R17me2a), leading to activate transcription via chromatin remodeling. During nuclear hormone receptor activation and TCF7L2/TCF4 activation, acts synergically with EP300/P300 and either one of the p160 histone acetyltransferases NCOA1/SRC1, NCOA2/GRIP1 and NCOA3/ACTR or CTNNB1/beta-catenin to activate transcription. During myogenic transcriptional activation, acts together with NCOA3/ACTR as a coactivator for MEF2C. During monocyte inflammatory stimulation, acts together with EP300/P300 as a coactivator for NF-kappa-B. Acts as coactivator for PPARG, promotes adipocyte differentiation and the accumulation of brown fat tissue. Plays a role in the regulation of pre-mRNA alternative splicing by methylation of splicing factors. Also seems to be involved in p53/TP53 transcriptional activation. Methylates EP300/P300, both at 'Arg-2142', which may loosen its interaction with NCOA2/GRIP1, and at 'Arg-580' and 'Arg-604' in the KIX domain, which impairs its interaction with CREB and inhibits CREB-dependent transcriptional activation. Also methylates arginine residues in RNA-binding proteins PABPC1, ELAVL1 and ELAV4, which may affect their mRNA-stabilizing properties and the half-life of their target mRNAs. {ECO:0000269|PubMed:16497732, ECO:0000269|PubMed:19405910}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000327064, ENST00000344150, 
ENST00000354276, ENST00000413144, 
ENST00000599921, ENST00000596510, 
ENST00000599111, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score14 X 10 X 10=14005 X 7 X 3=105
# samples 206
** MAII scorelog2(20/1400*10)=-2.8073549220576
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(6/105*10)=-0.807354922057604
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: CARM1 [Title/Abstract] AND PLA2G4C [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CARM1 [Title/Abstract] AND PLA2G4C [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CARM1(10982598)-PLA2G4C(48558306), # samples:5
Anticipated loss of major functional domain due to fusion event.CARM1-PLA2G4C 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.
CARM1-PLA2G4C 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.
CARM1-PLA2G4C seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF.
CARM1-PLA2G4C seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
CARM1-PLA2G4C seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
CARM1-PLA2G4C seems lost the major protein functional domain in Tgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
CARM1-PLA2G4C 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
HgeneCARM1

GO:0016571

histone methylation

19405910

TgenePLA2G4C

GO:0046475

glycerophospholipid catabolic process

10085124



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/chr19:10982598/chr19:48558306)
- 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 CARM1 (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 PLA2G4C (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)
ENST00000327064CARM1chr1910982598+ENST00000599111PLA2G4Cchr1948556404-110741046606186
ENST00000327064CARM1chr1910982598+ENST00000413144PLA2G4Cchr1948556404-60741046606187
ENST00000327064CARM1chr1910982598+ENST00000599921PLA2G4Cchr1948556404-60741046606187
ENST00000344150CARM1chr1910982598+ENST00000599111PLA2G4Cchr1948556404-9172200416138
ENST00000344150CARM1chr1910982598+ENST00000413144PLA2G4Cchr1948556404-4172200416138
ENST00000344150CARM1chr1910982598+ENST00000599921PLA2G4Cchr1948556404-4172200416138

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
ENST00000327064ENST00000599111CARM1chr1910982598+PLA2G4Cchr1948556404-0.0052486170.9947514
ENST00000327064ENST00000413144CARM1chr1910982598+PLA2G4Cchr1948556404-0.003590340.9964097
ENST00000327064ENST00000599921CARM1chr1910982598+PLA2G4Cchr1948556404-0.003590340.9964097
ENST00000344150ENST00000599111CARM1chr1910982598+PLA2G4Cchr1948556404-0.004120430.99587953
ENST00000344150ENST00000413144CARM1chr1910982598+PLA2G4Cchr1948556404-0.0062239990.99377596
ENST00000344150ENST00000599921CARM1chr1910982598+PLA2G4Cchr1948556404-0.0062239990.99377596

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 CARM1-PLA2G4C

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CARM1chr1910982598PLA2G4Cchr194855640422072VRAGPDSAGIALYSRDIEAWSDTYDT

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Potential FusionNeoAntigen Information of CARM1-PLA2G4C 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.
CARM1-PLA2G4C_10982598_48556404.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)
CARM1-PLA2G4Cchr1910982598chr1948556404220HLA-B57:01YSRDIEAW0.99980.98081220
CARM1-PLA2G4Cchr1910982598chr1948556404220HLA-B58:02YSRDIEAW0.99930.94281220
CARM1-PLA2G4Cchr1910982598chr1948556404220HLA-B58:01YSRDIEAW0.99920.94681220
CARM1-PLA2G4Cchr1910982598chr1948556404220HLA-B57:03YSRDIEAW0.99860.98321220
CARM1-PLA2G4Cchr1910982598chr1948556404220HLA-A02:22ALYSRDIEA0.99780.60281019
CARM1-PLA2G4Cchr1910982598chr1948556404220HLA-A02:27ALYSRDIEA0.99720.681019
CARM1-PLA2G4Cchr1910982598chr1948556404220HLA-A02:60ALYSRDIEA0.9970.64251019
CARM1-PLA2G4Cchr1910982598chr1948556404220HLA-A02:11ALYSRDIEA0.9970.71561019
CARM1-PLA2G4Cchr1910982598chr1948556404220HLA-A02:24ALYSRDIEA0.99690.69611019
CARM1-PLA2G4Cchr1910982598chr1948556404220HLA-A02:30ALYSRDIEA0.99690.69611019
CARM1-PLA2G4Cchr1910982598chr1948556404220HLA-A02:13ALYSRDIEA0.99690.74751019
CARM1-PLA2G4Cchr1910982598chr1948556404220HLA-A02:67ALYSRDIEA0.99690.69611019
CARM1-PLA2G4Cchr1910982598chr1948556404220HLA-A02:38ALYSRDIEA0.99670.67721019
CARM1-PLA2G4Cchr1910982598chr1948556404220HLA-A02:16ALYSRDIEA0.99660.71531019
CARM1-PLA2G4Cchr1910982598chr1948556404220HLA-A02:21ALYSRDIEA0.99610.79891019
CARM1-PLA2G4Cchr1910982598chr1948556404220HLA-A02:04ALYSRDIEA0.99360.6511019
CARM1-PLA2G4Cchr1910982598chr1948556404220HLA-B08:09ALYSRDIEA0.98170.59811019
CARM1-PLA2G4Cchr1910982598chr1948556404220HLA-A02:35ALYSRDIEA0.950.72641019
CARM1-PLA2G4Cchr1910982598chr1948556404220HLA-A02:29ALYSRDIEA0.92790.6931019
CARM1-PLA2G4Cchr1910982598chr1948556404220HLA-A02:20ALYSRDIEA0.89380.69721019
CARM1-PLA2G4Cchr1910982598chr1948556404220HLA-A32:13ALYSRDIEAW0.96830.88391020
CARM1-PLA2G4Cchr1910982598chr1948556404220HLA-B57:01IALYSRDIEAW0.99990.9684920
CARM1-PLA2G4Cchr1910982598chr1948556404220HLA-B58:02IALYSRDIEAW0.99980.9429920
CARM1-PLA2G4Cchr1910982598chr1948556404220HLA-B58:01IALYSRDIEAW0.99950.9001920
CARM1-PLA2G4Cchr1910982598chr1948556404220HLA-B57:03IALYSRDIEAW0.9990.9758920
CARM1-PLA2G4Cchr1910982598chr1948556404220HLA-A02:01ALYSRDIEA0.99690.69611019
CARM1-PLA2G4Cchr1910982598chr1948556404220HLA-B57:10YSRDIEAW0.99980.98081220
CARM1-PLA2G4Cchr1910982598chr1948556404220HLA-B57:04YSRDIEAW0.99970.68431220
CARM1-PLA2G4Cchr1910982598chr1948556404220HLA-B58:06YSRDIEAW0.99940.86341220
CARM1-PLA2G4Cchr1910982598chr1948556404220HLA-B57:02YSRDIEAW0.99850.85681220
CARM1-PLA2G4Cchr1910982598chr1948556404220HLA-A02:03ALYSRDIEA0.99880.72911019
CARM1-PLA2G4Cchr1910982598chr1948556404220HLA-A02:06ALYSRDIEA0.99610.79891019
CARM1-PLA2G4Cchr1910982598chr1948556404220HLA-B15:24ALYSRDIEAW0.99860.98531020
CARM1-PLA2G4Cchr1910982598chr1948556404220HLA-A32:01ALYSRDIEAW0.98090.93641020
CARM1-PLA2G4Cchr1910982598chr1948556404220HLA-B15:13ALYSRDIEAW0.95130.8511020
CARM1-PLA2G4Cchr1910982598chr1948556404220HLA-B57:10IALYSRDIEAW0.99990.9684920
CARM1-PLA2G4Cchr1910982598chr1948556404220HLA-B57:04IALYSRDIEAW0.99980.6816920
CARM1-PLA2G4Cchr1910982598chr1948556404220HLA-B57:02IALYSRDIEAW0.9980.874920

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Potential FusionNeoAntigen Information of CARM1-PLA2G4C 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 CARM1-PLA2G4C

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
8388SAGIALYSRDIEAWCARM1PLA2G4Cchr1910982598chr1948556404220

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CARM1-PLA2G4C

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-B14:023BVN8388SAGIALYSRDIEAW-7.15543-7.26883
HLA-B14:023BVN8388SAGIALYSRDIEAW-4.77435-5.80965
HLA-B52:013W398388SAGIALYSRDIEAW-6.80875-6.92215
HLA-B52:013W398388SAGIALYSRDIEAW-4.20386-5.23916
HLA-A11:014UQ28388SAGIALYSRDIEAW-7.5194-8.5547
HLA-A11:014UQ28388SAGIALYSRDIEAW-6.9601-7.0735
HLA-A24:025HGA8388SAGIALYSRDIEAW-7.52403-7.63743
HLA-A24:025HGA8388SAGIALYSRDIEAW-5.82433-6.85963
HLA-B27:056PYJ8388SAGIALYSRDIEAW-3.28285-4.31815
HLA-B44:053DX88388SAGIALYSRDIEAW-5.91172-6.94702
HLA-B44:053DX88388SAGIALYSRDIEAW-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of CARM1-PLA2G4C

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
CARM1-PLA2G4Cchr1910982598chr19485564041019ALYSRDIEATCTACAGCCGTGATATTGAGGCATGGA
CARM1-PLA2G4Cchr1910982598chr19485564041020ALYSRDIEAWTCTACAGCCGTGATATTGAGGCATGGAGTG
CARM1-PLA2G4Cchr1910982598chr19485564041220YSRDIEAWGCCGTGATATTGAGGCATGGAGTG
CARM1-PLA2G4Cchr1910982598chr1948556404920IALYSRDIEAWCCCTCTACAGCCGTGATATTGAGGCATGGAGTG

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 CARM1-PLA2G4C

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
ESCACARM1-PLA2G4Cchr1910982598ENST00000344150chr1948556404ENST00000413144TCGA-L5-A891

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Potential target of CAR-T therapy development for CARM1-PLA2G4C

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 CARM1-PLA2G4C

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 CARM1-PLA2G4C

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