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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:EHMT1-PPP1R37

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: EHMT1-PPP1R37
FusionPDB ID: 25586
FusionGDB2.0 ID: 25586
HgeneTgene
Gene symbol

EHMT1

PPP1R37

Gene ID

79813

284352

Gene nameeuchromatic histone lysine methyltransferase 1protein phosphatase 1 regulatory subunit 37
SynonymsEHMT1-IT1|EUHMTASE1|Eu-HMTase1|FP13812|GLP|GLP1|KLEFS1|KMT1DLRRC68
Cytomap

9q34.3

19q13.32

Type of geneprotein-codingprotein-coding
Descriptionhistone-lysine N-methyltransferase EHMT1EHMT1 intronic transcript 1G9a-like protein 1H3-K9-HMTase 5euchromatic histone-lysine N-methyltransferase 1histone H3-K9 methyltransferase 5histone-lysine N-methyltransferase, H3 lysine-9 specific 5lysine N-mprotein phosphatase 1 regulatory subunit 37leucine rich repeat containing 68leucine-rich repeat-containing protein 68
Modification date2020031320200313
UniProtAcc

Q9H9B1

Main function of 5'-partner protein: FUNCTION: Histone methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting HP1 proteins to methylated histones. Also weakly methylates 'Lys-27' of histone H3 (H3K27me). Also required for DNA methylation, the histone methyltransferase activity is not required for DNA methylation, suggesting that these 2 activities function independently. Probably targeted to histone H3 by different DNA-binding proteins like E2F6, MGA, MAX and/or DP1. During G0 phase, it probably contributes to silencing of MYC- and E2F-responsive genes, suggesting a role in G0/G1 transition in cell cycle. In addition to the histone methyltransferase activity, also methylates non-histone proteins: mediates dimethylation of 'Lys-373' of p53/TP53. Represses the expression of mitochondrial function-related genes, perhaps by occupying their promoter regions, working in concert with probable chromatin reader BAZ2B (By similarity). {ECO:0000250|UniProtKB:Q5DW34, ECO:0000269|PubMed:12004135, ECO:0000269|PubMed:20118233}.

O75864

Main function of 5'-partner protein: FUNCTION: Inhibits phosphatase activity of protein phosphatase 1 (PP1) complexes. {ECO:0000269|PubMed:19389623}.
Ensembl transtripts involved in fusion geneENST idsENST00000371394, ENST00000334856, 
ENST00000460843, ENST00000462484, 
ENST00000221462, ENST00000421905, 
ENST00000496125, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score15 X 9 X 8=10806 X 4 X 4=96
# samples 207
** MAII scorelog2(20/1080*10)=-2.43295940727611
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(7/96*10)=-0.45567948377619
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: EHMT1 [Title/Abstract] AND PPP1R37 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: EHMT1 [Title/Abstract] AND PPP1R37 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)EHMT1(140622981)-PPP1R37(45641772), # samples:2
Anticipated loss of major functional domain due to fusion event.EHMT1-PPP1R37 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.
EHMT1-PPP1R37 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.
EHMT1-PPP1R37 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.
EHMT1-PPP1R37 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
HgeneEHMT1

GO:0006325

chromatin organization

12004135

HgeneEHMT1

GO:0016571

histone methylation

12004135

HgeneEHMT1

GO:0018027

peptidyl-lysine dimethylation

20118233

TgenePPP1R37

GO:0010923

negative regulation of phosphatase activity

19389623



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/chr9:140622981/chr19:45641772)
- 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 EHMT1 (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 PPP1R37 (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)
ENST00000462484EHMT1chr9140622981+ENST00000421905PPP1R37chr1945641772+2722860222721900
ENST00000462484EHMT1chr9140622981+ENST00000221462PPP1R37chr1945641772+3457860222733903
ENST00000334856EHMT1chr9140622981+ENST00000421905PPP1R37chr1945641772+2722860222721900
ENST00000334856EHMT1chr9140622981+ENST00000221462PPP1R37chr1945641772+3457860222733903
ENST00000460843EHMT1chr9140622981+ENST00000421905PPP1R37chr1945641772+2712850122711899
ENST00000460843EHMT1chr9140622981+ENST00000221462PPP1R37chr1945641772+3447850122723903
ENST00000462484EHMT1chr9140622981+ENST00000421905PPP1R37chr1945641771+2722860222721900
ENST00000462484EHMT1chr9140622981+ENST00000221462PPP1R37chr1945641771+3457860222733903
ENST00000334856EHMT1chr9140622981+ENST00000421905PPP1R37chr1945641771+2722860222721900
ENST00000334856EHMT1chr9140622981+ENST00000221462PPP1R37chr1945641771+3457860222733903
ENST00000460843EHMT1chr9140622981+ENST00000421905PPP1R37chr1945641771+2712850122711899
ENST00000460843EHMT1chr9140622981+ENST00000221462PPP1R37chr1945641771+3447850122723903

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
ENST00000462484ENST00000421905EHMT1chr9140622981+PPP1R37chr1945641772+0.021116520.9788835
ENST00000462484ENST00000221462EHMT1chr9140622981+PPP1R37chr1945641772+0.0127308690.98726916
ENST00000334856ENST00000421905EHMT1chr9140622981+PPP1R37chr1945641772+0.021116520.9788835
ENST00000334856ENST00000221462EHMT1chr9140622981+PPP1R37chr1945641772+0.0127308690.98726916
ENST00000460843ENST00000421905EHMT1chr9140622981+PPP1R37chr1945641772+0.0217497850.9782502
ENST00000460843ENST00000221462EHMT1chr9140622981+PPP1R37chr1945641772+0.0131818080.9868182
ENST00000462484ENST00000421905EHMT1chr9140622981+PPP1R37chr1945641771+0.021116520.9788835
ENST00000462484ENST00000221462EHMT1chr9140622981+PPP1R37chr1945641771+0.0127308690.98726916
ENST00000334856ENST00000421905EHMT1chr9140622981+PPP1R37chr1945641771+0.021116520.9788835
ENST00000334856ENST00000221462EHMT1chr9140622981+PPP1R37chr1945641771+0.0127308690.98726916
ENST00000460843ENST00000421905EHMT1chr9140622981+PPP1R37chr1945641771+0.0217497850.9782502
ENST00000460843ENST00000221462EHMT1chr9140622981+PPP1R37chr1945641771+0.0131818080.9868182

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 EHMT1-PPP1R37

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
EHMT1chr9140622981PPP1R37chr1945641771850279QNQCYMATTKSQTAQNVTVDEVIGAY
EHMT1chr9140622981PPP1R37chr1945641771860279QNQCYMATTKSQTAQNVTVDEVIGAY
EHMT1chr9140622981PPP1R37chr1945641772850279QNQCYMATTKSQTAQNVTVDEVIGAY
EHMT1chr9140622981PPP1R37chr1945641772860279QNQCYMATTKSQTAQNVTVDEVIGAY

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Potential FusionNeoAntigen Information of EHMT1-PPP1R37 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.
EHMT1-PPP1R37_140622981_45641771.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)
EHMT1-PPP1R37chr9140622981chr1945641771860HLA-B08:09MATTKSQTA0.97080.7643514
EHMT1-PPP1R37chr9140622981chr1945641771860HLA-B48:01SQTAQNVTV0.95740.85081019
EHMT1-PPP1R37chr9140622981chr1945641771860HLA-A02:21SQTAQNVTV0.91720.79651019
EHMT1-PPP1R37chr9140622981chr1945641771860HLA-B13:02SQTAQNVTV0.90120.9771019
EHMT1-PPP1R37chr9140622981chr1945641771860HLA-B13:01SQTAQNVTV0.77860.98841019
EHMT1-PPP1R37chr9140622981chr1945641771860HLA-B39:13SQTAQNVTV0.59420.98421019
EHMT1-PPP1R37chr9140622981chr1945641771860HLA-B52:01SQTAQNVTV0.09350.98711019
EHMT1-PPP1R37chr9140622981chr1945641771860HLA-B13:02KSQTAQNVTV0.58770.9789919
EHMT1-PPP1R37chr9140622981chr1945641771860HLA-B54:01MATTKSQTA0.99350.5281514
EHMT1-PPP1R37chr9140622981chr1945641771860HLA-A02:05SQTAQNVTV0.95780.63061019
EHMT1-PPP1R37chr9140622981chr1945641771860HLA-B78:01MATTKSQTA0.77150.8001514
EHMT1-PPP1R37chr9140622981chr1945641771860HLA-B48:03SQTAQNVTV0.67940.79871019
EHMT1-PPP1R37chr9140622981chr1945641771860HLA-B39:08SQTAQNVTV0.64360.92141019
EHMT1-PPP1R37chr9140622981chr1945641771860HLA-B39:05SQTAQNVTV0.55440.96111019
EHMT1-PPP1R37chr9140622981chr1945641771860HLA-A02:14SQTAQNVTV0.91840.74251019
EHMT1-PPP1R37chr9140622981chr1945641771860HLA-A02:06SQTAQNVTV0.91720.79651019
EHMT1-PPP1R37chr9140622981chr1945641771860HLA-B15:73SQTAQNVTV0.78410.98481019
EHMT1-PPP1R37chr9140622981chr1945641771860HLA-B78:02MATTKSQTA0.72380.81514
EHMT1-PPP1R37chr9140622981chr1945641771860HLA-B40:12SQTAQNVTV0.67940.79871019
EHMT1-PPP1R37chr9140622981chr1945641771860HLA-B40:49SQTAQNVTV0.66950.76871019
EHMT1-PPP1R37chr9140622981chr1945641771860HLA-B15:30SQTAQNVTV0.66250.97581019
EHMT1-PPP1R37chr9140622981chr1945641771860HLA-B40:21SQTAQNVTV0.6430.80931019
EHMT1-PPP1R37chr9140622981chr1945641771860HLA-B39:02SQTAQNVTV0.63450.98121019
EHMT1-PPP1R37chr9140622981chr1945641771860HLA-B39:11SQTAQNVTV0.57740.86631019

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Potential FusionNeoAntigen Information of EHMT1-PPP1R37 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.
EHMT1-PPP1R37_140622981_45641771.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)
EHMT1-PPP1R37chr9140622981chr1945641771860DRB1-1414NQCYMATTKSQTAQN116
EHMT1-PPP1R37chr9140622981chr1945641771860DRB1-1436NQCYMATTKSQTAQN116
EHMT1-PPP1R37chr9140622981chr1945641771860DRB1-1444NQCYMATTKSQTAQN116

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Fusion breakpoint peptide structures of EHMT1-PPP1R37

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
668ATTKSQTAQNVTVDEHMT1PPP1R37chr9140622981chr1945641771860

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of EHMT1-PPP1R37

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-B14:023BVN668ATTKSQTAQNVTVD-7.9962-8.1096
HLA-B14:023BVN668ATTKSQTAQNVTVD-5.70842-6.74372
HLA-B52:013W39668ATTKSQTAQNVTVD-6.83737-6.95077
HLA-B52:013W39668ATTKSQTAQNVTVD-4.4836-5.5189
HLA-A11:014UQ2668ATTKSQTAQNVTVD-10.0067-10.1201
HLA-A11:014UQ2668ATTKSQTAQNVTVD-9.03915-10.0745
HLA-A24:025HGA668ATTKSQTAQNVTVD-6.56204-6.67544
HLA-A24:025HGA668ATTKSQTAQNVTVD-5.42271-6.45801
HLA-B44:053DX8668ATTKSQTAQNVTVD-7.85648-8.89178
HLA-B44:053DX8668ATTKSQTAQNVTVD-5.3978-5.5112
HLA-A02:016TDR668ATTKSQTAQNVTVD-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of EHMT1-PPP1R37

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
EHMT1-PPP1R37chr9140622981chr19456417711019SQTAQNVTVCACAGACAGCCCAGAATGTGACCGTGG
EHMT1-PPP1R37chr9140622981chr1945641771514MATTKSQTATGGCCACCACAAAATCACAGACAGCCC
EHMT1-PPP1R37chr9140622981chr1945641771919KSQTAQNVTVAATCACAGACAGCCCAGAATGTGACCGTGG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
EHMT1-PPP1R37chr9140622981chr1945641771116NQCYMATTKSQTAQNACCAGTGCTACATGGCCACCACAAAATCACAGACAGCCCAGAATG

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Information of the samples that have these potential fusion neoantigens of EHMT1-PPP1R37

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
BLCAEHMT1-PPP1R37chr9140622981ENST00000334856chr1945641771ENST00000221462TCGA-H4-A2HO

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Potential target of CAR-T therapy development for EHMT1-PPP1R37

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 EHMT1-PPP1R37

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 EHMT1-PPP1R37

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