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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:DNMT1-FDX1L

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: DNMT1-FDX1L
FusionPDB ID: 23695
FusionGDB2.0 ID: 23695
HgeneTgene
Gene symbol

DNMT1

FDX1L

Gene ID

1786

112812

Gene nameDNA methyltransferase 1ferredoxin 2
SynonymsADCADN|AIM|CXXC9|DNMT|HSN1E|MCMT|m.HsaIFDX1L|MEOAL
Cytomap

19p13.2

19p13.2

Type of geneprotein-codingprotein-coding
DescriptionDNA (cytosine-5)-methyltransferase 1CXXC-type zinc finger protein 9DNA (cytosine-5-)-methyltransferase 1DNA MTase HsaIDNA methyltransferase HsaIferredoxin-2, mitochondrialadrenodoxin-like protein, mitochondrialferredoxin 1 like
Modification date2020031320200313
UniProtAcc

P26358

Main function of 5'-partner protein: FUNCTION: Methylates CpG residues. Preferentially methylates hemimethylated DNA. Associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand, that is essential for epigenetic inheritance. Associates with chromatin during G2 and M phases to maintain DNA methylation independently of replication. It is responsible for maintaining methylation patterns established in development. DNA methylation is coordinated with methylation of histones. Mediates transcriptional repression by direct binding to HDAC2. In association with DNMT3B and via the recruitment of CTCFL/BORIS, involved in activation of BAG1 gene expression by modulating dimethylation of promoter histone H3 at H3K4 and H3K9. Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells (PubMed:24623306). Also required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (PubMed:24623306). Promotes tumor growth (PubMed:24623306). {ECO:0000269|PubMed:16357870, ECO:0000269|PubMed:18413740, ECO:0000269|PubMed:18754681, ECO:0000269|PubMed:24623306}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000340748, ENST00000359526, 
ENST00000540357, ENST00000589538, 
ENST00000492239, ENST00000494368, 
ENST00000393708, ENST00000541276, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score14 X 12 X 11=18486 X 3 X 5=90
# samples 177
** MAII scorelog2(17/1848*10)=-3.44235810527836
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(7/90*10)=-0.362570079384708
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: DNMT1 [Title/Abstract] AND FDX1L [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: DNMT1 [Title/Abstract] AND FDX1L [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)DNMT1(10283766)-FDX1L(10421616), # samples:1
DNMT1(10283766)-FDX1L(10426435), # samples:1
Anticipated loss of major functional domain due to fusion event.DNMT1-FDX1L 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.
DNMT1-FDX1L 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.
DNMT1-FDX1L 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.
DNMT1-FDX1L 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.
DNMT1-FDX1L seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
DNMT1-FDX1L seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF.
DNMT1-FDX1L seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
DNMT1-FDX1L seems lost the major protein functional domain in Hgene partner, which is a transcription factor due to the frame-shifted ORF.
DNMT1-FDX1L seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted ORF.
DNMT1-FDX1L seems lost the major protein functional domain in Tgene partner, which is a essential gene 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
HgeneDNMT1

GO:0010216

maintenance of DNA methylation

18754681|21745816



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/chr19:10283766/chr19:10421616)
- 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 DNMT1 (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 FDX1L (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)
ENST00000340748DNMT1chr1910283766-ENST00000541276FDX1Lchr1910421616-2592956441003319
ENST00000540357DNMT1chr1910283766-ENST00000541276FDX1Lchr1910421616-2536900180947255
ENST00000359526DNMT1chr1910283766-ENST00000541276FDX1Lchr1910421616-2584948180995271
ENST00000340748DNMT1chr1910283766-ENST00000541276FDX1Lchr1910426435-2754956441015323
ENST00000540357DNMT1chr1910283766-ENST00000541276FDX1Lchr1910426435-2698900180959259
ENST00000359526DNMT1chr1910283766-ENST00000541276FDX1Lchr1910426435-27469481801007275

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
ENST00000340748ENST00000541276DNMT1chr1910283766-FDX1Lchr1910421616-0.0285038520.97149616
ENST00000540357ENST00000541276DNMT1chr1910283766-FDX1Lchr1910421616-0.012095410.9879046
ENST00000359526ENST00000541276DNMT1chr1910283766-FDX1Lchr1910421616-0.0115858660.98841405
ENST00000340748ENST00000541276DNMT1chr1910283766-FDX1Lchr1910426435-0.0341340820.9658659
ENST00000540357ENST00000541276DNMT1chr1910283766-FDX1Lchr1910426435-0.0129326240.9870674
ENST00000359526ENST00000541276DNMT1chr1910283766-FDX1Lchr1910426435-0.0098579470.99014205

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 DNMT1-FDX1L

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
DNMT1chr1910283766FDX1Lchr1910421616900240GTRTEKEEERDEKGPVKPPWPAPPAM
DNMT1chr1910283766FDX1Lchr1910421616948256GTRTEKEEERDEKGPVKPPWPAPPAM
DNMT1chr1910283766FDX1Lchr1910421616956304GTRTEKEEERDEKGPVKPPWPAPPAM
DNMT1chr1910283766FDX1Lchr1910426435900240GTRTEKEEERDEKARARLERRTRAAR
DNMT1chr1910283766FDX1Lchr1910426435948256GTRTEKEEERDEKARARLERRTRAAR
DNMT1chr1910283766FDX1Lchr1910426435956304GTRTEKEEERDEKARARLERRTRAAR

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Potential FusionNeoAntigen Information of DNMT1-FDX1L 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.
DNMT1-FDX1L_10283766_10421616.msa
DNMT1-FDX1L_10283766_10426435.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)
DNMT1-FDX1Lchr1910283766chr1910421616956HLA-B45:01DEKGPVKPP0.98650.72461019
DNMT1-FDX1Lchr1910283766chr1910421616956HLA-B50:02DEKGPVKPP0.83470.5171019
DNMT1-FDX1Lchr1910283766chr1910421616956HLA-B44:03DEKGPVKPPW0.99370.96131020
DNMT1-FDX1Lchr1910283766chr1910421616956HLA-B44:02DEKGPVKPPW0.98490.53061020
DNMT1-FDX1Lchr1910283766chr1910421616956HLA-B44:05DEKGPVKPPW0.96190.67331020
DNMT1-FDX1Lchr1910283766chr1910421616956HLA-B55:01KGPVKPPWPA0.79290.78461222
DNMT1-FDX1Lchr1910283766chr1910421616956HLA-B56:01KGPVKPPWPA0.64020.89631222
DNMT1-FDX1Lchr1910283766chr1910421616956HLA-B44:08DEKGPVKPPW0.97930.61181020
DNMT1-FDX1Lchr1910283766chr1910421616956HLA-B44:13DEKGPVKPPW0.99370.96131020
DNMT1-FDX1Lchr1910283766chr1910421616956HLA-B44:26DEKGPVKPPW0.99370.96131020
DNMT1-FDX1Lchr1910283766chr1910421616956HLA-B44:07DEKGPVKPPW0.99370.96131020
DNMT1-FDX1Lchr1910283766chr1910421616956HLA-B44:22DEKGPVKPPW0.98490.53061020
DNMT1-FDX1Lchr1910283766chr1910421616956HLA-B18:03DEKGPVKPPW0.87890.85481020
DNMT1-FDX1Lchr1910283766chr1910421616956HLA-B55:02KGPVKPPWPA0.7210.89691222
DNMT1-FDX1Lchr1910283766chr1910426435956HLA-B45:01EERDEKARA0.99680.7816716
DNMT1-FDX1Lchr1910283766chr1910426435956HLA-B45:01KEEERDEKA0.98630.602514
DNMT1-FDX1Lchr1910283766chr1910426435956HLA-B50:02KEEERDEKA0.95750.5163514
DNMT1-FDX1Lchr1910283766chr1910426435956HLA-B41:01KEEERDEKA0.34680.7574514
DNMT1-FDX1Lchr1910283766chr1910426435956HLA-B45:01EEERDEKARA0.9870.753616
DNMT1-FDX1Lchr1910283766chr1910426435956HLA-B39:01ERDEKARARL0.98020.7874818
DNMT1-FDX1Lchr1910283766chr1910426435956HLA-B39:08RDEKARARL0.29090.7321918
DNMT1-FDX1Lchr1910283766chr1910426435956HLA-B39:09ERDEKARARL0.97460.5429818
DNMT1-FDX1Lchr1910283766chr1910426435956HLA-B39:12ERDEKARARL0.97260.7951818
DNMT1-FDX1Lchr1910283766chr1910426435956HLA-B14:03ERDEKARARL0.9190.8558818
DNMT1-FDX1Lchr1910283766chr1910426435956HLA-B18:03DEKARARL0.98550.94221018
DNMT1-FDX1Lchr1910283766chr1910426435956HLA-A30:01KARARLERR0.98680.80151221
DNMT1-FDX1Lchr1910283766chr1910426435956HLA-B39:31ERDEKARARL0.98110.7879818

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Potential FusionNeoAntigen Information of DNMT1-FDX1L 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 DNMT1-FDX1L

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
1650EEERDEKARARLERDNMT1FDX1Lchr1910283766chr1910426435956
File nameBPseqHgeneTgeneHchrHbpTchrTbpAAlen
1651EEERDEKGPVKPPWDNMT1FDX1Lchr1910283766chr1910421616956

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of DNMT1-FDX1L

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-B14:023BVN1650EEERDEKARARLER-7.9962-8.1096
HLA-B14:023BVN1650EEERDEKARARLER-5.70842-6.74372
HLA-B52:013W391650EEERDEKARARLER-6.83737-6.95077
HLA-B52:013W391650EEERDEKARARLER-4.4836-5.5189
HLA-A11:014UQ21650EEERDEKARARLER-10.0067-10.1201
HLA-A11:014UQ21650EEERDEKARARLER-9.03915-10.0745
HLA-A24:025HGA1650EEERDEKARARLER-6.56204-6.67544
HLA-A24:025HGA1650EEERDEKARARLER-5.42271-6.45801
HLA-B44:053DX81650EEERDEKARARLER-7.85648-8.89178
HLA-B44:053DX81650EEERDEKARARLER-5.3978-5.5112
HLA-A02:016TDR1650EEERDEKARARLER-3.37154-4.40684
HLA-B14:023BVN1651EEERDEKGPVKPPW-4.62424-5.65954
HLA-B14:023BVN1651EEERDEKGPVKPPW-4.1114-4.2248
HLA-B52:013W391651EEERDEKGPVKPPW-6.8001-6.9135
HLA-B52:013W391651EEERDEKGPVKPPW-6.46104-7.49634
HLA-A24:025HGA1651EEERDEKGPVKPPW-9.1447-9.2581
HLA-A24:025HGA1651EEERDEKGPVKPPW-6.01279-7.04809
HLA-B44:053DX81651EEERDEKGPVKPPW-5.02862-5.14202
HLA-B44:053DX81651EEERDEKGPVKPPW-4.60714-5.64244

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Vaccine Design for the FusionNeoAntigens of DNMT1-FDX1L

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
DNMT1-FDX1Lchr1910283766chr19104216161019DEKGPVKPPGATGAAAAAGGGCCTGTGAAGCCTCCC
DNMT1-FDX1Lchr1910283766chr19104216161020DEKGPVKPPWGATGAAAAAGGGCCTGTGAAGCCTCCCTGG
DNMT1-FDX1Lchr1910283766chr19104216161222KGPVKPPWPAAAAGGGCCTGTGAAGCCTCCCTGGCCTGCT
DNMT1-FDX1Lchr1910283766chr19104264351018DEKARARLGATGAAAAAGCTCGCGCCCGGCTG
DNMT1-FDX1Lchr1910283766chr19104264351221KARARLERRAAAGCTCGCGCCCGGCTGGAGAGGAGG
DNMT1-FDX1Lchr1910283766chr1910426435514KEEERDEKAAAGGAAGAAGAAAGAGATGAAAAAGCT
DNMT1-FDX1Lchr1910283766chr1910426435616EEERDEKARAGAAGAAGAAAGAGATGAAAAAGCTCGCGCC
DNMT1-FDX1Lchr1910283766chr1910426435716EERDEKARAGAAGAAAGAGATGAAAAAGCTCGCGCC
DNMT1-FDX1Lchr1910283766chr1910426435818ERDEKARARLGAAAGAGATGAAAAAGCTCGCGCCCGGCTG
DNMT1-FDX1Lchr1910283766chr1910426435918RDEKARARLAGAGATGAAAAAGCTCGCGCCCGGCTG

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 DNMT1-FDX1L

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
LIHCDNMT1-FDX1Lchr1910283766ENST00000340748chr1910421616ENST00000541276TCGA-DD-A3A5-01A
UVMDNMT1-FDX1Lchr1910283766ENST00000340748chr1910426435ENST00000541276TCGA-V4-A9EX-01A

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Potential target of CAR-T therapy development for DNMT1-FDX1L

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 DNMT1-FDX1L

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 DNMT1-FDX1L

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