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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:DNM3-RFWD2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: DNM3-RFWD2
FusionPDB ID: 23675
FusionGDB2.0 ID: 23675
HgeneTgene
Gene symbol

DNM3

RFWD2

Gene ID

26052

64326

Gene namedynamin 3COP1 E3 ubiquitin ligase
SynonymsDyna IIICFAP78|FAP78|RFWD2|RNF200
Cytomap

1q24.3

1q25.1-q25.2

Type of geneprotein-codingprotein-coding
Descriptiondynamin-3T-dynamindynamin family memberdynamin, testicularE3 ubiquitin-protein ligase COP1E3 ubiquitin-protein ligase RFWD2RING finger protein 200RING-type E3 ubiquitin transferase RFWD2constitutive photomorphogenesis protein 1 homologconstitutive photomorphogenic protein 1putative ubiquitin ligase COP1ri
Modification date2020031320200313
UniProtAcc

Q9UQ16

Main function of 5'-partner protein: FUNCTION: Microtubule-associated force-producing protein involved in producing microtubule bundles and able to bind and hydrolyze GTP. Most probably involved in vesicular trafficking processes, in particular endocytosis (By similarity). {ECO:0000250}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000355305, ENST00000358155, 
ENST00000367731, ENST00000367733, 
ENST00000520906, 
ENST00000308769, 
ENST00000367669, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score9 X 7 X 5=31528 X 17 X 12=5712
# samples 927
** MAII scorelog2(9/315*10)=-1.8073549220576
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(27/5712*10)=-4.40296466697827
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: DNM3 [Title/Abstract] AND RFWD2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: DNM3 [Title/Abstract] AND RFWD2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)DNM3(171810957)-RFWD2(176015460), # samples:2
Anticipated loss of major functional domain due to fusion event.DNM3-RFWD2 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.
DNM3-RFWD2 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.
DNM3-RFWD2 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.
DNM3-RFWD2 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
TgeneRFWD2

GO:0010212

response to ionizing radiation

19805145



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/chr1:171810957/chr1:176015460)
- 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 DNM3 (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 RFWD2 (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)
ENST00000358155DNM3chr1171810957+ENST00000367669RFWD2chr1176015460-15783371521255367
ENST00000358155DNM3chr1171810957+ENST00000308769RFWD2chr1176015460-12563371521255368
ENST00000367733DNM3chr1171810957+ENST00000367669RFWD2chr1176015460-15613201351238367
ENST00000367733DNM3chr1171810957+ENST00000308769RFWD2chr1176015460-12393201351238367
ENST00000355305DNM3chr1171810957+ENST00000367669RFWD2chr1176015460-15593181331236367
ENST00000355305DNM3chr1171810957+ENST00000308769RFWD2chr1176015460-12373181331236368
ENST00000367731DNM3chr1171810957+ENST00000367669RFWD2chr1176015460-15593181331236367
ENST00000367731DNM3chr1171810957+ENST00000308769RFWD2chr1176015460-12373181331236368
ENST00000520906DNM3chr1171810957+ENST00000367669RFWD2chr1176015460-15302891041207367
ENST00000520906DNM3chr1171810957+ENST00000308769RFWD2chr1176015460-12082891041207368

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
ENST00000358155ENST00000367669DNM3chr1171810957+RFWD2chr1176015460-0.0012978730.99870217
ENST00000358155ENST00000308769DNM3chr1171810957+RFWD2chr1176015460-0.0031018530.9968982
ENST00000367733ENST00000367669DNM3chr1171810957+RFWD2chr1176015460-0.0013684470.99863154
ENST00000367733ENST00000308769DNM3chr1171810957+RFWD2chr1176015460-0.0033459480.99665403
ENST00000355305ENST00000367669DNM3chr1171810957+RFWD2chr1176015460-0.0013596910.99864036
ENST00000355305ENST00000308769DNM3chr1171810957+RFWD2chr1176015460-0.0033085160.99669147
ENST00000367731ENST00000367669DNM3chr1171810957+RFWD2chr1176015460-0.0013596910.99864036
ENST00000367731ENST00000308769DNM3chr1171810957+RFWD2chr1176015460-0.0033085160.99669147
ENST00000520906ENST00000367669DNM3chr1171810957+RFWD2chr1176015460-0.001131790.9988682
ENST00000520906ENST00000308769DNM3chr1171810957+RFWD2chr1176015460-0.0028393560.9971607

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 DNM3-RFWD2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
DNM3chr1171810957RFWD2chr117601546028961SAGKSSVLENFVGSIEFDRDCDYFAI
DNM3chr1171810957RFWD2chr117601546031861SAGKSSVLENFVGSIEFDRDCDYFAI
DNM3chr1171810957RFWD2chr117601546032061SAGKSSVLENFVGSIEFDRDCDYFAI
DNM3chr1171810957RFWD2chr117601546033761SAGKSSVLENFVGSIEFDRDCDYFAI

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Potential FusionNeoAntigen Information of DNM3-RFWD2 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.
DNM3-RFWD2_171810957_176015460.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)
DNM3-RFWD2chr1171810957chr1176015460318HLA-B18:01LENFVGSIEF0.98770.7613717
DNM3-RFWD2chr1171810957chr1176015460318HLA-C14:03NFVGSIEF0.91570.9338917
DNM3-RFWD2chr1171810957chr1176015460318HLA-C14:02NFVGSIEF0.91570.9338917
DNM3-RFWD2chr1171810957chr1176015460318HLA-B18:04ENFVGSIEF0.93420.7677817
DNM3-RFWD2chr1171810957chr1176015460318HLA-B35:20ENFVGSIEF0.89670.8944817
DNM3-RFWD2chr1171810957chr1176015460318HLA-B18:06ENFVGSIEF0.83790.7514817
DNM3-RFWD2chr1171810957chr1176015460318HLA-B18:07ENFVGSIEF0.82280.7101817
DNM3-RFWD2chr1171810957chr1176015460318HLA-B18:08ENFVGSIEF0.76480.6466817
DNM3-RFWD2chr1171810957chr1176015460318HLA-B18:03ENFVGSIEF0.76380.7326817
DNM3-RFWD2chr1171810957chr1176015460318HLA-B15:53LENFVGSIEF0.99610.7722717
DNM3-RFWD2chr1171810957chr1176015460318HLA-B18:08LENFVGSIEF0.98960.5842717
DNM3-RFWD2chr1171810957chr1176015460318HLA-B18:05LENFVGSIEF0.98770.7613717
DNM3-RFWD2chr1171810957chr1176015460318HLA-B18:11LENFVGSIEF0.96290.7423717
DNM3-RFWD2chr1171810957chr1176015460318HLA-B48:02LENFVGSIEF0.95730.8351717

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Potential FusionNeoAntigen Information of DNM3-RFWD2 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 DNM3-RFWD2

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
10067VLENFVGSIEFDRDDNM3RFWD2chr1171810957chr1176015460318

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of DNM3-RFWD2

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-B14:023BVN10067VLENFVGSIEFDRD-7.9962-8.1096
HLA-B14:023BVN10067VLENFVGSIEFDRD-5.70842-6.74372
HLA-B52:013W3910067VLENFVGSIEFDRD-6.83737-6.95077
HLA-B52:013W3910067VLENFVGSIEFDRD-4.4836-5.5189
HLA-A11:014UQ210067VLENFVGSIEFDRD-10.0067-10.1201
HLA-A11:014UQ210067VLENFVGSIEFDRD-9.03915-10.0745
HLA-A24:025HGA10067VLENFVGSIEFDRD-6.56204-6.67544
HLA-A24:025HGA10067VLENFVGSIEFDRD-5.42271-6.45801
HLA-B44:053DX810067VLENFVGSIEFDRD-7.85648-8.89178
HLA-B44:053DX810067VLENFVGSIEFDRD-5.3978-5.5112
HLA-B35:011A1N10067VLENFVGSIEFDRD-6.27422-6.38762
HLA-B35:011A1N10067VLENFVGSIEFDRD-5.27424-6.30954
HLA-A02:016TDR10067VLENFVGSIEFDRD-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of DNM3-RFWD2

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
DNM3-RFWD2chr1171810957chr1176015460717LENFVGSIEFCGAGAACTTCGTGGGCAGTATTGAATTTGA
DNM3-RFWD2chr1171810957chr1176015460817ENFVGSIEFGAACTTCGTGGGCAGTATTGAATTTGA
DNM3-RFWD2chr1171810957chr1176015460917NFVGSIEFCTTCGTGGGCAGTATTGAATTTGA

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 DNM3-RFWD2

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
HNSCDNM3-RFWD2chr1171810957ENST00000355305chr1176015460ENST00000308769TCGA-CQ-A4CI

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Potential target of CAR-T therapy development for DNM3-RFWD2

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 DNM3-RFWD2

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 DNM3-RFWD2

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