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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:TRIM35-CCDC25

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TRIM35-CCDC25
FusionPDB ID: 94088
FusionGDB2.0 ID: 94088
HgeneTgene
Gene symbol

TRIM35

CCDC25

Gene ID

23087

55246

Gene nametripartite motif containing 35coiled-coil domain containing 25
SynonymsHLS5|MAIR-
Cytomap

8p21.2

8p21.1

Type of geneprotein-codingprotein-coding
Descriptiontripartite motif-containing protein 35hemopoietic lineage switch protein 5coiled-coil domain-containing protein 25
Modification date2020031320200313
UniProtAcc.

Q86WR0

Main function of 5'-partner protein: FUNCTION: Transmembrane receptor that senses neutrophil extracellular traps (NETs) and triggers the ILK-PARVB pathway to enhance cell motility (PubMed:32528174). NETs are mainly composed of DNA fibers and are released by neutrophils to bind pathogens during inflammation (PubMed:32528174). Formation of NETs is also associated with cancer metastasis, NET-DNA acting as a chemotactic factor to attract cancer cells (PubMed:32528174). Specifically binds NETs on its extracellular region, in particular the 8-OHdG-enriched DNA present in NETs, and recruits ILK, initiating the ILK-PARVB cascade to induce cytoskeleton rearrangement and directional migration of cells (PubMed:32528174). In the context of cancer, promotes cancer metastasis by sensing NETs and promoting migration of tumor cells (PubMed:32528174). {ECO:0000269|PubMed:32528174}.
Ensembl transtripts involved in fusion geneENST idsENST00000305364, ENST00000521253, 
ENST00000522915, ENST00000539095, 
ENST00000356537, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 5 X 5=1504 X 3 X 3=36
# samples 74
** MAII scorelog2(7/150*10)=-1.09953567355091
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(4/36*10)=0.15200309344505
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: TRIM35 [Title/Abstract] AND CCDC25 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: TRIM35 [Title/Abstract] AND CCDC25 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TRIM35(27168318)-CCDC25(27610104), # samples:1
Anticipated loss of major functional domain due to fusion event.TRIM35-CCDC25 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.
TRIM35-CCDC25 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.
TRIM35-CCDC25 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.
TRIM35-CCDC25 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
HgeneTRIM35

GO:0043065

positive regulation of apoptotic process

14662771

HgeneTRIM35

GO:0045087

innate immune response

18248090

HgeneTRIM35

GO:0045930

negative regulation of mitotic cell cycle

14662771

HgeneTRIM35

GO:1902187

negative regulation of viral release from host cell

18248090



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/chr8:27168318/chr8:27610104)
- 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 TRIM35 (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 CCDC25 (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)
ENST00000305364TRIM35chr827168318-ENST00000356537CCDC25chr827610104-387651984977297
ENST00000521253TRIM35chr827168318-ENST00000356537CCDC25chr827610104-37954383896297

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
ENST00000305364ENST00000356537TRIM35chr827168318-CCDC25chr827610104-0.0005402170.9994598
ENST00000521253ENST00000356537TRIM35chr827168318-CCDC25chr827610104-0.0005228650.9994772

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 TRIM35-CCDC25

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
TRIM35chr827168318CCDC25chr827610104438143GHRVQPVKDTAHDFRGENIEDIPKEV
TRIM35chr827168318CCDC25chr827610104519143GHRVQPVKDTAHDFRGENIEDIPKEV

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Potential FusionNeoAntigen Information of TRIM35-CCDC25 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.
TRIM35-CCDC25_27168318_27610104.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)
TRIM35-CCDC25chr827168318chr827610104519HLA-B39:01AHDFRGENI0.9860.80611019
TRIM35-CCDC25chr827168318chr827610104519HLA-B38:01AHDFRGENI0.98120.94921019
TRIM35-CCDC25chr827168318chr827610104519HLA-B38:02AHDFRGENI0.98110.94471019
TRIM35-CCDC25chr827168318chr827610104519HLA-B15:10AHDFRGENI0.75990.61431019
TRIM35-CCDC25chr827168318chr827610104519HLA-B35:08QPVKDTAHDF0.85850.816414
TRIM35-CCDC25chr827168318chr827610104519HLA-B35:01QPVKDTAHDF0.8580.868414
TRIM35-CCDC25chr827168318chr827610104519HLA-B39:05AHDFRGENI0.97690.78851019
TRIM35-CCDC25chr827168318chr827610104519HLA-B14:03AHDFRGENI0.34480.74371019
TRIM35-CCDC25chr827168318chr827610104519HLA-C18:01AHDFRGENI0.99010.84641019
TRIM35-CCDC25chr827168318chr827610104519HLA-B38:05AHDFRGENI0.98120.94921019
TRIM35-CCDC25chr827168318chr827610104519HLA-B15:09AHDFRGENI0.84530.78291019
TRIM35-CCDC25chr827168318chr827610104519HLA-B39:11AHDFRGENI0.62950.75731019
TRIM35-CCDC25chr827168318chr827610104519HLA-B15:08QPVKDTAHDF0.91250.8351414
TRIM35-CCDC25chr827168318chr827610104519HLA-B35:43QPVKDTAHDF0.9010.8421414
TRIM35-CCDC25chr827168318chr827610104519HLA-B15:11QPVKDTAHDF0.88690.8457414
TRIM35-CCDC25chr827168318chr827610104519HLA-B35:23QPVKDTAHDF0.8620.8708414
TRIM35-CCDC25chr827168318chr827610104519HLA-B35:77QPVKDTAHDF0.8580.868414

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Potential FusionNeoAntigen Information of TRIM35-CCDC25 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 TRIM35-CCDC25

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
10030VKDTAHDFRGENIETRIM35CCDC25chr827168318chr827610104519

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of TRIM35-CCDC25

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-B14:023BVN10030VKDTAHDFRGENIE-7.9962-8.1096
HLA-B14:023BVN10030VKDTAHDFRGENIE-5.70842-6.74372
HLA-B52:013W3910030VKDTAHDFRGENIE-6.83737-6.95077
HLA-B52:013W3910030VKDTAHDFRGENIE-4.4836-5.5189
HLA-A11:014UQ210030VKDTAHDFRGENIE-10.0067-10.1201
HLA-A11:014UQ210030VKDTAHDFRGENIE-9.03915-10.0745
HLA-A24:025HGA10030VKDTAHDFRGENIE-6.56204-6.67544
HLA-A24:025HGA10030VKDTAHDFRGENIE-5.42271-6.45801
HLA-B44:053DX810030VKDTAHDFRGENIE-7.85648-8.89178
HLA-B44:053DX810030VKDTAHDFRGENIE-5.3978-5.5112
HLA-B35:011A1N10030VKDTAHDFRGENIE-6.27422-6.38762
HLA-B35:011A1N10030VKDTAHDFRGENIE-5.27424-6.30954
HLA-A02:016TDR10030VKDTAHDFRGENIE-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of TRIM35-CCDC25

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
TRIM35-CCDC25chr827168318chr8276101041019AHDFRGENIGACTTTCGGGGAGAGAATATAGAAGAC
TRIM35-CCDC25chr827168318chr827610104414QPVKDTAHDFGTGAAGGACACTGCCCACGACTTTCGGGGA

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 TRIM35-CCDC25

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
BRCATRIM35-CCDC25chr827168318ENST00000305364chr827610104ENST00000356537TCGA-A7-A26G-01A

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Potential target of CAR-T therapy development for TRIM35-CCDC25

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
TgeneCCDC25chr8:27168318chr8:27610104ENST000003565373967_830209.0TransmembraneHelical

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

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Related Drugs to TRIM35-CCDC25

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 TRIM35-CCDC25

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