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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-GSR

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TRIM35-GSR
FusionPDB ID: 94090
FusionGDB2.0 ID: 94090
HgeneTgene
Gene symbol

TRIM35

GSR

Gene ID

23087

2936

Gene nametripartite motif containing 35glutathione-disulfide reductase
SynonymsHLS5|MAIRGR|GSRD|HEL-75|HEL-S-122m
Cytomap

8p21.2

8p12

Type of geneprotein-codingprotein-coding
Descriptiontripartite motif-containing protein 35hemopoietic lineage switch protein 5glutathione reductase, mitochondrialGRaseepididymis luminal protein 75epididymis secretory sperm binding protein Li 122mglutathione S-reductase
Modification date2020031320200313
UniProtAcc.

P00390

Main function of 5'-partner protein: FUNCTION: Maintains high levels of reduced glutathione in the cytosol.
Ensembl transtripts involved in fusion geneENST idsENST00000305364, ENST00000521253, 
ENST00000221130, ENST00000414019, 
ENST00000537535, ENST00000541648, 
ENST00000546342, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 5 X 5=1506 X 5 X 4=120
# samples 76
** MAII scorelog2(7/150*10)=-1.09953567355091
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(6/120*10)=-1
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

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

Fusion neoantigen context

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

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TRIM35(27151597)-GSR(30569605), # samples:1
Anticipated loss of major functional domain due to fusion event.TRIM35-GSR 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-GSR 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-GSR 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-GSR 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/chr8:27151597/chr8:30569605)
- 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 GSR (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)
ENST00000305364TRIM35chr827151597-ENST00000221130GSRchr830569605-3563846842108674
ENST00000305364TRIM35chr827151597-ENST00000414019GSRchr830569605-3562846842108674
ENST00000305364TRIM35chr827151597-ENST00000546342GSRchr830569605-2022846842021645
ENST00000305364TRIM35chr827151597-ENST00000537535GSRchr830569605-1863846841862592
ENST00000305364TRIM35chr827151597-ENST00000541648GSRchr830569605-1950846841949621
ENST00000521253TRIM35chr827151597-ENST00000221130GSRchr830569605-338666931931642
ENST00000521253TRIM35chr827151597-ENST00000414019GSRchr830569605-338566931931642
ENST00000521253TRIM35chr827151597-ENST00000546342GSRchr830569605-184566931844613
ENST00000521253TRIM35chr827151597-ENST00000537535GSRchr830569605-168666931685560
ENST00000521253TRIM35chr827151597-ENST00000541648GSRchr830569605-177366931772589

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
ENST00000305364ENST00000221130TRIM35chr827151597-GSRchr830569605-0.0015442310.99845576
ENST00000305364ENST00000414019TRIM35chr827151597-GSRchr830569605-0.0015597910.9984402
ENST00000305364ENST00000546342TRIM35chr827151597-GSRchr830569605-0.0044539540.995546
ENST00000305364ENST00000537535TRIM35chr827151597-GSRchr830569605-0.0053006710.99469936
ENST00000305364ENST00000541648TRIM35chr827151597-GSRchr830569605-0.0056270280.99437296
ENST00000521253ENST00000221130TRIM35chr827151597-GSRchr830569605-0.0011189670.99888104
ENST00000521253ENST00000414019TRIM35chr827151597-GSRchr830569605-0.0011318560.9988682
ENST00000521253ENST00000546342TRIM35chr827151597-GSRchr830569605-0.0036487770.99635124
ENST00000521253ENST00000537535TRIM35chr827151597-GSRchr830569605-0.0046323450.99536765
ENST00000521253ENST00000541648TRIM35chr827151597-GSRchr830569605-0.0045016140.9954984

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-GSR

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
TRIM35chr827151597GSRchr830569605669222QMEMKEDDVSFLMVNVGCVPKKVMWN
TRIM35chr827151597GSRchr830569605846254QMEMKEDDVSFLMVNVGCVPKKVMWN

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Potential FusionNeoAntigen Information of TRIM35-GSR 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-GSR_27151597_30569605.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-GSRchr827151597chr830569605846HLA-B41:01KEDDVSFLMV0.87240.8523414
TRIM35-GSRchr827151597chr830569605846HLA-B39:08KEDDVSFLMV0.83340.7441414
TRIM35-GSRchr827151597chr830569605846HLA-A68:02DVSFLMVNV0.9990.9292716
TRIM35-GSRchr827151597chr830569605846HLA-A69:01DVSFLMVNV0.99720.8998716
TRIM35-GSRchr827151597chr830569605846HLA-A02:03FLMVNVGCV0.99670.56091019

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Potential FusionNeoAntigen Information of TRIM35-GSR 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-GSR

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
1037DDVSFLMVNVGCVPTRIM35GSRchr827151597chr830569605846

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

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-B14:023BVN1037DDVSFLMVNVGCVP-6.01316-6.12656
HLA-B14:023BVN1037DDVSFLMVNVGCVP-3.92858-4.96388
HLA-B52:013W391037DDVSFLMVNVGCVP-5.92102-6.95632
HLA-B52:013W391037DDVSFLMVNVGCVP-4.84472-4.95812
HLA-A24:025HGA1037DDVSFLMVNVGCVP-8.26357-9.29887
HLA-A24:025HGA1037DDVSFLMVNVGCVP-7.03366-7.14706
HLA-B44:053DX81037DDVSFLMVNVGCVP-6.13971-6.25311
HLA-B44:053DX81037DDVSFLMVNVGCVP-5.20728-6.24258
HLA-B35:011A1N1037DDVSFLMVNVGCVP-7.19274-7.30614
HLA-B35:011A1N1037DDVSFLMVNVGCVP-4.13724-5.17254
HLA-A02:016TDR1037DDVSFLMVNVGCVP-5.28864-5.40204

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Vaccine Design for the FusionNeoAntigens of TRIM35-GSR

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-GSRchr827151597chr8305696051019FLMVNVGCVTTTCTCATGGTGAATGTTGGATGTGTA
TRIM35-GSRchr827151597chr830569605414KEDDVSFLMVAAGGAGGACGACGTTTCTTTTCTCATGGTG
TRIM35-GSRchr827151597chr830569605716DVSFLMVNVGACGTTTCTTTTCTCATGGTGAATGTT

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-GSR

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-GSRchr827151597ENST00000305364chr830569605ENST00000221130TCGA-BH-A0DG-01A

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

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 TRIM35-GSR

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-GSR

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