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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:TRPC4AP-RAC1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TRPC4AP-RAC1
FusionPDB ID: 94359
FusionGDB2.0 ID: 94359
HgeneTgene
Gene symbol

TRPC4AP

RAC1

Gene ID

26133

6035

Gene nametransient receptor potential cation channel subfamily C member 4 associated proteinribonuclease A family member 1, pancreatic
SynonymsC20orf188|PPP1R158|TRRP4AP|TRUSSRAC1|RIB1|RNS1
Cytomap

20q11.22

14q11.2

Type of geneprotein-codingprotein-coding
Descriptionshort transient receptor potential channel 4-associated proteinTNF-receptor ubiquitous scaffolding/signaling proteinTRP4-associated proteinprotein phosphatase 1, regulatory subunit 158trpc4-associated proteintumor necrosis factor receptor-associated ribonuclease pancreaticHP-RNaseRIB-1RNase 1RNase ARNase upI-1ribonuclease 1ribonuclease A C1ribonuclease, RNase A family, 1 (pancreatic)
Modification date2020031320200313
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000252015, ENST00000432634, 
ENST00000451813, ENST00000539834, 
ENST00000488373, ENST00000348035, 
ENST00000356142, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score30 X 25 X 10=750017 X 10 X 5=850
# samples 3318
** MAII scorelog2(33/7500*10)=-4.50635266602479
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(18/850*10)=-2.23946593469539
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: TRPC4AP [Title/Abstract] AND RAC1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: TRPC4AP [Title/Abstract] AND RAC1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TRPC4AP(33680416)-RAC1(6439756), # samples:1
Anticipated loss of major functional domain due to fusion event.TRPC4AP-RAC1 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.
TRPC4AP-RAC1 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
HgeneTRPC4AP

GO:0006511

ubiquitin-dependent protein catabolic process

20551172

HgeneTRPC4AP

GO:0016567

protein ubiquitination

20551172

TgeneRAC1

GO:0051607

defense response to virus

9826755

TgeneRAC1

GO:0090501

RNA phosphodiester bond hydrolysis

9826755



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/chr20:33680416/chr7:6439756)
- 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 TRPC4AP (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 RAC1 (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)
ENST00000451813TRPC4APchr2033680416-ENST00000348035RAC1chr76439756+20791945547180
ENST00000451813TRPC4APchr2033680416-ENST00000356142RAC1chr76439756+6221945547180
ENST00000252015TRPC4APchr2033680416-ENST00000348035RAC1chr76439756+214325869611180
ENST00000252015TRPC4APchr2033680416-ENST00000356142RAC1chr76439756+68625869611180
ENST00000432634TRPC4APchr2033680416-ENST00000348035RAC1chr76439756+20791945547180
ENST00000432634TRPC4APchr2033680416-ENST00000356142RAC1chr76439756+6221945547180

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
ENST00000451813ENST00000348035TRPC4APchr2033680416-RAC1chr76439756+0.0110546360.9889453
ENST00000451813ENST00000356142TRPC4APchr2033680416-RAC1chr76439756+0.014708340.9852917
ENST00000252015ENST00000348035TRPC4APchr2033680416-RAC1chr76439756+0.0088180290.99118197
ENST00000252015ENST00000356142TRPC4APchr2033680416-RAC1chr76439756+0.0170669650.98293304
ENST00000432634ENST00000348035TRPC4APchr2033680416-RAC1chr76439756+0.0110546360.9889453
ENST00000432634ENST00000356142TRPC4APchr2033680416-RAC1chr76439756+0.014708340.9852917

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 TRPC4AP-RAC1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
TRPC4APchr2033680416RAC1chr7643975619463GQLTGRGLVRAVQDVFLICFSLVSPA
TRPC4APchr2033680416RAC1chr7643975625863GQLTGRGLVRAVQDVFLICFSLVSPA

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Potential FusionNeoAntigen Information of TRPC4AP-RAC1 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.
TRPC4AP-RAC1_33680416_6439756.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)
TRPC4AP-RAC1chr2033680416chr76439756258HLA-B15:01LVRAVQDVF0.99830.7924716
TRPC4AP-RAC1chr2033680416chr76439756258HLA-B27:07VRAVQDVFL0.99630.5034817
TRPC4AP-RAC1chr2033680416chr76439756258HLA-B58:01RAVQDVFLI0.9950.9682918
TRPC4AP-RAC1chr2033680416chr76439756258HLA-B15:25LVRAVQDVF0.98880.9143716
TRPC4AP-RAC1chr2033680416chr76439756258HLA-B15:16RAVQDVFLI0.98650.8867918
TRPC4AP-RAC1chr2033680416chr76439756258HLA-B15:02LVRAVQDVF0.98620.9288716
TRPC4AP-RAC1chr2033680416chr76439756258HLA-B57:03RAVQDVFLI0.96110.9759918
TRPC4AP-RAC1chr2033680416chr76439756258HLA-B38:01VRAVQDVFL0.94710.9387817
TRPC4AP-RAC1chr2033680416chr76439756258HLA-B38:02VRAVQDVFL0.92450.9436817
TRPC4AP-RAC1chr2033680416chr76439756258HLA-B13:02RAVQDVFLI0.72080.6724918
TRPC4AP-RAC1chr2033680416chr76439756258HLA-B52:01RAVQDVFLI0.38070.8291918
TRPC4AP-RAC1chr2033680416chr76439756258HLA-B57:01RAVQDVFLICF0.99950.9617920
TRPC4AP-RAC1chr2033680416chr76439756258HLA-B57:03RAVQDVFLICF0.99840.9482920
TRPC4AP-RAC1chr2033680416chr76439756258HLA-B58:01RAVQDVFLICF0.99790.8983920
TRPC4AP-RAC1chr2033680416chr76439756258HLA-B15:07LVRAVQDVF0.99790.5909716
TRPC4AP-RAC1chr2033680416chr76439756258HLA-C07:95VRAVQDVFL0.98510.6155817
TRPC4AP-RAC1chr2033680416chr76439756258HLA-C07:05VRAVQDVFL0.97730.9374817
TRPC4AP-RAC1chr2033680416chr76439756258HLA-C07:27VRAVQDVFL0.95830.9379817
TRPC4AP-RAC1chr2033680416chr76439756258HLA-C07:29VRAVQDVFL0.9360.9056817
TRPC4AP-RAC1chr2033680416chr76439756258HLA-C07:13VRAVQDVFL0.92130.9075817
TRPC4AP-RAC1chr2033680416chr76439756258HLA-B15:05LVRAVQDVF0.91890.8885716
TRPC4AP-RAC1chr2033680416chr76439756258HLA-C07:19VRAVQDVFL0.81450.6833817
TRPC4AP-RAC1chr2033680416chr76439756258HLA-C07:46VRAVQDVFL0.79920.8723817
TRPC4AP-RAC1chr2033680416chr76439756258HLA-B15:33LVRAVQDVF0.99830.7924716
TRPC4AP-RAC1chr2033680416chr76439756258HLA-B15:34LVRAVQDVF0.99830.7924716
TRPC4AP-RAC1chr2033680416chr76439756258HLA-B15:125LVRAVQDVF0.99830.7924716
TRPC4AP-RAC1chr2033680416chr76439756258HLA-B15:27LVRAVQDVF0.99820.7842716
TRPC4AP-RAC1chr2033680416chr76439756258HLA-B15:135LVRAVQDVF0.99820.8298716
TRPC4AP-RAC1chr2033680416chr76439756258HLA-B15:11LVRAVQDVF0.99810.7491716
TRPC4AP-RAC1chr2033680416chr76439756258HLA-B15:08LVRAVQDVF0.99790.7552716
TRPC4AP-RAC1chr2033680416chr76439756258HLA-B15:35LVRAVQDVF0.99760.7382716
TRPC4AP-RAC1chr2033680416chr76439756258HLA-B35:43LVRAVQDVF0.99760.774716
TRPC4AP-RAC1chr2033680416chr76439756258HLA-C15:02RAVQDVFLI0.99750.8836918
TRPC4AP-RAC1chr2033680416chr76439756258HLA-B15:24LVRAVQDVF0.9970.713716
TRPC4AP-RAC1chr2033680416chr76439756258HLA-C15:05RAVQDVFLI0.99620.8879918
TRPC4AP-RAC1chr2033680416chr76439756258HLA-B27:06VRAVQDVFL0.99610.6988817
TRPC4AP-RAC1chr2033680416chr76439756258HLA-B27:09VRAVQDVFL0.99440.7153817
TRPC4AP-RAC1chr2033680416chr76439756258HLA-B15:39LVRAVQDVF0.98760.711716
TRPC4AP-RAC1chr2033680416chr76439756258HLA-B15:50LVRAVQDVF0.98710.7062716
TRPC4AP-RAC1chr2033680416chr76439756258HLA-C07:01VRAVQDVFL0.98450.6042817
TRPC4AP-RAC1chr2033680416chr76439756258HLA-B15:13LVRAVQDVF0.96570.5639716
TRPC4AP-RAC1chr2033680416chr76439756258HLA-B38:05VRAVQDVFL0.94710.9387817
TRPC4AP-RAC1chr2033680416chr76439756258HLA-B15:12LVRAVQDVF0.89380.7282716
TRPC4AP-RAC1chr2033680416chr76439756258HLA-C07:22VRAVQDVFL0.81780.661817
TRPC4AP-RAC1chr2033680416chr76439756258HLA-C06:08VRAVQDVFL0.77670.9798817
TRPC4AP-RAC1chr2033680416chr76439756258HLA-C06:06VRAVQDVFL0.35660.992817
TRPC4AP-RAC1chr2033680416chr76439756258HLA-C06:17VRAVQDVFL0.04450.9888817
TRPC4AP-RAC1chr2033680416chr76439756258HLA-C06:02VRAVQDVFL0.04450.9888817
TRPC4AP-RAC1chr2033680416chr76439756258HLA-B57:10RAVQDVFLICF0.99950.9617920

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Potential FusionNeoAntigen Information of TRPC4AP-RAC1 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 TRPC4AP-RAC1

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
2970GLVRAVQDVFLICFTRPC4APRAC1chr2033680416chr76439756258

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of TRPC4AP-RAC1

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-B14:023BVN2970GLVRAVQDVFLICF-7.15543-7.26883
HLA-B14:023BVN2970GLVRAVQDVFLICF-4.77435-5.80965
HLA-B52:013W392970GLVRAVQDVFLICF-6.80875-6.92215
HLA-B52:013W392970GLVRAVQDVFLICF-4.20386-5.23916
HLA-A11:014UQ22970GLVRAVQDVFLICF-7.5194-8.5547
HLA-A11:014UQ22970GLVRAVQDVFLICF-6.9601-7.0735
HLA-A24:025HGA2970GLVRAVQDVFLICF-7.52403-7.63743
HLA-A24:025HGA2970GLVRAVQDVFLICF-5.82433-6.85963
HLA-B27:056PYJ2970GLVRAVQDVFLICF-3.28285-4.31815
HLA-B44:053DX82970GLVRAVQDVFLICF-5.91172-6.94702
HLA-B44:053DX82970GLVRAVQDVFLICF-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of TRPC4AP-RAC1

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
TRPC4AP-RAC1chr2033680416chr76439756716LVRAVQDVFCTGGTCCGGGCGGTGCAGGATGTGTTC
TRPC4AP-RAC1chr2033680416chr76439756817VRAVQDVFLGTCCGGGCGGTGCAGGATGTGTTCTTA
TRPC4AP-RAC1chr2033680416chr76439756918RAVQDVFLICGGGCGGTGCAGGATGTGTTCTTAATT
TRPC4AP-RAC1chr2033680416chr76439756920RAVQDVFLICFCGGGCGGTGCAGGATGTGTTCTTAATTTGCTTT

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 TRPC4AP-RAC1

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
OVTRPC4AP-RAC1chr2033680416ENST00000252015chr76439756ENST00000348035TCGA-25-1635

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Potential target of CAR-T therapy development for TRPC4AP-RAC1

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 TRPC4AP-RAC1

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 TRPC4AP-RAC1

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