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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:FBXO31-ZNRF1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: FBXO31-ZNRF1
FusionPDB ID: 29795
FusionGDB2.0 ID: 29795
HgeneTgene
Gene symbol

FBXO31

ZNRF1

Gene ID

79791

84937

Gene nameF-box protein 31zinc and ring finger 1
SynonymsFBX14|FBXO14|Fbx31|MRT45|pp2386NIN283
Cytomap

16q24.2

16q23.1

Type of geneprotein-codingprotein-coding
DescriptionF-box only protein 31SCF ubiquitin ligase specificity factorputative breast cancer tumor-suppressorE3 ubiquitin-protein ligase ZNRF1RING-type E3 ubiquitin transferase ZNRF1nerve injury gene 283nerve injury-induced gene 283 proteinzinc and ring finger 1, E3 ubiquitin protein ligasezinc and ring finger protein 1zinc/RING finger protein 1
Modification date2020031320200313
UniProtAcc

Q5XUX0

Main function of 5'-partner protein: FUNCTION: Component of some SCF (SKP1-cullin-F-box) protein ligase complex that plays a central role in G1 arrest following DNA damage. Specifically recognizes phosphorylated cyclin-D1 (CCND1), promoting its ubiquitination and degradation by the proteasome, resulting in G1 arrest. May act as a tumor suppressor. {ECO:0000269|PubMed:16357137, ECO:0000269|PubMed:19412162}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000311635, ENST00000563956, 
ENST00000564320, ENST00000320619, 
ENST00000335325, ENST00000566250, 
ENST00000567962, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score4 X 4 X 4=647 X 7 X 6=294
# samples 69
** MAII scorelog2(6/64*10)=-0.0931094043914815
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(9/294*10)=-1.70781924850669
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: FBXO31 [Title/Abstract] AND ZNRF1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: FBXO31 [Title/Abstract] AND ZNRF1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)FBXO31(87393901)-ZNRF1(75127470), # samples:3
Anticipated loss of major functional domain due to fusion event.FBXO31-ZNRF1 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.
FBXO31-ZNRF1 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.
FBXO31-ZNRF1 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.
FBXO31-ZNRF1 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
HgeneFBXO31

GO:0006974

cellular response to DNA damage stimulus

19412162

HgeneFBXO31

GO:0031146

SCF-dependent proteasomal ubiquitin-dependent protein catabolic process

19412162



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/chr16:87393901/chr16:75127470)
- 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 FBXO31 (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 ZNRF1 (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)
ENST00000311635FBXO31chr1687393901-ENST00000335325ZNRF1chr1675127470+39794254684226
ENST00000311635FBXO31chr1687393901-ENST00000320619ZNRF1chr1675127470+18454254837277
ENST00000311635FBXO31chr1687393901-ENST00000566250ZNRF1chr1675127470+7434254630208
ENST00000311635FBXO31chr1687393901-ENST00000567962ZNRF1chr1675127470+9084254684226
ENST00000311635FBXO31chr1687393900-ENST00000335325ZNRF1chr1675127469+39794254684226
ENST00000311635FBXO31chr1687393900-ENST00000320619ZNRF1chr1675127469+18454254837277
ENST00000311635FBXO31chr1687393900-ENST00000566250ZNRF1chr1675127469+7434254630208
ENST00000311635FBXO31chr1687393900-ENST00000567962ZNRF1chr1675127469+9084254684226

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
ENST00000311635ENST00000335325FBXO31chr1687393901-ZNRF1chr1675127470+0.04911720.9508828
ENST00000311635ENST00000320619FBXO31chr1687393901-ZNRF1chr1675127470+0.096077430.9039226
ENST00000311635ENST00000566250FBXO31chr1687393901-ZNRF1chr1675127470+0.0297495560.9702505
ENST00000311635ENST00000567962FBXO31chr1687393901-ZNRF1chr1675127470+0.0250096060.9749904
ENST00000311635ENST00000335325FBXO31chr1687393900-ZNRF1chr1675127469+0.04911720.9508828
ENST00000311635ENST00000320619FBXO31chr1687393900-ZNRF1chr1675127469+0.096077430.9039226
ENST00000311635ENST00000566250FBXO31chr1687393900-ZNRF1chr1675127469+0.0297495560.9702505
ENST00000311635ENST00000567962FBXO31chr1687393900-ZNRF1chr1675127469+0.0250096060.9749904

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 FBXO31-ZNRF1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
FBXO31chr1687393900ZNRF1chr1675127469425141ITGVSCRDVYAKRFKCPICSKSVASD
FBXO31chr1687393901ZNRF1chr1675127470425141ITGVSCRDVYAKRFKCPICSKSVASD

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Potential FusionNeoAntigen Information of FBXO31-ZNRF1 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.
FBXO31-ZNRF1_87393900_75127469.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)
FBXO31-ZNRF1chr1687393900chr1675127469425HLA-B08:09DVYAKRFKC0.72250.7215716
FBXO31-ZNRF1chr1687393900chr1675127469425HLA-B27:05KRFKCPICSK0.99980.85231121
FBXO31-ZNRF1chr1687393900chr1675127469425HLA-B27:04KRFKCPICSK0.99730.75021121
FBXO31-ZNRF1chr1687393900chr1675127469425HLA-B27:14KRFKCPICS0.99660.79551120
FBXO31-ZNRF1chr1687393900chr1675127469425HLA-B27:14KRFKCPICSK0.99970.72471121
FBXO31-ZNRF1chr1687393900chr1675127469425HLA-B27:03KRFKCPICSK0.9960.86781121
FBXO31-ZNRF1chr1687393900chr1675127469425HLA-A30:01RFKCPICSK0.99460.78641221
FBXO31-ZNRF1chr1687393900chr1675127469425HLA-B27:10KRFKCPICSK0.99960.85241121
FBXO31-ZNRF1chr1687393900chr1675127469425HLA-B27:08KRFKCPICSK0.99950.72531121

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Potential FusionNeoAntigen Information of FBXO31-ZNRF1 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 FBXO31-ZNRF1

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
7755RDVYAKRFKCPICSFBXO31ZNRF1chr1687393900chr1675127469425

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of FBXO31-ZNRF1

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-B14:023BVN7755RDVYAKRFKCPICS-6.7759-6.8893
HLA-B14:023BVN7755RDVYAKRFKCPICS-4.69541-5.73071
HLA-B52:013W397755RDVYAKRFKCPICS-7.29079-7.40419
HLA-B52:013W397755RDVYAKRFKCPICS-4.68863-5.72393
HLA-A24:025HGA7755RDVYAKRFKCPICS-6.91369-7.94899
HLA-A24:025HGA7755RDVYAKRFKCPICS-5.33553-5.44893
HLA-B44:053DX87755RDVYAKRFKCPICS-8.15615-8.26955
HLA-B44:053DX87755RDVYAKRFKCPICS-4.08952-5.12482

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Vaccine Design for the FusionNeoAntigens of FBXO31-ZNRF1

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
FBXO31-ZNRF1chr1687393900chr16751274691120KRFKCPICSCGAAGCGTTTCAAGTGCCCCATTTGCT
FBXO31-ZNRF1chr1687393900chr16751274691121KRFKCPICSKCGAAGCGTTTCAAGTGCCCCATTTGCTCCA
FBXO31-ZNRF1chr1687393900chr16751274691221RFKCPICSKAGCGTTTCAAGTGCCCCATTTGCTCCA
FBXO31-ZNRF1chr1687393900chr1675127469716DVYAKRFKCGGGACGTCTATGCGAAGCGTTTCAAGT

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 FBXO31-ZNRF1

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
BLCAFBXO31-ZNRF1chr1687393900ENST00000311635chr1675127469ENST00000320619TCGA-E5-A4TZ

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Potential target of CAR-T therapy development for FBXO31-ZNRF1

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 FBXO31-ZNRF1

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 FBXO31-ZNRF1

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