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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:C9orf85-FXN

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: C9orf85-FXN
FusionPDB ID: 12149
FusionGDB2.0 ID: 12149
HgeneTgene
Gene symbol

C9orf85

FXN

Gene ID

138241

2395

Gene namechromosome 9 open reading frame 85frataxin
Synonyms-CyaY|FA|FARR|FRDA|X25
Cytomap

9q21.13

9q21.11

Type of geneprotein-codingprotein-coding
Descriptionuncharacterized protein C9orf85frataxin, mitochondrialFriedreich ataxia protein
Modification date2020031320200315
UniProtAcc

Q96MD7

Main function of 5'-partner protein:

Q16595

Main function of 5'-partner protein: FUNCTION: Promotes the biosynthesis of heme and assembly and repair of iron-sulfur clusters by delivering Fe(2+) to proteins involved in these pathways. May play a role in the protection against iron-catalyzed oxidative stress through its ability to catalyze the oxidation of Fe(2+) to Fe(3+); the oligomeric form but not the monomeric form has in vitro ferroxidase activity. May be able to store large amounts of iron in the form of a ferrihydrite mineral by oligomerization; however, the physiological relevance is unsure as reports are conflicting and the function has only been shown using heterologous overexpression systems. Modulates the RNA-binding activity of ACO1. {ECO:0000269|PubMed:12785837, ECO:0000269|PubMed:15247478, ECO:0000269|PubMed:15641778, ECO:0000269|PubMed:16239244, ECO:0000269|PubMed:16608849, ECO:0000269|PubMed:20053667}.
Ensembl transtripts involved in fusion geneENST idsENST00000334731, ENST00000377031, 
ENST00000486911, 
ENST00000377270, 
ENST00000396364, ENST00000396366, 
ENST00000498653, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score7 X 5 X 3=1058 X 8 X 7=448
# samples 710
** MAII scorelog2(7/105*10)=-0.584962500721156
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(10/448*10)=-2.16349873228288
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: C9orf85 [Title/Abstract] AND FXN [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: C9orf85 [Title/Abstract] AND FXN [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)C9orf85(74526752)-FXN(71679854), # samples:2
Anticipated loss of major functional domain due to fusion event.C9orf85-FXN 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.
C9orf85-FXN 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
TgeneFXN

GO:0010722

regulation of ferrochelatase activity

15123683

TgeneFXN

GO:0016226

iron-sulfur cluster assembly

29491838

TgeneFXN

GO:0016540

protein autoprocessing

12785837

TgeneFXN

GO:0018283

iron incorporation into metallo-sulfur cluster

12785837

TgeneFXN

GO:0051349

positive regulation of lyase activity

20053667

TgeneFXN

GO:0070301

cellular response to hydrogen peroxide

15641778



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/chr9:74526752/chr9:71679854)
- 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 C9orf85 (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 FXN (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)
ENST00000334731C9orf85chr974526752+ENST00000396364FXNchr971679854+668292285195
ENST00000334731C9orf85chr974526752+ENST00000377270FXNchr971679854+1992292178540120
ENST00000334731C9orf85chr974526752+ENST00000396366FXNchr971679854+809292178498106
ENST00000334731C9orf85chr974526752+ENST00000498653FXNchr971679854+884292178540120
ENST00000377031C9orf85chr974526752+ENST00000396364FXNchr971679854+668292285195
ENST00000377031C9orf85chr974526752+ENST00000377270FXNchr971679854+1992292178540120
ENST00000377031C9orf85chr974526752+ENST00000396366FXNchr971679854+809292178498106
ENST00000377031C9orf85chr974526752+ENST00000498653FXNchr971679854+884292178540120
ENST00000486911C9orf85chr974526752+ENST00000396364FXNchr971679854+5521766230781
ENST00000486911C9orf85chr974526752+ENST00000377270FXNchr971679854+187617662424120
ENST00000486911C9orf85chr974526752+ENST00000396366FXNchr971679854+69317662382106
ENST00000486911C9orf85chr974526752+ENST00000498653FXNchr971679854+76817662424120

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
ENST00000334731ENST00000396364C9orf85chr974526752+FXNchr971679854+0.52413580.47586417
ENST00000334731ENST00000377270C9orf85chr974526752+FXNchr971679854+0.05308240.94691765
ENST00000334731ENST00000396366C9orf85chr974526752+FXNchr971679854+0.087476910.91252315
ENST00000334731ENST00000498653C9orf85chr974526752+FXNchr971679854+0.0232348050.9767652
ENST00000377031ENST00000396364C9orf85chr974526752+FXNchr971679854+0.52413580.47586417
ENST00000377031ENST00000377270C9orf85chr974526752+FXNchr971679854+0.05308240.94691765
ENST00000377031ENST00000396366C9orf85chr974526752+FXNchr971679854+0.087476910.91252315
ENST00000377031ENST00000498653C9orf85chr974526752+FXNchr971679854+0.0232348050.9767652
ENST00000486911ENST00000396364C9orf85chr974526752+FXNchr971679854+0.239947470.76005256
ENST00000486911ENST00000377270C9orf85chr974526752+FXNchr971679854+0.0287590720.97124094
ENST00000486911ENST00000396366C9orf85chr974526752+FXNchr971679854+0.0547094530.9452906
ENST00000486911ENST00000498653C9orf85chr974526752+FXNchr971679854+0.0151203220.9848797

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 C9orf85-FXN

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
C9orf85chr974526752FXNchr97167985417638FKNDKFDKSVQTKSGVLTVKLGGDLG
C9orf85chr974526752FXNchr97167985429238FKNDKFDKSVQTKSGVLTVKLGGDLG

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Potential FusionNeoAntigen Information of C9orf85-FXN 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.
C9orf85-FXN_74526752_71679854.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)
C9orf85-FXNchr974526752chr971679854292HLA-A30:08QTKSGVLTV0.9860.55271019
C9orf85-FXNchr974526752chr971679854292HLA-B57:03KSGVLTVKL0.9830.98781221
C9orf85-FXNchr974526752chr971679854292HLA-B15:16QTKSGVLTV0.86650.94251019
C9orf85-FXNchr974526752chr971679854292HLA-B13:02QTKSGVLTV0.54640.89231019
C9orf85-FXNchr974526752chr971679854292HLA-A30:08QTKSGVLTVK0.99370.65531020
C9orf85-FXNchr974526752chr971679854292HLA-B13:02VQTKSGVLTV0.63990.8095919
C9orf85-FXNchr974526752chr971679854292HLA-C15:04QTKSGVLTV0.99930.91821019
C9orf85-FXNchr974526752chr971679854292HLA-C15:06QTKSGVLTV0.99890.90711019
C9orf85-FXNchr974526752chr971679854292HLA-C12:04QTKSGVLTV0.99770.98421019
C9orf85-FXNchr974526752chr971679854292HLA-C06:03QTKSGVLTV0.99740.98561019
C9orf85-FXNchr974526752chr971679854292HLA-C12:12QTKSGVLTV0.99080.92291019
C9orf85-FXNchr974526752chr971679854292HLA-C02:06QTKSGVLTV0.80380.9491019
C9orf85-FXNchr974526752chr971679854292HLA-B15:04VQTKSGVLTV0.83280.7711919
C9orf85-FXNchr974526752chr971679854292HLA-C15:02QTKSGVLTV0.99930.87911019
C9orf85-FXNchr974526752chr971679854292HLA-C15:09QTKSGVLTV0.99930.91821019
C9orf85-FXNchr974526752chr971679854292HLA-C15:05QTKSGVLTV0.99920.80081019
C9orf85-FXNchr974526752chr971679854292HLA-C15:05KSGVLTVKL0.99630.90971221
C9orf85-FXNchr974526752chr971679854292HLA-C15:02KSGVLTVKL0.99610.89881221
C9orf85-FXNchr974526752chr971679854292HLA-C12:03QTKSGVLTV0.98860.97081019
C9orf85-FXNchr974526752chr971679854292HLA-A30:01QTKSGVLTV0.98720.75621019
C9orf85-FXNchr974526752chr971679854292HLA-C16:02QTKSGVLTV0.94080.98251019
C9orf85-FXNchr974526752chr971679854292HLA-B57:02KSGVLTVKL0.92280.94841221
C9orf85-FXNchr974526752chr971679854292HLA-A69:01QTKSGVLTV0.80010.56691019
C9orf85-FXNchr974526752chr971679854292HLA-B08:12SVQTKSGVL0.67710.6886817
C9orf85-FXNchr974526752chr971679854292HLA-A30:01QTKSGVLTVK0.99260.82781020

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Potential FusionNeoAntigen Information of C9orf85-FXN 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 C9orf85-FXN

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
1191DKSVQTKSGVLTVKC9orf85FXNchr974526752chr971679854292

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of C9orf85-FXN

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-B53:011A1O1191DKSVQTKSGVLTVK-1.54455-2.57985
HLA-B51:011E281191DKSVQTKSGVLTVK-3.9567-4.992
HLA-B51:011E281191DKSVQTKSGVLTVK-2.78017-2.89357
HLA-B57:032BVO1191DKSVQTKSGVLTVK-2.28399-2.39739
HLA-A03:012XPG1191DKSVQTKSGVLTVK-5.29375-6.32905
HLA-A03:012XPG1191DKSVQTKSGVLTVK-5.13376-5.24716
HLA-B14:023BVN1191DKSVQTKSGVLTVK-5.94457-6.05797
HLA-B14:023BVN1191DKSVQTKSGVLTVK-4.02623-5.06153
HLA-B27:093CZF1191DKSVQTKSGVLTVK1.938620.90332
HLA-B52:013W391191DKSVQTKSGVLTVK-4.85197-4.96537
HLA-B52:013W391191DKSVQTKSGVLTVK-3.54046-4.57576
HLA-B18:014JQV1191DKSVQTKSGVLTVK-2.48822-2.60162
HLA-B18:014JQV1191DKSVQTKSGVLTVK-1.14207-2.17737
HLA-A11:014UQ21191DKSVQTKSGVLTVK-7.94504-8.05844
HLA-A11:014UQ21191DKSVQTKSGVLTVK-6.28371-7.31901
HLA-A24:025HGA1191DKSVQTKSGVLTVK-5.26524-5.37864
HLA-A24:025HGA1191DKSVQTKSGVLTVK-5.08104-6.11634
HLA-B57:015VUD1191DKSVQTKSGVLTVK-1.4053-2.4406
HLA-C08:026JTP1191DKSVQTKSGVLTVK-3.55917-3.67257
HLA-C08:026JTP1191DKSVQTKSGVLTVK-2.30839-3.34369
HLA-B27:056PYJ1191DKSVQTKSGVLTVK-3.69179-4.72709
HLA-B27:056PYJ1191DKSVQTKSGVLTVK-2.46172-2.57512
HLA-B27:036PZ51191DKSVQTKSGVLTVK-2.34314-3.37844
HLA-B27:036PZ51191DKSVQTKSGVLTVK-1.78038-1.89378
HLA-B44:053DX81191DKSVQTKSGVLTVK-5.34386-5.45726
HLA-B44:053DX81191DKSVQTKSGVLTVK-3.58277-4.61807
HLA-B44:021M6O1191DKSVQTKSGVLTVK-2.22341-2.33681
HLA-B44:021M6O1191DKSVQTKSGVLTVK-1.22324-2.25854
HLA-A02:016TDR1191DKSVQTKSGVLTVK-5.40572-5.51912
HLA-A02:016TDR1191DKSVQTKSGVLTVK-3.93841-4.97371

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Vaccine Design for the FusionNeoAntigens of C9orf85-FXN

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
C9orf85-FXNchr974526752chr9716798541019QTKSGVLTVCAGACCAAGAGTGGTGTCTTAACTGTC
C9orf85-FXNchr974526752chr9716798541020QTKSGVLTVKCAGACCAAGAGTGGTGTCTTAACTGTCAAA
C9orf85-FXNchr974526752chr9716798541221KSGVLTVKLAAGAGTGGTGTCTTAACTGTCAAACTG
C9orf85-FXNchr974526752chr971679854817SVQTKSGVLAGTGTGCAGACCAAGAGTGGTGTCTTA
C9orf85-FXNchr974526752chr971679854919VQTKSGVLTVGTGCAGACCAAGAGTGGTGTCTTAACTGTC

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 C9orf85-FXN

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
SKCMC9orf85-FXNchr974526752ENST00000334731chr971679854ENST00000377270TCGA-FS-A1ZP-06A

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Potential target of CAR-T therapy development for C9orf85-FXN

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 C9orf85-FXN

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 C9orf85-FXN

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