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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:ELP2-MOCOS

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ELP2-MOCOS
FusionPDB ID: 26325
FusionGDB2.0 ID: 26325
HgeneTgene
Gene symbol

ELP2

MOCOS

Gene ID

55250

55034

Gene nameelongator acetyltransferase complex subunit 2molybdenum cofactor sulfurase
SynonymsMRT58|SHINC-2|STATIP1|StIPHMCS|MCS|MOS
Cytomap

18q12.2

18q12.2

Type of geneprotein-codingprotein-coding
Descriptionelongator complex protein 2STAT3-interacting protein 1elongation protein 2 homologelongator protein 2signal transducer and activator of transcription 3 interacting protein 1molybdenum cofactor sulfurase
Modification date2020031320200313
UniProtAcc

Q6IA86

Main function of 5'-partner protein: FUNCTION: Component of the RNA polymerase II elongator complex, a multiprotein complex associated with the RNA polymerase II (Pol II) holoenzyme, and which is involved in transcriptional elongation (PubMed:11714725, PubMed:11818576). The elongator complex catalyzes formation of carboxymethyluridine in the wobble base at position 34 in tRNAs (PubMed:29332244). {ECO:0000269|PubMed:11714725, ECO:0000269|PubMed:11818576, ECO:0000303|PubMed:29332244}.

Q96EN8

Main function of 5'-partner protein: FUNCTION: Sulfurates the molybdenum cofactor. Sulfation of molybdenum is essential for xanthine dehydrogenase (XDH) and aldehyde oxidase (ADO) enzymes in which molybdenum cofactor is liganded by 1 oxygen and 1 sulfur atom in active form. In vitro, the C-terminal domain is able to reduce N-hydroxylated prodrugs, such as benzamidoxime. {ECO:0000255|HAMAP-Rule:MF_03050, ECO:0000269|PubMed:16973608}.
Ensembl transtripts involved in fusion geneENST idsENST00000350494, ENST00000351393, 
ENST00000358232, ENST00000423854, 
ENST00000442325, ENST00000542824, 
ENST00000542050, 
ENST00000588132, 
ENST00000261326, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score8 X 10 X 6=4804 X 5 X 5=100
# samples 1210
** MAII scorelog2(12/480*10)=-2
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(10/100*10)=0
Fusion gene context

PubMed: ELP2 [Title/Abstract] AND MOCOS [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ELP2 [Title/Abstract] AND MOCOS [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ELP2(33713279)-MOCOS(33828885), # samples:1
ELP2(33710034)-MOCOS(33831122), # samples:1
ELP2(33726344)-MOCOS(33828885), # samples:1
MOCOS(33828963)-ELP2(33751010), # samples:1
MOCOS(33767644)-ELP2(33724902), # samples:1
MOCOS(33767644)-ELP2(33722789), # samples:1
Anticipated loss of major functional domain due to fusion event.ELP2-MOCOS 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.
ELP2-MOCOS 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.
MOCOS-ELP2 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.
MOCOS-ELP2 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.
ELP2-MOCOS seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF.
ELP2-MOCOS seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
ELP2-MOCOS seems lost the major protein functional domain in Tgene partner, which is a cell metabolism gene due to the frame-shifted 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


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/chr18:33713279/chr18:33828885)
- 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 ELP2 (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 MOCOS (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)
ENST00000358232ELP2chr1833713279+ENST00000261326MOCOSchr1833828885+445928063986307
ENST00000351393ELP2chr1833713279+ENST00000261326MOCOSchr1833828885+443926043966307
ENST00000442325ELP2chr1833713279+ENST00000261326MOCOSchr1833828885+443225336959307
ENST00000423854ELP2chr1833713279+ENST00000261326MOCOSchr1833828885+443125235958307
ENST00000350494ELP2chr1833713279+ENST00000261326MOCOSchr1833828885+441023114937307
ENST00000542824ELP2chr1833713279+ENST00000261326MOCOSchr1833828885+440622710933307

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
ENST00000358232ENST00000261326ELP2chr1833713279+MOCOSchr1833828885+0.0020257580.9979742
ENST00000351393ENST00000261326ELP2chr1833713279+MOCOSchr1833828885+0.0020669130.99793315
ENST00000442325ENST00000261326ELP2chr1833713279+MOCOSchr1833828885+0.0020545940.99794537
ENST00000423854ENST00000261326ELP2chr1833713279+MOCOSchr1833828885+0.0020559240.99794406
ENST00000350494ENST00000261326ELP2chr1833713279+MOCOSchr1833828885+0.0020540050.99794596
ENST00000542824ENST00000261326ELP2chr1833713279+MOCOSchr1833828885+0.0020347220.99796534

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 ELP2-MOCOS

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

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Potential FusionNeoAntigen Information of ELP2-MOCOS 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.

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)

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Potential FusionNeoAntigen Information of ELP2-MOCOS 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 ELP2-MOCOS

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.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ELP2-MOCOS

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

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Vaccine Design for the FusionNeoAntigens of ELP2-MOCOS

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

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 ELP2-MOCOS

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

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Potential target of CAR-T therapy development for ELP2-MOCOS

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 ELP2-MOCOS

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 ELP2-MOCOS

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