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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:MED15-AHRR

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: MED15-AHRR
FusionPDB ID: 52605
FusionGDB2.0 ID: 52605
HgeneTgene
Gene symbol

MED15

AHRR

Gene ID

51586

57491

Gene namemediator complex subunit 15aryl-hydrocarbon receptor repressor
SynonymsARC105|CAG7A|CTG7A|PCQAP|TIG-1|TIG1|TNRC7AHH|AHHR|bHLHe77
Cytomap

22q11.21

5p15.33

Type of geneprotein-codingprotein-coding
Descriptionmediator of RNA polymerase II transcription subunit 15CTG repeat protein 7aPC2 (positive cofactor 2, multiprotein complex) glutamine/Q-rich-associated proteinPC2 glutamine/Q-rich-associated proteinPC2-glutamine-rich-associated proteinTPA inducible gearyl hydrocarbon receptor repressorahR repressoraryl hydrocarbon hydroxylase regulatorclass E basic helix-loop-helix protein 77dioxin receptor repressor
Modification date2020031320200322
UniProtAcc

Q96RN5

Main function of 5'-partner protein: FUNCTION: Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. Required for cholesterol-dependent gene regulation. Positively regulates the Nodal signaling pathway. {ECO:0000269|PubMed:12167862, ECO:0000269|PubMed:16630888, ECO:0000269|PubMed:16799563}.

A9YTQ3

Main function of 5'-partner protein: FUNCTION: Mediates dioxin toxicity and is involved in regulation of cell growth and differentiation. Represses the transcription activity of AHR by competing with this transcription factor for heterodimer formation with the ARNT and subsequently binding to the xenobiotic response element (XRE) sequence present in the promoter regulatory region of variety of genes. Represses CYP1A1 by binding the XRE sequence and recruiting ANKRA2, HDAC4 and/or HDAC5. Autoregulates its expression by associating with its own XRE site. {ECO:0000269|PubMed:17890447, ECO:0000269|PubMed:18172554}.
Ensembl transtripts involved in fusion geneENST idsENST00000263205, ENST00000292733, 
ENST00000406969, ENST00000541476, 
ENST00000382974, ENST00000425759, 
ENST00000478831, ENST00000542773, 
ENST00000506456, ENST00000512529, 
ENST00000515206, ENST00000316418, 
ENST00000505113, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score17 X 11 X 9=16837 X 6 X 4=168
# samples 209
** MAII scorelog2(20/1683*10)=-3.07296327155522
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(9/168*10)=-0.900464326449086
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: MED15 [Title/Abstract] AND AHRR [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: MED15 [Title/Abstract] AND AHRR [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MED15(20909435)-AHRR(376725), # samples:3
Anticipated loss of major functional domain due to fusion event.MED15-AHRR 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.
MED15-AHRR 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.
MED15-AHRR 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.
MED15-AHRR 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


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/chr22:20909435/chr5:376725)
- 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 MED15 (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 AHRR (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)
ENST00000292733MED15chr2220909435+ENST00000505113AHRRchr5376725+2401528772377766
ENST00000292733MED15chr2220909435+ENST00000316418AHRRchr5376725+5889528772431784
ENST00000263205MED15chr2220909435+ENST00000505113AHRRchr5376725+2393520692369766
ENST00000263205MED15chr2220909435+ENST00000316418AHRRchr5376725+5881520692423784
ENST00000406969MED15chr2220909435+ENST00000505113AHRRchr5376725+237450122350782
ENST00000406969MED15chr2220909435+ENST00000316418AHRRchr5376725+586250122404800
ENST00000541476MED15chr2220909435+ENST00000505113AHRRchr5376725+26497764032625740
ENST00000541476MED15chr2220909435+ENST00000316418AHRRchr5376725+61377764032679758

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
ENST00000292733ENST00000505113MED15chr2220909435+AHRRchr5376725+0.054147460.9458525
ENST00000292733ENST00000316418MED15chr2220909435+AHRRchr5376725+0.0157280560.98427194
ENST00000263205ENST00000505113MED15chr2220909435+AHRRchr5376725+0.0539479070.9460521
ENST00000263205ENST00000316418MED15chr2220909435+AHRRchr5376725+0.0157312170.9842688
ENST00000406969ENST00000505113MED15chr2220909435+AHRRchr5376725+0.069441340.9305586
ENST00000406969ENST00000316418MED15chr2220909435+AHRRchr5376725+0.0278500430.97214997
ENST00000541476ENST00000505113MED15chr2220909435+AHRRchr5376725+0.0563300030.94367
ENST00000541476ENST00000316418MED15chr2220909435+AHRRchr5376725+0.0255907960.9744092

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 MED15-AHRR

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
MED15chr2220909435AHRRchr5376725501106VSDPMNALQSLTGGPAAGAAGIGMPP
MED15chr2220909435AHRRchr537672552090VSDPMNALQSLTGGPAAGAAGIGMPP
MED15chr2220909435AHRRchr537672552890VSDPMNALQSLTGGPAAGAAGIGMPP
MED15chr2220909435AHRRchr537672577664VSDPMNALQSLTGGPAAGAAGIGMPP

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Potential FusionNeoAntigen Information of MED15-AHRR 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 MED15-AHRR 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.
MED15-AHRR_20909435_376725.msa

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)
MED15-AHRRchr2220909435chr5376725520DRB1-0101MNALQSLTGGPAAGA419
MED15-AHRRchr2220909435chr5376725520DRB1-0102MNALQSLTGGPAAGA419
MED15-AHRRchr2220909435chr5376725520DRB1-0102PMNALQSLTGGPAAG318
MED15-AHRRchr2220909435chr5376725520DRB1-0102NALQSLTGGPAAGAA520
MED15-AHRRchr2220909435chr5376725520DRB1-0105MNALQSLTGGPAAGA419
MED15-AHRRchr2220909435chr5376725520DRB1-0107MNALQSLTGGPAAGA419
MED15-AHRRchr2220909435chr5376725520DRB1-0119MNALQSLTGGPAAGA419
MED15-AHRRchr2220909435chr5376725520DRB1-0123MNALQSLTGGPAAGA419
MED15-AHRRchr2220909435chr5376725520DRB1-0123PMNALQSLTGGPAAG318
MED15-AHRRchr2220909435chr5376725520DRB1-0123NALQSLTGGPAAGAA520
MED15-AHRRchr2220909435chr5376725520DRB1-0123SDPMNALQSLTGGPA116
MED15-AHRRchr2220909435chr5376725520DRB1-0125MNALQSLTGGPAAGA419
MED15-AHRRchr2220909435chr5376725520DRB1-0127MNALQSLTGGPAAGA419
MED15-AHRRchr2220909435chr5376725520DRB1-0131MNALQSLTGGPAAGA419
MED15-AHRRchr2220909435chr5376725520DRB1-0415SDPMNALQSLTGGPA116
MED15-AHRRchr2220909435chr5376725520DRB1-0415VSDPMNALQSLTGGP015
MED15-AHRRchr2220909435chr5376725520DRB1-0436SDPMNALQSLTGGPA116
MED15-AHRRchr2220909435chr5376725520DRB1-0436VSDPMNALQSLTGGP015
MED15-AHRRchr2220909435chr5376725520DRB1-0440SDPMNALQSLTGGPA116
MED15-AHRRchr2220909435chr5376725520DRB1-0442SDPMNALQSLTGGPA116
MED15-AHRRchr2220909435chr5376725520DRB1-0453SDPMNALQSLTGGPA116
MED15-AHRRchr2220909435chr5376725520DRB1-0455SDPMNALQSLTGGPA116
MED15-AHRRchr2220909435chr5376725520DRB1-0458SDPMNALQSLTGGPA116
MED15-AHRRchr2220909435chr5376725520DRB1-0468SDPMNALQSLTGGPA116
MED15-AHRRchr2220909435chr5376725520DRB1-0470SDPMNALQSLTGGPA116
MED15-AHRRchr2220909435chr5376725520DRB1-0479SDPMNALQSLTGGPA116
MED15-AHRRchr2220909435chr5376725520DRB1-1002SDPMNALQSLTGGPA116

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Fusion breakpoint peptide structures of MED15-AHRR

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 MED15-AHRR

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 MED15-AHRR

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
MED15-AHRRchr2220909435chr5376725015VSDPMNALQSLTGGPCTCACAGCATGGCTGTCGTGTCTACGGCAACTCCACAGATCGTGC
MED15-AHRRchr2220909435chr5376725116SDPMNALQSLTGGPAACAGCATGGCTGTCGTGTCTACGGCAACTCCACAGATCGTGCAGG
MED15-AHRRchr2220909435chr5376725318PMNALQSLTGGPAAGTGGCTGTCGTGTCTACGGCAACTCCACAGATCGTGCAGGAGCAGA
MED15-AHRRchr2220909435chr5376725419MNALQSLTGGPAAGACTGTCGTGTCTACGGCAACTCCACAGATCGTGCAGGAGCAGAGCT
MED15-AHRRchr2220909435chr5376725520NALQSLTGGPAAGAATCGTGTCTACGGCAACTCCACAGATCGTGCAGGAGCAGAGCTCAC

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Information of the samples that have these potential fusion neoantigens of MED15-AHRR

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 MED15-AHRR

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 MED15-AHRR

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 MED15-AHRR

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