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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:NCOA3-ACTR5

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NCOA3-ACTR5
FusionPDB ID: 57729
FusionGDB2.0 ID: 57729
HgeneTgene
Gene symbol

NCOA3

ACTR5

Gene ID

8202

79913

Gene namenuclear receptor coactivator 3actin related protein 5
SynonymsACTR|AIB-1|AIB1|CAGH16|CTG26|KAT13B|RAC3|SRC-3|SRC3|TNRC14|TNRC16|TRAM-1|bHLHe42|pCIPArp5|INO80M
Cytomap

20q13.12

20q11.23

Type of geneprotein-codingprotein-coding
Descriptionnuclear receptor coactivator 3CBP-interacting proteinamplified in breast cancer 1 proteinclass E basic helix-loop-helix protein 42receptor-associated coactivator 3steroid receptor coactivator protein 3thyroid hormone receptor activator molecule 1actin-related protein 5ARP5 actin related protein 5 homologINO80 complex subunit MhARP5sarcoma antigen NY-SAR-16
Modification date2020031320200313
UniProtAcc

Q9Y6Q9

Main function of 5'-partner protein: FUNCTION: Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Plays a central role in creating a multisubunit coactivator complex, which probably acts via remodeling of chromatin. Involved in the coactivation of different nuclear receptors, such as for steroids (GR and ER), retinoids (RARs and RXRs), thyroid hormone (TRs), vitamin D3 (VDR) and prostanoids (PPARs). Displays histone acetyltransferase activity. Also involved in the coactivation of the NF-kappa-B pathway via its interaction with the NFKB1 subunit.

Q9H9F9

Main function of 5'-partner protein: FUNCTION: Proposed core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair. Involved in DNA double-strand break repair and UV-damage excision repair. {ECO:0000269|PubMed:19014934, ECO:0000269|PubMed:20855601}.
Ensembl transtripts involved in fusion geneENST idsENST00000497292, ENST00000341724, 
ENST00000371997, ENST00000371998, 
ENST00000372004, 
ENST00000243903, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score27 X 14 X 11=41584 X 3 X 3=36
# samples 354
** MAII scorelog2(35/4158*10)=-3.57046293102604
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(4/36*10)=0.15200309344505
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: NCOA3 [Title/Abstract] AND ACTR5 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: NCOA3 [Title/Abstract] AND ACTR5 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NCOA3(46256767)-ACTR5(37383599), # samples:1
Anticipated loss of major functional domain due to fusion event.NCOA3-ACTR5 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.
NCOA3-ACTR5 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.
NCOA3-ACTR5 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.
NCOA3-ACTR5 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
HgeneNCOA3

GO:0045944

positive regulation of transcription by RNA polymerase II

9267036

HgeneNCOA3

GO:0071392

cellular response to estradiol stimulus

15831516



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/chr20:46256767/chr20:37383599)
- 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 NCOA3 (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 ACTR5 (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)
ENST00000341724NCOA3chr2046256767+ENST00000243903ACTR5chr2037383599+250810842612132623
ENST00000372004NCOA3chr2046256767+ENST00000243903ACTR5chr2037383599+246310392162087623
ENST00000371998NCOA3chr2046256767+ENST00000243903ACTR5chr2037383599+243810141912062623
ENST00000371997NCOA3chr2046256767+ENST00000243903ACTR5chr2037383599+242410001772048623

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
ENST00000341724ENST00000243903NCOA3chr2046256767+ACTR5chr2037383599+0.0019429470.99805707
ENST00000372004ENST00000243903NCOA3chr2046256767+ACTR5chr2037383599+0.0019892630.9980108
ENST00000371998ENST00000243903NCOA3chr2046256767+ACTR5chr2037383599+0.0018696860.9981304
ENST00000371997ENST00000243903NCOA3chr2046256767+ACTR5chr2037383599+0.0018966840.99810326

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 NCOA3-ACTR5

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
NCOA3chr2046256767ACTR5chr20373835991000274SNPESFITRHDLSELHKWRCPDYYEN
NCOA3chr2046256767ACTR5chr20373835991014274SNPESFITRHDLSELHKWRCPDYYEN
NCOA3chr2046256767ACTR5chr20373835991039274SNPESFITRHDLSELHKWRCPDYYEN
NCOA3chr2046256767ACTR5chr20373835991084274SNPESFITRHDLSELHKWRCPDYYEN

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Potential FusionNeoAntigen Information of NCOA3-ACTR5 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.
NCOA3-ACTR5_46256767_37383599.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)
NCOA3-ACTR5chr2046256767chr20373835991084HLA-B39:01TRHDLSEL0.99970.8829715
NCOA3-ACTR5chr2046256767chr20373835991084HLA-B14:02TRHDLSEL0.99930.7068715
NCOA3-ACTR5chr2046256767chr20373835991084HLA-B14:01TRHDLSEL0.99930.7068715
NCOA3-ACTR5chr2046256767chr20373835991084HLA-B15:10TRHDLSEL0.99750.5535715
NCOA3-ACTR5chr2046256767chr20373835991084HLA-B15:37TRHDLSEL0.98660.5025715
NCOA3-ACTR5chr2046256767chr20373835991084HLA-B44:03HDLSELHKW0.99610.9768918
NCOA3-ACTR5chr2046256767chr20373835991084HLA-B58:02HDLSELHKW0.98610.9369918
NCOA3-ACTR5chr2046256767chr20373835991084HLA-B44:05HDLSELHKW0.98560.6052918
NCOA3-ACTR5chr2046256767chr20373835991084HLA-B45:01SELHKWRCP0.97820.93361221
NCOA3-ACTR5chr2046256767chr20373835991084HLA-B15:17ITRHDLSEL0.96420.7484615
NCOA3-ACTR5chr2046256767chr20373835991084HLA-B15:16ITRHDLSEL0.95790.6635615
NCOA3-ACTR5chr2046256767chr20373835991084HLA-B27:05TRHDLSELHK0.99930.8136717
NCOA3-ACTR5chr2046256767chr20373835991084HLA-B38:01RHDLSELHKW0.68390.933818
NCOA3-ACTR5chr2046256767chr20373835991084HLA-B38:02RHDLSELHKW0.65960.9168818
NCOA3-ACTR5chr2046256767chr20373835991084HLA-B39:12TRHDLSEL0.99960.8845715
NCOA3-ACTR5chr2046256767chr20373835991084HLA-B14:03TRHDLSEL0.96070.8417715
NCOA3-ACTR5chr2046256767chr20373835991084HLA-C12:16TRHDLSEL0.88120.934715
NCOA3-ACTR5chr2046256767chr20373835991084HLA-C03:08ITRHDLSEL0.99730.8058615
NCOA3-ACTR5chr2046256767chr20373835991084HLA-C15:06ITRHDLSEL0.99650.8813615
NCOA3-ACTR5chr2046256767chr20373835991084HLA-C12:12ITRHDLSEL0.99610.9067615
NCOA3-ACTR5chr2046256767chr20373835991084HLA-B27:14TRHDLSELH0.99430.6154716
NCOA3-ACTR5chr2046256767chr20373835991084HLA-B44:08HDLSELHKW0.99180.5867918
NCOA3-ACTR5chr2046256767chr20373835991084HLA-B44:10HDLSELHKW0.52810.6502918
NCOA3-ACTR5chr2046256767chr20373835991084HLA-B27:14TRHDLSELHK0.99880.7246717
NCOA3-ACTR5chr2046256767chr20373835991084HLA-B44:08RHDLSELHKW0.87040.7059818
NCOA3-ACTR5chr2046256767chr20373835991084HLA-B39:31TRHDLSEL0.99970.8826715
NCOA3-ACTR5chr2046256767chr20373835991084HLA-B15:13DLSELHKW0.99170.68031018
NCOA3-ACTR5chr2046256767chr20373835991084HLA-C06:02TRHDLSEL0.83520.9879715
NCOA3-ACTR5chr2046256767chr20373835991084HLA-C06:17TRHDLSEL0.83520.9879715
NCOA3-ACTR5chr2046256767chr20373835991084HLA-B27:08TRHDLSELH0.99670.5817716
NCOA3-ACTR5chr2046256767chr20373835991084HLA-B44:13HDLSELHKW0.99610.9768918
NCOA3-ACTR5chr2046256767chr20373835991084HLA-B44:07HDLSELHKW0.99610.9768918
NCOA3-ACTR5chr2046256767chr20373835991084HLA-B44:26HDLSELHKW0.99610.9768918
NCOA3-ACTR5chr2046256767chr20373835991084HLA-C03:05ITRHDLSEL0.9890.8415615
NCOA3-ACTR5chr2046256767chr20373835991084HLA-B07:13ITRHDLSEL0.94630.8283615
NCOA3-ACTR5chr2046256767chr20373835991084HLA-B27:10TRHDLSELHK0.9990.7863717
NCOA3-ACTR5chr2046256767chr20373835991084HLA-B38:05RHDLSELHKW0.68390.933818

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Potential FusionNeoAntigen Information of NCOA3-ACTR5 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.
NCOA3-ACTR5_46256767_37383599.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)
NCOA3-ACTR5chr2046256767chr20373835991084DRB1-0803PESFITRHDLSELHK217
NCOA3-ACTR5chr2046256767chr20373835991084DRB1-0814PESFITRHDLSELHK217
NCOA3-ACTR5chr2046256767chr20373835991084DRB1-0823PESFITRHDLSELHK217
NCOA3-ACTR5chr2046256767chr20373835991084DRB1-0827PESFITRHDLSELHK217
NCOA3-ACTR5chr2046256767chr20373835991084DRB1-0833PESFITRHDLSELHK217
NCOA3-ACTR5chr2046256767chr20373835991084DRB1-0835PESFITRHDLSELHK217
NCOA3-ACTR5chr2046256767chr20373835991084DRB1-0836PESFITRHDLSELHK217
NCOA3-ACTR5chr2046256767chr20373835991084DRB1-0838PESFITRHDLSELHK217

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Fusion breakpoint peptide structures of NCOA3-ACTR5

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
4037ITRHDLSELHKWRCNCOA3ACTR5chr2046256767chr20373835991084

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of NCOA3-ACTR5

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-B14:023BVN4037ITRHDLSELHKWRC-7.15543-7.26883
HLA-B14:023BVN4037ITRHDLSELHKWRC-4.77435-5.80965
HLA-B52:013W394037ITRHDLSELHKWRC-6.80875-6.92215
HLA-B52:013W394037ITRHDLSELHKWRC-4.20386-5.23916
HLA-A11:014UQ24037ITRHDLSELHKWRC-7.5194-8.5547
HLA-A11:014UQ24037ITRHDLSELHKWRC-6.9601-7.0735
HLA-A24:025HGA4037ITRHDLSELHKWRC-7.52403-7.63743
HLA-A24:025HGA4037ITRHDLSELHKWRC-5.82433-6.85963
HLA-B27:056PYJ4037ITRHDLSELHKWRC-3.28285-4.31815
HLA-B44:053DX84037ITRHDLSELHKWRC-5.91172-6.94702
HLA-B44:053DX84037ITRHDLSELHKWRC-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of NCOA3-ACTR5

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
NCOA3-ACTR5chr2046256767chr20373835991018DLSELHKWATCTTTCAGAATTACACAAATGGC
NCOA3-ACTR5chr2046256767chr20373835991221SELHKWRCPCAGAATTACACAAATGGCGGTGTCCTG
NCOA3-ACTR5chr2046256767chr2037383599615ITRHDLSELTTACCAGACATGATCTTTCAGAATTAC
NCOA3-ACTR5chr2046256767chr2037383599715TRHDLSELCCAGACATGATCTTTCAGAATTAC
NCOA3-ACTR5chr2046256767chr2037383599716TRHDLSELHCCAGACATGATCTTTCAGAATTACACA
NCOA3-ACTR5chr2046256767chr2037383599717TRHDLSELHKCCAGACATGATCTTTCAGAATTACACAAAT
NCOA3-ACTR5chr2046256767chr2037383599818RHDLSELHKWGACATGATCTTTCAGAATTACACAAATGGC
NCOA3-ACTR5chr2046256767chr2037383599918HDLSELHKWATGATCTTTCAGAATTACACAAATGGC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
NCOA3-ACTR5chr2046256767chr2037383599217PESFITRHDLSELHKCTGAGAGCTTTATTACCAGACATGATCTTTCAGAATTACACAAAT

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Information of the samples that have these potential fusion neoantigens of NCOA3-ACTR5

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
BRCANCOA3-ACTR5chr2046256767ENST00000341724chr2037383599ENST00000243903TCGA-GI-A2C9

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Potential target of CAR-T therapy development for NCOA3-ACTR5

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 NCOA3-ACTR5

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 NCOA3-ACTR5

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