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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:NOP58-ACTL6A

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NOP58-ACTL6A
FusionPDB ID: 59650
FusionGDB2.0 ID: 59650
HgeneTgene
Gene symbol

NOP58

ACTL6A

Gene ID

51602

86

Gene nameNOP58 ribonucleoproteinactin like 6A
SynonymsHSPC120|NOP5|NOP5/NOP58ACTL6|ARPN-BETA|Arp4|BAF53A|INO80K
Cytomap

2q33.1

3q26.33

Type of geneprotein-codingprotein-coding
Descriptionnucleolar protein 58NOP58 ribonucleoprotein homolognucleolar protein 5nucleolar protein NOP5/NOP58actin-like protein 6A53 kDa BRG1-associated factor ABAF complex 53 kDa subunitBAF53BRG1-associated factor 53AINO80 complex subunit Kactin-related protein 4actin-related protein Baf53aarpNbetahArpN beta
Modification date2020031320200315
UniProtAcc

Q9Y2X3

Main function of 5'-partner protein: FUNCTION: Required for 60S ribosomal subunit biogenesis (By similarity). Core component of box C/D small nucleolar ribonucleoprotein (snoRNP) particles. Required for the biogenesis of box C/D snoRNAs such as U3, U8 and U14 snoRNAs. {ECO:0000250, ECO:0000269|PubMed:15574333, ECO:0000269|PubMed:17636026, ECO:0000269|PubMed:19620283}.

O96019

Main function of 5'-partner protein: FUNCTION: Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Required for maximal ATPase activity of SMARCA4/BRG1/BAF190A and for association of the SMARCA4/BRG1/BAF190A containing remodeling complex BAF with chromatin/nuclear matrix. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and is required for the proliferation of neural progenitors. During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (By similarity). Component of the NuA4 histone acetyltransferase (HAT) complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage. Putative core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair. {ECO:0000250|UniProtKB:Q9Z2N8, ECO:0000269|PubMed:14966270, ECO:0000269|PubMed:29374058, ECO:0000303|PubMed:15196461, ECO:0000303|PubMed:22952240, ECO:0000303|PubMed:26601204}.
Ensembl transtripts involved in fusion geneENST idsENST00000264279, ENST00000467734, 
ENST00000467615, ENST00000392662, 
ENST00000429709, ENST00000450518, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score9 X 9 X 6=4867 X 7 X 3=147
# samples 107
** MAII scorelog2(10/486*10)=-2.28095631383106
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(7/147*10)=-1.0703893278914
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: NOP58 [Title/Abstract] AND ACTL6A [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: NOP58 [Title/Abstract] AND ACTL6A [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NOP58(203157626)-ACTL6A(179291156), # samples:1
Anticipated loss of major functional domain due to fusion event.NOP58-ACTL6A 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.
NOP58-ACTL6A 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
TgeneACTL6A

GO:0006338

chromatin remodeling

11726552

TgeneACTL6A

GO:0043967

histone H4 acetylation

14966270

TgeneACTL6A

GO:0043968

histone H2A acetylation

14966270



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/chr2:203157626/chr3:179291156)
- 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 NOP58 (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 ACTL6A (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)
ENST00000264279NOP58chr2203157626+ENST00000429709ACTL6Achr3179291156+254411332262145639
ENST00000264279NOP58chr2203157626+ENST00000450518ACTL6Achr3179291156+254311332262145639
ENST00000264279NOP58chr2203157626+ENST00000392662ACTL6Achr3179291156+253411332262145639

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
ENST00000264279ENST00000429709NOP58chr2203157626+ACTL6Achr3179291156+0.001300060.9986999
ENST00000264279ENST00000450518NOP58chr2203157626+ACTL6Achr3179291156+0.0012960010.99870396
ENST00000264279ENST00000392662NOP58chr2203157626+ACTL6Achr3179291156+0.0013187040.99868125

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 NOP58-ACTL6A

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
NOP58chr2203157626ACTL6Achr31792911561133302VGELVGARLIAHAVEDWDSFQAILDH

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Potential FusionNeoAntigen Information of NOP58-ACTL6A 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.
NOP58-ACTL6A_203157626_179291156.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)
NOP58-ACTL6Achr2203157626chr31792911561133HLA-B35:08HAVEDWDSF0.99650.8441120
NOP58-ACTL6Achr2203157626chr31792911561133HLA-B35:01HAVEDWDSF0.99290.86051120
NOP58-ACTL6Achr2203157626chr31792911561133HLA-B35:05HAVEDWDSF0.97490.67261120
NOP58-ACTL6Achr2203157626chr31792911561133HLA-B35:03HAVEDWDSF0.95540.88391120
NOP58-ACTL6Achr2203157626chr31792911561133HLA-B35:02HAVEDWDSF0.75990.94681120
NOP58-ACTL6Achr2203157626chr31792911561133HLA-B35:04HAVEDWDSF0.75990.94681120
NOP58-ACTL6Achr2203157626chr31792911561133HLA-A32:13RLIAHAVEDW0.98010.9503717
NOP58-ACTL6Achr2203157626chr31792911561133HLA-B38:02AHAVEDWDSF0.96690.83341020
NOP58-ACTL6Achr2203157626chr31792911561133HLA-B38:01AHAVEDWDSF0.96050.85981020
NOP58-ACTL6Achr2203157626chr31792911561133HLA-B15:31HAVEDWDSF0.99340.8481120
NOP58-ACTL6Achr2203157626chr31792911561133HLA-B15:21HAVEDWDSF0.9920.87541120
NOP58-ACTL6Achr2203157626chr31792911561133HLA-B35:12HAVEDWDSF0.75990.94681120
NOP58-ACTL6Achr2203157626chr31792911561133HLA-C03:14HAVEDWDSF0.75930.95931120
NOP58-ACTL6Achr2203157626chr31792911561133HLA-C03:02HAVEDWDSF0.99530.97041120
NOP58-ACTL6Achr2203157626chr31792911561133HLA-B35:77HAVEDWDSF0.99290.86051120
NOP58-ACTL6Achr2203157626chr31792911561133HLA-B35:23HAVEDWDSF0.99220.89431120
NOP58-ACTL6Achr2203157626chr31792911561133HLA-B35:20HAVEDWDSF0.99210.88941120
NOP58-ACTL6Achr2203157626chr31792911561133HLA-B35:11HAVEDWDSF0.99180.86571120
NOP58-ACTL6Achr2203157626chr31792911561133HLA-B15:13HAVEDWDSF0.97980.89711120
NOP58-ACTL6Achr2203157626chr31792911561133HLA-B35:30HAVEDWDSF0.97780.78861120
NOP58-ACTL6Achr2203157626chr31792911561133HLA-B35:17HAVEDWDSF0.97780.78861120
NOP58-ACTL6Achr2203157626chr31792911561133HLA-B35:13HAVEDWDSF0.93210.88961120
NOP58-ACTL6Achr2203157626chr31792911561133HLA-A25:01HAVEDWDSF0.92930.73981120
NOP58-ACTL6Achr2203157626chr31792911561133HLA-B15:11HAVEDWDSF0.91390.80681120
NOP58-ACTL6Achr2203157626chr31792911561133HLA-B15:08HAVEDWDSF0.91230.80091120
NOP58-ACTL6Achr2203157626chr31792911561133HLA-B35:24HAVEDWDSF0.9020.8561120
NOP58-ACTL6Achr2203157626chr31792911561133HLA-B35:43HAVEDWDSF0.88290.79881120
NOP58-ACTL6Achr2203157626chr31792911561133HLA-C12:02HAVEDWDSF0.79050.94511120
NOP58-ACTL6Achr2203157626chr31792911561133HLA-C03:06HAVEDWDSF0.78710.98911120
NOP58-ACTL6Achr2203157626chr31792911561133HLA-B35:09HAVEDWDSF0.75990.94681120
NOP58-ACTL6Achr2203157626chr31792911561133HLA-B15:24RLIAHAVEDW0.99860.889717
NOP58-ACTL6Achr2203157626chr31792911561133HLA-A32:01RLIAHAVEDW0.9940.9706717
NOP58-ACTL6Achr2203157626chr31792911561133HLA-B38:05AHAVEDWDSF0.96050.85981020
NOP58-ACTL6Achr2203157626chr31792911561133HLA-B39:11AHAVEDWDSF0.93410.69741020

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Potential FusionNeoAntigen Information of NOP58-ACTL6A 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 NOP58-ACTL6A

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
552ARLIAHAVEDWDSFNOP58ACTL6Achr2203157626chr31792911561133

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of NOP58-ACTL6A

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-B14:023BVN552ARLIAHAVEDWDSF-7.15543-7.26883
HLA-B14:023BVN552ARLIAHAVEDWDSF-4.77435-5.80965
HLA-B52:013W39552ARLIAHAVEDWDSF-6.80875-6.92215
HLA-B52:013W39552ARLIAHAVEDWDSF-4.20386-5.23916
HLA-A11:014UQ2552ARLIAHAVEDWDSF-7.5194-8.5547
HLA-A11:014UQ2552ARLIAHAVEDWDSF-6.9601-7.0735
HLA-A24:025HGA552ARLIAHAVEDWDSF-7.52403-7.63743
HLA-A24:025HGA552ARLIAHAVEDWDSF-5.82433-6.85963
HLA-B27:056PYJ552ARLIAHAVEDWDSF-3.28285-4.31815
HLA-B44:053DX8552ARLIAHAVEDWDSF-5.91172-6.94702
HLA-B44:053DX8552ARLIAHAVEDWDSF-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of NOP58-ACTL6A

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
NOP58-ACTL6Achr2203157626chr31792911561020AHAVEDWDSFCTCATGCAGTTGAAGACTGGGATAGTTTCC
NOP58-ACTL6Achr2203157626chr31792911561120HAVEDWDSFATGCAGTTGAAGACTGGGATAGTTTCC
NOP58-ACTL6Achr2203157626chr3179291156717RLIAHAVEDWGGCTTATTGCTCATGCAGTTGAAGACTGGG

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 NOP58-ACTL6A

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
ESCANOP58-ACTL6Achr2203157626ENST00000264279chr3179291156ENST00000392662TCGA-VR-AA7D

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Potential target of CAR-T therapy development for NOP58-ACTL6A

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 NOP58-ACTL6A

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 NOP58-ACTL6A

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