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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:NAA15-PAPSS1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NAA15-PAPSS1
FusionPDB ID: 56946
FusionGDB2.0 ID: 56946
HgeneTgene
Gene symbol

NAA15

PAPSS1

Gene ID

80155

9061

Gene nameN-alpha-acetyltransferase 15, NatA auxiliary subunit3'-phosphoadenosine 5'-phosphosulfate synthase 1
SynonymsGa19|MRD50|NARG1|NAT1P|NATH|TBDN|TBDN100ATPSK1|PAPSS|SK1
Cytomap

4q31.1

4q25

Type of geneprotein-codingprotein-coding
DescriptionN-alpha-acetyltransferase 15, NatA auxiliary subunitN-terminal acetyltransferaseNMDA receptor regulated 1NMDA receptor-regulated protein 1gastric cancer antigen Ga19protein tubedown-1transcriptional coactivator tubedown-100tubedown-1bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 13-prime-phosphoadenosine 5-prime-phosphosulfate synthase 1PAPS synthase 1PAPSS 1SK 1adenylyl-sulfate kinasesulfate adenylyltransferasesulfurylase kinase 1
Modification date2020031320200313
UniProtAcc

Q9BXJ9

Main function of 5'-partner protein: FUNCTION: Auxillary subunit of the N-terminal acetyltransferase A (NatA) complex which displays alpha (N-terminal) acetyltransferase activity. The NAT activity may be important for vascular, hematopoietic and neuronal growth and development. Required to control retinal neovascularization in adult ocular endothelial cells. In complex with XRCC6 and XRCC5 (Ku80), up-regulates transcription from the osteocalcin promoter. {ECO:0000269|PubMed:11687548, ECO:0000269|PubMed:12145306, ECO:0000269|PubMed:15496142}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000296543, ENST00000398947, 
ENST00000480277, ENST00000515576, 
ENST00000511304, ENST00000265174, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score18 X 10 X 7=126010 X 9 X 6=540
# samples 2110
** MAII scorelog2(21/1260*10)=-2.58496250072116
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(10/540*10)=-2.43295940727611
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: NAA15 [Title/Abstract] AND PAPSS1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: NAA15 [Title/Abstract] AND PAPSS1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NAA15(140222985)-PAPSS1(108553016), # samples:1
Anticipated loss of major functional domain due to fusion event.NAA15-PAPSS1 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.
NAA15-PAPSS1 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
HgeneNAA15

GO:0006474

N-terminal protein amino acid acetylation

15496142

HgeneNAA15

GO:0045893

positive regulation of transcription, DNA-templated

12145306

TgenePAPSS1

GO:0000103

sulfate assimilation

14747722

TgenePAPSS1

GO:0050428

3'-phosphoadenosine 5'-phosphosulfate biosynthetic process

14747722|23207770



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/chr4:140222985/chr4:108553016)
- 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 NAA15 (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 PAPSS1 (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)
ENST00000296543NAA15chr4140222985+ENST00000265174PAPSS1chr4108553016-1329377323745140
ENST00000398947NAA15chr4140222985+ENST00000265174PAPSS1chr4108553016-1196244190612140

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
ENST00000296543ENST00000265174NAA15chr4140222985+PAPSS1chr4108553016-0.0055470780.9944529
ENST00000398947ENST00000265174NAA15chr4140222985+PAPSS1chr4108553016-0.004004060.9959959

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 NAA15-PAPSS1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
NAA15chr4140222985PAPSS1chr410855301624418LPPKENALFKRILVQWHCRARMVAGA
NAA15chr4140222985PAPSS1chr410855301637718LPPKENALFKRILVQWHCRARMVAGA

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Potential FusionNeoAntigen Information of NAA15-PAPSS1 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.
NAA15-PAPSS1_140222985_108553016.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)
NAA15-PAPSS1chr4140222985chr4108553016377HLA-B27:05KRILVQWHC0.99890.6491918
NAA15-PAPSS1chr4140222985chr4108553016377HLA-B27:04KRILVQWHC0.99860.699918
NAA15-PAPSS1chr4140222985chr4108553016377HLA-B27:07KRILVQWHC0.99690.5768918
NAA15-PAPSS1chr4140222985chr4108553016377HLA-B08:01NALFKRILV0.99650.5203514
NAA15-PAPSS1chr4140222985chr4108553016377HLA-B08:09NALFKRILV0.99630.605514
NAA15-PAPSS1chr4140222985chr4108553016377HLA-A74:11RILVQWHCR0.98870.69531019
NAA15-PAPSS1chr4140222985chr4108553016377HLA-A74:09RILVQWHCR0.98870.69531019
NAA15-PAPSS1chr4140222985chr4108553016377HLA-A74:03RILVQWHCR0.98870.69531019
NAA15-PAPSS1chr4140222985chr4108553016377HLA-A31:06RILVQWHCR0.96790.51351019
NAA15-PAPSS1chr4140222985chr4108553016377HLA-A31:02RILVQWHCR0.9410.69691019
NAA15-PAPSS1chr4140222985chr4108553016377HLA-B57:01ALFKRILVQW0.99860.9914616
NAA15-PAPSS1chr4140222985chr4108553016377HLA-A32:13ALFKRILVQW0.9830.9689616
NAA15-PAPSS1chr4140222985chr4108553016377HLA-B57:01NALFKRILVQW0.99980.972516
NAA15-PAPSS1chr4140222985chr4108553016377HLA-B27:14KRILVQWHC0.99890.649918
NAA15-PAPSS1chr4140222985chr4108553016377HLA-A31:01RILVQWHCR0.9890.67281019
NAA15-PAPSS1chr4140222985chr4108553016377HLA-B27:03KRILVQWHC0.98650.6599918
NAA15-PAPSS1chr4140222985chr4108553016377HLA-B73:01KRILVQWHC0.87060.9127918
NAA15-PAPSS1chr4140222985chr4108553016377HLA-B27:08KRILVQWHC0.99880.5683918
NAA15-PAPSS1chr4140222985chr4108553016377HLA-B27:10KRILVQWHC0.99870.802918
NAA15-PAPSS1chr4140222985chr4108553016377HLA-B08:18NALFKRILV0.99650.5203514
NAA15-PAPSS1chr4140222985chr4108553016377HLA-B27:09KRILVQWHC0.99610.6508918
NAA15-PAPSS1chr4140222985chr4108553016377HLA-A74:01RILVQWHCR0.98870.69531019
NAA15-PAPSS1chr4140222985chr4108553016377HLA-B27:10KRILVQWHCR0.99970.569919
NAA15-PAPSS1chr4140222985chr4108553016377HLA-B57:10ALFKRILVQW0.99860.9914616
NAA15-PAPSS1chr4140222985chr4108553016377HLA-A32:01ALFKRILVQW0.99380.9911616
NAA15-PAPSS1chr4140222985chr4108553016377HLA-B15:24ALFKRILVQW0.98860.9518616
NAA15-PAPSS1chr4140222985chr4108553016377HLA-B57:10NALFKRILVQW0.99980.972516

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Potential FusionNeoAntigen Information of NAA15-PAPSS1 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 NAA15-PAPSS1

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
360ALFKRILVQWHCRANAA15PAPSS1chr4140222985chr4108553016377

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of NAA15-PAPSS1

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-B14:023BVN360ALFKRILVQWHCRA-6.50768-6.63468
HLA-B14:023BVN360ALFKRILVQWHCRA-5.19253-7.43813
HLA-B14:023BVN360ALFKRILVQWHCRA-3.46925-4.51815
HLA-B52:013W39360ALFKRILVQWHCRA-6.50518-6.63218
HLA-B52:013W39360ALFKRILVQWHCRA-6.34639-7.39529
HLA-B52:013W39360ALFKRILVQWHCRA-5.62893-5.75593
HLA-B52:013W39360ALFKRILVQWHCRA-5.01274-6.06164
HLA-B52:013W39360ALFKRILVQWHCRA-3.72286-5.96846
HLA-B52:013W39360ALFKRILVQWHCRA-3.70638-5.95198
HLA-A24:025HGA360ALFKRILVQWHCRA-6.81825-6.94525
HLA-A24:025HGA360ALFKRILVQWHCRA-5.9074-8.153
HLA-A24:025HGA360ALFKRILVQWHCRA-4.30585-5.35475
HLA-B27:056PYJ360ALFKRILVQWHCRA-6.42606-7.47496
HLA-B44:053DX8360ALFKRILVQWHCRA-6.71035-6.83735
HLA-B44:053DX8360ALFKRILVQWHCRA-5.91067-6.95957
HLA-B44:053DX8360ALFKRILVQWHCRA-5.75093-5.87793
HLA-B44:053DX8360ALFKRILVQWHCRA-2.89749-5.14309
HLA-B44:053DX8360ALFKRILVQWHCRA-2.31007-3.35897
HLA-B44:053DX8360ALFKRILVQWHCRA-2.27884-4.52444
HLA-A02:016TDR360ALFKRILVQWHCRA-3.34106-4.38996

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Vaccine Design for the FusionNeoAntigens of NAA15-PAPSS1

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
NAA15-PAPSS1chr4140222985chr41085530161019RILVQWHCRCGGATCTTGGTCCAGTGGCATTGCAGA
NAA15-PAPSS1chr4140222985chr4108553016514NALFKRILVAATGCGCTCTTCAAGCGGATCTTGGTC
NAA15-PAPSS1chr4140222985chr4108553016516NALFKRILVQWAATGCGCTCTTCAAGCGGATCTTGGTCCAGTGG
NAA15-PAPSS1chr4140222985chr4108553016616ALFKRILVQWGCGCTCTTCAAGCGGATCTTGGTCCAGTGG
NAA15-PAPSS1chr4140222985chr4108553016918KRILVQWHCAAGCGGATCTTGGTCCAGTGGCATTGC
NAA15-PAPSS1chr4140222985chr4108553016919KRILVQWHCRAAGCGGATCTTGGTCCAGTGGCATTGCAGA

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 NAA15-PAPSS1

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
BRCANAA15-PAPSS1chr4140222985ENST00000296543chr4108553016ENST00000265174TCGA-A8-A07G-01A

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Potential target of CAR-T therapy development for NAA15-PAPSS1

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 NAA15-PAPSS1

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 NAA15-PAPSS1

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