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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:RNF13-ATP8A2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: RNF13-ATP8A2
FusionPDB ID: 74793
FusionGDB2.0 ID: 74793
HgeneTgene
Gene symbol

RNF13

ATP8A2

Gene ID

11342

51761

Gene namering finger protein 13ATPase phospholipid transporting 8A2
SynonymsEIEE73|RZFATP|ATPIB|CAMRQ4|IB|ML-1
Cytomap

3q25.1

13q12.13

Type of geneprotein-codingprotein-coding
DescriptionE3 ubiquitin-protein ligase RNF13RING zinc finger proteinRING-type E3 ubiquitin transferase RNF13phospholipid-transporting ATPase IBATPase, aminophospholipid transporter, class I, type 8A, member 2ATPase, aminophospholipid transporter-like, class I, type 8A, member 2P4-ATPase flippase complex alpha subunit ATP8A2probable phospholipid-transporting
Modification date2020031320200329
UniProtAcc

Q8WVD3

Main function of 5'-partner protein: FUNCTION: E3 ubiquitin-protein ligase involved in DNA damage response by promoting DNA resection and homologous recombination (PubMed:26502055, PubMed:26502057). Recruited to sites of double-strand breaks following DNA damage and specifically promotes double-strand break repair via homologous recombination (PubMed:26502055, PubMed:26502057). Two different, non-exclusive, mechanisms have been proposed. According to a report, regulates the choice of double-strand break repair by favoring homologous recombination over non-homologous end joining (NHEJ): acts by mediating ubiquitination of XRCC5/Ku80, leading to remove the Ku complex from DNA breaks, thereby promoting homologous recombination (PubMed:26502055). According to another report, cooperates with UBE2Ds E2 ubiquitin ligases (UBE2D1, UBE2D2, UBE2D3 or UBE2D4) to promote homologous recombination by mediating ubiquitination of RBBP8/CtIP (PubMed:26502057). Together with NLK, involved in the ubiquitination and degradation of TCF/LEF (PubMed:16714285). Also exhibits auto-ubiquitination activity in combination with UBE2K (PubMed:16714285). May act as a negative regulator in the Wnt/beta-catenin-mediated signaling pathway (PubMed:16714285). {ECO:0000269|PubMed:16714285, ECO:0000269|PubMed:26502055, ECO:0000269|PubMed:26502057}.

Q9NTI2

Main function of 5'-partner protein: FUNCTION: Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and ensures the maintenance of asymmetric distribution of phospholipids. Phospholipid translocation seems also to be implicated in vesicle formation and in uptake of lipid signaling molecules. Reconstituted to liposomes, the ATP8A2:TMEM30A flippase complex predominantly transports phosphatidylserine (PS) and to a lesser extent phosphatidylethanolamine (PE). Phospholipid translocation is not associated with a countertransport of an inorganic ion or other charged substrate from the cytoplasmic side toward the exoplasm in connection with the phosphorylation from ATP. ATP8A2:TMEM30A may be involved in regulation of neurite outgrowth. Proposed to function in the generation and maintenance of phospholipid asymmetry in photoreceptor disk membranes and neuronal axon membranes. May be involved in vesicle trafficking in neuronal cells. Required for normal visual and auditory function; involved in photoreceptor and inner ear spiral ganglion cell survival. {ECO:0000250|UniProtKB:C7EXK4}.
Ensembl transtripts involved in fusion geneENST idsENST00000344229, ENST00000392894, 
ENST00000361785, 
ENST00000491840, 
ENST00000255283, ENST00000381655, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score10 X 9 X 7=63013 X 13 X 7=1183
# samples 1315
** MAII scorelog2(13/630*10)=-2.27684020535882
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(15/1183*10)=-2.97941566784391
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: RNF13 [Title/Abstract] AND ATP8A2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: RNF13 [Title/Abstract] AND ATP8A2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)RNF13(149570383)-ATP8A2(26273311), # samples:1
Anticipated loss of major functional domain due to fusion event.RNF13-ATP8A2 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.
RNF13-ATP8A2 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/chr3:149570383/chr13:26273311)
- 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 RNF13 (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 ATP8A2 (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)
ENST00000392894RNF13chr3149570383-ENST00000381655ATP8A2chr1326273311+80798576622212516
ENST00000392894RNF13chr3149570383-ENST00000255283ATP8A2chr1326273311+23948576622137491
ENST00000344229RNF13chr3149570383-ENST00000381655ATP8A2chr1326273311+81198977022252516
ENST00000344229RNF13chr3149570383-ENST00000255283ATP8A2chr1326273311+24348977022177491

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
ENST00000392894ENST00000381655RNF13chr3149570383-ATP8A2chr1326273311+0.0006739920.999326
ENST00000392894ENST00000255283RNF13chr3149570383-ATP8A2chr1326273311+0.0036534810.99634653
ENST00000344229ENST00000381655RNF13chr3149570383-ATP8A2chr1326273311+0.0007283990.9992716
ENST00000344229ENST00000255283RNF13chr3149570383-ATP8A2chr1326273311+0.0041454310.9958546

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 RNF13-ATP8A2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
RNF13chr3149570383ATP8A2chr132627331185765ARFGYRLPAEGLKATRAAITQHCTDL
RNF13chr3149570383ATP8A2chr132627331189765ARFGYRLPAEGLKATRAAITQHCTDL

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Potential FusionNeoAntigen Information of RNF13-ATP8A2 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.
RNF13-ATP8A2_149570383_26273311.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)
RNF13-ATP8A2chr3149570383chr1326273311897HLA-B45:01AEGLKATRA0.99810.9652817
RNF13-ATP8A2chr3149570383chr1326273311897HLA-B50:02AEGLKATRA0.99410.7952817
RNF13-ATP8A2chr3149570383chr1326273311897HLA-B56:01LPAEGLKAT0.93620.6839615
RNF13-ATP8A2chr3149570383chr1326273311897HLA-B55:01LPAEGLKAT0.81410.5944615
RNF13-ATP8A2chr3149570383chr1326273311897HLA-B41:01AEGLKATRA0.22610.9483817
RNF13-ATP8A2chr3149570383chr1326273311897HLA-B50:01AEGLKATRA0.16460.8586817
RNF13-ATP8A2chr3149570383chr1326273311897HLA-B39:06YRLPAEGLKA0.99630.9891414
RNF13-ATP8A2chr3149570383chr1326273311897HLA-B45:01AEGLKATRAA0.99410.9801818
RNF13-ATP8A2chr3149570383chr1326273311897HLA-B50:02AEGLKATRAA0.98430.824818
RNF13-ATP8A2chr3149570383chr1326273311897HLA-B41:01AEGLKATRAA0.86450.9688818
RNF13-ATP8A2chr3149570383chr1326273311897HLA-B50:01AEGLKATRAA0.80220.9067818
RNF13-ATP8A2chr3149570383chr1326273311897HLA-B56:01LPAEGLKATRA0.99840.836617
RNF13-ATP8A2chr3149570383chr1326273311897HLA-B55:01LPAEGLKATRA0.99740.7266617
RNF13-ATP8A2chr3149570383chr1326273311897HLA-B54:01LPAEGLKA0.99180.8251614
RNF13-ATP8A2chr3149570383chr1326273311897HLA-B40:06AEGLKATRA0.99530.8419817
RNF13-ATP8A2chr3149570383chr1326273311897HLA-B54:01LPAEGLKAT0.9880.9086615
RNF13-ATP8A2chr3149570383chr1326273311897HLA-B56:04LPAEGLKAT0.76340.8645615
RNF13-ATP8A2chr3149570383chr1326273311897HLA-B78:01LPAEGLKAT0.41420.936615
RNF13-ATP8A2chr3149570383chr1326273311897HLA-B27:14YRLPAEGLKA0.99940.6986414
RNF13-ATP8A2chr3149570383chr1326273311897HLA-B73:01YRLPAEGLKA0.99650.9533414
RNF13-ATP8A2chr3149570383chr1326273311897HLA-B40:06AEGLKATRAA0.99020.9395818
RNF13-ATP8A2chr3149570383chr1326273311897HLA-B54:01LPAEGLKATRA0.99970.9365617
RNF13-ATP8A2chr3149570383chr1326273311897HLA-B78:02LPAEGLKA0.9960.8933614
RNF13-ATP8A2chr3149570383chr1326273311897HLA-B55:02LPAEGLKA0.97580.6377614
RNF13-ATP8A2chr3149570383chr1326273311897HLA-B55:02LPAEGLKAT0.93490.7341615
RNF13-ATP8A2chr3149570383chr1326273311897HLA-B56:02LPAEGLKAT0.76340.8645615
RNF13-ATP8A2chr3149570383chr1326273311897HLA-B56:05LPAEGLKAT0.6650.8059615
RNF13-ATP8A2chr3149570383chr1326273311897HLA-B78:02LPAEGLKAT0.35810.9565615
RNF13-ATP8A2chr3149570383chr1326273311897HLA-B50:05AEGLKATRA0.16460.8586817
RNF13-ATP8A2chr3149570383chr1326273311897HLA-B50:04AEGLKATRA0.16460.8586817
RNF13-ATP8A2chr3149570383chr1326273311897HLA-B50:05AEGLKATRAA0.80220.9067818
RNF13-ATP8A2chr3149570383chr1326273311897HLA-B50:04AEGLKATRAA0.80220.9067818
RNF13-ATP8A2chr3149570383chr1326273311897HLA-B55:02LPAEGLKATRA0.99890.8538617

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Potential FusionNeoAntigen Information of RNF13-ATP8A2 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 RNF13-ATP8A2

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
5362LPAEGLKATRAAITRNF13ATP8A2chr3149570383chr1326273311897

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of RNF13-ATP8A2

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-B14:023BVN5362LPAEGLKATRAAIT-6.99517-8.03047
HLA-B14:023BVN5362LPAEGLKATRAAIT-5.77825-5.89165
HLA-B52:013W395362LPAEGLKATRAAIT-6.61322-6.72662
HLA-B52:013W395362LPAEGLKATRAAIT-4.70835-5.74365
HLA-A11:014UQ25362LPAEGLKATRAAIT-6.07503-6.18843
HLA-A11:014UQ25362LPAEGLKATRAAIT-6.00288-7.03818
HLA-A24:025HGA5362LPAEGLKATRAAIT-8.39569-8.50909
HLA-A24:025HGA5362LPAEGLKATRAAIT-4.10619-5.14149
HLA-B44:053DX85362LPAEGLKATRAAIT-6.04138-6.15478
HLA-B44:053DX85362LPAEGLKATRAAIT-2.34691-3.38221

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Vaccine Design for the FusionNeoAntigens of RNF13-ATP8A2

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
RNF13-ATP8A2chr3149570383chr1326273311414YRLPAEGLKATATAGACTTCCAGCTGAAGGTTTAAAGGCC
RNF13-ATP8A2chr3149570383chr1326273311614LPAEGLKACTTCCAGCTGAAGGTTTAAAGGCC
RNF13-ATP8A2chr3149570383chr1326273311615LPAEGLKATCTTCCAGCTGAAGGTTTAAAGGCCACA
RNF13-ATP8A2chr3149570383chr1326273311617LPAEGLKATRACTTCCAGCTGAAGGTTTAAAGGCCACAAGGGCA
RNF13-ATP8A2chr3149570383chr1326273311817AEGLKATRAGCTGAAGGTTTAAAGGCCACAAGGGCA
RNF13-ATP8A2chr3149570383chr1326273311818AEGLKATRAAGCTGAAGGTTTAAAGGCCACAAGGGCAGCC

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 RNF13-ATP8A2

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
BRCARNF13-ATP8A2chr3149570383ENST00000344229chr1326273311ENST00000255283TCGA-A7-A4SE-01A

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Potential target of CAR-T therapy development for RNF13-ATP8A2

check button Predicted 3D structure. We used RoseTTAFold.
382_RNF13-ATP8A2_37f16_pred.pdb


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
TgeneATP8A2chr3:149570383chr13:26273311ENST0000038165523371029_104901189.0TransmembraneHelical
TgeneATP8A2chr3:149570383chr13:26273311ENST0000038165523371064_108401189.0TransmembraneHelical
TgeneATP8A2chr3:149570383chr13:26273311ENST000003816552337888_90801189.0TransmembraneHelical
TgeneATP8A2chr3:149570383chr13:26273311ENST000003816552337911_93101189.0TransmembraneHelical
TgeneATP8A2chr3:149570383chr13:26273311ENST000003816552337960_98001189.0TransmembraneHelical
TgeneATP8A2chr3:149570383chr13:26273311ENST000003816552337998_101801189.0TransmembraneHelical

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
RNF13chr3149570383ENST00000344229ATP8A2chr1326273311ENST00000255283
RNF13chr3149570383ENST00000344229ATP8A2chr1326273311ENST00000381655

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Related Drugs to RNF13-ATP8A2

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 RNF13-ATP8A2

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