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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:ATP6V0A2-RBCK1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ATP6V0A2-RBCK1
FusionPDB ID: 8102
FusionGDB2.0 ID: 8102
HgeneTgene
Gene symbol

ATP6V0A2

RBCK1

Gene ID

23545

10616

Gene nameATPase H+ transporting V0 subunit a2RANBP2-type and C3HC4-type zinc finger containing 1
SynonymsA2|ARCL|ARCL2A|ATP6A2|ATP6N1D|J6B7|RTF|STV1|TJ6|TJ6M|TJ6S|VPH1|WSSC20orf18|HOIL-1|HOIL1|PBMEI|PGBM1|RBCK2|RNF54|UBCE7IP3|XAP3|XAP4|ZRANB4
Cytomap

12q24.31

20p13

Type of geneprotein-codingprotein-coding
DescriptionV-type proton ATPase 116 kDa subunit a isoform 2V-type proton ATPase 116 kDa subunit aA2V-ATPaseATPase, H+ transporting, lysosomal V0 subunit a2lysosomal H(+)-transporting ATPase V0 subunit a2regeneration and tolerance factorv-ATPase 116 kDav-type ranBP-type and C3HC4-type zinc finger-containing protein 1HBV-associated factor 4RBCC protein interacting with PKC1RING finger protein 54RING-type E3 ubiquitin transferase HOIL-1heme-oxidized IRP2 ubiquitin ligase 1hepatitis B virus X-associated pro
Modification date2020031320200327
UniProtAcc

Q9Y487

Main function of 5'-partner protein: FUNCTION: Part of the proton channel of V-ATPases. Essential component of the endosomal pH-sensing machinery. May play a role in maintaining the Golgi functions, such as glycosylation maturation, by controlling the Golgi pH. In aerobic conditions, involved in intracellular iron homeostasis, thus triggering the activity of Fe(2+) prolyl hydroxylase (PHD) enzymes, and leading to HIF1A hydroxylation and subsequent proteasomal degradation (PubMed:28296633). {ECO:0000269|PubMed:16415858, ECO:0000269|PubMed:18157129, ECO:0000269|PubMed:28296633}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000330342, ENST00000543687, 
ENST00000544833, 
ENST00000400245, 
ENST00000400247, ENST00000475269, 
ENST00000353660, ENST00000356286, 
ENST00000382181, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score3 X 3 X 2=186 X 5 X 2=60
# samples 38
** MAII scorelog2(3/18*10)=0.736965594166206
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
log2(8/60*10)=0.415037499278844
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: ATP6V0A2 [Title/Abstract] AND RBCK1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ATP6V0A2 [Title/Abstract] AND RBCK1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ATP6V0A2(124221818)-RBCK1(407957), # samples:1
Anticipated loss of major functional domain due to fusion event.ATP6V0A2-RBCK1 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.
ATP6V0A2-RBCK1 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.
ATP6V0A2-RBCK1 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.
ATP6V0A2-RBCK1 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
TgeneRBCK1

GO:0000209

protein polyubiquitination

12629548|17006537

TgeneRBCK1

GO:0032088

negative regulation of NF-kappaB transcription factor activity

17449468

TgeneRBCK1

GO:0043123

positive regulation of I-kappaB kinase/NF-kappaB signaling

19136968|21455173

TgeneRBCK1

GO:0050852

T cell receptor signaling pathway

20005846

TgeneRBCK1

GO:0051092

positive regulation of NF-kappaB transcription factor activity

19136968

TgeneRBCK1

GO:0097039

protein linear polyubiquitination

21455173|21455180|21455181|23453807



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/chr12:124221818/chr20:407957)
- 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 ATP6V0A2 (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 RBCK1 (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)
ENST00000330342ATP6V0A2chr12124221818+ENST00000356286RBCK1chr20407957+232612862481789513
ENST00000330342ATP6V0A2chr12124221818+ENST00000353660RBCK1chr20407957+232612862481789513
ENST00000330342ATP6V0A2chr12124221818+ENST00000382181RBCK1chr20407957+232612862481789513

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
ENST00000330342ENST00000356286ATP6V0A2chr12124221818+RBCK1chr20407957+0.0025820750.9974179
ENST00000330342ENST00000353660ATP6V0A2chr12124221818+RBCK1chr20407957+0.0025820750.9974179
ENST00000330342ENST00000382181ATP6V0A2chr12124221818+RBCK1chr20407957+0.0025820750.9974179

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 ATP6V0A2-RBCK1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ATP6V0A2chr12124221818RBCK1chr204079571286346DLQDLRRALEEGSLLTPEDYQRFLDL

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Potential FusionNeoAntigen Information of ATP6V0A2-RBCK1 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.
ATP6V0A2-RBCK1_124221818_407957.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)
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-B27:07RRALEEGSL0.99760.7175514
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-B15:17RALEEGSLL0.98580.9671615
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-B15:16RALEEGSLL0.97850.9627615
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-B45:01LEEGSLLTP0.96240.904817
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-B50:02LEEGSLLTP0.94370.7915817
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-B48:01RALEEGSLL0.77760.7438615
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-B41:01LEEGSLLTP0.3720.9546817
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-B50:01LEEGSLLTP0.23670.7977817
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-B52:01RALEEGSLL0.11910.9848615
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-B13:01RALEEGSLL0.09590.9924615
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-B07:10RRALEEGSL0.04480.7193514
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-B27:05RRALEEGSLL0.99970.7106515
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-B27:04RRALEEGSLL0.99970.8121515
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-B27:07RRALEEGSLL0.99950.7766515
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-A74:03SLLTPEDYQR0.79260.68331222
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-A74:09SLLTPEDYQR0.79260.68331222
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-A74:11SLLTPEDYQR0.79260.68331222
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-B45:01ALEEGSLLTP0.72730.9336717
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-B50:02ALEEGSLLTP0.72510.7962717
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-B41:01ALEEGSLLTP0.48350.9738717
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-C03:19RALEEGSLL0.99930.9926615
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-C03:07RALEEGSLL0.99920.9876615
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-C15:06RALEEGSLL0.99880.967615
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-C03:08RALEEGSLL0.99850.9585615
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-C04:06RALEEGSLL0.99440.9595615
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-C08:04RALEEGSLL0.9760.9874615
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-C08:13RALEEGSLL0.9760.9874615
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-C12:12RALEEGSLL0.95140.9665615
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-C02:06RALEEGSLL0.92590.9661615
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-C08:15RALEEGSLL0.92330.9908615
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-C03:14RALEEGSLL0.92220.9852615
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-C08:03RALEEGSLL0.80230.9958615
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-B48:03RALEEGSLL0.22070.589615
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-B27:14RRALEEGSLL0.99970.7359515
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-B27:03RRALEEGSLL0.99040.736515
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-C15:02RALEEGSLL0.99880.954615
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-C15:05RALEEGSLL0.99860.9564615
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-C03:17RALEEGSLL0.99840.9814615
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-C03:05RALEEGSLL0.9980.9554615
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-B27:06RRALEEGSL0.9980.8688514
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-B27:08RRALEEGSL0.99790.7017514
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-B27:09RRALEEGSL0.99720.7498514
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-C03:04RALEEGSLL0.99640.9927615
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-C03:03RALEEGSLL0.99640.9927615
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-C03:02RALEEGSLL0.98910.9846615
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-C16:02RALEEGSLL0.98280.995615
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-C03:06RALEEGSLL0.97460.9932615
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-C16:01RALEEGSLL0.96950.9887615
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-C08:02RALEEGSLL0.92330.9908615
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-C17:01RALEEGSLL0.90240.9859615
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-C08:01RALEEGSLL0.80230.9958615
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-B15:30RALEEGSLL0.64890.9636615
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-B07:13RALEEGSLL0.60660.8895615
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-B35:13RALEEGSLL0.59480.9509615
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-B50:05LEEGSLLTP0.23670.7977817
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-B50:04LEEGSLLTP0.23670.7977817
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-B40:12RALEEGSLL0.22070.589615
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-B40:21RALEEGSLL0.08590.7373615
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-B27:10RRALEEGSLL0.99970.8735515
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-B27:08RRALEEGSLL0.99970.642515
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-B27:09RRALEEGSLL0.99950.7133515
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-B27:06RRALEEGSLL0.99950.8586515
ATP6V0A2-RBCK1chr12124221818chr204079571286HLA-A74:01SLLTPEDYQR0.79260.68331222

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Potential FusionNeoAntigen Information of ATP6V0A2-RBCK1 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 ATP6V0A2-RBCK1

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
7690RALEEGSLLTPEDYATP6V0A2RBCK1chr12124221818chr204079571286

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ATP6V0A2-RBCK1

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-B14:023BVN7690RALEEGSLLTPEDY-8.79968-8.91308
HLA-B14:023BVN7690RALEEGSLLTPEDY-2.93446-3.96976
HLA-B52:013W397690RALEEGSLLTPEDY-5.96997-6.08337
HLA-B52:013W397690RALEEGSLLTPEDY-4.23042-5.26572
HLA-A11:014UQ27690RALEEGSLLTPEDY-8.20522-8.31862
HLA-A11:014UQ27690RALEEGSLLTPEDY-4.67476-5.71006
HLA-A24:025HGA7690RALEEGSLLTPEDY-9.05525-9.16865
HLA-A24:025HGA7690RALEEGSLLTPEDY-6.47443-7.50973
HLA-B44:053DX87690RALEEGSLLTPEDY-6.9286-7.042
HLA-B44:053DX87690RALEEGSLLTPEDY-2.31135-3.34665
HLA-A02:016TDR7690RALEEGSLLTPEDY-4.18158-5.21688

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Vaccine Design for the FusionNeoAntigens of ATP6V0A2-RBCK1

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
ATP6V0A2-RBCK1chr12124221818chr204079571222SLLTPEDYQRTCGCTCCTGACCCCTGAGGATTACCAGCGA
ATP6V0A2-RBCK1chr12124221818chr20407957514RRALEEGSLCGCCGGGCACTGGAGGAGGGCTCGCTC
ATP6V0A2-RBCK1chr12124221818chr20407957515RRALEEGSLLCGCCGGGCACTGGAGGAGGGCTCGCTCCTG
ATP6V0A2-RBCK1chr12124221818chr20407957615RALEEGSLLCGGGCACTGGAGGAGGGCTCGCTCCTG
ATP6V0A2-RBCK1chr12124221818chr20407957717ALEEGSLLTPGCACTGGAGGAGGGCTCGCTCCTGACCCCT
ATP6V0A2-RBCK1chr12124221818chr20407957817LEEGSLLTPCTGGAGGAGGGCTCGCTCCTGACCCCT

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 ATP6V0A2-RBCK1

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
STADATP6V0A2-RBCK1chr12124221818ENST00000330342chr20407957ENST00000353660TCGA-D7-5577-01A

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Potential target of CAR-T therapy development for ATP6V0A2-RBCK1

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 ATP6V0A2-RBCK1

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 ATP6V0A2-RBCK1

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