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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:ADCY2-RPAP2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ADCY2-RPAP2
FusionPDB ID: 2224
FusionGDB2.0 ID: 2224
HgeneTgene
Gene symbol

ADCY2

RPAP2

Gene ID

108

79871

Gene nameadenylate cyclase 2RNA polymerase II associated protein 2
SynonymsAC2|HBAC2C1orf82|Rtr1
Cytomap

5p15.31

1p22.1

Type of geneprotein-codingprotein-coding
Descriptionadenylate cyclase type 23',5'-cyclic AMP synthetaseATP pyrophosphate-lyase 2adenylate cyclase 2 (brain)adenylate cyclase IIadenylate cyclase type IIadenylyl cyclase 2type II adenylate cyclaseputative RNA polymerase II subunit B1 CTD phosphatase RPAP2
Modification date2020031320200313
UniProtAcc

Q08462

Main function of 5'-partner protein: FUNCTION: Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling (PubMed:15385642). Down-stream signaling cascades mediate changes in gene expression patterns and lead to increased IL6 production. Functions in signaling cascades downstream of the muscarinic acetylcholine receptors (By similarity). {ECO:0000250|UniProtKB:P26769, ECO:0000269|PubMed:15385642}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000338316, ENST00000537121, 
ENST00000513693, 
ENST00000484158, 
ENST00000610020, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score11 X 9 X 6=5942 X 2 X 2=8
# samples 102
** MAII scorelog2(10/594*10)=-2.57046293102604
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(2/8*10)=1.32192809488736
Fusion gene context

PubMed: ADCY2 [Title/Abstract] AND RPAP2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ADCY2 [Title/Abstract] AND RPAP2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ADCY2(7698487)-RPAP2(92846281), # samples:1
Anticipated loss of major functional domain due to fusion event.ADCY2-RPAP2 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.
ADCY2-RPAP2 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/chr5:7698487/chr1:92846281)
- 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 ADCY2 (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 RPAP2 (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)
ENST00000338316ADCY2chr57698487-ENST00000610020RPAP2chr192846281+163941198891348419
ENST00000537121ADCY2chr57698487-ENST00000610020RPAP2chr192846281+1583163566785239

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
ENST00000338316ENST00000610020ADCY2chr57698487-RPAP2chr192846281+0.0057207540.99427927
ENST00000537121ENST00000610020ADCY2chr57698487-RPAP2chr192846281+0.0010491070.99895084

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 ADCY2-RPAP2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ADCY2chr57698487RPAP2chr1928462811198370CVKMGLDMCEAIKLTPILGIQKHSQE
ADCY2chr57698487RPAP2chr192846281635190CVKMGLDMCEAIKLTPILGIQKHSQE

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Potential FusionNeoAntigen Information of ADCY2-RPAP2 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.
ADCY2-RPAP2_7698487_92846281.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)
ADCY2-RPAP2chr57698487chr1928462811198HLA-B35:03EAIKLTPIL0.99410.8535918
ADCY2-RPAP2chr57698487chr1928462811198HLA-B35:02EAIKLTPIL0.97040.9173918
ADCY2-RPAP2chr57698487chr1928462811198HLA-B35:04EAIKLTPIL0.97040.9173918
ADCY2-RPAP2chr57698487chr1928462811198HLA-B52:01IKLTPILGI0.02910.9781120
ADCY2-RPAP2chr57698487chr1928462811198HLA-A30:08KLTPILGIQK0.98990.82531222
ADCY2-RPAP2chr57698487chr1928462811198HLA-B51:07EAIKLTPI0.99970.594917
ADCY2-RPAP2chr57698487chr1928462811198HLA-C03:08EAIKLTPIL0.99970.8527918
ADCY2-RPAP2chr57698487chr1928462811198HLA-B35:12EAIKLTPIL0.97040.9173918
ADCY2-RPAP2chr57698487chr1928462811198HLA-B39:10EAIKLTPIL0.80680.8606918
ADCY2-RPAP2chr57698487chr1928462811198HLA-C03:04EAIKLTPIL0.99980.9848918
ADCY2-RPAP2chr57698487chr1928462811198HLA-C03:03EAIKLTPIL0.99980.9848918
ADCY2-RPAP2chr57698487chr1928462811198HLA-C03:17EAIKLTPIL0.99960.9378918
ADCY2-RPAP2chr57698487chr1928462811198HLA-A68:02EAIKLTPIL0.99790.528918
ADCY2-RPAP2chr57698487chr1928462811198HLA-A25:01EAIKLTPIL0.99740.9424918
ADCY2-RPAP2chr57698487chr1928462811198HLA-C03:06EAIKLTPIL0.99660.9856918
ADCY2-RPAP2chr57698487chr1928462811198HLA-A69:01EAIKLTPIL0.99530.5003918
ADCY2-RPAP2chr57698487chr1928462811198HLA-B35:13EAIKLTPIL0.9940.8719918
ADCY2-RPAP2chr57698487chr1928462811198HLA-B35:23EAIKLTPIL0.99060.7818918
ADCY2-RPAP2chr57698487chr1928462811198HLA-B35:17EAIKLTPIL0.98020.6455918
ADCY2-RPAP2chr57698487chr1928462811198HLA-B35:30EAIKLTPIL0.98020.6455918
ADCY2-RPAP2chr57698487chr1928462811198HLA-B35:09EAIKLTPIL0.97040.9173918
ADCY2-RPAP2chr57698487chr1928462811198HLA-B35:24EAIKLTPIL0.93350.7867918

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Potential FusionNeoAntigen Information of ADCY2-RPAP2 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.
ADCY2-RPAP2_7698487_92846281.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)
ADCY2-RPAP2chr57698487chr1928462811198DRB1-0822IKLTPILGIQKHSQE1126
ADCY2-RPAP2chr57698487chr1928462811198DRB1-0828IKLTPILGIQKHSQE1126
ADCY2-RPAP2chr57698487chr1928462811198DRB1-0831IKLTPILGIQKHSQE1126
ADCY2-RPAP2chr57698487chr1928462811198DRB1-1104IKLTPILGIQKHSQE1126
ADCY2-RPAP2chr57698487chr1928462811198DRB1-1106IKLTPILGIQKHSQE1126
ADCY2-RPAP2chr57698487chr1928462811198DRB1-1118IKLTPILGIQKHSQE1126
ADCY2-RPAP2chr57698487chr1928462811198DRB1-1125IKLTPILGIQKHSQE1126
ADCY2-RPAP2chr57698487chr1928462811198DRB1-1135IKLTPILGIQKHSQE1126
ADCY2-RPAP2chr57698487chr1928462811198DRB1-1138IKLTPILGIQKHSQE1126
ADCY2-RPAP2chr57698487chr1928462811198DRB1-1141IKLTPILGIQKHSQE1126
ADCY2-RPAP2chr57698487chr1928462811198DRB1-1142IKLTPILGIQKHSQE1126
ADCY2-RPAP2chr57698487chr1928462811198DRB1-1143IKLTPILGIQKHSQE1126
ADCY2-RPAP2chr57698487chr1928462811198DRB1-1144IKLTPILGIQKHSQE1126
ADCY2-RPAP2chr57698487chr1928462811198DRB1-1146IKLTPILGIQKHSQE1126
ADCY2-RPAP2chr57698487chr1928462811198DRB1-1147IKLTPILGIQKHSQE1126
ADCY2-RPAP2chr57698487chr1928462811198DRB1-1154IKLTPILGIQKHSQE1126
ADCY2-RPAP2chr57698487chr1928462811198DRB1-1157IKLTPILGIQKHSQE1126
ADCY2-RPAP2chr57698487chr1928462811198DRB1-1158IKLTPILGIQKHSQE1126
ADCY2-RPAP2chr57698487chr1928462811198DRB1-1159IKLTPILGIQKHSQE1126
ADCY2-RPAP2chr57698487chr1928462811198DRB1-1160IKLTPILGIQKHSQE1126
ADCY2-RPAP2chr57698487chr1928462811198DRB1-1167IKLTPILGIQKHSQE1126
ADCY2-RPAP2chr57698487chr1928462811198DRB1-1177IKLTPILGIQKHSQE1126
ADCY2-RPAP2chr57698487chr1928462811198DRB1-1178IKLTPILGIQKHSQE1126
ADCY2-RPAP2chr57698487chr1928462811198DRB1-1184IKLTPILGIQKHSQE1126
ADCY2-RPAP2chr57698487chr1928462811198DRB1-1306IKLTPILGIQKHSQE1126
ADCY2-RPAP2chr57698487chr1928462811198DRB1-1311IKLTPILGIQKHSQE1126
ADCY2-RPAP2chr57698487chr1928462811198DRB1-1318IKLTPILGIQKHSQE1126
ADCY2-RPAP2chr57698487chr1928462811198DRB1-1342IKLTPILGIQKHSQE1126
ADCY2-RPAP2chr57698487chr1928462811198DRB1-1478IKLTPILGIQKHSQE1126

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Fusion breakpoint peptide structures of ADCY2-RPAP2

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
1250DMCEAIKLTPILGIADCY2RPAP2chr57698487chr1928462811198

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ADCY2-RPAP2

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-B14:023BVN1250DMCEAIKLTPILGI-7.75776-7.86956
HLA-B14:023BVN1250DMCEAIKLTPILGI-4.52646-5.56956
HLA-B52:013W391250DMCEAIKLTPILGI-7.1873-7.2991
HLA-B52:013W391250DMCEAIKLTPILGI-2.81174-3.85484
HLA-A11:014UQ21250DMCEAIKLTPILGI-5.13576-5.24756
HLA-A24:025HGA1250DMCEAIKLTPILGI-8.42076-8.53256
HLA-A24:025HGA1250DMCEAIKLTPILGI-7.10496-8.14806
HLA-B27:056PYJ1250DMCEAIKLTPILGI-9.28296-9.39476
HLA-B44:053DX81250DMCEAIKLTPILGI-6.88262-6.99442
HLA-B44:053DX81250DMCEAIKLTPILGI-5.46822-6.51132

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Vaccine Design for the FusionNeoAntigens of ADCY2-RPAP2

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
ADCY2-RPAP2chr57698487chr1928462811120IKLTPILGICATAAAACTGACCCCAATTCTTGGCAT
ADCY2-RPAP2chr57698487chr1928462811222KLTPILGIQKAAAACTGACCCCAATTCTTGGCATTCAGAA
ADCY2-RPAP2chr57698487chr192846281917EAIKLTPITGAAGCCATAAAACTGACCCCAAT
ADCY2-RPAP2chr57698487chr192846281918EAIKLTPILTGAAGCCATAAAACTGACCCCAATTCT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
ADCY2-RPAP2chr57698487chr1928462811126IKLTPILGIQKHSQECATAAAACTGACCCCAATTCTTGGCATTCAGAAACATTCTCAGGA

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Information of the samples that have these potential fusion neoantigens of ADCY2-RPAP2

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
BLCAADCY2-RPAP2chr57698487ENST00000338316chr192846281ENST00000610020TCGA-FD-A3SR-01A

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Potential target of CAR-T therapy development for ADCY2-RPAP2

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
HgeneADCY2chr5:7698487chr1:92846281ENST00000338316-725108_1283691092.0TransmembraneHelical
HgeneADCY2chr5:7698487chr1:92846281ENST00000338316-725133_1533691092.0TransmembraneHelical
HgeneADCY2chr5:7698487chr1:92846281ENST00000338316-725159_1793691092.0TransmembraneHelical
HgeneADCY2chr5:7698487chr1:92846281ENST00000338316-725187_2073691092.0TransmembraneHelical
HgeneADCY2chr5:7698487chr1:92846281ENST00000338316-72546_663691092.0TransmembraneHelical
HgeneADCY2chr5:7698487chr1:92846281ENST00000338316-72576_963691092.0TransmembraneHelical

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

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Related Drugs to ADCY2-RPAP2

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 ADCY2-RPAP2

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