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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:ADCY9-RMI2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ADCY9-RMI2
FusionPDB ID: 2270
FusionGDB2.0 ID: 2270
HgeneTgene
Gene symbol

ADCY9

RMI2

Gene ID

115

116028

Gene nameadenylate cyclase 9RecQ mediated genome instability 2
SynonymsAC9|ACIXBLAP18|C16orf75
Cytomap

16p13.3

16p13.13

Type of geneprotein-codingprotein-coding
Descriptionadenylate cyclase type 9ATP pyrophosphate-lyase 9adenylate cyclase type IXadenylyl cyclase 9type IX ATP pyrophosphate-lyaserecQ-mediated genome instability protein 2BLM-associated protein of 18 kDaRMI2, RecQ mediated genome instability 2, homolog
Modification date2020031320200313
UniProtAcc

O60503

Main function of 5'-partner protein: FUNCTION: Adenylyl cyclase that catalyzes the formation of the signaling molecule cAMP in response to activation of G protein-coupled receptors (PubMed:9628827, PubMed:12972952, PubMed:15879435, PubMed:10987815). Contributes to signaling cascades activated by CRH (corticotropin-releasing factor), corticosteroids and beta-adrenergic receptors (PubMed:9628827). {ECO:0000269|PubMed:10987815, ECO:0000269|PubMed:12972952, ECO:0000269|PubMed:15879435, ECO:0000269|PubMed:9628827}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000294016, ENST00000571889, 
ENST00000312499, ENST00000381820, 
ENST00000572992, ENST00000576027, 
ENST00000572173, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score27 X 12 X 11=35646 X 2 X 4=48
# samples 276
** MAII scorelog2(27/3564*10)=-3.72246602447109
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(6/48*10)=0.321928094887362
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: ADCY9 [Title/Abstract] AND RMI2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ADCY9 [Title/Abstract] AND RMI2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ADCY9(4163751)-RMI2(11444499), # samples:1
Anticipated loss of major functional domain due to fusion event.ADCY9-RMI2 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.
ADCY9-RMI2 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.
ADCY9-RMI2 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.
ADCY9-RMI2 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
HgeneADCY9

GO:0006171

cAMP biosynthetic process

9628827|10987815

HgeneADCY9

GO:0007189

adenylate cyclase-activating G protein-coupled receptor signaling pathway

9628827



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/chr16:4163751/chr16:11444499)
- 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 ADCY9 (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 RMI2 (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)
ENST00000294016ADCY9chr164163751-ENST00000572173RMI2chr1611444499+334622325392380613

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
ENST00000294016ENST00000572173ADCY9chr164163751-RMI2chr1611444499+0.0093075230.99069244

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 ADCY9-RMI2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ADCY9chr164163751RMI2chr16114444992232564ERLGQSVVADQLKGKYVMVMGVVQAC

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Potential FusionNeoAntigen Information of ADCY9-RMI2 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.
ADCY9-RMI2_4163751_11444499.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)
ADCY9-RMI2chr164163751chr16114444992232HLA-B08:01QLKGKYVM0.99970.64411018
ADCY9-RMI2chr164163751chr16114444992232HLA-B08:09QLKGKYVMV0.99790.86451019
ADCY9-RMI2chr164163751chr16114444992232HLA-B08:01QLKGKYVMV0.99760.71081019
ADCY9-RMI2chr164163751chr16114444992232HLA-B14:02DQLKGKYVM0.99730.8106918
ADCY9-RMI2chr164163751chr16114444992232HLA-B14:01DQLKGKYVM0.99730.8106918
ADCY9-RMI2chr164163751chr16114444992232HLA-B39:24DQLKGKYVM0.96080.674918
ADCY9-RMI2chr164163751chr16114444992232HLA-B35:08VADQLKGKY0.95310.812716
ADCY9-RMI2chr164163751chr16114444992232HLA-A02:13QLKGKYVMV0.93210.74541019
ADCY9-RMI2chr164163751chr16114444992232HLA-B15:37DQLKGKYVM0.89580.5087918
ADCY9-RMI2chr164163751chr16114444992232HLA-B39:01DQLKGKYVM0.89010.9361918
ADCY9-RMI2chr164163751chr16114444992232HLA-B18:01DQLKGKYVM0.88530.8675918
ADCY9-RMI2chr164163751chr16114444992232HLA-B15:18DQLKGKYVM0.63030.7221918
ADCY9-RMI2chr164163751chr16114444992232HLA-B15:10DQLKGKYVM0.6170.5331918
ADCY9-RMI2chr164163751chr16114444992232HLA-B08:01QLKGKYVMVM0.98520.80721020
ADCY9-RMI2chr164163751chr16114444992232HLA-B51:07DQLKGKYV0.99210.8706917
ADCY9-RMI2chr164163751chr16114444992232HLA-C05:09VADQLKGKY0.98350.9019716
ADCY9-RMI2chr164163751chr16114444992232HLA-B39:09DQLKGKYVM0.93540.7098918
ADCY9-RMI2chr164163751chr16114444992232HLA-B39:12DQLKGKYVM0.88930.9349918
ADCY9-RMI2chr164163751chr16114444992232HLA-C08:15VADQLKGKY0.83950.9298716
ADCY9-RMI2chr164163751chr16114444992232HLA-C15:04VADQLKGKY0.76990.7454716
ADCY9-RMI2chr164163751chr16114444992232HLA-B14:03DQLKGKYVM0.7610.7813918
ADCY9-RMI2chr164163751chr16114444992232HLA-B39:05DQLKGKYVM0.73210.9344918
ADCY9-RMI2chr164163751chr16114444992232HLA-B15:21DQLKGKYVM0.70450.8985918
ADCY9-RMI2chr164163751chr16114444992232HLA-B15:31DQLKGKYVM0.62260.9369918
ADCY9-RMI2chr164163751chr16114444992232HLA-B51:07DQLKGKYVM0.35860.8873918
ADCY9-RMI2chr164163751chr16114444992232HLA-C03:14VADQLKGKY0.29890.947716
ADCY9-RMI2chr164163751chr16114444992232HLA-B08:18QLKGKYVM0.99970.64411018
ADCY9-RMI2chr164163751chr16114444992232HLA-B08:12QLKGKYVM0.95670.82421018
ADCY9-RMI2chr164163751chr16114444992232HLA-B08:18QLKGKYVMV0.99760.71081019
ADCY9-RMI2chr164163751chr16114444992232HLA-A02:03QLKGKYVMV0.99420.681019
ADCY9-RMI2chr164163751chr16114444992232HLA-C05:01VADQLKGKY0.98350.9019716
ADCY9-RMI2chr164163751chr16114444992232HLA-B18:04DQLKGKYVM0.95720.8803918
ADCY9-RMI2chr164163751chr16114444992232HLA-B39:02DQLKGKYVM0.91980.9501918
ADCY9-RMI2chr164163751chr16114444992232HLA-B18:06DQLKGKYVM0.91360.866918
ADCY9-RMI2chr164163751chr16114444992232HLA-B18:07DQLKGKYVM0.9090.8092918
ADCY9-RMI2chr164163751chr16114444992232HLA-C03:02VADQLKGKY0.90430.9013716
ADCY9-RMI2chr164163751chr16114444992232HLA-B39:31DQLKGKYVM0.90070.9351918
ADCY9-RMI2chr164163751chr16114444992232HLA-B18:05DQLKGKYVM0.88530.8675918
ADCY9-RMI2chr164163751chr16114444992232HLA-B35:11VADQLKGKY0.87730.7693716
ADCY9-RMI2chr164163751chr16114444992232HLA-B18:08DQLKGKYVM0.87510.8442918
ADCY9-RMI2chr164163751chr16114444992232HLA-B18:03DQLKGKYVM0.84710.8428918
ADCY9-RMI2chr164163751chr16114444992232HLA-C08:02VADQLKGKY0.83950.9298716
ADCY9-RMI2chr164163751chr16114444992232HLA-B08:12QLKGKYVMV0.77090.80441019
ADCY9-RMI2chr164163751chr16114444992232HLA-C15:09VADQLKGKY0.76990.7454716
ADCY9-RMI2chr164163751chr16114444992232HLA-B08:12DQLKGKYVM0.70360.8379918
ADCY9-RMI2chr164163751chr16114444992232HLA-B18:11DQLKGKYVM0.67790.9292918
ADCY9-RMI2chr164163751chr16114444992232HLA-B35:20DQLKGKYVM0.60150.9738918
ADCY9-RMI2chr164163751chr16114444992232HLA-B39:11DQLKGKYVM0.57590.941918
ADCY9-RMI2chr164163751chr16114444992232HLA-B15:09DQLKGKYVM0.2830.8445918
ADCY9-RMI2chr164163751chr16114444992232HLA-C16:02VADQLKGKY0.19720.9797716
ADCY9-RMI2chr164163751chr16114444992232HLA-C16:01VADQLKGKY0.11790.949716
ADCY9-RMI2chr164163751chr16114444992232HLA-C02:10VADQLKGKY0.07970.9306716
ADCY9-RMI2chr164163751chr16114444992232HLA-C02:02VADQLKGKY0.07970.9306716
ADCY9-RMI2chr164163751chr16114444992232HLA-C12:02VADQLKGKY0.0610.9148716
ADCY9-RMI2chr164163751chr16114444992232HLA-B08:18QLKGKYVMVM0.98520.80721020

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Potential FusionNeoAntigen Information of ADCY9-RMI2 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 ADCY9-RMI2

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
10339VVADQLKGKYVMVMADCY9RMI2chr164163751chr16114444992232

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ADCY9-RMI2

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

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Vaccine Design for the FusionNeoAntigens of ADCY9-RMI2

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
ADCY9-RMI2chr164163751chr16114444991018QLKGKYVMAGTTGAAAGGAAAGTATGTGATGG
ADCY9-RMI2chr164163751chr16114444991019QLKGKYVMVAGTTGAAAGGAAAGTATGTGATGGTGA
ADCY9-RMI2chr164163751chr16114444991020QLKGKYVMVMAGTTGAAAGGAAAGTATGTGATGGTGATGG
ADCY9-RMI2chr164163751chr1611444499716VADQLKGKYTTGCTGACCAGTTGAAAGGAAAGTATG
ADCY9-RMI2chr164163751chr1611444499917DQLKGKYVACCAGTTGAAAGGAAAGTATGTGA
ADCY9-RMI2chr164163751chr1611444499918DQLKGKYVMACCAGTTGAAAGGAAAGTATGTGATGG

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 ADCY9-RMI2

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
BRCAADCY9-RMI2chr164163751ENST00000294016chr1611444499ENST00000572173TCGA-S3-AA0Z-01A

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Potential target of CAR-T therapy development for ADCY9-RMI2

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
HgeneADCY9chr16:4163751chr16:11444499ENST00000294016-211118_1385641354.0TransmembraneHelical
HgeneADCY9chr16:4163751chr16:11444499ENST00000294016-211142_1625641354.0TransmembraneHelical
HgeneADCY9chr16:4163751chr16:11444499ENST00000294016-211172_1925641354.0TransmembraneHelical
HgeneADCY9chr16:4163751chr16:11444499ENST00000294016-211216_2355641354.0TransmembraneHelical
HgeneADCY9chr16:4163751chr16:11444499ENST00000294016-211242_2595641354.0TransmembraneHelical
HgeneADCY9chr16:4163751chr16:11444499ENST00000294016-211281_3015641354.0TransmembraneHelical

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 ADCY9-RMI2

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 ADCY9-RMI2

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