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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:CREBBP-ADCY9

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CREBBP-ADCY9
FusionPDB ID: 19349
FusionGDB2.0 ID: 19349
HgeneTgene
Gene symbol

CREBBP

ADCY9

Gene ID

1387

115

Gene nameCREB binding proteinadenylate cyclase 9
SynonymsCBP|KAT3A|MKHK1|RSTS|RSTS1AC9|ACIX
Cytomap

16p13.3

16p13.3

Type of geneprotein-codingprotein-coding
DescriptionCREB-binding proteinhistone lysine acetyltransferase CREBBPprotein-lysine acetyltransferase CREBBPadenylate cyclase type 9ATP pyrophosphate-lyase 9adenylate cyclase type IXadenylyl cyclase 9type IX ATP pyrophosphate-lyase
Modification date2020032920200313
UniProtAcc

Q92793

Main function of 5'-partner protein: FUNCTION: Acetylates histones, giving a specific tag for transcriptional activation (PubMed:24616510). Also acetylates non-histone proteins, like DDX21, FBL, IRF2, MAFG, NCOA3, POLR1E/PAF53 and FOXO1 (PubMed:10490106, PubMed:11154691, PubMed:12738767, PubMed:12929931, PubMed:9707565, PubMed:24207024, PubMed:28790157, PubMed:30540930). Binds specifically to phosphorylated CREB and enhances its transcriptional activity toward cAMP-responsive genes. Acts as a coactivator of ALX1. Acts as a circadian transcriptional coactivator which enhances the activity of the circadian transcriptional activators: NPAS2-ARNTL/BMAL1 and CLOCK-ARNTL/BMAL1 heterodimers (PubMed:14645221). Acetylates PCNA; acetylation promotes removal of chromatin-bound PCNA and its degradation during nucleotide excision repair (NER) (PubMed:24939902). Acetylates POLR1E/PAF53, leading to decreased association of RNA polymerase I with the rDNA promoter region and coding region (PubMed:24207024). Acetylates DDX21, thereby inhibiting DDX21 helicase activity (PubMed:28790157). Acetylates FBL, preventing methylation of 'Gln-105' of histone H2A (H2AQ104me) (PubMed:30540930). Functions as a transcriptional coactivator for SMAD4 in the TGF-beta signaling pathway (PubMed:25514493). {ECO:0000269|PubMed:10490106, ECO:0000269|PubMed:11154691, ECO:0000269|PubMed:12738767, ECO:0000269|PubMed:12929931, ECO:0000269|PubMed:14645221, ECO:0000269|PubMed:24207024, ECO:0000269|PubMed:24616510, ECO:0000269|PubMed:24939902, ECO:0000269|PubMed:25514493, ECO:0000269|PubMed:28790157, ECO:0000269|PubMed:30540930, ECO:0000269|PubMed:9707565}.

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 idsENST00000262367, ENST00000382070, 
ENST00000571889, ENST00000294016, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score43 X 38 X 17=277788 X 7 X 6=336
# samples 619
** MAII scorelog2(61/27778*10)=-5.50898967694577
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(9/336*10)=-1.90046432644909
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

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

Fusion neoantigen context

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

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ADCY9(4163751)-CREBBP(3901010), # samples:2
CREBBP(3929833)-ADCY9(4016967), # samples:2
Anticipated loss of major functional domain due to fusion event.ADCY9-CREBBP 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-CREBBP 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.
CREBBP-ADCY9 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.
CREBBP-ADCY9 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.
CREBBP-ADCY9 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.
CREBBP-ADCY9 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
HgeneCREBBP

GO:0000122

negative regulation of transcription by RNA polymerase II

21539536

HgeneCREBBP

GO:0006355

regulation of transcription, DNA-templated

12169688

HgeneCREBBP

GO:0006473

protein acetylation

15273251|24207024|24939902|28790157|30540930

HgeneCREBBP

GO:0016573

histone acetylation

11742995

HgeneCREBBP

GO:0018076

N-terminal peptidyl-lysine acetylation

12435739

HgeneCREBBP

GO:0034644

cellular response to UV

24939902

HgeneCREBBP

GO:0045893

positive regulation of transcription, DNA-templated

11742995

HgeneCREBBP

GO:1990258

histone glutamine methylation

30540930

TgeneADCY9

GO:0006171

cAMP biosynthetic process

9628827|10987815

TgeneADCY9

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/chr16:3901010)
- 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 CREBBP (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 ADCY9 (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)
ENST00000262367CREBBPchr163929833-ENST00000294016ADCY9chr164043511-61978958143072752
ENST00000382070CREBBPchr163929833-ENST00000294016ADCY9chr164043511-55912892082466752

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
ENST00000262367ENST00000294016CREBBPchr163929833-ADCY9chr164043511-0.00178650.9982135
ENST00000382070ENST00000294016CREBBPchr163929833-ADCY9chr164043511-0.0014755050.9985245

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 CREBBP-ADCY9

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CREBBPchr163929833ADCY9chr16404351128927NSARPVSRRMTAQTCPSCGITFAPKS
CREBBPchr163929833ADCY9chr16404351189527NSARPVSRRMTAQTCPSCGITFAPKS

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Potential FusionNeoAntigen Information of CREBBP-ADCY9 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.
CREBBP-ADCY9_3929833_4043511.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)
CREBBP-ADCY9chr163929833chr164043511895HLA-B39:06SRRMTAQTC0.84570.7273615
CREBBP-ADCY9chr163929833chr164043511895HLA-B57:01QTCPSCGITF0.99540.97111222
CREBBP-ADCY9chr163929833chr164043511895HLA-B58:02QTCPSCGITF0.9760.93271222
CREBBP-ADCY9chr163929833chr164043511895HLA-B15:16QTCPSCGITF0.97580.81341222
CREBBP-ADCY9chr163929833chr164043511895HLA-B57:03QTCPSCGITF0.96350.98051222
CREBBP-ADCY9chr163929833chr164043511895HLA-B58:01QTCPSCGITF0.95320.93931222
CREBBP-ADCY9chr163929833chr164043511895HLA-B73:01RRMTAQTCP0.83260.7038716
CREBBP-ADCY9chr163929833chr164043511895HLA-B57:04QTCPSCGITF0.99720.78121222
CREBBP-ADCY9chr163929833chr164043511895HLA-B57:10QTCPSCGITF0.99540.97111222
CREBBP-ADCY9chr163929833chr164043511895HLA-B57:02QTCPSCGITF0.98960.95971222
CREBBP-ADCY9chr163929833chr164043511895HLA-B58:06QTCPSCGITF0.98420.9161222

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Potential FusionNeoAntigen Information of CREBBP-ADCY9 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 CREBBP-ADCY9

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
8980SRRMTAQTCPSCGICREBBPADCY9chr163929833chr164043511895

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

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-B14:023BVN8980SRRMTAQTCPSCGI-7.15543-7.26883
HLA-B14:023BVN8980SRRMTAQTCPSCGI-4.77435-5.80965
HLA-B52:013W398980SRRMTAQTCPSCGI-6.80875-6.92215
HLA-B52:013W398980SRRMTAQTCPSCGI-4.20386-5.23916
HLA-A11:014UQ28980SRRMTAQTCPSCGI-7.5194-8.5547
HLA-A11:014UQ28980SRRMTAQTCPSCGI-6.9601-7.0735
HLA-A24:025HGA8980SRRMTAQTCPSCGI-7.52403-7.63743
HLA-A24:025HGA8980SRRMTAQTCPSCGI-5.82433-6.85963
HLA-B27:056PYJ8980SRRMTAQTCPSCGI-3.28285-4.31815
HLA-B44:053DX88980SRRMTAQTCPSCGI-5.91172-6.94702
HLA-B44:053DX88980SRRMTAQTCPSCGI-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of CREBBP-ADCY9

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
CREBBP-ADCY9chr163929833chr1640435111222QTCPSCGITFCAGACCTGCCCTTCGTGCGGAATCACATTT
CREBBP-ADCY9chr163929833chr164043511615SRRMTAQTCTCTCGGCGAATGACAGCACAGACCTGC
CREBBP-ADCY9chr163929833chr164043511716RRMTAQTCPCGGCGAATGACAGCACAGACCTGCCCT

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 CREBBP-ADCY9

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
ESCACREBBP-ADCY9chr163929833ENST00000262367chr164043511ENST00000294016TCGA-L5-A43M-01A

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

check button Predicted 3D structure. We used RoseTTAFold.
123_CREBBP-ADCY9_t000_.e2e.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
TgeneADCY9chr16:3929833chr16:4016967ENST00000294016911976_99601354.0TransmembraneHelical
TgeneADCY9chr16:3929833chr16:4043511ENST00000294016211787_80701354.0TransmembraneHelical
TgeneADCY9chr16:3929833chr16:4043511ENST00000294016211819_83901354.0TransmembraneHelical
TgeneADCY9chr16:3929833chr16:4043511ENST00000294016211868_88801354.0TransmembraneHelical
TgeneADCY9chr16:3929833chr16:4043511ENST00000294016211892_91201354.0TransmembraneHelical
TgeneADCY9chr16:3929833chr16:4043511ENST00000294016211921_94101354.0TransmembraneHelical
TgeneADCY9chr16:3929833chr16:4043511ENST00000294016211976_99601354.0TransmembraneHelical

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
CREBBPchr163929833ENST00000262367ADCY9chr164043511ENST00000294016

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Related Drugs to CREBBP-ADCY9

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 CREBBP-ADCY9

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
HgeneCREBBPC4551859RUBINSTEIN-TAYBI SYNDROME 112CLINGEN;GENOMICS_ENGLAND;UNIPROT
HgeneCREBBPC0035934Rubinstein-Taybi Syndrome6CLINGEN;CTD_human
HgeneCREBBPC0033578Prostatic Neoplasms2CTD_human
HgeneCREBBPC0376358Malignant neoplasm of prostate2CTD_human
HgeneCREBBPC4511003Acute myeloid leukemia with t(8;16)(p11;p13) translocation2ORPHANET
HgeneCREBBPC0005684Malignant neoplasm of urinary bladder1CTD_human
HgeneCREBBPC0005695Bladder Neoplasm1CTD_human
HgeneCREBBPC0007137Squamous cell carcinoma1CTD_human
HgeneCREBBPC0007138Carcinoma, Transitional Cell1CTD_human
HgeneCREBBPC0010606Adenoid Cystic Carcinoma1CTD_human
HgeneCREBBPC0011573Endogenous depression1PSYGENET
HgeneCREBBPC0024301Lymphoma, Follicular1CTD_human
HgeneCREBBPC0036920Sezary Syndrome1CTD_human
HgeneCREBBPC0079745Lymphoma, Large-Cell, Follicular1CTD_human
HgeneCREBBPC0079758Lymphoma, Mixed-Cell, Follicular1CTD_human
HgeneCREBBPC0079765Lymphoma, Small Cleaved-Cell, Follicular1CTD_human
HgeneCREBBPC0149925Small cell carcinoma of lung1CTD_human
HgeneCREBBPC0152013Adenocarcinoma of lung (disorder)1CTD_human
HgeneCREBBPC0279626Squamous cell carcinoma of esophagus1CTD_human
HgeneCREBBPC1862939AMYOTROPHIC LATERAL SCLEROSIS 11CTD_human
HgeneCREBBPC1862941Amyotrophic Lateral Sclerosis, Sporadic1CTD_human
HgeneCREBBPC1956130Lymphoma, Follicular, Grade 11CTD_human
HgeneCREBBPC1956131Lymphoma, Follicular, Grade 31CTD_human
HgeneCREBBPC1956132Lymphoma, Follicular, Grade 21CTD_human
HgeneCREBBPC4551993Amyotrophic Lateral Sclerosis, Familial1CTD_human