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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:DISP2-CREBBP

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: DISP2-CREBBP
FusionPDB ID: 22945
FusionGDB2.0 ID: 22945
HgeneTgene
Gene symbol

DISP2

CREBBP

Gene ID

85455

1387

Gene namedispatched RND transporter family member 2CREB binding protein
SynonymsC15orf36|DISPB|HsT16908|LINC00594CBP|KAT3A|MKHK1|RSTS|RSTS1
Cytomap

15q15.1

16p13.3

Type of geneprotein-codingprotein-coding
Descriptionprotein dispatched homolog 2dispatched Blong intergenic non-protein coding RNA 594CREB-binding proteinhistone lysine acetyltransferase CREBBPprotein-lysine acetyltransferase CREBBP
Modification date2020031320200329
UniProtAcc

A7MBM2

Main function of 5'-partner protein:

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}.
Ensembl transtripts involved in fusion geneENST idsENST00000267889, ENST00000262367, 
ENST00000382070, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score4 X 4 X 3=4818 X 30 X 8=4320
# samples 428
** MAII scorelog2(4/48*10)=-0.263034405833794
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(28/4320*10)=-3.94753258010586
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: DISP2 [Title/Abstract] AND CREBBP [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: DISP2 [Title/Abstract] AND CREBBP [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)DISP2(40657926)-CREBBP(3860780), # samples:1
Anticipated loss of major functional domain due to fusion event.DISP2-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.
DISP2-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.
DISP2-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.
DISP2-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.
* 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
TgeneCREBBP

GO:0000122

negative regulation of transcription by RNA polymerase II

21539536

TgeneCREBBP

GO:0006355

regulation of transcription, DNA-templated

12169688

TgeneCREBBP

GO:0006473

protein acetylation

15273251|24207024|24939902|28790157|30540930

TgeneCREBBP

GO:0016573

histone acetylation

11742995

TgeneCREBBP

GO:0018076

N-terminal peptidyl-lysine acetylation

12435739

TgeneCREBBP

GO:0034644

cellular response to UV

24939902

TgeneCREBBP

GO:0045893

positive regulation of transcription, DNA-templated

11742995

TgeneCREBBP

GO:1990258

histone glutamine methylation

30540930



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/chr15:40657926/chr16:3860780)
- 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 DISP2 (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 CREBBP (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)
ENST00000267889DISP2chr1540657926+ENST00000262367CREBBPchr163860780-1022710328775622491
ENST00000267889DISP2chr1540657926+ENST00000382070CREBBPchr163860780-762810328774482453

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
ENST00000267889ENST00000262367DISP2chr1540657926+CREBBPchr163860780-0.0029797930.9970202
ENST00000267889ENST00000382070DISP2chr1540657926+CREBBPchr163860780-0.0101855970.9898144

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 DISP2-CREBBP

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
DISP2chr1540657926CREBBPchr1638607801032314LHAIHSMCRMEQDQMGITGNTSPFGQ

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Potential FusionNeoAntigen Information of DISP2-CREBBP 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.

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)

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Potential FusionNeoAntigen Information of DISP2-CREBBP 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.
DISP2-CREBBP_40657926_3860780.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)
DISP2-CREBBPchr1540657926chr1638607801032DRB3-0201QDQMGITGNTSPFGQ1126
DISP2-CREBBPchr1540657926chr1638607801032DRB3-0224QDQMGITGNTSPFGQ1126

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Fusion breakpoint peptide structures of DISP2-CREBBP

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.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of DISP2-CREBBP

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 DISP2-CREBBP

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

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
DISP2-CREBBPchr1540657926chr1638607801126QDQMGITGNTSPFGQGACCAGATGGGAATAACTGGGAACACAAGTCCATTTGGACAGCCC

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Information of the samples that have these potential fusion neoantigens of DISP2-CREBBP

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

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Potential target of CAR-T therapy development for DISP2-CREBBP

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
HgeneDISP2chr15:40657926chr16:3860780ENST00000267889+78170_1903151402.0TransmembraneHelical

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 DISP2-CREBBP

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 DISP2-CREBBP

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
TgeneCREBBPC4551859RUBINSTEIN-TAYBI SYNDROME 112CLINGEN;GENOMICS_ENGLAND;UNIPROT
TgeneCREBBPC0035934Rubinstein-Taybi Syndrome6CLINGEN;CTD_human
TgeneCREBBPC0033578Prostatic Neoplasms2CTD_human
TgeneCREBBPC0376358Malignant neoplasm of prostate2CTD_human
TgeneCREBBPC4511003Acute myeloid leukemia with t(8;16)(p11;p13) translocation2ORPHANET
TgeneCREBBPC0005684Malignant neoplasm of urinary bladder1CTD_human
TgeneCREBBPC0005695Bladder Neoplasm1CTD_human
TgeneCREBBPC0007137Squamous cell carcinoma1CTD_human
TgeneCREBBPC0007138Carcinoma, Transitional Cell1CTD_human
TgeneCREBBPC0010606Adenoid Cystic Carcinoma1CTD_human
TgeneCREBBPC0011573Endogenous depression1PSYGENET
TgeneCREBBPC0024301Lymphoma, Follicular1CTD_human
TgeneCREBBPC0036920Sezary Syndrome1CTD_human
TgeneCREBBPC0079745Lymphoma, Large-Cell, Follicular1CTD_human
TgeneCREBBPC0079758Lymphoma, Mixed-Cell, Follicular1CTD_human
TgeneCREBBPC0079765Lymphoma, Small Cleaved-Cell, Follicular1CTD_human
TgeneCREBBPC0149925Small cell carcinoma of lung1CTD_human
TgeneCREBBPC0152013Adenocarcinoma of lung (disorder)1CTD_human
TgeneCREBBPC0279626Squamous cell carcinoma of esophagus1CTD_human
TgeneCREBBPC1862939AMYOTROPHIC LATERAL SCLEROSIS 11CTD_human
TgeneCREBBPC1862941Amyotrophic Lateral Sclerosis, Sporadic1CTD_human
TgeneCREBBPC1956130Lymphoma, Follicular, Grade 11CTD_human
TgeneCREBBPC1956131Lymphoma, Follicular, Grade 31CTD_human
TgeneCREBBPC1956132Lymphoma, Follicular, Grade 21CTD_human
TgeneCREBBPC4551993Amyotrophic Lateral Sclerosis, Familial1CTD_human