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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:CREB3L2-CPA2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CREB3L2-CPA2
FusionPDB ID: 19319
FusionGDB2.0 ID: 19319
HgeneTgene
Gene symbol

CREB3L2

CPA2

Gene ID

64764

1358

Gene namecAMP responsive element binding protein 3 like 2carboxypeptidase A2
SynonymsBBF2H7-
Cytomap

7q33

7q32.2

Type of geneprotein-codingprotein-coding
Descriptioncyclic AMP-responsive element-binding protein 3-like protein 2B-ZIB transcription factorBBF2 human homolog on chromosome 7FUS/BBF2H7 proteinTCAG_1951439basic transcription factor 2cAMP-responsive element-binding protein 3-like protein 2carboxypeptidase A2carboxypeptidase A2 (pancreatic)
Modification date2020031320200313
UniProtAcc

Q70SY1

Main function of 5'-partner protein: FUNCTION: Transcription factor involved in unfolded protein response (UPR). In the absence of endoplasmic reticulum (ER) stress, inserted into ER membranes, with N-terminal DNA-binding and transcription activation domains oriented toward the cytosolic face of the membrane. In response to ER stress, transported to the Golgi, where it is cleaved in a site-specific manner by resident proteases S1P/MBTPS1 and S2P/MBTPS2. The released N-terminal cytosolic domain is translocated to the nucleus to effect transcription of specific target genes. Plays a critical role in chondrogenesis by activating the transcription of SEC23A, which promotes the transport and secretion of cartilage matrix proteins, and possibly that of ER biogenesis-related genes (By similarity). In a neuroblastoma cell line, protects cells from ER stress-induced death (PubMed:17178827). In vitro activates transcription of target genes via direct binding to the CRE site (PubMed:17178827). {ECO:0000250|UniProtKB:Q8BH52, ECO:0000269|PubMed:17178827}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000468127, ENST00000330387, 
ENST00000452463, ENST00000456390, 
ENST00000458726, 
ENST00000222481, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score15 X 16 X 7=16802 X 3 X 2=12
# samples 183
** MAII scorelog2(18/1680*10)=-3.22239242133645
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(3/12*10)=1.32192809488736
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: CREB3L2 [Title/Abstract] AND CPA2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CREB3L2 [Title/Abstract] AND CPA2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CREB3L2(137686350)-CPA2(129921944), # samples:3
Anticipated loss of major functional domain due to fusion event.CREB3L2-CPA2 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.
CREB3L2-CPA2 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
HgeneCREB3L2

GO:0045893

positive regulation of transcription, DNA-templated

17178827



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/chr7:137686350/chr7:129921944)
- 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 CREB3L2 (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 CPA2 (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)
ENST00000330387CREB3L2chr7137686350-ENST00000222481CPA2chr7129921944+778454352726124
ENST00000456390CREB3L2chr7137686350-ENST00000222481CPA2chr7129921944+788464362736124
ENST00000452463CREB3L2chr7137686350-ENST00000222481CPA2chr7129921944+768444342716124
ENST00000330387CREB3L2chr7137686349-ENST00000222481CPA2chr7129921943+778454352726124
ENST00000456390CREB3L2chr7137686349-ENST00000222481CPA2chr7129921943+788464362736124
ENST00000452463CREB3L2chr7137686349-ENST00000222481CPA2chr7129921943+768444342716124

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
ENST00000330387ENST00000222481CREB3L2chr7137686350-CPA2chr7129921944+0.0456757020.9543243
ENST00000456390ENST00000222481CREB3L2chr7137686350-CPA2chr7129921944+0.0504468120.94955313
ENST00000452463ENST00000222481CREB3L2chr7137686350-CPA2chr7129921944+0.0501511020.94984895
ENST00000330387ENST00000222481CREB3L2chr7137686349-CPA2chr7129921943+0.0456757020.9543243
ENST00000456390ENST00000222481CREB3L2chr7137686349-CPA2chr7129921943+0.0504468120.94955313
ENST00000452463ENST00000222481CREB3L2chr7137686349-CPA2chr7129921943+0.0501511020.94984895

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 CREB3L2-CPA2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CREB3L2chr7137686349CPA2chr712992194344434SEPGDGEALMYHTSEVAQKAAQSLRS
CREB3L2chr7137686349CPA2chr712992194345434SEPGDGEALMYHTSEVAQKAAQSLRS
CREB3L2chr7137686349CPA2chr712992194346434SEPGDGEALMYHTSEVAQKAAQSLRS
CREB3L2chr7137686350CPA2chr712992194444434SEPGDGEALMYHTSEVAQKAAQSLRS
CREB3L2chr7137686350CPA2chr712992194445434SEPGDGEALMYHTSEVAQKAAQSLRS
CREB3L2chr7137686350CPA2chr712992194446434SEPGDGEALMYHTSEVAQKAAQSLRS

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Potential FusionNeoAntigen Information of CREB3L2-CPA2 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.
CREB3L2-CPA2_137686349_129921943.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)
CREB3L2-CPA2chr7137686349chr7129921943454HLA-A02:22ALMYHTSEV0.99860.6444716
CREB3L2-CPA2chr7137686349chr7129921943454HLA-A02:13ALMYHTSEV0.99780.677716
CREB3L2-CPA2chr7137686349chr7129921943454HLA-A02:27ALMYHTSEV0.99770.6195716
CREB3L2-CPA2chr7137686349chr7129921943454HLA-A02:11ALMYHTSEV0.99670.5474716
CREB3L2-CPA2chr7137686349chr7129921943454HLA-A02:24ALMYHTSEV0.99650.5254716
CREB3L2-CPA2chr7137686349chr7129921943454HLA-A02:67ALMYHTSEV0.99650.5254716
CREB3L2-CPA2chr7137686349chr7129921943454HLA-A02:30ALMYHTSEV0.99650.5254716
CREB3L2-CPA2chr7137686349chr7129921943454HLA-A02:60ALMYHTSEV0.99650.5355716
CREB3L2-CPA2chr7137686349chr7129921943454HLA-A02:38ALMYHTSEV0.99640.6432716
CREB3L2-CPA2chr7137686349chr7129921943454HLA-A02:21ALMYHTSEV0.99490.6185716
CREB3L2-CPA2chr7137686349chr7129921943454HLA-A02:04ALMYHTSEV0.99220.6579716
CREB3L2-CPA2chr7137686349chr7129921943454HLA-A02:29ALMYHTSEV0.98920.5306716
CREB3L2-CPA2chr7137686349chr7129921943454HLA-A02:35ALMYHTSEV0.98230.5527716
CREB3L2-CPA2chr7137686349chr7129921943454HLA-A02:20ALMYHTSEV0.96760.5372716
CREB3L2-CPA2chr7137686349chr7129921943454HLA-B45:01GEALMYHTS0.96670.8142514
CREB3L2-CPA2chr7137686349chr7129921943454HLA-B50:02GEALMYHTS0.92540.5383514
CREB3L2-CPA2chr7137686349chr7129921943454HLA-B50:01GEALMYHTS0.13070.5359514
CREB3L2-CPA2chr7137686349chr7129921943454HLA-B13:02ALMYHTSEV0.06140.6342716
CREB3L2-CPA2chr7137686349chr7129921943454HLA-B39:06YHTSEVAQKA0.99830.85851020
CREB3L2-CPA2chr7137686349chr7129921943454HLA-B39:06YHTSEVAQKAA0.99980.93541021
CREB3L2-CPA2chr7137686349chr7129921943454HLA-A02:02ALMYHTSEV0.99860.5397716
CREB3L2-CPA2chr7137686349chr7129921943454HLA-A02:05ALMYHTSEV0.99780.6301716
CREB3L2-CPA2chr7137686349chr7129921943454HLA-A02:07ALMYHTSEV0.99650.5669716
CREB3L2-CPA2chr7137686349chr7129921943454HLA-A02:01ALMYHTSEV0.99650.5254716
CREB3L2-CPA2chr7137686349chr7129921943454HLA-A02:03ALMYHTSEV0.99920.6834716
CREB3L2-CPA2chr7137686349chr7129921943454HLA-A02:06ALMYHTSEV0.99490.6185716
CREB3L2-CPA2chr7137686349chr7129921943454HLA-A02:14ALMYHTSEV0.99480.5808716
CREB3L2-CPA2chr7137686349chr7129921943454HLA-A69:01HTSEVAQKA0.98090.6061120
CREB3L2-CPA2chr7137686349chr7129921943454HLA-B50:04GEALMYHTS0.13070.5359514
CREB3L2-CPA2chr7137686349chr7129921943454HLA-B50:05GEALMYHTS0.13070.5359514
CREB3L2-CPA2chr7137686349chr7129921943454HLA-C07:04ALMYHTSEV0.11640.9463716

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Potential FusionNeoAntigen Information of CREB3L2-CPA2 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.
CREB3L2-CPA2_137686349_129921943.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)
CREB3L2-CPA2chr7137686349chr7129921943454DRB1-0437GEALMYHTSEVAQKA520
CREB3L2-CPA2chr7137686349chr7129921943454DRB1-0902ALMYHTSEVAQKAAQ722
CREB3L2-CPA2chr7137686349chr7129921943454DRB1-1367GEALMYHTSEVAQKA520
CREB3L2-CPA2chr7137686349chr7129921943454DRB1-1457GEALMYHTSEVAQKA520
CREB3L2-CPA2chr7137686349chr7129921943454DRB1-1457DGEALMYHTSEVAQK419
CREB3L2-CPA2chr7137686349chr7129921943454DRB1-1510GEALMYHTSEVAQKA520
CREB3L2-CPA2chr7137686349chr7129921943454DRB5-0112ALMYHTSEVAQKAAQ722
CREB3L2-CPA2chr7137686349chr7129921943454DRB5-0112EALMYHTSEVAQKAA621
CREB3L2-CPA2chr7137686349chr7129921943454DRB5-0112GEALMYHTSEVAQKA520

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Fusion breakpoint peptide structures of CREB3L2-CPA2

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
1536EALMYHTSEVAQKACREB3L2CPA2chr7137686349chr7129921943454

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CREB3L2-CPA2

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-B14:023BVN1536EALMYHTSEVAQKA-7.9962-8.1096
HLA-B14:023BVN1536EALMYHTSEVAQKA-5.70842-6.74372
HLA-B52:013W391536EALMYHTSEVAQKA-6.83737-6.95077
HLA-B52:013W391536EALMYHTSEVAQKA-4.4836-5.5189
HLA-A11:014UQ21536EALMYHTSEVAQKA-10.0067-10.1201
HLA-A11:014UQ21536EALMYHTSEVAQKA-9.03915-10.0745
HLA-A24:025HGA1536EALMYHTSEVAQKA-6.56204-6.67544
HLA-A24:025HGA1536EALMYHTSEVAQKA-5.42271-6.45801
HLA-B44:053DX81536EALMYHTSEVAQKA-7.85648-8.89178
HLA-B44:053DX81536EALMYHTSEVAQKA-5.3978-5.5112
HLA-A02:016TDR1536EALMYHTSEVAQKA-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of CREB3L2-CPA2

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
CREB3L2-CPA2chr7137686349chr71299219431020YHTSEVAQKATACCACACGAGTGAAGTGGCCCAAAAGGCT
CREB3L2-CPA2chr7137686349chr71299219431021YHTSEVAQKAATACCACACGAGTGAAGTGGCCCAAAAGGCTGCC
CREB3L2-CPA2chr7137686349chr71299219431120HTSEVAQKACACACGAGTGAAGTGGCCCAAAAGGCT
CREB3L2-CPA2chr7137686349chr7129921943514GEALMYHTSGGCGAGGCCCTCATGTACCACACGAGT
CREB3L2-CPA2chr7137686349chr7129921943716ALMYHTSEVGCCCTCATGTACCACACGAGTGAAGTG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
CREB3L2-CPA2chr7137686349chr7129921943419DGEALMYHTSEVAQKGACGGCGAGGCCCTCATGTACCACACGAGTGAAGTGGCCCAAAAG
CREB3L2-CPA2chr7137686349chr7129921943520GEALMYHTSEVAQKAGGCGAGGCCCTCATGTACCACACGAGTGAAGTGGCCCAAAAGGCT
CREB3L2-CPA2chr7137686349chr7129921943621EALMYHTSEVAQKAAGAGGCCCTCATGTACCACACGAGTGAAGTGGCCCAAAAGGCTGCC
CREB3L2-CPA2chr7137686349chr7129921943722ALMYHTSEVAQKAAQGCCCTCATGTACCACACGAGTGAAGTGGCCCAAAAGGCTGCCCAA

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Information of the samples that have these potential fusion neoantigens of CREB3L2-CPA2

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
ACCCREB3L2-CPA2chr7137686349ENST00000330387chr7129921943ENST00000222481TCGA-OR-A5JY

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Potential target of CAR-T therapy development for CREB3L2-CPA2

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 CREB3L2-CPA2

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 CREB3L2-CPA2

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