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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:CAMK2G-AGAP5

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CAMK2G-AGAP5
FusionPDB ID: 12675
FusionGDB2.0 ID: 12675
HgeneTgene
Gene symbol

CAMK2G

AGAP5

Gene ID

818

729092

Gene namecalcium/calmodulin dependent protein kinase II gammaArfGAP with GTPase domain, ankyrin repeat and PH domain 5
SynonymsCAMK|CAMK-II|CAMKG|MRD59CTGLF2
Cytomap

10q22.2

10q22.2

Type of geneprotein-codingprotein-coding
Descriptioncalcium/calmodulin-dependent protein kinase type II subunit gammacaMK-II subunit gammacalcium/calmodulin-dependent protein kinase (CaM kinase) II gammaarf-GAP with GTPase, ANK repeat and PH domain-containing protein 5AGAP-5centaurin, gamma-like family, member 2
Modification date2020031320200313
UniProtAcc

Q13555

Main function of 5'-partner protein: FUNCTION: Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation, and is involved in sarcoplasmic reticulum Ca(2+) transport in skeletal muscle and may function in dendritic spine and synapse formation and neuronal plasticity. In slow-twitch muscles, is involved in regulation of sarcoplasmic reticulum (SR) Ca(2+) transport and in fast-twitch muscle participates in the control of Ca(2+) release from the SR through phosphorylation of the ryanodine receptor-coupling factor triadin. In the central nervous system, it is involved in the regulation of neurite formation and arborization (PubMed:30184290). It may participate in the promotion of dendritic spine and synapse formation and maintenance of synaptic plasticity which enables long-term potentiation (LTP) and hippocampus-dependent learning. {ECO:0000269|PubMed:16690701, ECO:0000269|PubMed:30184290}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000472912, ENST00000305762, 
ENST00000322635, ENST00000322680, 
ENST00000351293, ENST00000372765, 
ENST00000394762, ENST00000423381, 
ENST00000444854, 
ENST00000374094, 
ENST00000443782, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score9 X 11 X 7=6931 X 1 X 1=1
# samples 121
** MAII scorelog2(12/693*10)=-2.5298209465287
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(1/1*10)=3.32192809488736
Fusion gene context

PubMed: CAMK2G [Title/Abstract] AND AGAP5 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CAMK2G [Title/Abstract] AND AGAP5 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CAMK2G(75632747)-AGAP5(75442552), # samples:2
Anticipated loss of major functional domain due to fusion event.CAMK2G-AGAP5 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.
CAMK2G-AGAP5 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.
CAMK2G-AGAP5 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.
CAMK2G-AGAP5 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/chr10:75632747/chr10:75442552)
- 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 CAMK2G (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 AGAP5 (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)
ENST00000351293CAMK2Gchr1075632747-ENST00000374094AGAP5chr1075442552-22072182091882557
ENST00000351293CAMK2Gchr1075632747-ENST00000443782AGAP5chr1075442552-21952182091882557
ENST00000322635CAMK2Gchr1075632747-ENST00000374094AGAP5chr1075442552-22682792701943557
ENST00000322635CAMK2Gchr1075632747-ENST00000443782AGAP5chr1075442552-22562792701943557
ENST00000394762CAMK2Gchr1075632747-ENST00000374094AGAP5chr1075442552-22732842751948557
ENST00000394762CAMK2Gchr1075632747-ENST00000443782AGAP5chr1075442552-22612842751948557
ENST00000423381CAMK2Gchr1075632747-ENST00000374094AGAP5chr1075442552-22732842751948557
ENST00000423381CAMK2Gchr1075632747-ENST00000443782AGAP5chr1075442552-22612842751948557
ENST00000322680CAMK2Gchr1075632747-ENST00000374094AGAP5chr1075442552-22732842751948557
ENST00000322680CAMK2Gchr1075632747-ENST00000443782AGAP5chr1075442552-22612842751948557
ENST00000305762CAMK2Gchr1075632747-ENST00000374094AGAP5chr1075442552-21491601511824557
ENST00000305762CAMK2Gchr1075632747-ENST00000443782AGAP5chr1075442552-21371601511824557
ENST00000372765CAMK2Gchr1075632747-ENST00000374094AGAP5chr1075442552-21902011921865557
ENST00000372765CAMK2Gchr1075632747-ENST00000443782AGAP5chr1075442552-21782011921865557
ENST00000444854CAMK2Gchr1075632747-ENST00000374094AGAP5chr1075442552-22702812721945557
ENST00000444854CAMK2Gchr1075632747-ENST00000443782AGAP5chr1075442552-22582812721945557

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
ENST00000351293ENST00000374094CAMK2Gchr1075632747-AGAP5chr1075442552-0.0264094680.97359055
ENST00000351293ENST00000443782CAMK2Gchr1075632747-AGAP5chr1075442552-0.027512480.9724875
ENST00000322635ENST00000374094CAMK2Gchr1075632747-AGAP5chr1075442552-0.0287966110.9712034
ENST00000322635ENST00000443782CAMK2Gchr1075632747-AGAP5chr1075442552-0.030000350.9699996
ENST00000394762ENST00000374094CAMK2Gchr1075632747-AGAP5chr1075442552-0.0278103820.9721896
ENST00000394762ENST00000443782CAMK2Gchr1075632747-AGAP5chr1075442552-0.0289080570.971092
ENST00000423381ENST00000374094CAMK2Gchr1075632747-AGAP5chr1075442552-0.0278103820.9721896
ENST00000423381ENST00000443782CAMK2Gchr1075632747-AGAP5chr1075442552-0.0289080570.971092
ENST00000322680ENST00000374094CAMK2Gchr1075632747-AGAP5chr1075442552-0.0278103820.9721896
ENST00000322680ENST00000443782CAMK2Gchr1075632747-AGAP5chr1075442552-0.0289080570.971092
ENST00000305762ENST00000374094CAMK2Gchr1075632747-AGAP5chr1075442552-0.024491420.9755086
ENST00000305762ENST00000443782CAMK2Gchr1075632747-AGAP5chr1075442552-0.0255901810.97440976
ENST00000372765ENST00000374094CAMK2Gchr1075632747-AGAP5chr1075442552-0.0268170270.97318304
ENST00000372765ENST00000443782CAMK2Gchr1075632747-AGAP5chr1075442552-0.0279486480.9720514
ENST00000444854ENST00000374094CAMK2Gchr1075632747-AGAP5chr1075442552-0.0286821460.9713179
ENST00000444854ENST00000443782CAMK2Gchr1075632747-AGAP5chr1075442552-0.0298389070.970161

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 CAMK2G-AGAP5

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

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Potential FusionNeoAntigen Information of CAMK2G-AGAP5 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 CAMK2G-AGAP5 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 CAMK2G-AGAP5

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 CAMK2G-AGAP5

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 CAMK2G-AGAP5

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

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Information of the samples that have these potential fusion neoantigens of CAMK2G-AGAP5

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 CAMK2G-AGAP5

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 CAMK2G-AGAP5

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 CAMK2G-AGAP5

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