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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:CNOT2-SRGAP1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CNOT2-SRGAP1
FusionPDB ID: 17753
FusionGDB2.0 ID: 17753
HgeneTgene
Gene symbol

CNOT2

SRGAP1

Gene ID

4848

57522

Gene nameCCR4-NOT transcription complex subunit 2SLIT-ROBO Rho GTPase activating protein 1
SynonymsCDC36|HSPC131|IDNADFS|NOT2|NOT2HARHGAP13|NMTC2
Cytomap

12q15

12q14.2

Type of geneprotein-codingprotein-coding
DescriptionCCR4-NOT transcription complex subunit 2CCR4-associated factor 2negative regulator of transcription 2SLIT-ROBO Rho GTPase-activating protein 1rho GTPase-activating protein 13
Modification date2020031320200313
UniProtAcc

Q9NZN8

Main function of 5'-partner protein: FUNCTION: Component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. Required for the CCR4-NOT complex structural integrity. Can repress transcription and may link the CCR4-NOT complex to transcriptional regulation; the repressive function may specifically involve the N-Cor repressor complex containing HDAC3, NCOR1 and NCOR2. Involved in the maintenance of embryonic stem (ES) cell identity. {ECO:0000269|PubMed:14707134, ECO:0000269|PubMed:16712523, ECO:0000269|PubMed:21299754, ECO:0000269|PubMed:22367759}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000229195, ENST00000418359, 
ENST00000548230, ENST00000551483, 
ENST00000543397, ENST00000355086, 
ENST00000357825, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score41 X 13 X 11=586318 X 13 X 8=1872
# samples 4621
** MAII scorelog2(46/5863*10)=-3.6719332904521
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(21/1872*10)=-3.15611920191728
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: CNOT2 [Title/Abstract] AND SRGAP1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CNOT2 [Title/Abstract] AND SRGAP1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CNOT2(70713144)-SRGAP1(64377727), # samples:3
Anticipated loss of major functional domain due to fusion event.CNOT2-SRGAP1 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.
CNOT2-SRGAP1 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.
CNOT2-SRGAP1 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.
CNOT2-SRGAP1 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
HgeneCNOT2

GO:0000122

negative regulation of transcription by RNA polymerase II

14707134|16712523



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/chr12:70713144/chr12:64377727)
- 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 CNOT2 (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 SRGAP1 (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)
ENST00000229195CNOT2chr1270713144+ENST00000355086SRGAP1chr1264377727+916981754040071155
ENST00000229195CNOT2chr1270713144+ENST00000357825SRGAP1chr1264377727+910081754039381132
ENST00000418359CNOT2chr1270713144+ENST00000355086SRGAP1chr1264377727+904168941238791155
ENST00000418359CNOT2chr1270713144+ENST00000357825SRGAP1chr1264377727+897268941238101132

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
ENST00000229195ENST00000355086CNOT2chr1270713144+SRGAP1chr1264377727+0.0002083860.9997917
ENST00000229195ENST00000357825CNOT2chr1270713144+SRGAP1chr1264377727+0.0002903290.99970967
ENST00000418359ENST00000355086CNOT2chr1270713144+SRGAP1chr1264377727+0.0001823280.99981767
ENST00000418359ENST00000357825CNOT2chr1270713144+SRGAP1chr1264377727+0.0002535810.9997464

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 CNOT2-SRGAP1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CNOT2chr1270713144SRGAP1chr126437772768993LSQFGASLYGQQKIRAQLVEQQKCLE
CNOT2chr1270713144SRGAP1chr126437772781793LSQFGASLYGQQKIRAQLVEQQKCLE

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Potential FusionNeoAntigen Information of CNOT2-SRGAP1 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.
CNOT2-SRGAP1_70713144_64377727.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)
CNOT2-SRGAP1chr1270713144chr1264377727817HLA-B48:01GQQKIRAQL0.99560.5953918
CNOT2-SRGAP1chr1270713144chr1264377727817HLA-B08:09QQKIRAQLV0.98570.6471019
CNOT2-SRGAP1chr1270713144chr1264377727817HLA-B13:02GQQKIRAQL0.77790.7916918
CNOT2-SRGAP1chr1270713144chr1264377727817HLA-B39:13GQQKIRAQL0.75010.8434918
CNOT2-SRGAP1chr1270713144chr1264377727817HLA-B13:01GQQKIRAQL0.73710.9056918
CNOT2-SRGAP1chr1270713144chr1264377727817HLA-B13:02QQKIRAQLV0.57030.84931019
CNOT2-SRGAP1chr1270713144chr1264377727817HLA-B52:01QQKIRAQLV0.08760.90161019
CNOT2-SRGAP1chr1270713144chr1264377727817HLA-B13:02GQQKIRAQLV0.70460.8656919
CNOT2-SRGAP1chr1270713144chr1264377727817HLA-A30:08KIRAQLVEQQK0.99790.74821223
CNOT2-SRGAP1chr1270713144chr1264377727817HLA-B15:04GQQKIRAQL0.950.7696918
CNOT2-SRGAP1chr1270713144chr1264377727817HLA-B15:07GQQKIRAQL0.86380.5569918
CNOT2-SRGAP1chr1270713144chr1264377727817HLA-B39:08GQQKIRAQL0.78380.8158918
CNOT2-SRGAP1chr1270713144chr1264377727817HLA-B08:12QQKIRAQL0.99770.61011018
CNOT2-SRGAP1chr1270713144chr1264377727817HLA-C15:02ASLYGQQKI0.99610.7945514
CNOT2-SRGAP1chr1270713144chr1264377727817HLA-C15:05ASLYGQQKI0.99510.8094514
CNOT2-SRGAP1chr1270713144chr1264377727817HLA-B15:50GQQKIRAQL0.9650.7446918
CNOT2-SRGAP1chr1270713144chr1264377727817HLA-B39:02GQQKIRAQL0.9280.8436918
CNOT2-SRGAP1chr1270713144chr1264377727817HLA-A30:01KIRAQLVEQ0.92410.89381221
CNOT2-SRGAP1chr1270713144chr1264377727817HLA-B15:35GQQKIRAQL0.91740.7202918
CNOT2-SRGAP1chr1270713144chr1264377727817HLA-B15:73GQQKIRAQL0.90680.8306918
CNOT2-SRGAP1chr1270713144chr1264377727817HLA-B15:53GQQKIRAQL0.84910.6745918
CNOT2-SRGAP1chr1270713144chr1264377727817HLA-B15:54GQQKIRAQL0.83840.6299918
CNOT2-SRGAP1chr1270713144chr1264377727817HLA-B15:30GQQKIRAQL0.73660.8335918
CNOT2-SRGAP1chr1270713144chr1264377727817HLA-B40:21GQQKIRAQL0.73380.5257918
CNOT2-SRGAP1chr1270713144chr1264377727817HLA-A02:03SLYGQQKIRA0.98920.5273616
CNOT2-SRGAP1chr1270713144chr1264377727817HLA-A30:01KIRAQLVEQQK0.99780.84511223

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Potential FusionNeoAntigen Information of CNOT2-SRGAP1 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.
CNOT2-SRGAP1_70713144_64377727.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)
CNOT2-SRGAP1chr1270713144chr1264377727817DRB4-0101YGQQKIRAQLVEQQK823
CNOT2-SRGAP1chr1270713144chr1264377727817DRB4-0101GQQKIRAQLVEQQKC924
CNOT2-SRGAP1chr1270713144chr1264377727817DRB4-0101QQKIRAQLVEQQKCL1025
CNOT2-SRGAP1chr1270713144chr1264377727817DRB4-0101QKIRAQLVEQQKCLE1126
CNOT2-SRGAP1chr1270713144chr1264377727817DRB4-0103YGQQKIRAQLVEQQK823
CNOT2-SRGAP1chr1270713144chr1264377727817DRB4-0103GQQKIRAQLVEQQKC924
CNOT2-SRGAP1chr1270713144chr1264377727817DRB4-0103QQKIRAQLVEQQKCL1025
CNOT2-SRGAP1chr1270713144chr1264377727817DRB4-0103QKIRAQLVEQQKCLE1126
CNOT2-SRGAP1chr1270713144chr1264377727817DRB4-0104YGQQKIRAQLVEQQK823
CNOT2-SRGAP1chr1270713144chr1264377727817DRB4-0104GQQKIRAQLVEQQKC924
CNOT2-SRGAP1chr1270713144chr1264377727817DRB4-0104QQKIRAQLVEQQKCL1025
CNOT2-SRGAP1chr1270713144chr1264377727817DRB4-0104QKIRAQLVEQQKCLE1126
CNOT2-SRGAP1chr1270713144chr1264377727817DRB4-0106YGQQKIRAQLVEQQK823
CNOT2-SRGAP1chr1270713144chr1264377727817DRB4-0106GQQKIRAQLVEQQKC924
CNOT2-SRGAP1chr1270713144chr1264377727817DRB4-0106QQKIRAQLVEQQKCL1025
CNOT2-SRGAP1chr1270713144chr1264377727817DRB4-0106QKIRAQLVEQQKCLE1126
CNOT2-SRGAP1chr1270713144chr1264377727817DRB4-0107YGQQKIRAQLVEQQK823
CNOT2-SRGAP1chr1270713144chr1264377727817DRB4-0107GQQKIRAQLVEQQKC924
CNOT2-SRGAP1chr1270713144chr1264377727817DRB4-0107QQKIRAQLVEQQKCL1025
CNOT2-SRGAP1chr1270713144chr1264377727817DRB4-0107QKIRAQLVEQQKCLE1126
CNOT2-SRGAP1chr1270713144chr1264377727817DRB4-0108YGQQKIRAQLVEQQK823
CNOT2-SRGAP1chr1270713144chr1264377727817DRB4-0108GQQKIRAQLVEQQKC924
CNOT2-SRGAP1chr1270713144chr1264377727817DRB4-0108QQKIRAQLVEQQKCL1025
CNOT2-SRGAP1chr1270713144chr1264377727817DRB4-0108QKIRAQLVEQQKCLE1126

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Fusion breakpoint peptide structures of CNOT2-SRGAP1

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
8810SLYGQQKIRAQLVECNOT2SRGAP1chr1270713144chr1264377727817

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CNOT2-SRGAP1

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-B52:013W398810SLYGQQKIRAQLVE-6.52654-6.52654
HLA-B44:053DX88810SLYGQQKIRAQLVE-7.44348-7.44348

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Vaccine Design for the FusionNeoAntigens of CNOT2-SRGAP1

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
CNOT2-SRGAP1chr1270713144chr12643777271018QQKIRAQLGGCAACAAAAAATTCGAGCTCAAC
CNOT2-SRGAP1chr1270713144chr12643777271019QQKIRAQLVGGCAACAAAAAATTCGAGCTCAACTGG
CNOT2-SRGAP1chr1270713144chr12643777271221KIRAQLVEQAAAAAATTCGAGCTCAACTGGTAGAAC
CNOT2-SRGAP1chr1270713144chr12643777271223KIRAQLVEQQKAAAAAATTCGAGCTCAACTGGTAGAACAACAAA
CNOT2-SRGAP1chr1270713144chr1264377727514ASLYGQQKIGGGCAAGTTTATACGGGCAACAAAAAA
CNOT2-SRGAP1chr1270713144chr1264377727616SLYGQQKIRACAAGTTTATACGGGCAACAAAAAATTCGAG
CNOT2-SRGAP1chr1270713144chr1264377727918GQQKIRAQLACGGGCAACAAAAAATTCGAGCTCAAC
CNOT2-SRGAP1chr1270713144chr1264377727919GQQKIRAQLVACGGGCAACAAAAAATTCGAGCTCAACTGG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
CNOT2-SRGAP1chr1270713144chr12643777271025QQKIRAQLVEQQKCLGGCAACAAAAAATTCGAGCTCAACTGGTAGAACAACAAAAATGCC
CNOT2-SRGAP1chr1270713144chr12643777271126QKIRAQLVEQQKCLEAACAAAAAATTCGAGCTCAACTGGTAGAACAACAAAAATGCCTGG
CNOT2-SRGAP1chr1270713144chr1264377727823YGQQKIRAQLVEQQKTATACGGGCAACAAAAAATTCGAGCTCAACTGGTAGAACAACAAA
CNOT2-SRGAP1chr1270713144chr1264377727924GQQKIRAQLVEQQKCACGGGCAACAAAAAATTCGAGCTCAACTGGTAGAACAACAAAAAT

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Information of the samples that have these potential fusion neoantigens of CNOT2-SRGAP1

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
BRCACNOT2-SRGAP1chr1270713144ENST00000229195chr1264377727ENST00000355086TCGA-3C-AAAU-01A

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Potential target of CAR-T therapy development for CNOT2-SRGAP1

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 CNOT2-SRGAP1

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 CNOT2-SRGAP1

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