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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:AGAP3-CUX1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: AGAP3-CUX1
FusionPDB ID: 2817
FusionGDB2.0 ID: 2817
HgeneTgene
Gene symbol

AGAP3

CUX1

Gene ID

116988

1523

Gene nameArfGAP with GTPase domain, ankyrin repeat and PH domain 3cut like homeobox 1
SynonymsAGAP-3|CENTG3|CRAG|MRIP-1|cnt-g3CASP|CDP|CDP/Cut|CDP1|COY1|CUTL1|CUX|Clox|Cux/CDP|GDDI|GOLIM6|Nbla10317|p100|p110|p200|p75
Cytomap

7q36.1

7q22.1

Type of geneprotein-codingprotein-coding
Descriptionarf-GAP with GTPase, ANK repeat and PH domain-containing protein 3CRAM-associated GTPaseCRMP (collapsin response mediator protein) associatedMR1-interacting proteincentaurin-gamma-3protein CASPHomeobox protein cut-like 1CCAAT displacement proteinCUX1 gene Alternatively Spliced Productcut homologgolgi integral membrane protein 6homeobox protein cux-1putative protein product of Nbla10317
Modification date2020031320200320
UniProtAcc

Q96P47

Main function of 5'-partner protein: FUNCTION: GTPase-activating protein for the ADP ribosylation factor family (Potential). GTPase which may be involved in the degradation of expanded polyglutamine proteins through the ubiquitin-proteasome pathway. {ECO:0000269|PubMed:16461359, ECO:0000305}.

P39880

Main function of 5'-partner protein: FUNCTION: Transcription factor involved in the control of neuronal differentiation in the brain. Regulates dendrite development and branching, and dendritic spine formation in cortical layers II-III. Also involved in the control of synaptogenesis. In addition, it has probably a broad role in mammalian development as a repressor of developmentally regulated gene expression. May act by preventing binding of positively-activing CCAAT factors to promoters. Component of nf-munr repressor; binds to the matrix attachment regions (MARs) (5' and 3') of the immunoglobulin heavy chain enhancer. Represses T-cell receptor (TCR) beta enhancer function by binding to MARbeta, an ATC-rich DNA sequence located upstream of the TCR beta enhancer. Binds to the TH enhancer; may require the basic helix-loop-helix protein TCF4 as a coactivator. {ECO:0000250|UniProtKB:P53564}.; FUNCTION: [CDP/Cux p110]: Plays a role in cell cycle progression, in particular at the G1/S transition. As cells progress into S phase, a fraction of CUX1 molecules is proteolytically processed into N-terminally truncated proteins of 110 kDa. While CUX1 only transiently binds to DNA and carries the CCAAT-displacement activity, CDP/Cux p110 makes a stable interaction with DNA and stimulates expression of genes such as POLA1. {ECO:0000269|PubMed:15099520}.
Ensembl transtripts involved in fusion geneENST idsENST00000397238, ENST00000473312, 
ENST00000479901, ENST00000335367, 
ENST00000463381, ENST00000476375, 
ENST00000560541, ENST00000292535, 
ENST00000360264, ENST00000425244, 
ENST00000546411, ENST00000549414, 
ENST00000550008, ENST00000556210, 
ENST00000292538, ENST00000393824, 
ENST00000437600, ENST00000547394, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score15 X 6 X 10=90026 X 23 X 9=5382
# samples 1429
** MAII scorelog2(14/900*10)=-2.68449817427207
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(29/5382*10)=-4.21401758562548
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: AGAP3 [Title/Abstract] AND CUX1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: AGAP3 [Title/Abstract] AND CUX1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)AGAP3(150784159)-CUX1(101916637), # samples:1
Anticipated loss of major functional domain due to fusion event.AGAP3-CUX1 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.
AGAP3-CUX1 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.
AGAP3-CUX1 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.
AGAP3-CUX1 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/chr7:150784159/chr7:101916637)
- 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 AGAP3 (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 CUX1 (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)
ENST00000473312AGAP3chr7150784159+ENST00000437600CUX1chr7101916637+198033101112370
ENST00000473312AGAP3chr7150784159+ENST00000292538CUX1chr7101916637+198033101112370
ENST00000473312AGAP3chr7150784159+ENST00000393824CUX1chr7101916637+150133101112370
ENST00000473312AGAP3chr7150784159+ENST00000547394CUX1chr7101916637+198033101112370
ENST00000479901AGAP3chr7150784159+ENST00000437600CUX1chr7101916637+198033101112370
ENST00000479901AGAP3chr7150784159+ENST00000292538CUX1chr7101916637+198033101112370
ENST00000479901AGAP3chr7150784159+ENST00000393824CUX1chr7101916637+150133101112370
ENST00000479901AGAP3chr7150784159+ENST00000547394CUX1chr7101916637+198033101112370
ENST00000397238AGAP3chr7150784159+ENST00000437600CUX1chr7101916637+198033101112370
ENST00000397238AGAP3chr7150784159+ENST00000292538CUX1chr7101916637+198033101112370
ENST00000397238AGAP3chr7150784159+ENST00000393824CUX1chr7101916637+150133101112370
ENST00000397238AGAP3chr7150784159+ENST00000547394CUX1chr7101916637+198033101112370

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
ENST00000473312ENST00000437600AGAP3chr7150784159+CUX1chr7101916637+0.0208845960.97911537
ENST00000473312ENST00000292538AGAP3chr7150784159+CUX1chr7101916637+0.0208845960.97911537
ENST00000473312ENST00000393824AGAP3chr7150784159+CUX1chr7101916637+0.0189080010.981092
ENST00000473312ENST00000547394AGAP3chr7150784159+CUX1chr7101916637+0.0208845960.97911537
ENST00000479901ENST00000437600AGAP3chr7150784159+CUX1chr7101916637+0.0208845960.97911537
ENST00000479901ENST00000292538AGAP3chr7150784159+CUX1chr7101916637+0.0208845960.97911537
ENST00000479901ENST00000393824AGAP3chr7150784159+CUX1chr7101916637+0.0189080010.981092
ENST00000479901ENST00000547394AGAP3chr7150784159+CUX1chr7101916637+0.0208845960.97911537
ENST00000397238ENST00000437600AGAP3chr7150784159+CUX1chr7101916637+0.0208845960.97911537
ENST00000397238ENST00000292538AGAP3chr7150784159+CUX1chr7101916637+0.0208845960.97911537
ENST00000397238ENST00000393824AGAP3chr7150784159+CUX1chr7101916637+0.0189080010.981092
ENST00000397238ENST00000547394AGAP3chr7150784159+CUX1chr7101916637+0.0208845960.97911537

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 AGAP3-CUX1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
AGAP3chr7150784159CUX1chr7101916637331110LQNQIREHVISIEGRCAELQVRITEA

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Potential FusionNeoAntigen Information of AGAP3-CUX1 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.
AGAP3-CUX1_150784159_101916637.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)
AGAP3-CUX1chr7150784159chr7101916637331HLA-C01:03SIEGRCAEL0.99980.87181019

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Potential FusionNeoAntigen Information of AGAP3-CUX1 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 AGAP3-CUX1

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
1787EHVISIEGRCAELQAGAP3CUX1chr7150784159chr7101916637331

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of AGAP3-CUX1

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-B14:023BVN1787EHVISIEGRCAELQ-7.9962-8.1096
HLA-B14:023BVN1787EHVISIEGRCAELQ-5.70842-6.74372
HLA-B52:013W391787EHVISIEGRCAELQ-6.83737-6.95077
HLA-B52:013W391787EHVISIEGRCAELQ-4.4836-5.5189
HLA-A11:014UQ21787EHVISIEGRCAELQ-10.0067-10.1201
HLA-A11:014UQ21787EHVISIEGRCAELQ-9.03915-10.0745
HLA-A24:025HGA1787EHVISIEGRCAELQ-6.56204-6.67544
HLA-A24:025HGA1787EHVISIEGRCAELQ-5.42271-6.45801
HLA-B44:053DX81787EHVISIEGRCAELQ-7.85648-8.89178
HLA-B44:053DX81787EHVISIEGRCAELQ-5.3978-5.5112
HLA-A02:016TDR1787EHVISIEGRCAELQ-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of AGAP3-CUX1

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
AGAP3-CUX1chr7150784159chr71019166371019SIEGRCAELCCATCGAGGGACGCTGTGCAGAGCTGC

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 AGAP3-CUX1

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
Non-CancerAGAP3-CUX1chr7150784159ENST00000397238chr7101916637ENST00000292538ERR315466

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Potential target of CAR-T therapy development for AGAP3-CUX1

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
TgeneCUX1chr7:150784159chr7:101916637ENST000002925381323620_6400679.0TransmembraneHelical%3B Anchor for type IV membrane protein
TgeneCUX1chr7:150784159chr7:101916637ENST000003938241222620_6400640.0TransmembraneHelical%3B Anchor for type IV membrane protein
TgeneCUX1chr7:150784159chr7:101916637ENST000004376001323620_6400677.0TransmembraneHelical%3B Anchor for type IV membrane protein
TgeneCUX1chr7:150784159chr7:101916637ENST000005473941222620_6400663.0TransmembraneHelical%3B Anchor for type IV membrane protein

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 AGAP3-CUX1

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 AGAP3-CUX1

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