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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:AGAP1-WDR11

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: AGAP1-WDR11
FusionPDB ID: 2803
FusionGDB2.0 ID: 2803
HgeneTgene
Gene symbol

AGAP1

WDR11

Gene ID

116987

55717

Gene nameArfGAP with GTPase domain, ankyrin repeat and PH domain 1WD repeat domain 11
SynonymsAGAP-1|CENTG2|GGAP1|cnt-g2BRWD2|DR11|HH14|SRI1|WDR15
Cytomap

2q37.2

10q26.12

Type of geneprotein-codingprotein-coding
Descriptionarf-GAP with GTPase, ANK repeat and PH domain-containing protein 1Arf GAP with GTP-binding protein-like, ANK repeat and PH domains 1GTP-binding and GTPase-activating protein 1centaurin, gamma 2WD repeat-containing protein 11WD repeat domain 15WD repeat-containing protein 15bromodomain and WD repeat-containing protein 2sensitization to ricin complex subunit 1
Modification date2020031320200313
UniProtAcc

Q9UPQ3

Main function of 5'-partner protein: FUNCTION: GTPase-activating protein for ARF1 and, to a lesser extent, ARF5. Directly and specifically regulates the adapter protein 3 (AP-3)-dependent trafficking of proteins in the endosomal-lysosomal system. {ECO:0000269|PubMed:12640130}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000304032, ENST00000336665, 
ENST00000409457, ENST00000409538, 
ENST00000428334, 
ENST00000604509, 
ENST00000263461, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score49 X 18 X 17=149943 X 3 X 1=9
# samples 484
** MAII scorelog2(48/14994*10)=-4.96520709119934
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(4/9*10)=2.15200309344505
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: AGAP1 [Title/Abstract] AND WDR11 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: AGAP1 [Title/Abstract] AND WDR11 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)AGAP1(236403493)-WDR11(122659541), # samples:3
Anticipated loss of major functional domain due to fusion event.AGAP1-WDR11 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.
AGAP1-WDR11 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
TgeneWDR11

GO:0006886

intracellular protein transport

29426865

TgeneWDR11

GO:0099041

vesicle tethering to Golgi

29426865



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/chr2:236403493/chr10:122659541)
- 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 AGAP1 (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 WDR11 (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)
ENST00000336665AGAP1chr2236403493+ENST00000263461WDR11chr10122659541+27147434211902493
ENST00000304032AGAP1chr2236403493+ENST00000263461WDR11chr10122659541+27147434211902493
ENST00000409457AGAP1chr2236403493+ENST00000263461WDR11chr10122659541+27327614391920493
ENST00000336665AGAP1chr2236403493+ENST00000263461WDR11chr10122659540+27147434211902493
ENST00000304032AGAP1chr2236403493+ENST00000263461WDR11chr10122659540+27147434211902493
ENST00000409457AGAP1chr2236403493+ENST00000263461WDR11chr10122659540+27327614391920493

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
ENST00000336665ENST00000263461AGAP1chr2236403493+WDR11chr10122659541+0.0015682440.99843174
ENST00000304032ENST00000263461AGAP1chr2236403493+WDR11chr10122659541+0.0015682440.99843174
ENST00000409457ENST00000263461AGAP1chr2236403493+WDR11chr10122659541+0.001635210.99836475
ENST00000336665ENST00000263461AGAP1chr2236403493+WDR11chr10122659540+0.0015682440.99843174
ENST00000304032ENST00000263461AGAP1chr2236403493+WDR11chr10122659540+0.0015682440.99843174
ENST00000409457ENST00000263461AGAP1chr2236403493+WDR11chr10122659540+0.001635210.99836475

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 AGAP1-WDR11

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
AGAP1chr2236403493WDR11chr10122659540743102VEEPVLQNQIREHVIAIEEPVWCPYL
AGAP1chr2236403493WDR11chr10122659540761102VEEPVLQNQIREHVIAIEEPVWCPYL
AGAP1chr2236403493WDR11chr10122659541743102VEEPVLQNQIREHVIAIEEPVWCPYL
AGAP1chr2236403493WDR11chr10122659541761102VEEPVLQNQIREHVIAIEEPVWCPYL

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Potential FusionNeoAntigen Information of AGAP1-WDR11 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.
AGAP1-WDR11_236403493_122659540.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)
AGAP1-WDR11chr2236403493chr10122659540743HLA-B08:09QIREHVIAI0.99220.6151817
AGAP1-WDR11chr2236403493chr10122659540743HLA-B39:06EHVIAIEEP0.97450.8561120
AGAP1-WDR11chr2236403493chr10122659540743HLA-B39:06NQIREHVIA0.96790.847716
AGAP1-WDR11chr2236403493chr10122659540743HLA-A30:08QIREHVIAI0.95110.8073817
AGAP1-WDR11chr2236403493chr10122659540743HLA-B57:01HVIAIEEPVW0.99960.99541222
AGAP1-WDR11chr2236403493chr10122659540743HLA-B58:01HVIAIEEPVW0.99890.98861222
AGAP1-WDR11chr2236403493chr10122659540743HLA-B53:01HVIAIEEPVW0.96790.56231222
AGAP1-WDR11chr2236403493chr10122659540743HLA-B57:03HVIAIEEPVW0.94290.99721222
AGAP1-WDR11chr2236403493chr10122659540743HLA-B15:04QIREHVIAI0.98460.9551817
AGAP1-WDR11chr2236403493chr10122659540743HLA-A02:05HVIAIEEPV0.97520.51181221
AGAP1-WDR11chr2236403493chr10122659540743HLA-A68:02HVIAIEEPV0.99820.71221
AGAP1-WDR11chr2236403493chr10122659540743HLA-A69:01HVIAIEEPV0.99550.91111221
AGAP1-WDR11chr2236403493chr10122659540743HLA-A02:03QIREHVIAI0.98070.6311817
AGAP1-WDR11chr2236403493chr10122659540743HLA-B15:73QIREHVIAI0.980.8969817
AGAP1-WDR11chr2236403493chr10122659540743HLA-B15:30QIREHVIAI0.96820.9505817
AGAP1-WDR11chr2236403493chr10122659540743HLA-B57:10HVIAIEEPVW0.99960.99541222
AGAP1-WDR11chr2236403493chr10122659540743HLA-B57:04HVIAIEEPVW0.99830.83781222
AGAP1-WDR11chr2236403493chr10122659540743HLA-B57:02HVIAIEEPVW0.98270.97851222
AGAP1-WDR11chr2236403493chr10122659540743HLA-B15:13HVIAIEEPVW0.97650.89581222
AGAP1-WDR11chr2236403493chr10122659540743HLA-A25:01HVIAIEEPVW0.85890.90551222
AGAP1-WDR11chr2236403493chr10122659540743HLA-A68:02EHVIAIEEPV0.81810.60721121

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Potential FusionNeoAntigen Information of AGAP1-WDR11 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 AGAP1-WDR11

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
7432QNQIREHVIAIEEPAGAP1WDR11chr2236403493chr10122659540743

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of AGAP1-WDR11

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-B14:023BVN7432QNQIREHVIAIEEP-7.15543-7.26883
HLA-B14:023BVN7432QNQIREHVIAIEEP-4.77435-5.80965
HLA-B52:013W397432QNQIREHVIAIEEP-6.80875-6.92215
HLA-B52:013W397432QNQIREHVIAIEEP-4.20386-5.23916
HLA-A11:014UQ27432QNQIREHVIAIEEP-7.5194-8.5547
HLA-A11:014UQ27432QNQIREHVIAIEEP-6.9601-7.0735
HLA-A24:025HGA7432QNQIREHVIAIEEP-7.52403-7.63743
HLA-A24:025HGA7432QNQIREHVIAIEEP-5.82433-6.85963
HLA-B27:056PYJ7432QNQIREHVIAIEEP-3.28285-4.31815
HLA-B44:053DX87432QNQIREHVIAIEEP-5.91172-6.94702
HLA-B44:053DX87432QNQIREHVIAIEEP-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of AGAP1-WDR11

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
AGAP1-WDR11chr2236403493chr101226595401120EHVIAIEEPTCGAAGAGCCTGTGTGGTGCCCCTATC
AGAP1-WDR11chr2236403493chr101226595401121EHVIAIEEPVTCGAAGAGCCTGTGTGGTGCCCCTATCTCC
AGAP1-WDR11chr2236403493chr101226595401221HVIAIEEPVAAGAGCCTGTGTGGTGCCCCTATCTCC
AGAP1-WDR11chr2236403493chr101226595401222HVIAIEEPVWAAGAGCCTGTGTGGTGCCCCTATCTCCTTG
AGAP1-WDR11chr2236403493chr10122659540716NQIREHVIAACGTCATCGCCATCGAAGAGCCTGTGT
AGAP1-WDR11chr2236403493chr10122659540817QIREHVIAITCATCGCCATCGAAGAGCCTGTGTGGT

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 AGAP1-WDR11

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
BRCAAGAP1-WDR11chr2236403493ENST00000304032chr10122659540ENST00000263461TCGA-A8-A08O

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Potential target of CAR-T therapy development for AGAP1-WDR11

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 AGAP1-WDR11

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 AGAP1-WDR11

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