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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:DEPDC5-CELSR1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: DEPDC5-CELSR1
FusionPDB ID: 22311
FusionGDB2.0 ID: 22311
HgeneTgene
Gene symbol

DEPDC5

CELSR1

Gene ID

9681

9620

Gene nameDEP domain containing 5, GATOR1 subcomplex subunitcadherin EGF LAG seven-pass G-type receptor 1
SynonymsDEP.5|FFEVF|FFEVF1ADGRC1|CDHF9|FMI2|HFMI2|ME2
Cytomap

22q12.2-q12.3

22q13.31

Type of geneprotein-codingprotein-coding
DescriptionGATOR complex protein DEPDC5DEP domain containing 5DEP domain-containing protein 5cadherin EGF LAG seven-pass G-type receptor 1adhesion G protein-coupled receptor C1cadherin family member 9cadherin, EGF LAG seven-pass G-type receptor 1 (flamingo homolog, Drosophila)flamingo homolog 2protocadherin flamingo 2
Modification date2020031520200322
UniProtAcc

O75140

Main function of 5'-partner protein: FUNCTION: As a component of the GATOR1 complex functions as an inhibitor of the amino acid-sensing branch of the TORC1 pathway. The GATOR1 complex strongly increases GTP hydrolysis by RRAGA and RRAGB within RRAGC-containing heterodimers, thereby deactivating RRAGs, releasing mTORC1 from lysosomal surface and inhibiting mTORC1 signaling. The GATOR1 complex is negatively regulated by GATOR2 the other GATOR subcomplex in this amino acid-sensing branch of the TORC1 pathway. {ECO:0000269|PubMed:23723238, ECO:0000269|PubMed:25457612, ECO:0000269|PubMed:29769719}.

Q9NYQ6

Main function of 5'-partner protein: FUNCTION: Receptor that may have an important role in cell/cell signaling during nervous system formation.
Ensembl transtripts involved in fusion geneENST idsENST00000266091, ENST00000382105, 
ENST00000382111, ENST00000382112, 
ENST00000400246, ENST00000400248, 
ENST00000400249, ENST00000535622, 
ENST00000539165, ENST00000400242, 
ENST00000494060, ENST00000536766, 
ENST00000395964, ENST00000497509, 
ENST00000262738, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score15 X 15 X 5=11257 X 7 X 4=196
# samples 147
** MAII scorelog2(14/1125*10)=-3.00642626915943
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(7/196*10)=-1.48542682717024
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: DEPDC5 [Title/Abstract] AND CELSR1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: DEPDC5 [Title/Abstract] AND CELSR1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)DEPDC5(32275603)-CELSR1(46792627), # samples:1
Anticipated loss of major functional domain due to fusion event.DEPDC5-CELSR1 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.
DEPDC5-CELSR1 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.
DEPDC5-CELSR1 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.
DEPDC5-CELSR1 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.
DEPDC5-CELSR1 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
DEPDC5-CELSR1 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
DEPDC5-CELSR1 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted 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/chr22:32275603/chr22:46792627)
- 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 DEPDC5 (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 CELSR1 (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)
ENST00000535622DEPDC5chr2232275603+ENST00000262738CELSR1chr2246792627-939037187838001240
ENST00000400246DEPDC5chr2232275603+ENST00000262738CELSR1chr2246792627-9754408214241641340
ENST00000266091DEPDC5chr2232275603+ENST00000262738CELSR1chr2246792627-9688401614240981318
ENST00000400249DEPDC5chr2232275603+ENST00000262738CELSR1chr2246792627-9661398914240711309
ENST00000382112DEPDC5chr2232275603+ENST00000262738CELSR1chr2246792627-965539837040651331
ENST00000382111DEPDC5chr2232275603+ENST00000262738CELSR1chr2246792627-967240006040821340
ENST00000400248DEPDC5chr2232275603+ENST00000262738CELSR1chr2246792627-957839065939881309
ENST00000539165DEPDC5chr2232275603+ENST00000262738CELSR1chr2246792627-655187943985288296

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
ENST00000535622ENST00000262738DEPDC5chr2232275603+CELSR1chr2246792627-0.0004327270.9995672
ENST00000400246ENST00000262738DEPDC5chr2232275603+CELSR1chr2246792627-0.0012521630.9987478
ENST00000266091ENST00000262738DEPDC5chr2232275603+CELSR1chr2246792627-0.0011601790.9988398
ENST00000400249ENST00000262738DEPDC5chr2232275603+CELSR1chr2246792627-0.0007969840.999203
ENST00000382112ENST00000262738DEPDC5chr2232275603+CELSR1chr2246792627-0.0008854870.99911445
ENST00000382111ENST00000262738DEPDC5chr2232275603+CELSR1chr2246792627-0.0011439060.99885607
ENST00000400248ENST00000262738DEPDC5chr2232275603+CELSR1chr2246792627-0.0007221430.9992779
ENST00000539165ENST00000262738DEPDC5chr2232275603+CELSR1chr2246792627-0.45418220.5458178

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 DEPDC5-CELSR1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
DEPDC5chr2232275603CELSR1chr224679262737181206SRHSSFSRSFGGRSQAAALLGNREAS
DEPDC5chr2232275603CELSR1chr224679262739061275SRHSSFSRSFGGRSQAAALLGNREAS
DEPDC5chr2232275603CELSR1chr224679262739831297SRHSSFSRSFGGRSQAAALLGNREAS
DEPDC5chr2232275603CELSR1chr224679262739891275SRHSSFSRSFGGRSQAAALLGNREAS
DEPDC5chr2232275603CELSR1chr224679262740001306SRHSSFSRSFGGRSQAAALLGNREAS
DEPDC5chr2232275603CELSR1chr224679262740161284SRHSSFSRSFGGRSQAAALLGNREAS
DEPDC5chr2232275603CELSR1chr224679262740821306SRHSSFSRSFGGRSQAAALLGNREAS

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Potential FusionNeoAntigen Information of DEPDC5-CELSR1 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.
DEPDC5-CELSR1_32275603_46792627.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)
DEPDC5-CELSR1chr2232275603chr22467926274016HLA-B27:07GRSQAAALL0.99940.6511120
DEPDC5-CELSR1chr2232275603chr22467926274016HLA-B27:04GRSQAAALL0.99930.75941120
DEPDC5-CELSR1chr2232275603chr22467926274016HLA-B27:05GRSQAAALL0.99920.75971120
DEPDC5-CELSR1chr2232275603chr22467926274016HLA-B39:01GRSQAAALL0.99070.88451120
DEPDC5-CELSR1chr2232275603chr22467926274016HLA-A30:08RSFGGRSQA0.98690.8364716
DEPDC5-CELSR1chr2232275603chr22467926274016HLA-B38:02GRSQAAALL0.97140.96221120
DEPDC5-CELSR1chr2232275603chr22467926274016HLA-B07:10GRSQAAALL0.02040.63191120
DEPDC5-CELSR1chr2232275603chr22467926274016HLA-A30:08RSFGGRSQAA0.98710.8558717
DEPDC5-CELSR1chr2232275603chr22467926274016HLA-B27:14GRSQAAALL0.99930.7131120
DEPDC5-CELSR1chr2232275603chr22467926274016HLA-C07:95GRSQAAALL0.99590.67481120
DEPDC5-CELSR1chr2232275603chr22467926274016HLA-C07:05GRSQAAALL0.98950.94311120
DEPDC5-CELSR1chr2232275603chr22467926274016HLA-C07:27GRSQAAALL0.98940.9441120
DEPDC5-CELSR1chr2232275603chr22467926274016HLA-B39:12GRSQAAALL0.98830.88951120
DEPDC5-CELSR1chr2232275603chr22467926274016HLA-C07:29GRSQAAALL0.98530.8881120
DEPDC5-CELSR1chr2232275603chr22467926274016HLA-C07:13GRSQAAALL0.98390.91321120
DEPDC5-CELSR1chr2232275603chr22467926274016HLA-B27:03GRSQAAALL0.97280.78321120
DEPDC5-CELSR1chr2232275603chr22467926274016HLA-C07:19GRSQAAALL0.80750.71971120
DEPDC5-CELSR1chr2232275603chr22467926274016HLA-C12:16GRSQAAALL0.04770.94931120
DEPDC5-CELSR1chr2232275603chr22467926274016HLA-B27:14SRSFGGRSQA0.99870.5879616
DEPDC5-CELSR1chr2232275603chr22467926274016HLA-B73:01SRSFGGRSQA0.99220.9404616
DEPDC5-CELSR1chr2232275603chr22467926274016HLA-B73:01SRSFGGRSQAA0.99840.9647617
DEPDC5-CELSR1chr2232275603chr22467926274016HLA-B27:10GRSQAAALL0.99930.82991120
DEPDC5-CELSR1chr2232275603chr22467926274016HLA-B27:06GRSQAAALL0.99930.78121120
DEPDC5-CELSR1chr2232275603chr22467926274016HLA-B27:08GRSQAAALL0.99920.66061120
DEPDC5-CELSR1chr2232275603chr22467926274016HLA-B27:09GRSQAAALL0.99920.75541120
DEPDC5-CELSR1chr2232275603chr22467926274016HLA-C07:01GRSQAAALL0.99640.6731120
DEPDC5-CELSR1chr2232275603chr22467926274016HLA-B39:31GRSQAAALL0.98630.88661120
DEPDC5-CELSR1chr2232275603chr22467926274016HLA-A30:01RSFGGRSQA0.98550.9291716
DEPDC5-CELSR1chr2232275603chr22467926274016HLA-C06:08GRSQAAALL0.85930.98921120
DEPDC5-CELSR1chr2232275603chr22467926274016HLA-C07:22GRSQAAALL0.81120.68521120
DEPDC5-CELSR1chr2232275603chr22467926274016HLA-C06:17GRSQAAALL0.06950.99021120
DEPDC5-CELSR1chr2232275603chr22467926274016HLA-C06:02GRSQAAALL0.06950.99021120
DEPDC5-CELSR1chr2232275603chr22467926274016HLA-B27:09GGRSQAAALL0.9720.65751020

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Potential FusionNeoAntigen Information of DEPDC5-CELSR1 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 DEPDC5-CELSR1

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
8983SRSFGGRSQAAALLDEPDC5CELSR1chr2232275603chr22467926274016

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of DEPDC5-CELSR1

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-B14:023BVN8983SRSFGGRSQAAALL-7.05536-7.16716
HLA-B14:023BVN8983SRSFGGRSQAAALL-6.9273-7.9704
HLA-B52:013W398983SRSFGGRSQAAALL-6.36322-6.47502
HLA-B52:013W398983SRSFGGRSQAAALL-5.17233-6.21543
HLA-A24:025HGA8983SRSFGGRSQAAALL-8.66506-8.77686
HLA-A24:025HGA8983SRSFGGRSQAAALL-3.85054-4.89364
HLA-B27:056PYJ8983SRSFGGRSQAAALL-6.25517-6.36697
HLA-B44:053DX88983SRSFGGRSQAAALL-5.57569-6.61879
HLA-B44:053DX88983SRSFGGRSQAAALL-4.98797-5.09977
HLA-A02:016TDR8983SRSFGGRSQAAALL-5.24931-5.36111

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Vaccine Design for the FusionNeoAntigens of DEPDC5-CELSR1

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
DEPDC5-CELSR1chr2232275603chr22467926271020GGRSQAAALLCACTTTTAGGAAACCGTGAGGCAAGCCCGT
DEPDC5-CELSR1chr2232275603chr22467926271120GRSQAAALLTTTTAGGAAACCGTGAGGCAAGCCCGT
DEPDC5-CELSR1chr2232275603chr2246792627616SRSFGGRSQAGCCAGGCGGCAGCACTTTTAGGAAACCGTG
DEPDC5-CELSR1chr2232275603chr2246792627617SRSFGGRSQAAGCCAGGCGGCAGCACTTTTAGGAAACCGTGAGG
DEPDC5-CELSR1chr2232275603chr2246792627716RSFGGRSQAAGGCGGCAGCACTTTTAGGAAACCGTG
DEPDC5-CELSR1chr2232275603chr2246792627717RSFGGRSQAAAGGCGGCAGCACTTTTAGGAAACCGTGAGG

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 DEPDC5-CELSR1

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
N/ADEPDC5-CELSR1chr2232275603ENST00000266091chr2246792627ENST00000262738BF845393

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Potential target of CAR-T therapy development for DEPDC5-CELSR1

check button Predicted 3D structure. We used RoseTTAFold.
135_DEPDC5-CELSR1_t000_.e2e.pdb


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
TgeneCELSR1chr22:32275603chr22:46792627ENST000002627380352470_249003015.0TransmembraneHelical%3B Name%3D1
TgeneCELSR1chr22:32275603chr22:46792627ENST000002627380352502_252203015.0TransmembraneHelical%3B Name%3D2
TgeneCELSR1chr22:32275603chr22:46792627ENST000002627380352528_254803015.0TransmembraneHelical%3B Name%3D3
TgeneCELSR1chr22:32275603chr22:46792627ENST000002627380352573_259303015.0TransmembraneHelical%3B Name%3D4
TgeneCELSR1chr22:32275603chr22:46792627ENST000002627380352612_263203015.0TransmembraneHelical%3B Name%3D5
TgeneCELSR1chr22:32275603chr22:46792627ENST000002627380352656_267603015.0TransmembraneHelical%3B Name%3D6
TgeneCELSR1chr22:32275603chr22:46792627ENST000002627380352684_270403015.0TransmembraneHelical%3B Name%3D7

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
DEPDC5chr2232275603ENST00000266091CELSR1chr2246792627ENST00000262738
DEPDC5chr2232275603ENST00000382111CELSR1chr2246792627ENST00000262738
DEPDC5chr2232275603ENST00000382112CELSR1chr2246792627ENST00000262738
DEPDC5chr2232275603ENST00000400248CELSR1chr2246792627ENST00000262738
DEPDC5chr2232275603ENST00000535622CELSR1chr2246792627ENST00000262738
DEPDC5chr2232275603ENST00000539165CELSR1chr2246792627ENST00000262738

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Related Drugs to DEPDC5-CELSR1

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 DEPDC5-CELSR1

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