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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:PLXNC1-APPL2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PLXNC1-APPL2
FusionPDB ID: 66582
FusionGDB2.0 ID: 66582
HgeneTgene
Gene symbol

PLXNC1

APPL2

Gene ID

10154

55198

Gene nameplexin C1adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 2
SynonymsCD232|PLXN-C1|VESPRDIP13B
Cytomap

12q22

12q23.3

Type of geneprotein-codingprotein-coding
Descriptionplexin-C1plexin (semaphorin receptor)receptor for viral semaphorin proteinreceptor for virally-encoded semaphorinvirus-encoded semaphorin protein receptorDCC-interacting protein 13-betaDIP13 betaadapter protein containing PH domain, PTB domain and leucine zipper motif 2adaptor protein, phosphotyrosine interaction, PH domain and leucine zipper containing 2
Modification date2020031320200313
UniProtAcc.

Q8NEU8

Main function of 5'-partner protein: FUNCTION: Multifunctional adapter protein that binds to various membrane receptors, nuclear factors and signaling proteins to regulate many processes, such as cell proliferation, immune response, endosomal trafficking and cell metabolism (PubMed:26583432, PubMed:15016378, PubMed:24879834). Regulates signaling pathway leading to cell proliferation through interaction with RAB5A and subunits of the NuRD/MeCP1 complex (PubMed:15016378). Plays a role in immune response by modulating phagocytosis, inflammatory and innate immune responses. In macrophages, enhances Fc-gamma receptor-mediated phagocytosis through interaction with RAB31 leading to activation of PI3K/Akt signaling. In response to LPS, modulates inflammatory responses by playing a key role on the regulation of TLR4 signaling and in the nuclear translocation of RELA/NF-kappa-B p65 and the secretion of pro- and anti-inflammatory cytokines. Also functions as a negative regulator of innate immune response via inhibition of AKT1 signaling pathway by forming a complex with APPL1 and PIK3R1 (By similarity). Plays a role in endosomal trafficking of TGFBR1 from the endosomes to the nucleus (PubMed:26583432). Plays a role in cell metabolism by regulating adiponecting ans insulin signaling pathways and adaptative thermogenesis (PubMed:24879834) (By similarity). In muscle, negatively regulates adiponectin-simulated glucose uptake and fatty acid oxidation by inhibiting adiponectin signaling pathway through APPL1 sequestration thereby antagonizing APPL1 action (By similarity). In muscles, negativeliy regulates insulin-induced plasma membrane recruitment of GLUT4 and glucose uptake through interaction with TBC1D1 (PubMed:24879834). Plays a role in cold and diet-induced adaptive thermogenesis by activating ventromedial hypothalamus (VMH) neurons throught AMPK inhibition which enhances sympathetic outflow to subcutaneous white adipose tissue (sWAT), sWAT beiging and cold tolerance (By similarity). Also plays a role in other signaling pathways namely Wnt/beta-catenin, HGF and glucocorticoid receptor signaling (PubMed:19433865) (By similarity). Positive regulator of beta-catenin/TCF-dependent transcription through direct interaction with RUVBL2/reptin resulting in the relief of RUVBL2-mediated repression of beta-catenin/TCF target genes by modulating the interactions within the beta-catenin-reptin-HDAC complex (PubMed:19433865). May affect adult neurogenesis in hippocampus and olfactory system via regulating the sensitivity of glucocorticoid receptor. Required for fibroblast migration through HGF cell signaling (By similarity). {ECO:0000250|UniProtKB:Q8K3G9, ECO:0000269|PubMed:15016378, ECO:0000269|PubMed:19433865, ECO:0000269|PubMed:24879834, ECO:0000269|PubMed:26583432}.
Ensembl transtripts involved in fusion geneENST idsENST00000258526, ENST00000547057, 
ENST00000545312, ENST00000551495, 
ENST00000539978, ENST00000546731, 
ENST00000549573, ENST00000551662, 
ENST00000258530, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score7 X 6 X 5=2108 X 6 X 5=240
# samples 109
** MAII scorelog2(10/210*10)=-1.0703893278914
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(9/240*10)=-1.41503749927884
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: PLXNC1 [Title/Abstract] AND APPL2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PLXNC1 [Title/Abstract] AND APPL2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PLXNC1(94659001)-APPL2(105623001), # samples:1
Anticipated loss of major functional domain due to fusion event.PLXNC1-APPL2 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.
PLXNC1-APPL2 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.
PLXNC1-APPL2 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.
PLXNC1-APPL2 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
TgeneAPPL2

GO:0006606

protein import into nucleus

26583432

TgeneAPPL2

GO:0051289

protein homotetramerization

23055524

TgeneAPPL2

GO:2000045

regulation of G1/S transition of mitotic cell cycle

15016378



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/chr12:94659001/chr12:105623001)
- 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 PLXNC1 (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 APPL2 (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)
ENST00000258526PLXNC1chr1294659001+ENST00000258530APPL2chr12105623001-680538463357861917
ENST00000547057PLXNC1chr1294659001+ENST00000258530APPL2chr12105623001-39349751412915924

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
ENST00000258526ENST00000258530PLXNC1chr1294659001+APPL2chr12105623001-0.0006785080.99932146
ENST00000547057ENST00000258530PLXNC1chr1294659001+APPL2chr12105623001-0.0006035770.99939644

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 PLXNC1-APPL2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
PLXNC1chr1294659001APPL2chr1210562300138461271DWLLWQVPEFSTVTRSLLSVFEEDAG
PLXNC1chr1294659001APPL2chr12105623001975278DWLLWQVPEFSTVTRSLLSVFEEDAG

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Potential FusionNeoAntigen Information of PLXNC1-APPL2 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.
PLXNC1-APPL2_94659001_105623001.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)
PLXNC1-APPL2chr1294659001chr121056230013846HLA-B15:01VTRSLLSVF0.99840.83991221
PLXNC1-APPL2chr1294659001chr121056230013846HLA-B57:01VTRSLLSVF0.99790.95441221
PLXNC1-APPL2chr1294659001chr121056230013846HLA-B15:17VTRSLLSVF0.99540.84661221
PLXNC1-APPL2chr1294659001chr121056230013846HLA-B15:25VTRSLLSVF0.99510.91061221
PLXNC1-APPL2chr1294659001chr121056230013846HLA-B58:02VTRSLLSVF0.99480.8771221
PLXNC1-APPL2chr1294659001chr121056230013846HLA-B15:16VTRSLLSVF0.99420.54521221
PLXNC1-APPL2chr1294659001chr121056230013846HLA-B57:03VTRSLLSVF0.98690.97231221
PLXNC1-APPL2chr1294659001chr121056230013846HLA-A02:21TVTRSLLSV0.90540.65011120
PLXNC1-APPL2chr1294659001chr121056230013846HLA-B14:02EFSTVTRSL0.86930.5878817
PLXNC1-APPL2chr1294659001chr121056230013846HLA-B14:01EFSTVTRSL0.86930.5878817
PLXNC1-APPL2chr1294659001chr121056230013846HLA-A32:13VTRSLLSVF0.74510.90871221
PLXNC1-APPL2chr1294659001chr121056230013846HLA-A30:08VTRSLLSVF0.68220.71441221
PLXNC1-APPL2chr1294659001chr121056230013846HLA-A34:01QVPEFSTVTR0.98350.5117515
PLXNC1-APPL2chr1294659001chr121056230013846HLA-A34:05QVPEFSTVTR0.98350.5117515
PLXNC1-APPL2chr1294659001chr121056230013846HLA-A68:08QVPEFSTVTR0.95320.6634515
PLXNC1-APPL2chr1294659001chr121056230013846HLA-A68:06QVPEFSTVTR0.94140.6383515
PLXNC1-APPL2chr1294659001chr121056230013846HLA-A66:03QVPEFSTVTR0.93120.5597515
PLXNC1-APPL2chr1294659001chr121056230013846HLA-A34:02QVPEFSTVTR0.85710.6495515
PLXNC1-APPL2chr1294659001chr121056230013846HLA-B35:03VPEFSTVTRSL0.96430.9498617
PLXNC1-APPL2chr1294659001chr121056230013846HLA-B35:04VPEFSTVTRSL0.92280.9758617
PLXNC1-APPL2chr1294659001chr121056230013846HLA-B35:02VPEFSTVTRSL0.92280.9758617
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C03:08FSTVTRSL0.99990.958917
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C03:19FSTVTRSL0.99990.993917
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C03:07FSTVTRSL0.99990.987917
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C15:06FSTVTRSL0.99970.9559917
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C08:04FSTVTRSL0.99930.979917
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C08:13FSTVTRSL0.99930.979917
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C12:12FSTVTRSL0.99930.961917
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C12:04FSTVTRSL0.99860.9979917
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C06:03FSTVTRSL0.99860.9976917
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C02:06FSTVTRSL0.96780.9872917
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C03:08FSTVTRSLL0.99940.9575918
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C03:19FSTVTRSLL0.99910.9928918
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C15:06FSTVTRSLL0.99880.9511918
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C03:07FSTVTRSLL0.99870.9864918
PLXNC1-APPL2chr1294659001chr121056230013846HLA-B15:07VTRSLLSVF0.99810.65161221
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C08:04FSTVTRSLL0.99140.9791918
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C08:13FSTVTRSLL0.99140.9791918
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C01:17FSTVTRSLL0.98870.9658918
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C12:12FSTVTRSLL0.98780.9641918
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C06:03FSTVTRSLL0.98570.9976918
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C12:04FSTVTRSLL0.98550.9978918
PLXNC1-APPL2chr1294659001chr121056230013846HLA-B15:04VTRSLLSVF0.95670.87651221
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C15:04VTRSLLSVF0.95090.86421221
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C12:12VTRSLLSVF0.9490.95421221
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C01:30FSTVTRSLL0.86490.9812918
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C02:06FSTVTRSLL0.75040.9868918
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C12:04VTRSLLSVF0.73830.99031221
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C03:14VTRSLLSVF0.68230.97361221
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C07:13EFSTVTRSL0.35720.9336817
PLXNC1-APPL2chr1294659001chr121056230013846HLA-B14:03EFSTVTRSL0.35560.9116817
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C07:29EFSTVTRSL0.34590.9761817
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C04:14EFSTVTRSL0.12040.8429817
PLXNC1-APPL2chr1294659001chr121056230013846HLA-B07:12VPEFSTVTRSL0.99660.6042617
PLXNC1-APPL2chr1294659001chr121056230013846HLA-B42:02VPEFSTVTRSL0.9360.8717617
PLXNC1-APPL2chr1294659001chr121056230013846HLA-B42:01VPEFSTVTRSL0.9270.8639617
PLXNC1-APPL2chr1294659001chr121056230013846HLA-B35:12VPEFSTVTRSL0.92280.9758617
PLXNC1-APPL2chr1294659001chr121056230013846HLA-B39:10VPEFSTVTRSL0.90540.9631617
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C03:03FSTVTRSL0.99990.9933917
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C03:17FSTVTRSL0.99990.978917
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C03:02FSTVTRSL0.99990.9842917
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C03:05FSTVTRSL0.99990.9558917
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C03:04FSTVTRSL0.99990.9933917
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C03:67FSTVTRSL0.99990.9833917
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C15:05FSTVTRSL0.99960.9408917
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C16:04FSTVTRSL0.99940.9904917
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C15:02FSTVTRSL0.99940.9323917
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C12:02FSTVTRSL0.99930.9871917
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C12:03FSTVTRSL0.99920.991917
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C16:01FSTVTRSL0.9970.9857917
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C16:02FSTVTRSL0.99670.9949917
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C03:06FSTVTRSL0.99320.9932917
PLXNC1-APPL2chr1294659001chr121056230013846HLA-B07:13FSTVTRSL0.80520.9917
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C03:04FSTVTRSLL0.99930.9931918
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C03:03FSTVTRSLL0.99930.9931918
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C15:05FSTVTRSLL0.99860.9378918
PLXNC1-APPL2chr1294659001chr121056230013846HLA-B15:135VTRSLLSVF0.99860.84711221
PLXNC1-APPL2chr1294659001chr121056230013846HLA-B15:27VTRSLLSVF0.99840.83851221
PLXNC1-APPL2chr1294659001chr121056230013846HLA-B15:125VTRSLLSVF0.99840.83991221
PLXNC1-APPL2chr1294659001chr121056230013846HLA-B15:34VTRSLLSVF0.99840.83991221
PLXNC1-APPL2chr1294659001chr121056230013846HLA-B15:33VTRSLLSVF0.99840.83991221
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C15:02TVTRSLLSV0.99840.76421120
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C03:05FSTVTRSLL0.99820.9501918
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C15:02FSTVTRSLL0.99820.9298918
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C15:05TVTRSLLSV0.99810.8131120
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C03:17FSTVTRSLL0.9980.9773918
PLXNC1-APPL2chr1294659001chr121056230013846HLA-B15:35VTRSLLSVF0.9980.7591221
PLXNC1-APPL2chr1294659001chr121056230013846HLA-B57:10VTRSLLSVF0.99790.95441221
PLXNC1-APPL2chr1294659001chr121056230013846HLA-B15:24VTRSLLSVF0.99780.69181221
PLXNC1-APPL2chr1294659001chr121056230013846HLA-B15:50VTRSLLSVF0.99760.88241221
PLXNC1-APPL2chr1294659001chr121056230013846HLA-B58:06VTRSLLSVF0.99730.57661221
PLXNC1-APPL2chr1294659001chr121056230013846HLA-B57:04VTRSLLSVF0.99640.73021221
PLXNC1-APPL2chr1294659001chr121056230013846HLA-B15:39VTRSLLSVF0.99480.76361221
PLXNC1-APPL2chr1294659001chr121056230013846HLA-A69:01TVTRSLLSV0.99090.67711120
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C16:04FSTVTRSLL0.98950.9909918
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C01:02FSTVTRSLL0.98940.9641918
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C12:03FSTVTRSLL0.98750.9916918
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C03:02VTRSLLSVF0.98690.95761221
PLXNC1-APPL2chr1294659001chr121056230013846HLA-B57:02VTRSLLSVF0.98330.82941221
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C16:02FSTVTRSLL0.97790.9948918
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C03:06FSTVTRSLL0.97060.9931918
PLXNC1-APPL2chr1294659001chr121056230013846HLA-B15:12VTRSLLSVF0.96160.88821221
PLXNC1-APPL2chr1294659001chr121056230013846HLA-A32:01VTRSLLSVF0.95330.82311221
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C15:09VTRSLLSVF0.95090.86421221
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C16:01FSTVTRSLL0.94460.9854918
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C12:02VTRSLLSVF0.92370.9711221
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C12:03VTRSLLSVF0.91480.97661221
PLXNC1-APPL2chr1294659001chr121056230013846HLA-A02:06TVTRSLLSV0.90540.65011120
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C16:04VTRSLLSVF0.89640.96261221
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C02:02VTRSLLSVF0.52170.96451221
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C02:10VTRSLLSVF0.52170.96451221
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C17:01FSTVTRSLL0.49190.9322918
PLXNC1-APPL2chr1294659001chr121056230013846HLA-B07:13FSTVTRSLL0.39860.8985918
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C03:67EFSTVTRSL0.37420.99817
PLXNC1-APPL2chr1294659001chr121056230013846HLA-B08:12EFSTVTRSL0.22480.8824817
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C07:04EFSTVTRSL0.12670.9488817
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C04:04EFSTVTRSL0.10010.8819817
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C14:03EFSTVTRSL0.04860.9749817
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C14:02EFSTVTRSL0.04860.9749817
PLXNC1-APPL2chr1294659001chr121056230013846HLA-C06:06EFSTVTRSL0.04410.9885817
PLXNC1-APPL2chr1294659001chr121056230013846HLA-A66:02QVPEFSTVTR0.96580.5575515
PLXNC1-APPL2chr1294659001chr121056230013846HLA-B35:09VPEFSTVTRSL0.92280.9758617
PLXNC1-APPL2chr1294659001chr121056230013846HLA-B67:01VPEFSTVTRSL0.90310.7569617

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Potential FusionNeoAntigen Information of PLXNC1-APPL2 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.
PLXNC1-APPL2_94659001_105623001.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)
PLXNC1-APPL2chr1294659001chr121056230013846DRB1-1407QVPEFSTVTRSLLSV520
PLXNC1-APPL2chr1294659001chr121056230013846DRB1-1407WQVPEFSTVTRSLLS419
PLXNC1-APPL2chr1294659001chr121056230013846DRB1-1407VPEFSTVTRSLLSVF621
PLXNC1-APPL2chr1294659001chr121056230013846DRB1-1414QVPEFSTVTRSLLSV520
PLXNC1-APPL2chr1294659001chr121056230013846DRB1-1436QVPEFSTVTRSLLSV520
PLXNC1-APPL2chr1294659001chr121056230013846DRB1-1442QVPEFSTVTRSLLSV520
PLXNC1-APPL2chr1294659001chr121056230013846DRB1-1442VPEFSTVTRSLLSVF621
PLXNC1-APPL2chr1294659001chr121056230013846DRB1-1442WQVPEFSTVTRSLLS419
PLXNC1-APPL2chr1294659001chr121056230013846DRB1-1444QVPEFSTVTRSLLSV520
PLXNC1-APPL2chr1294659001chr121056230013846DRB1-1468QVPEFSTVTRSLLSV520
PLXNC1-APPL2chr1294659001chr121056230013846DRB1-1468WQVPEFSTVTRSLLS419
PLXNC1-APPL2chr1294659001chr121056230013846DRB1-1468VPEFSTVTRSLLSVF621

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Fusion breakpoint peptide structures of PLXNC1-APPL2

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
10165VPEFSTVTRSLLSVPLXNC1APPL2chr1294659001chr121056230013846

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PLXNC1-APPL2

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-B14:023BVN10165VPEFSTVTRSLLSV-7.9962-8.1096
HLA-B14:023BVN10165VPEFSTVTRSLLSV-5.70842-6.74372
HLA-B52:013W3910165VPEFSTVTRSLLSV-6.83737-6.95077
HLA-B52:013W3910165VPEFSTVTRSLLSV-4.4836-5.5189
HLA-A11:014UQ210165VPEFSTVTRSLLSV-10.0067-10.1201
HLA-A11:014UQ210165VPEFSTVTRSLLSV-9.03915-10.0745
HLA-A24:025HGA10165VPEFSTVTRSLLSV-6.56204-6.67544
HLA-A24:025HGA10165VPEFSTVTRSLLSV-5.42271-6.45801
HLA-B44:053DX810165VPEFSTVTRSLLSV-7.85648-8.89178
HLA-B44:053DX810165VPEFSTVTRSLLSV-5.3978-5.5112
HLA-B35:011A1N10165VPEFSTVTRSLLSV-6.27422-6.38762
HLA-B35:011A1N10165VPEFSTVTRSLLSV-5.27424-6.30954
HLA-A02:016TDR10165VPEFSTVTRSLLSV-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of PLXNC1-APPL2

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
PLXNC1-APPL2chr1294659001chr121056230011120TVTRSLLSVACTGTGACTCGCTCTTTACTGAGCGTG
PLXNC1-APPL2chr1294659001chr121056230011221VTRSLLSVFGTGACTCGCTCTTTACTGAGCGTGTTT
PLXNC1-APPL2chr1294659001chr12105623001515QVPEFSTVTRCAGGTTCCGGAATTCAGTACTGTGACTCGC
PLXNC1-APPL2chr1294659001chr12105623001617VPEFSTVTRSLGTTCCGGAATTCAGTACTGTGACTCGCTCTTTA
PLXNC1-APPL2chr1294659001chr12105623001817EFSTVTRSLGAATTCAGTACTGTGACTCGCTCTTTA
PLXNC1-APPL2chr1294659001chr12105623001917FSTVTRSLTTCAGTACTGTGACTCGCTCTTTA
PLXNC1-APPL2chr1294659001chr12105623001918FSTVTRSLLTTCAGTACTGTGACTCGCTCTTTACTG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
PLXNC1-APPL2chr1294659001chr12105623001419WQVPEFSTVTRSLLSTGGCAGGTTCCGGAATTCAGTACTGTGACTCGCTCTTTACTGAGC
PLXNC1-APPL2chr1294659001chr12105623001520QVPEFSTVTRSLLSVCAGGTTCCGGAATTCAGTACTGTGACTCGCTCTTTACTGAGCGTG
PLXNC1-APPL2chr1294659001chr12105623001621VPEFSTVTRSLLSVFGTTCCGGAATTCAGTACTGTGACTCGCTCTTTACTGAGCGTGTTT

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Information of the samples that have these potential fusion neoantigens of PLXNC1-APPL2

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
GBMPLXNC1-APPL2chr1294659001ENST00000258526chr12105623001ENST00000258530TCGA-06-0129-01A

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Potential target of CAR-T therapy development for PLXNC1-APPL2

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
HgenePLXNC1chr12:94659001chr12:105623001ENST00000258526+2131945_96511991569.0TransmembraneHelical

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 PLXNC1-APPL2

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 PLXNC1-APPL2

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