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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:NDRG2-SPARC

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NDRG2-SPARC
FusionPDB ID: 58000
FusionGDB2.0 ID: 58000
HgeneTgene
Gene symbol

NDRG2

SPARC

Gene ID

57447

6678

Gene nameNDRG family member 2secreted protein acidic and cysteine rich
SynonymsSYLDBM-40|OI17|ON|ONT
Cytomap

14q11.2

5q33.1

Type of geneprotein-codingprotein-coding
Descriptionprotein NDRG2N-myc downstream regulator 2N-myc downstream-regulated gene 2 proteinNDR1-related protein NDR2cytoplasmic protein Ndr1syld709613 proteinSPARCbasement-membrane protein 40secreted protein, acidic, cysteine-rich (osteonectin)
Modification date2020031320200329
UniProtAcc

Q9UN36

Main function of 5'-partner protein: FUNCTION: Contributes to the regulation of the Wnt signaling pathway. Down-regulates CTNNB1-mediated transcriptional activation of target genes, such as CCND1, and may thereby act as tumor suppressor. May be involved in dendritic cell and neuron differentiation. {ECO:0000269|PubMed:12845671, ECO:0000269|PubMed:16103061, ECO:0000269|PubMed:21247902}.

SMAP2,SMOC2

Main function of 5'-partner protein: 446
Ensembl transtripts involved in fusion geneENST idsENST00000298684, ENST00000298687, 
ENST00000350792, ENST00000360463, 
ENST00000397844, ENST00000397851, 
ENST00000397853, ENST00000397855, 
ENST00000397856, ENST00000397858, 
ENST00000403829, ENST00000553503, 
ENST00000554104, ENST00000554143, 
ENST00000555158, ENST00000556147, 
ENST00000397847, ENST00000554277, 
ENST00000537849, ENST00000231061, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score17 X 14 X 3=71434 X 31 X 7=7378
# samples 1838
** MAII scorelog2(18/714*10)=-1.98792716769943
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(38/7378*10)=-4.27915846536387
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: NDRG2 [Title/Abstract] AND SPARC [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: NDRG2 [Title/Abstract] AND SPARC [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NDRG2(21486922)-SPARC(151049345), # samples:1
Anticipated loss of major functional domain due to fusion event.NDRG2-SPARC 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.
NDRG2-SPARC 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.
NDRG2-SPARC 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.
NDRG2-SPARC 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.
NDRG2-SPARC seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted ORF.
NDRG2-SPARC seems lost the major protein functional domain in Tgene partner, which is a tumor suppressor 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
TgeneSPARC

GO:0001937

negative regulation of endothelial cell proliferation

12867428

TgeneSPARC

GO:0010595

positive regulation of endothelial cell migration

12867428

TgeneSPARC

GO:0016525

negative regulation of angiogenesis

12867428

TgeneSPARC

GO:0022604

regulation of cell morphogenesis

15389586



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/chr14:21486922/chr5:151049345)
- 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 NDRG2 (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 SPARC (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)
ENST00000403829NDRG2chr1421486922-ENST00000231061SPARCchr5151049345-387982291403464
ENST00000397858NDRG2chr1421486922-ENST00000231061SPARCchr5151049345-39769191061500464
ENST00000360463NDRG2chr1421486922-ENST00000231061SPARCchr5151049345-39779201491501450
ENST00000556147NDRG2chr1421486922-ENST00000231061SPARCchr5151049345-481117549112335474
ENST00000554143NDRG2chr1421486922-ENST00000231061SPARCchr5151049345-3911854831435450
ENST00000397851NDRG2chr1421486922-ENST00000231061SPARCchr5151049345-3953896831477464
ENST00000298684NDRG2chr1421486922-ENST00000231061SPARCchr5151049345-3753696121277421

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
ENST00000403829ENST00000231061NDRG2chr1421486922-SPARCchr5151049345-0.0009123770.9990876
ENST00000397858ENST00000231061NDRG2chr1421486922-SPARCchr5151049345-0.0012274890.99877244
ENST00000360463ENST00000231061NDRG2chr1421486922-SPARCchr5151049345-0.0009398250.9990602
ENST00000556147ENST00000231061NDRG2chr1421486922-SPARCchr5151049345-0.0009968880.9990031
ENST00000554143ENST00000231061NDRG2chr1421486922-SPARCchr5151049345-0.0008124460.9991875
ENST00000397851ENST00000231061NDRG2chr1421486922-SPARCchr5151049345-0.0011059910.99889404
ENST00000298684ENST00000231061NDRG2chr1421486922-SPARCchr5151049345-0.0011399950.99886

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 NDRG2-SPARC

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
NDRG2chr1421486922SPARCchr51510493451754281LVVGDQAPHEDAVVCSNDNKTFDSSC
NDRG2chr1421486922SPARCchr5151049345696228LVVGDQAPHEDAVVCSNDNKTFDSSC
NDRG2chr1421486922SPARCchr5151049345822271LVVGDQAPHEDAVVCSNDNKTFDSSC
NDRG2chr1421486922SPARCchr5151049345854257LVVGDQAPHEDAVVCSNDNKTFDSSC
NDRG2chr1421486922SPARCchr5151049345896271LVVGDQAPHEDAVVCSNDNKTFDSSC
NDRG2chr1421486922SPARCchr5151049345919271LVVGDQAPHEDAVVCSNDNKTFDSSC
NDRG2chr1421486922SPARCchr5151049345920257LVVGDQAPHEDAVVCSNDNKTFDSSC

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Potential FusionNeoAntigen Information of NDRG2-SPARC 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.
NDRG2-SPARC_21486922_151049345.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)
NDRG2-SPARCchr1421486922chr5151049345696HLA-B39:10APHEDAVVC0.15410.8507615
NDRG2-SPARCchr1421486922chr5151049345696HLA-B67:01APHEDAVVC0.20320.6707615

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Potential FusionNeoAntigen Information of NDRG2-SPARC 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 NDRG2-SPARC

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
484APHEDAVVCSNDNKNDRG2SPARCchr1421486922chr5151049345696

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of NDRG2-SPARC

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-B14:023BVN484APHEDAVVCSNDNK-7.9962-8.1096
HLA-B14:023BVN484APHEDAVVCSNDNK-5.70842-6.74372
HLA-B52:013W39484APHEDAVVCSNDNK-6.83737-6.95077
HLA-B52:013W39484APHEDAVVCSNDNK-4.4836-5.5189
HLA-A11:014UQ2484APHEDAVVCSNDNK-10.0067-10.1201
HLA-A11:014UQ2484APHEDAVVCSNDNK-9.03915-10.0745
HLA-A24:025HGA484APHEDAVVCSNDNK-6.56204-6.67544
HLA-A24:025HGA484APHEDAVVCSNDNK-5.42271-6.45801
HLA-B44:053DX8484APHEDAVVCSNDNK-7.85648-8.89178
HLA-B44:053DX8484APHEDAVVCSNDNK-5.3978-5.5112
HLA-A02:016TDR484APHEDAVVCSNDNK-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of NDRG2-SPARC

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
NDRG2-SPARCchr1421486922chr5151049345615APHEDAVVCGCACCTCATGAAGATGCAGTGGTGTGC

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 NDRG2-SPARC

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
LGGNDRG2-SPARCchr1421486922ENST00000298684chr5151049345ENST00000231061TCGA-HT-7680-01A

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Potential target of CAR-T therapy development for NDRG2-SPARC

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 NDRG2-SPARC

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 NDRG2-SPARC

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