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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:NDRG3-BCAS4

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NDRG3-BCAS4
FusionPDB ID: 58003
FusionGDB2.0 ID: 58003
HgeneTgene
Gene symbol

NDRG3

BCAS4

Gene ID

57446

55653

Gene nameNDRG family member 3breast carcinoma amplified sequence 4
Synonyms-CNOL
Cytomap

20q11.23

20q13.13

Type of geneprotein-codingprotein-coding
Descriptionprotein NDRG3N-myc downstream-regulated gene 3 proteinbreast carcinoma-amplified sequence 4BCAS4/BCAS3 fusionbreast carcinoma amplified sequence 4/3 fusion protein
Modification date2020031320200313
UniProtAcc

Q9UGV2

Main function of 5'-partner protein:

Q8TDM0

Main function of 5'-partner protein:
Ensembl transtripts involved in fusion geneENST idsENST00000349004, ENST00000359675, 
ENST00000373773, ENST00000373803, 
ENST00000540765, 
ENST00000485049, 
ENST00000262591, ENST00000358791, 
ENST00000371608, ENST00000609336, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score13 X 13 X 5=84511 X 8 X 9=792
# samples 1411
** MAII scorelog2(14/845*10)=-2.59352451422458
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(11/792*10)=-2.84799690655495
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: NDRG3 [Title/Abstract] AND BCAS4 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: NDRG3 [Title/Abstract] AND BCAS4 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NDRG3(35310921)-BCAS4(49434748), # samples:2
Anticipated loss of major functional domain due to fusion event.NDRG3-BCAS4 seems lost the major protein functional domain in Tgene partner, which is a essential gene 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/chr20:35310921/chr20:49434748)
- 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 NDRG3 (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 BCAS4 (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)
ENST00000373803NDRG3chr2035310921-ENST00000358791BCAS4chr2049434748+159950157956299
ENST00000373803NDRG3chr2035310921-ENST00000262591BCAS4chr2049434748+136650157797246
ENST00000373803NDRG3chr2035310921-ENST00000371608BCAS4chr2049434748+150250157932291
ENST00000373803NDRG3chr2035310921-ENST00000609336BCAS4chr2049434748+114550157956299
ENST00000359675NDRG3chr2035310921-ENST00000358791BCAS4chr2049434748+157747971934287
ENST00000359675NDRG3chr2035310921-ENST00000262591BCAS4chr2049434748+134447971775234
ENST00000359675NDRG3chr2035310921-ENST00000371608BCAS4chr2049434748+148047971910279
ENST00000359675NDRG3chr2035310921-ENST00000609336BCAS4chr2049434748+112347971934287
ENST00000349004NDRG3chr2035310921-ENST00000358791BCAS4chr2049434748+162452682981299
ENST00000349004NDRG3chr2035310921-ENST00000262591BCAS4chr2049434748+139152682822246
ENST00000349004NDRG3chr2035310921-ENST00000371608BCAS4chr2049434748+152752682957291
ENST00000349004NDRG3chr2035310921-ENST00000609336BCAS4chr2049434748+117052682981299
ENST00000540765NDRG3chr2035310921-ENST00000358791BCAS4chr2049434748+1353255123710195
ENST00000540765NDRG3chr2035310921-ENST00000262591BCAS4chr2049434748+1120255123551142
ENST00000540765NDRG3chr2035310921-ENST00000371608BCAS4chr2049434748+1256255123686187
ENST00000540765NDRG3chr2035310921-ENST00000609336BCAS4chr2049434748+899255123710195

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
ENST00000373803ENST00000358791NDRG3chr2035310921-BCAS4chr2049434748+0.0013899290.99861
ENST00000373803ENST00000262591NDRG3chr2035310921-BCAS4chr2049434748+0.0011354220.99886465
ENST00000373803ENST00000371608NDRG3chr2035310921-BCAS4chr2049434748+0.0010639570.998936
ENST00000373803ENST00000609336NDRG3chr2035310921-BCAS4chr2049434748+0.0019146120.9980854
ENST00000359675ENST00000358791NDRG3chr2035310921-BCAS4chr2049434748+0.0049477680.9950523
ENST00000359675ENST00000262591NDRG3chr2035310921-BCAS4chr2049434748+0.002595470.9974045
ENST00000359675ENST00000371608NDRG3chr2035310921-BCAS4chr2049434748+0.003334970.99666506
ENST00000359675ENST00000609336NDRG3chr2035310921-BCAS4chr2049434748+0.0071580150.99284196
ENST00000349004ENST00000358791NDRG3chr2035310921-BCAS4chr2049434748+0.0013300530.99867
ENST00000349004ENST00000262591NDRG3chr2035310921-BCAS4chr2049434748+0.0010563890.9989436
ENST00000349004ENST00000371608NDRG3chr2035310921-BCAS4chr2049434748+0.0010345960.9989654
ENST00000349004ENST00000609336NDRG3chr2035310921-BCAS4chr2049434748+0.0017959990.998204
ENST00000540765ENST00000358791NDRG3chr2035310921-BCAS4chr2049434748+0.0080060830.9919939
ENST00000540765ENST00000262591NDRG3chr2035310921-BCAS4chr2049434748+0.0129739030.98702604
ENST00000540765ENST00000371608NDRG3chr2035310921-BCAS4chr2049434748+0.0047574260.9952426
ENST00000540765ENST00000609336NDRG3chr2035310921-BCAS4chr2049434748+0.0103196360.98968035

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 NDRG3-BCAS4

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
NDRG3chr2035310921BCAS4chr204943474825538KSIIGIGVGAGAYILSRFAAKEVEET
NDRG3chr2035310921BCAS4chr2049434748479130KSIIGIGVGAGAYILSRFAAKEVEET
NDRG3chr2035310921BCAS4chr2049434748501142KSIIGIGVGAGAYILSRFAAKEVEET
NDRG3chr2035310921BCAS4chr2049434748526142KSIIGIGVGAGAYILSRFAAKEVEET

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Potential FusionNeoAntigen Information of NDRG3-BCAS4 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.

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)

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Potential FusionNeoAntigen Information of NDRG3-BCAS4 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.
NDRG3-BCAS4_35310921_49434748.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)
NDRG3-BCAS4chr2035310921chr2049434748526DRB1-0806GAYILSRFAAKEVEE1025
NDRG3-BCAS4chr2035310921chr2049434748526DRB1-0810GAYILSRFAAKEVEE1025
NDRG3-BCAS4chr2035310921chr2049434748526DRB1-0812GAYILSRFAAKEVEE1025
NDRG3-BCAS4chr2035310921chr2049434748526DRB1-0822GAYILSRFAAKEVEE1025
NDRG3-BCAS4chr2035310921chr2049434748526DRB1-1510AYILSRFAAKEVEET1126
NDRG3-BCAS4chr2035310921chr2049434748526DRB1-1518AYILSRFAAKEVEET1126
NDRG3-BCAS4chr2035310921chr2049434748526DRB1-1521AYILSRFAAKEVEET1126
NDRG3-BCAS4chr2035310921chr2049434748526DRB1-1521GAYILSRFAAKEVEE1025
NDRG3-BCAS4chr2035310921chr2049434748526DRB1-1535AYILSRFAAKEVEET1126

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Fusion breakpoint peptide structures of NDRG3-BCAS4

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.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of NDRG3-BCAS4

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

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Vaccine Design for the FusionNeoAntigens of NDRG3-BCAS4

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

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
NDRG3-BCAS4chr2035310921chr20494347481025GAYILSRFAAKEVEEAGATTTGCAGCGAAGGAGGTGGAGGAGACCATCGAGGGCATGCTC
NDRG3-BCAS4chr2035310921chr20494347481126AYILSRFAAKEVEETTTTGCAGCGAAGGAGGTGGAGGAGACCATCGAGGGCATGCTCCTC

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Information of the samples that have these potential fusion neoantigens of NDRG3-BCAS4

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

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Potential target of CAR-T therapy development for NDRG3-BCAS4

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 NDRG3-BCAS4

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 NDRG3-BCAS4

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