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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:DPYD-STAB2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: DPYD-STAB2
FusionPDB ID: 24107
FusionGDB2.0 ID: 24107
HgeneTgene
Gene symbol

DPYD

STAB2

Gene ID

1806

55576

Gene namedihydropyrimidine dehydrogenasestabilin 2
SynonymsDHP|DHPDHASE|DPDFEEL2|FELE-2|FELL2|FEX2|HARE|SCARH1
Cytomap

1p21.3

12q23.3

Type of geneprotein-codingprotein-coding
Descriptiondihydropyrimidine dehydrogenase [NADP(+)]dihydrothymine dehydrogenasedihydrouracil dehydrogenasestabilin-2CD44-like precursor FELLFAS1 EGF-like and X-link domain containing adhesion molecule-2fasciclin egf-like, laminin-type egf-like, and link domain-containing scavenger receptor-2hepatic hyaluronan clearance receptorhyaluronan receptor for end
Modification date2020031320200313
UniProtAcc

Q12882

Main function of 5'-partner protein: FUNCTION: Involved in pyrimidine base degradation. Catalyzes the reduction of uracil and thymine. Also involved the degradation of the chemotherapeutic drug 5-fluorouracil.
.
Ensembl transtripts involved in fusion geneENST idsENST00000306031, ENST00000370192, 
ENST00000423006, ENST00000474241, 
ENST00000388887, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score15 X 13 X 8=15607 X 8 X 3=168
# samples 186
** MAII scorelog2(18/1560*10)=-3.11547721741994
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(6/168*10)=-1.48542682717024
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: DPYD [Title/Abstract] AND STAB2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: DPYD [Title/Abstract] AND STAB2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)DPYD(98348820)-STAB2(104054109), # samples:3
Anticipated loss of major functional domain due to fusion event.DPYD-STAB2 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.
DPYD-STAB2 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.
DPYD-STAB2 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.
DPYD-STAB2 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
HgeneDPYD

GO:0006210

thymine catabolic process

10410956

HgeneDPYD

GO:0006212

uracil catabolic process

1512248|18075467

HgeneDPYD

GO:0006214

thymidine catabolic process

1512248

TgeneSTAB2

GO:0042742

defense response to bacterium

12077138

TgeneSTAB2

GO:0050830

defense response to Gram-positive bacterium

11829752



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/chr1:98348820/chr12:104054109)
- 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 DPYD (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 STAB2 (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)
ENST00000370192DPYDchr198348820-ENST00000388887STAB2chr12104054109+65642514761722041
ENST00000306031DPYDchr198348820-ENST00000388887STAB2chr12104054109+65902772261982058

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
ENST00000370192ENST00000388887DPYDchr198348820-STAB2chr12104054109+0.0012178840.9987821
ENST00000306031ENST00000388887DPYDchr198348820-STAB2chr12104054109+0.0012609880.99873906

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 DPYD-STAB2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
DPYDchr198348820STAB2chr1210405410925168KKHWKRNPDKNCFGSRKLLELVRYHI
DPYDchr198348820STAB2chr1210405410927785KKHWKRNPDKNCFGSRKLLELVRYHI

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Potential FusionNeoAntigen Information of DPYD-STAB2 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.
DPYD-STAB2_98348820_104054109.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)
DPYD-STAB2chr198348820chr12104054109277HLA-B08:01FGSRKLLEL0.99790.72941221
DPYD-STAB2chr198348820chr12104054109277HLA-B08:09FGSRKLLEL0.99660.77461221
DPYD-STAB2chr198348820chr12104054109277HLA-C03:07FGSRKLLEL0.99880.98791221
DPYD-STAB2chr198348820chr12104054109277HLA-C03:19FGSRKLLEL0.99870.98731221
DPYD-STAB2chr198348820chr12104054109277HLA-C03:08FGSRKLLEL0.99870.89011221
DPYD-STAB2chr198348820chr12104054109277HLA-C15:06FGSRKLLEL0.99830.97231221
DPYD-STAB2chr198348820chr12104054109277HLA-C06:03FGSRKLLEL0.99170.99831221
DPYD-STAB2chr198348820chr12104054109277HLA-C08:04FGSRKLLEL0.96840.98851221
DPYD-STAB2chr198348820chr12104054109277HLA-C08:13FGSRKLLEL0.96840.98851221
DPYD-STAB2chr198348820chr12104054109277HLA-C07:13FGSRKLLEL0.95510.97561221
DPYD-STAB2chr198348820chr12104054109277HLA-C02:06FGSRKLLEL0.93020.98681221
DPYD-STAB2chr198348820chr12104054109277HLA-C01:30FGSRKLLEL0.90540.98331221
DPYD-STAB2chr198348820chr12104054109277HLA-C08:03FGSRKLLEL0.8230.99571221
DPYD-STAB2chr198348820chr12104054109277HLA-C03:04FGSRKLLEL0.99880.9811221
DPYD-STAB2chr198348820chr12104054109277HLA-C03:03FGSRKLLEL0.99880.9811221
DPYD-STAB2chr198348820chr12104054109277HLA-C03:05FGSRKLLEL0.99860.91441221
DPYD-STAB2chr198348820chr12104054109277HLA-C03:17FGSRKLLEL0.99830.96921221
DPYD-STAB2chr198348820chr12104054109277HLA-C03:67FGSRKLLEL0.99790.96771221
DPYD-STAB2chr198348820chr12104054109277HLA-B08:18FGSRKLLEL0.99790.72941221
DPYD-STAB2chr198348820chr12104054109277HLA-C15:05FGSRKLLEL0.99760.95921221
DPYD-STAB2chr198348820chr12104054109277HLA-C15:02FGSRKLLEL0.99670.95351221
DPYD-STAB2chr198348820chr12104054109277HLA-C07:04FGSRKLLEL0.99040.96911221
DPYD-STAB2chr198348820chr12104054109277HLA-C16:04FGSRKLLEL0.98920.99541221
DPYD-STAB2chr198348820chr12104054109277HLA-B08:12FGSRKLLEL0.9860.8321221
DPYD-STAB2chr198348820chr12104054109277HLA-C16:02FGSRKLLEL0.97130.99771221
DPYD-STAB2chr198348820chr12104054109277HLA-C16:01FGSRKLLEL0.96390.99331221
DPYD-STAB2chr198348820chr12104054109277HLA-C08:01FGSRKLLEL0.8230.99571221
DPYD-STAB2chr198348820chr12104054109277HLA-C17:01FGSRKLLEL0.81250.95851221
DPYD-STAB2chr198348820chr12104054109277HLA-B07:13FGSRKLLEL0.49240.91111221

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Potential FusionNeoAntigen Information of DPYD-STAB2 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 DPYD-STAB2

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
6304NPDKNCFGSRKLLEDPYDSTAB2chr198348820chr12104054109277

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of DPYD-STAB2

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-B14:023BVN6304NPDKNCFGSRKLLE-6.74468-6.85808
HLA-B14:023BVN6304NPDKNCFGSRKLLE-5.93282-6.96812
HLA-B52:013W396304NPDKNCFGSRKLLE-6.27244-6.38584
HLA-B52:013W396304NPDKNCFGSRKLLE-3.39059-4.42589
HLA-A11:014UQ26304NPDKNCFGSRKLLE-6.34898-6.46238
HLA-A24:025HGA6304NPDKNCFGSRKLLE-6.00443-6.11783
HLA-A24:025HGA6304NPDKNCFGSRKLLE-4.69739-5.73269
HLA-B44:053DX86304NPDKNCFGSRKLLE-6.89558-7.93088
HLA-B44:053DX86304NPDKNCFGSRKLLE-6.03891-6.15231
HLA-A02:016TDR6304NPDKNCFGSRKLLE-5.0104-5.1238

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Vaccine Design for the FusionNeoAntigens of DPYD-STAB2

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
DPYD-STAB2chr198348820chr121040541091221FGSRKLLELTTTGGATCTCGGAAGCTTCTGGAACTC

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 DPYD-STAB2

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
BRCADPYD-STAB2chr198348820ENST00000306031chr12104054109ENST00000388887TCGA-BH-A1EU-01A

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Potential target of CAR-T therapy development for DPYD-STAB2

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
TgeneSTAB2chr1:98348820chr12:104054109ENST0000038888714692459_247902552.0TransmembraneHelical

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 DPYD-STAB2

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 DPYD-STAB2

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