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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:BMPR2-ATG4B

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: BMPR2-ATG4B
FusionPDB ID: 9922
FusionGDB2.0 ID: 9922
HgeneTgene
Gene symbol

BMPR2

ATG4B

Gene ID

659

23192

Gene namebone morphogenetic protein receptor type 2autophagy related 4B cysteine peptidase
SynonymsBMPR-II|BMPR3|BMR2|BRK-3|POVD1|PPH1|T-ALKAPG4B|AUTL1
Cytomap

2q33.1-q33.2

2q37.3

Type of geneprotein-codingprotein-coding
Descriptionbone morphogenetic protein receptor type-2BMP type II receptorBMP type-2 receptorbone morphogenetic protein receptor type IIbone morphogenetic protein receptor, type II (serine/threonine kinase)type II activin receptor-like kinasetype II receptor focysteine protease ATG4BAPG4 autophagy 4 homolog BATG4 autophagy related 4 homolog BAUT-like 1 cysteine endopeptidaseautophagin-1autophagy-related cysteine endopeptidase 1autophagy-related protein 4 homolog BhAPG4B
Modification date2020031320200329
UniProtAcc

Q13873

Main function of 5'-partner protein: FUNCTION: On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Binds to BMP7, BMP2 and, less efficiently, BMP4. Binding is weak but enhanced by the presence of type I receptors for BMPs. Mediates induction of adipogenesis by GDF6. {ECO:0000250|UniProtKB:O35607}.

Q9Y4P1

Main function of 5'-partner protein: FUNCTION: Cysteine protease required for the cytoplasm to vacuole transport (Cvt) and autophagy. Cleaves the C-terminal amino acid of ATG8 family proteins MAP1LC3, GABARAPL1, GABARAPL2 and GABARAP, to reveal a C-terminal glycine. Exposure of the glycine at the C-terminus is essential for ATG8 proteins conjugation to phosphatidylethanolamine (PE) and insertion to membranes, which is necessary for autophagy. Has also an activity of delipidating enzyme for the PE-conjugated forms. {ECO:0000269|PubMed:15169837, ECO:0000269|PubMed:15187094, ECO:0000269|PubMed:17347651, ECO:0000269|PubMed:19322194, ECO:0000269|PubMed:21177865, ECO:0000269|PubMed:22302004}.
Ensembl transtripts involved in fusion geneENST idsENST00000479069, ENST00000374574, 
ENST00000374580, 
ENST00000405546, 
ENST00000491867, ENST00000396411, 
ENST00000402096, ENST00000404914, 
ENST00000474739, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score20 X 12 X 9=21604 X 4 X 3=48
# samples 215
** MAII scorelog2(21/2160*10)=-3.36257007938471
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(5/48*10)=0.0588936890535686
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: BMPR2 [Title/Abstract] AND ATG4B [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: BMPR2 [Title/Abstract] AND ATG4B [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)BMPR2(203332412)-ATG4B(242590425), # samples:1
Anticipated loss of major functional domain due to fusion event.BMPR2-ATG4B 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.
BMPR2-ATG4B 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
HgeneBMPR2

GO:0007178

transmembrane receptor protein serine/threonine kinase signaling pathway

12045205

HgeneBMPR2

GO:0010634

positive regulation of epithelial cell migration

12819188

HgeneBMPR2

GO:0030308

negative regulation of cell growth

12819188

HgeneBMPR2

GO:0030509

BMP signaling pathway

18436533

TgeneATG4B

GO:0006508

proteolysis

15169837|18387192

TgeneATG4B

GO:0006914

autophagy

18387192

TgeneATG4B

GO:0051697

protein delipidation

25327288



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/chr2:203332412/chr2:242590425)
- 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 BMPR2 (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 ATG4B (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)
ENST00000374580BMPR2chr2203332412-ENST00000405546ATG4Bchr2242590425+37399575242089521
ENST00000374574BMPR2chr2203332412-ENST00000405546ATG4Bchr2242590425+3241459261591521

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
ENST00000374580ENST00000405546BMPR2chr2203332412-ATG4Bchr2242590425+0.0118748160.9881252
ENST00000374574ENST00000405546BMPR2chr2203332412-ATG4Bchr2242590425+0.0101266970.9898733

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 BMPR2-ATG4B

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
BMPR2chr2203332412ATG4Bchr224259042545924RPWRVPWLPWTILLVSTAAASQNQER
BMPR2chr2203332412ATG4Bchr224259042595724RPWRVPWLPWTILLVSTAAASQNQER

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Potential FusionNeoAntigen Information of BMPR2-ATG4B 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.
BMPR2-ATG4B_203332412_242590425.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)
BMPR2-ATG4Bchr2203332412chr2242590425459HLA-B35:03VPWLPWTILL0.91670.8092414
BMPR2-ATG4Bchr2203332412chr2242590425459HLA-B81:01VPWLPWTILL0.75560.5415414
BMPR2-ATG4Bchr2203332412chr2242590425459HLA-B42:01VPWLPWTILL0.73950.803414
BMPR2-ATG4Bchr2203332412chr2242590425459HLA-A32:01RVPWLPWTILL0.97010.9261314

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Potential FusionNeoAntigen Information of BMPR2-ATG4B 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.
BMPR2-ATG4B_203332412_242590425.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)
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0403PWTILLVSTAAASQN823
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0413PWTILLVSTAAASQN823
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0415PWTILLVSTAAASQN823
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0415LPWTILLVSTAAASQ722
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0419PWTILLVSTAAASQN823
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0427PWTILLVSTAAASQN823
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0431PWTILLVSTAAASQN823
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0436PWTILLVSTAAASQN823
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0436LPWTILLVSTAAASQ722
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0439PWTILLVSTAAASQN823
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0440PWTILLVSTAAASQN823
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0440LPWTILLVSTAAASQ722
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0441PWTILLVSTAAASQN823
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0442PWTILLVSTAAASQN823
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0442LPWTILLVSTAAASQ722
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0443PWTILLVSTAAASQN823
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0444PWTILLVSTAAASQN823
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0444LPWTILLVSTAAASQ722
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0446PWTILLVSTAAASQN823
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0449PWTILLVSTAAASQN823
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0449LPWTILLVSTAAASQ722
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0450PWTILLVSTAAASQN823
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0451PWTILLVSTAAASQN823
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0452PWTILLVSTAAASQN823
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0453PWTILLVSTAAASQN823
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0453LPWTILLVSTAAASQ722
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0454PWTILLVSTAAASQN823
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0455PWTILLVSTAAASQN823
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0455LPWTILLVSTAAASQ722
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0456PWTILLVSTAAASQN823
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0456LPWTILLVSTAAASQ722
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0458PWTILLVSTAAASQN823
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0458LPWTILLVSTAAASQ722
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0459PWTILLVSTAAASQN823
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0460PWTILLVSTAAASQN823
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0461PWTILLVSTAAASQN823
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0465PWTILLVSTAAASQN823
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0468PWTILLVSTAAASQN823
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0468LPWTILLVSTAAASQ722
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0470PWTILLVSTAAASQN823
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0470LPWTILLVSTAAASQ722
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0471PWTILLVSTAAASQN823
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0473PWTILLVSTAAASQN823
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0478PWTILLVSTAAASQN823
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0478LPWTILLVSTAAASQ722
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0479PWTILLVSTAAASQN823
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0479LPWTILLVSTAAASQ722
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0485PWTILLVSTAAASQN823
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0488PWTILLVSTAAASQN823
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-0488LPWTILLVSTAAASQ722
BMPR2-ATG4Bchr2203332412chr2242590425459DRB1-1410PWTILLVSTAAASQN823

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Fusion breakpoint peptide structures of BMPR2-ATG4B

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
10505WLPWTILLVSTAAABMPR2ATG4Bchr2203332412chr2242590425459

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of BMPR2-ATG4B

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-B52:013W3910505WLPWTILLVSTAAA-5.00688-5.00688
HLA-B44:053DX810505WLPWTILLVSTAAA-7.62168-7.62168
HLA-A02:016TDR10505WLPWTILLVSTAAA-0.491095-0.491095

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Vaccine Design for the FusionNeoAntigens of BMPR2-ATG4B

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
BMPR2-ATG4Bchr2203332412chr2242590425314RVPWLPWTILLATTTTCCACCTCCTGACACAACACCACTCACTA
BMPR2-ATG4Bchr2203332412chr2242590425414VPWLPWTILLTTCCACCTCCTGACACAACACCACTCACTA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
BMPR2-ATG4Bchr2203332412chr2242590425722LPWTILLVSTAAASQCTGACACAACACCACTCACTACTCTGACCTACGACACTCTCCGGT
BMPR2-ATG4Bchr2203332412chr2242590425823PWTILLVSTAAASQNACACAACACCACTCACTACTCTGACCTACGACACTCTCCGGTTTG

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Information of the samples that have these potential fusion neoantigens of BMPR2-ATG4B

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
LUSCBMPR2-ATG4Bchr2203332412ENST00000374574chr2242590425ENST00000405546TCGA-63-6202-01A

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Potential target of CAR-T therapy development for BMPR2-ATG4B

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 BMPR2-ATG4B

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 BMPR2-ATG4B

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