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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:ADIPOR1-DAD1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ADIPOR1-DAD1
FusionPDB ID: 2437
FusionGDB2.0 ID: 2437
HgeneTgene
Gene symbol

ADIPOR1

DAD1

Gene ID

51094

1603

Gene nameadiponectin receptor 1defender against cell death 1
SynonymsACDCR1|CGI-45|CGI45|PAQR1|TESBP1AOST2
Cytomap

1q32.1

14q11.2

Type of geneprotein-codingprotein-coding
Descriptionadiponectin receptor protein 1progestin and adipoQ receptor family member 1progestin and adipoQ receptor family member Idolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit DAD1DAD-1oligosaccharyl transferase subunit DAD1oligosaccharyltransferase 2 homologoligosaccharyltransferase subunit 2 (non-catalytic)
Modification date2020031320200327
UniProtAcc

Q96A54

Main function of 5'-partner protein: FUNCTION: Receptor for ADIPOQ, an essential hormone secreted by adipocytes that regulates glucose and lipid metabolism (PubMed:25855295, PubMed:12802337). Required for normal glucose and fat homeostasis and for maintaining a normal body weight. ADIPOQ-binding activates a signaling cascade that leads to increased AMPK activity, and ultimately to increased fatty acid oxidation, increased glucose uptake and decreased gluconeogenesis. Has high affinity for globular adiponectin and low affinity for full-length adiponectin (By similarity). {ECO:0000250|UniProtKB:Q91VH1, ECO:0000269|PubMed:12802337, ECO:0000269|PubMed:25855295}.

P61803

Main function of 5'-partner protein: FUNCTION: Subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophosphate to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains, the first step in protein N-glycosylation (PubMed:22467853). N-glycosylation occurs cotranslationally and the complex associates with the Sec61 complex at the channel-forming translocon complex that mediates protein translocation across the endoplasmic reticulum (ER). All subunits are required for a maximal enzyme activity (By similarity). Required for the assembly of both SST3A- and SS3B-containing OST complexes. Loss of the DAD1 protein triggers apoptosis (PubMed:22467853). {ECO:0000250|UniProtKB:E2R4X3, ECO:0000269|PubMed:22467853}.
Ensembl transtripts involved in fusion geneENST idsENST00000340990, ENST00000367254, 
ENST00000436244, 
ENST00000489532, 
ENST00000538631, ENST00000543337, 
ENST00000250498, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score4 X 5 X 2=4012 X 7 X 6=504
# samples 414
** MAII scorelog2(4/40*10)=0log2(14/504*10)=-1.84799690655495
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ADIPOR1 [Title/Abstract] AND DAD1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ADIPOR1 [Title/Abstract] AND DAD1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ADIPOR1(202915567)-DAD1(23044133), # samples:1
Anticipated loss of major functional domain due to fusion event.ADIPOR1-DAD1 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
ADIPOR1-DAD1 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
ADIPOR1-DAD1 seems lost the major protein functional domain in Tgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
ADIPOR1-DAD1 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
HgeneADIPOR1

GO:0009755

hormone-mediated signaling pathway

12802337

HgeneADIPOR1

GO:0019395

fatty acid oxidation

12802337

HgeneADIPOR1

GO:0033211

adiponectin-activated signaling pathway

12802337



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/chr1:202915567/chr14:23044133)
- 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 ADIPOR1 (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 DAD1 (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)
ENST00000340990ADIPOR1chr1202915567-ENST00000250498DAD1chr1423044133-1137729299859186
ENST00000367254ADIPOR1chr1202915567-ENST00000250498DAD1chr1423044133-1037629199759186

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
ENST00000340990ENST00000250498ADIPOR1chr1202915567-DAD1chr1423044133-0.0047086090.99529135
ENST00000367254ENST00000250498ADIPOR1chr1202915567-DAD1chr1423044133-0.0051824140.99481755

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 ADIPOR1-DAD1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ADIPOR1chr1202915567DAD1chr1423044133629143IHTETGNIWTHLLVCLRIQINPQNKA
ADIPOR1chr1202915567DAD1chr1423044133729143IHTETGNIWTHLLVCLRIQINPQNKA

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Potential FusionNeoAntigen Information of ADIPOR1-DAD1 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.
ADIPOR1-DAD1_202915567_23044133.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)
ADIPOR1-DAD1chr1202915567chr1423044133729HLA-B38:01THLLVCLRI0.98490.8965918
ADIPOR1-DAD1chr1202915567chr1423044133729HLA-B38:05THLLVCLRI0.98490.8965918

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Potential FusionNeoAntigen Information of ADIPOR1-DAD1 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 ADIPOR1-DAD1

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
6220NIWTHLLVCLRIQIADIPOR1DAD1chr1202915567chr1423044133729

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ADIPOR1-DAD1

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-B14:023BVN6220NIWTHLLVCLRIQI-7.54146-7.65486
HLA-B14:023BVN6220NIWTHLLVCLRIQI-5.05101-6.08631
HLA-B52:013W396220NIWTHLLVCLRIQI-7.48565-7.59905
HLA-B52:013W396220NIWTHLLVCLRIQI-5.61839-6.65369
HLA-A11:014UQ26220NIWTHLLVCLRIQI-5.36758-5.48098
HLA-A11:014UQ26220NIWTHLLVCLRIQI-2.41377-3.44907
HLA-A24:025HGA6220NIWTHLLVCLRIQI-8.3266-8.44
HLA-A24:025HGA6220NIWTHLLVCLRIQI-5.24481-6.28011
HLA-B44:053DX86220NIWTHLLVCLRIQI-4.07996-5.11526
HLA-B44:053DX86220NIWTHLLVCLRIQI-3.86967-3.98307

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Vaccine Design for the FusionNeoAntigens of ADIPOR1-DAD1

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
ADIPOR1-DAD1chr1202915567chr1423044133918THLLVCLRICCCATCTGCTTGTTTGCCTGAGAATAC

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 ADIPOR1-DAD1

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
BRCAADIPOR1-DAD1chr1202915567ENST00000340990chr1423044133ENST00000250498TCGA-D8-A1J8-01A

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Potential target of CAR-T therapy development for ADIPOR1-DAD1

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
TgeneDAD1chr1:202915567chr14:23044133ENST000002504980393_113084.0TransmembraneHelical

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 ADIPOR1-DAD1

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 ADIPOR1-DAD1

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