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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:AGTRAP-BRAF

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: AGTRAP-BRAF
FusionPDB ID: 3035
FusionGDB2.0 ID: 3035
HgeneTgene
Gene symbol

AGTRAP

BRAF

Gene ID

57085

673

Gene nameangiotensin II receptor associated proteinB-Raf proto-oncogene, serine/threonine kinase
SynonymsATRAPB-RAF1|B-raf|BRAF1|NS7|RAFB1
Cytomap

1p36.22

7q34

Type of geneprotein-codingprotein-coding
Descriptiontype-1 angiotensin II receptor-associated proteinAT1 receptor-associated proteinATI receptor-associated proteinangiotensin II, type I receptor-associated proteinserine/threonine-protein kinase B-raf94 kDa B-raf proteinB-Raf proto-oncogene serine/threonine-protein kinase (p94)B-Raf serine/threonine-proteinmurine sarcoma viral (v-raf) oncogene homolog B1proto-oncogene B-Rafv-raf murine sarcoma viral oncogene
Modification date2020032720200329
UniProtAcc

Q6RW13

Main function of 5'-partner protein: FUNCTION: Appears to be a negative regulator of type-1 angiotensin II receptor-mediated signaling by regulating receptor internalisation as well as mechanism of receptor desensitization such as phosphorylation. Induces also a decrease in cell proliferation and angiotensin II-stimulated transcriptional activity. {ECO:0000269|PubMed:12960423}.

P15056

Main function of 5'-partner protein: FUNCTION: Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus (Probable). Phosphorylates MAP2K1, and thereby activates the MAP kinase signal transduction pathway (PubMed:21441910, PubMed:29433126). May play a role in the postsynaptic responses of hippocampal neurons (PubMed:1508179). {ECO:0000269|PubMed:1508179, ECO:0000269|PubMed:21441910, ECO:0000269|PubMed:29433126, ECO:0000305}.
Ensembl transtripts involved in fusion geneENST idsENST00000376627, ENST00000376637, 
ENST00000400895, ENST00000452018, 
ENST00000491346, ENST00000314340, 
ENST00000376629, ENST00000510878, 
ENST00000288602, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score4 X 5 X 4=8048 X 58 X 16=44544
# samples 669
** MAII scorelog2(6/80*10)=-0.415037499278844
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(69/44544*10)=-6.0124909441832
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: AGTRAP [Title/Abstract] AND BRAF [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: AGTRAP [Title/Abstract] AND BRAF [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)AGTRAP(11810243)-BRAF(140433813), # samples:1
AGTRAP(11810243)-BRAF(140494268), # samples:1
Anticipated loss of major functional domain due to fusion event.AGTRAP-BRAF 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.
AGTRAP-BRAF 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.
AGTRAP-BRAF 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.
AGTRAP-BRAF 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.
AGTRAP-BRAF seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
AGTRAP-BRAF seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF.
AGTRAP-BRAF seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
AGTRAP-BRAF seems lost the major protein functional domain in Tgene partner, which is a kinase 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
TgeneBRAF

GO:0000186

activation of MAPKK activity

29433126

TgeneBRAF

GO:0006468

protein phosphorylation

17563371

TgeneBRAF

GO:0010828

positive regulation of glucose transmembrane transport

23010278

TgeneBRAF

GO:0033138

positive regulation of peptidyl-serine phosphorylation

19667065

TgeneBRAF

GO:0043066

negative regulation of apoptotic process

19667065

TgeneBRAF

GO:0070374

positive regulation of ERK1 and ERK2 cascade

22065586

TgeneBRAF

GO:0071277

cellular response to calcium ion

18567582

TgeneBRAF

GO:0090150

establishment of protein localization to membrane

23010278



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/chr1:11810243/chr7:140433813)
- 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 AGTRAP (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 BRAF (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)
ENST00000510878AGTRAPchr111810243+ENST00000288602BRAFchr7140494268-21787399022059385

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
ENST00000510878ENST00000288602AGTRAPchr111810243+BRAFchr7140494268-0.0060991520.9939009

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 AGTRAP-BRAF

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

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Potential FusionNeoAntigen Information of AGTRAP-BRAF 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 AGTRAP-BRAF 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 AGTRAP-BRAF

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 AGTRAP-BRAF

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 AGTRAP-BRAF

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

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Information of the samples that have these potential fusion neoantigens of AGTRAP-BRAF

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 AGTRAP-BRAF

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 AGTRAP-BRAF

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 AGTRAP-BRAF

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
TgeneBRAFC0025202melanoma24CGI;CTD_human;UNIPROT
TgeneBRAFC1275081Cardio-facio-cutaneous syndrome14CLINGEN;CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT
TgeneBRAFC0009402Colorectal Carcinoma8CTD_human;UNIPROT
TgeneBRAFC0028326Noonan Syndrome8CLINGEN;CTD_human;GENOMICS_ENGLAND;ORPHANET
TgeneBRAFC0238463Papillary thyroid carcinoma8CTD_human;ORPHANET
TgeneBRAFC0040136Thyroid Neoplasm6CGI;CTD_human
TgeneBRAFC0151468Thyroid Gland Follicular Adenoma6CTD_human
TgeneBRAFC0175704LEOPARD Syndrome6CLINGEN;GENOMICS_ENGLAND
TgeneBRAFC0549473Thyroid carcinoma6CGI;CTD_human
TgeneBRAFC3150970NOONAN SYNDROME 75CTD_human;GENOMICS_ENGLAND;UNIPROT
TgeneBRAFC0009404Colorectal Neoplasms4CTD_human
TgeneBRAFC3150971LEOPARD SYNDROME 34CTD_human;GENOMICS_ENGLAND;UNIPROT
TgeneBRAFC1519086Pilomyxoid astrocytoma3ORPHANET
TgeneBRAFC0004565Melanoma, B162CTD_human
TgeneBRAFC0009075Melanoma, Cloudman S912CTD_human
TgeneBRAFC0018598Melanoma, Harding-Passey2CTD_human
TgeneBRAFC0023443Hairy Cell Leukemia2CGI;ORPHANET
TgeneBRAFC0025205Melanoma, Experimental2CTD_human
TgeneBRAFC0033578Prostatic Neoplasms2CTD_human
TgeneBRAFC0152013Adenocarcinoma of lung (disorder)2CGI;CTD_human
TgeneBRAFC0376358Malignant neoplasm of prostate2CTD_human
TgeneBRAFC0587248Costello syndrome (disorder)2CLINGEN;CTD_human
TgeneBRAFC3501843Nonmedullary Thyroid Carcinoma2CTD_human
TgeneBRAFC3501844Familial Nonmedullary Thyroid Cancer2CTD_human
TgeneBRAFC0002448Ameloblastoma1CTD_human
TgeneBRAFC0004114Astrocytoma1CTD_human
TgeneBRAFC0010276Craniopharyngioma1CTD_human;ORPHANET
TgeneBRAFC0011860Diabetes Mellitus, Non-Insulin-Dependent1CTD_human
TgeneBRAFC0017638Glioma1CGI;CTD_human
TgeneBRAFC0019621Histiocytosis, Langerhans-Cell1CGI;ORPHANET
TgeneBRAFC0022665Kidney Neoplasm1CTD_human
TgeneBRAFC0023903Liver neoplasms1CTD_human
TgeneBRAFC0024232Lymphatic Metastasis1CTD_human
TgeneBRAFC0024694Mandibular Neoplasms1CTD_human
TgeneBRAFC0027659Neoplasms, Experimental1CTD_human
TgeneBRAFC0027962Melanocytic nevus1GENOMICS_ENGLAND
TgeneBRAFC0036920Sezary Syndrome1CTD_human
TgeneBRAFC0041409Turner Syndrome, Male1CTD_human
TgeneBRAFC0079773Lymphoma, T-Cell, Cutaneous1CTD_human
TgeneBRAFC0205768Subependymal Giant Cell Astrocytoma1CTD_human
TgeneBRAFC0206686Adrenocortical carcinoma1CTD_human
TgeneBRAFC0206754Neuroendocrine Tumors1CTD_human
TgeneBRAFC0259783mixed gliomas1CTD_human
TgeneBRAFC0278875Adult Craniopharyngioma1CTD_human
TgeneBRAFC0280783Juvenile Pilocytic Astrocytoma1CTD_human
TgeneBRAFC0280785Diffuse Astrocytoma1CTD_human
TgeneBRAFC0334579Anaplastic astrocytoma1CGI;CTD_human
TgeneBRAFC0334580Protoplasmic astrocytoma1CTD_human
TgeneBRAFC0334581Gemistocytic astrocytoma1CTD_human
TgeneBRAFC0334582Fibrillary Astrocytoma1CTD_human
TgeneBRAFC0334583Pilocytic Astrocytoma1CGI;CTD_human
TgeneBRAFC0338070Childhood Cerebral Astrocytoma1CTD_human
TgeneBRAFC0345904Malignant neoplasm of liver1CTD_human
TgeneBRAFC0376407Granulomatous Slack Skin1CTD_human
TgeneBRAFC0406803Syringocystadenoma Papilliferum1GENOMICS_ENGLAND
TgeneBRAFC0431128Papillary craniopharyngioma1CTD_human
TgeneBRAFC0431129Adamantinous Craniopharyngioma1CTD_human
TgeneBRAFC0547065Mixed oligoastrocytoma1CTD_human
TgeneBRAFC0555198Malignant Glioma1CTD_human
TgeneBRAFC0596263Carcinogenesis1CTD_human
TgeneBRAFC0684249Carcinoma of lung1CGI;UNIPROT
TgeneBRAFC0740457Malignant neoplasm of kidney1CTD_human
TgeneBRAFC0750935Cerebral Astrocytoma1CTD_human
TgeneBRAFC0750936Intracranial Astrocytoma1CTD_human
TgeneBRAFC0751061Craniopharyngioma, Child1CTD_human
TgeneBRAFC0920269Microsatellite Instability1CTD_human
TgeneBRAFC1527404Female Pseudo-Turner Syndrome1CTD_human
TgeneBRAFC1704230Grade I Astrocytoma1CTD_human
TgeneBRAFC1721098Replication Error Phenotype1CTD_human
TgeneBRAFC2239176Liver carcinoma1CTD_human
TgeneBRAFC4551484Leopard Syndrome 11GENOMICS_ENGLAND
TgeneBRAFC4551602Noonan Syndrome 11CTD_human
TgeneBRAFC4721532Lymphoma, Non-Hodgkin, Familial1UNIPROT
TgeneBRAFC4733333familial non-medullary thyroid cancer1GENOMICS_ENGLAND