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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:NRBF2-CYP26A1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NRBF2-CYP26A1
FusionPDB ID: 60196
FusionGDB2.0 ID: 60196
HgeneTgene
Gene symbol

NRBF2

CYP26A1

Gene ID

29982

1592

Gene namenuclear receptor binding factor 2cytochrome P450 family 26 subfamily A member 1
SynonymsCOPR|COPR1|COPR2|NRBF-2CP26|CYP26|P450RAI|P450RAI1
Cytomap

10q21.3

10q23.33

Type of geneprotein-codingprotein-coding
Descriptionnuclear receptor-binding factor 2comodulator of PPAR and RXR 1comodulator of PPAR and RXR 2cytochrome P450 26A1P450, retinoic acid-inactivating, 1cytochrome P450 retinoic acid-inactivating 1cytochrome P450, family 26, subfamily A, polypeptide 1cytochrome P450, subfamily XXVIA, polypeptide 1cytochrome P450RAIhP450RAIretinoic acid 4-hydrox
Modification date2020031320200329
UniProtAcc

Q96F24

Main function of 5'-partner protein: FUNCTION: May modulate transcriptional activation by target nuclear receptors. Can act as transcriptional activator (in vitro). {ECO:0000269|PubMed:15610520}.; FUNCTION: Involved in starvation-induced autophagy probably by its association with PI3K complex I (PI3KC3-C1). However, effects has been described variably. Involved in the induction of starvation-induced autophagy (PubMed:24785657). Stabilzes PI3KC3-C1 assembly and enhances ATG14-linked lipid kinase activity of PIK3C3 (By similarity). Proposed to negatively regulate basal and starvation-induced autophagy and to inhibit PIK3C3 activity by modulating interactions in PI3KC3-C1 (PubMed:25086043). May be involved in autophagosome biogenesis (PubMed:25086043). May play a role in neural progenitor cell survival during differentiation (By similarity). {ECO:0000250|UniProtKB:Q8VCQ3, ECO:0000269|PubMed:24785657, ECO:0000269|PubMed:25086043}.

O43174

Main function of 5'-partner protein: FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of all-trans retinoic acid (atRA), a signaling molecule that binds to retinoic acid receptors and regulates gene transcription. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase). Catalyzes the hydroxylation of carbon hydrogen bonds of atRA primarily at C-4 and C-18. Has no activity toward 9-cis and 13-cis retinoic acid stereoisomers (PubMed:22020119, PubMed:9228017, PubMed:9716180). May play a role in the oxidative metabolism of xenobiotics such as tazarotenic acid (PubMed:26937021). {ECO:0000269|PubMed:22020119, ECO:0000269|PubMed:26937021, ECO:0000269|PubMed:9228017, ECO:0000269|PubMed:9716180}.
Ensembl transtripts involved in fusion geneENST idsENST00000435510, ENST00000277746, 
ENST00000224356, ENST00000371531, 
ENST00000394139, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score9 X 6 X 5=2703 X 3 X 3=27
# samples 104
** MAII scorelog2(10/270*10)=-1.43295940727611
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(4/27*10)=0.567040592723894
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: NRBF2 [Title/Abstract] AND CYP26A1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: NRBF2 [Title/Abstract] AND CYP26A1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NRBF2(64893260)-CYP26A1(94835583), # samples:3
Anticipated loss of major functional domain due to fusion event.NRBF2-CYP26A1 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.
NRBF2-CYP26A1 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.
NRBF2-CYP26A1 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target 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
TgeneCYP26A1

GO:0006805

xenobiotic metabolic process

26937021

TgeneCYP26A1

GO:0034653

retinoic acid catabolic process

10823918

TgeneCYP26A1

GO:0042573

retinoic acid metabolic process

9716180|22020119



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/chr10:64893260/chr10:94835583)
- 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 NRBF2 (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 CYP26A1 (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)
ENST00000277746NRBF2chr1064893260+ENST00000371531CYP26A1chr1094835583+142121164840258
ENST00000277746NRBF2chr1064893260+ENST00000224356CYP26A1chr1094835583+142721164840258
ENST00000277746NRBF2chr1064893260+ENST00000394139CYP26A1chr1094835583+142721164840258

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
ENST00000277746ENST00000371531NRBF2chr1064893260+CYP26A1chr1094835583+0.0008052170.9991948
ENST00000277746ENST00000224356NRBF2chr1064893260+CYP26A1chr1094835583+0.0008188560.9991811
ENST00000277746ENST00000394139NRBF2chr1064893260+CYP26A1chr1094835583+0.0008188560.9991811

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 NRBF2-CYP26A1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
NRBF2chr1064893260CYP26A1chr109483558321149PGSMEVMEGPLNLALKQSSTELLFGG

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Potential FusionNeoAntigen Information of NRBF2-CYP26A1 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.
NRBF2-CYP26A1_64893260_94835583.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)
NRBF2-CYP26A1chr1064893260chr1094835583211HLA-B50:01MEGPLNLA0.9830.7917614
NRBF2-CYP26A1chr1064893260chr1094835583211HLA-B13:01MEGPLNLAL0.99720.8821615
NRBF2-CYP26A1chr1064893260chr1094835583211HLA-B44:03MEGPLNLAL0.97180.9456615
NRBF2-CYP26A1chr1064893260chr1094835583211HLA-B47:01MEGPLNLAL0.96370.5225615
NRBF2-CYP26A1chr1064893260chr1094835583211HLA-B18:01MEGPLNLAL0.95120.8228615
NRBF2-CYP26A1chr1064893260chr1094835583211HLA-B39:13MEGPLNLAL0.82470.9693615
NRBF2-CYP26A1chr1064893260chr1094835583211HLA-B39:01MEGPLNLAL0.81850.9341615
NRBF2-CYP26A1chr1064893260chr1094835583211HLA-B38:02MEGPLNLAL0.79780.9728615
NRBF2-CYP26A1chr1064893260chr1094835583211HLA-B41:01MEGPLNLAL0.52270.9639615
NRBF2-CYP26A1chr1064893260chr1094835583211HLA-B40:06MEGPLNLAL0.99950.5207615
NRBF2-CYP26A1chr1064893260chr1094835583211HLA-B39:09MEGPLNLAL0.83910.7331615
NRBF2-CYP26A1chr1064893260chr1094835583211HLA-B39:08MEGPLNLAL0.83750.9048615
NRBF2-CYP26A1chr1064893260chr1094835583211HLA-B39:05MEGPLNLAL0.81530.9213615
NRBF2-CYP26A1chr1064893260chr1094835583211HLA-B50:04MEGPLNLA0.9830.7917614
NRBF2-CYP26A1chr1064893260chr1094835583211HLA-B50:05MEGPLNLA0.9830.7917614
NRBF2-CYP26A1chr1064893260chr1094835583211HLA-B40:04MEGPLNLAL0.99950.6853615
NRBF2-CYP26A1chr1064893260chr1094835583211HLA-B18:04MEGPLNLAL0.97460.8378615
NRBF2-CYP26A1chr1064893260chr1094835583211HLA-B44:26MEGPLNLAL0.97180.9456615
NRBF2-CYP26A1chr1064893260chr1094835583211HLA-B44:07MEGPLNLAL0.97180.9456615
NRBF2-CYP26A1chr1064893260chr1094835583211HLA-B44:13MEGPLNLAL0.97180.9456615
NRBF2-CYP26A1chr1064893260chr1094835583211HLA-B18:07MEGPLNLAL0.95960.7839615
NRBF2-CYP26A1chr1064893260chr1094835583211HLA-B18:05MEGPLNLAL0.95120.8228615
NRBF2-CYP26A1chr1064893260chr1094835583211HLA-B18:08MEGPLNLAL0.95020.7723615
NRBF2-CYP26A1chr1064893260chr1094835583211HLA-B18:03MEGPLNLAL0.94420.8081615
NRBF2-CYP26A1chr1064893260chr1094835583211HLA-B18:06MEGPLNLAL0.94380.8364615
NRBF2-CYP26A1chr1064893260chr1094835583211HLA-B18:11MEGPLNLAL0.92090.7817615
NRBF2-CYP26A1chr1064893260chr1094835583211HLA-B39:11MEGPLNLAL0.84810.8732615
NRBF2-CYP26A1chr1064893260chr1094835583211HLA-B39:31MEGPLNLAL0.82940.9317615
NRBF2-CYP26A1chr1064893260chr1094835583211HLA-B39:02MEGPLNLAL0.82540.9705615
NRBF2-CYP26A1chr1064893260chr1094835583211HLA-B48:02MEGPLNLAL0.70430.8773615
NRBF2-CYP26A1chr1064893260chr1094835583211HLA-B41:03MEGPLNLAL0.66650.7082615
NRBF2-CYP26A1chr1064893260chr1094835583211HLA-B15:09MEGPLNLAL0.60660.7151615
NRBF2-CYP26A1chr1064893260chr1094835583211HLA-A68:02EVMEGPLNLA0.99570.7029414
NRBF2-CYP26A1chr1064893260chr1094835583211HLA-A69:01EVMEGPLNLA0.98870.6859414
NRBF2-CYP26A1chr1064893260chr1094835583211HLA-B15:73LALKQSSTEL0.93550.95621222
NRBF2-CYP26A1chr1064893260chr1094835583211HLA-B15:30LALKQSSTEL0.92110.93211222
NRBF2-CYP26A1chr1064893260chr1094835583211HLA-A69:01EVMEGPLNLAL0.99790.5785415

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Potential FusionNeoAntigen Information of NRBF2-CYP26A1 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 NRBF2-CYP26A1

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
5882MEGPLNLALKQSSTNRBF2CYP26A1chr1064893260chr1094835583211

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of NRBF2-CYP26A1

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-B14:023BVN5882MEGPLNLALKQSST-7.15543-7.26883
HLA-B14:023BVN5882MEGPLNLALKQSST-4.77435-5.80965
HLA-B52:013W395882MEGPLNLALKQSST-6.80875-6.92215
HLA-B52:013W395882MEGPLNLALKQSST-4.20386-5.23916
HLA-A11:014UQ25882MEGPLNLALKQSST-7.5194-8.5547
HLA-A11:014UQ25882MEGPLNLALKQSST-6.9601-7.0735
HLA-A24:025HGA5882MEGPLNLALKQSST-7.52403-7.63743
HLA-A24:025HGA5882MEGPLNLALKQSST-5.82433-6.85963
HLA-B27:056PYJ5882MEGPLNLALKQSST-3.28285-4.31815
HLA-B44:053DX85882MEGPLNLALKQSST-5.91172-6.94702
HLA-B44:053DX85882MEGPLNLALKQSST-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of NRBF2-CYP26A1

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
NRBF2-CYP26A1chr1064893260chr10948355831222LALKQSSTELCTGGCACTAAAGCAATCTTCAACCGAACTC
NRBF2-CYP26A1chr1064893260chr1094835583414EVMEGPLNLAGAAGTAATGGAAGGACCCCTCAACCTGGCA
NRBF2-CYP26A1chr1064893260chr1094835583415EVMEGPLNLALGAAGTAATGGAAGGACCCCTCAACCTGGCACTA
NRBF2-CYP26A1chr1064893260chr1094835583614MEGPLNLAATGGAAGGACCCCTCAACCTGGCA
NRBF2-CYP26A1chr1064893260chr1094835583615MEGPLNLALATGGAAGGACCCCTCAACCTGGCACTA

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 NRBF2-CYP26A1

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
BRCANRBF2-CYP26A1chr1064893260ENST00000277746chr1094835583ENST00000224356TCGA-E2-A576-01A

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Potential target of CAR-T therapy development for NRBF2-CYP26A1

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 NRBF2-CYP26A1

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 NRBF2-CYP26A1

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