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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:NRF1-STRIP2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NRF1-STRIP2
FusionPDB ID: 60269
FusionGDB2.0 ID: 60269
HgeneTgene
Gene symbol

NRF1

STRIP2

Gene ID

4899

57464

Gene namenuclear respiratory factor 1striatin interacting protein 2
SynonymsALPHA-PALFAM40B|FAR11B
Cytomap

7q32.2

7q32.1

Type of geneprotein-codingprotein-coding
Descriptionnuclear respiratory factor 1alpha palindromic-binding proteinstriatin-interacting protein 2FAR11 factor arrest 11 homolog Bfamily with sequence similarity 40, member Bhomolog of yeast FAR11 protein 2protein FAM40B
Modification date2020032920200313
UniProtAcc

Q16656

Main function of 5'-partner protein: FUNCTION: Transcription factor that activates the expression of the EIF2S1 (EIF2-alpha) gene. Links the transcriptional modulation of key metabolic genes to cellular growth and development. Implicated in the control of nuclear genes required for respiration, heme biosynthesis, and mitochondrial DNA transcription and replication.

Q9ULQ0

Main function of 5'-partner protein: FUNCTION: Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape. {ECO:0000269|PubMed:21834987}.
Ensembl transtripts involved in fusion geneENST idsENST00000539636, ENST00000223190, 
ENST00000311967, ENST00000353868, 
ENST00000393230, ENST00000393231, 
ENST00000393232, ENST00000477428, 
ENST00000249344, ENST00000435494, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score14 X 9 X 8=10084 X 5 X 5=100
# samples 165
** MAII scorelog2(16/1008*10)=-2.65535182861255
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(5/100*10)=-1
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: NRF1 [Title/Abstract] AND STRIP2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: NRF1 [Title/Abstract] AND STRIP2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NRF1(129297414)-STRIP2(129091454), # samples:1
NRF1(129367205)-STRIP2(129110490), # samples:1
Anticipated loss of major functional domain due to fusion event.NRF1-STRIP2 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.
NRF1-STRIP2 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.
NRF1-STRIP2 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.
NRF1-STRIP2 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.
NRF1-STRIP2 seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
NRF1-STRIP2 seems lost the major protein functional domain in Hgene partner, which is a transcription factor due to the frame-shifted ORF.
NRF1-STRIP2 seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor 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


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/chr7:129297414/chr7:129091454)
- 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 NRF1 (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 STRIP2 (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)
ENST00000393232NRF1chr7129297414+ENST00000249344STRIP2chr7129091454+51413401172570817
ENST00000393232NRF1chr7129297414+ENST00000435494STRIP2chr7129091454+29053401172342741
ENST00000353868NRF1chr7129297414+ENST00000249344STRIP2chr7129091454+51413401172570817
ENST00000353868NRF1chr7129297414+ENST00000435494STRIP2chr7129091454+29053401172342741
ENST00000311967NRF1chr7129297414+ENST00000249344STRIP2chr7129091454+5102301782531817
ENST00000311967NRF1chr7129297414+ENST00000435494STRIP2chr7129091454+2866301782303741
ENST00000223190NRF1chr7129297414+ENST00000249344STRIP2chr7129091454+5102301782531817
ENST00000223190NRF1chr7129297414+ENST00000435494STRIP2chr7129091454+2866301782303741
ENST00000393230NRF1chr7129297414+ENST00000249344STRIP2chr7129091454+51343331102563817
ENST00000393230NRF1chr7129297414+ENST00000435494STRIP2chr7129091454+28983331102335741
ENST00000393231NRF1chr7129297414+ENST00000249344STRIP2chr7129091454+502522412454817
ENST00000393231NRF1chr7129297414+ENST00000435494STRIP2chr7129091454+278922412226741

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
ENST00000393232ENST00000249344NRF1chr7129297414+STRIP2chr7129091454+0.0009594210.99904054
ENST00000393232ENST00000435494NRF1chr7129297414+STRIP2chr7129091454+0.0030606250.9969394
ENST00000353868ENST00000249344NRF1chr7129297414+STRIP2chr7129091454+0.0009594210.99904054
ENST00000353868ENST00000435494NRF1chr7129297414+STRIP2chr7129091454+0.0030606250.9969394
ENST00000311967ENST00000249344NRF1chr7129297414+STRIP2chr7129091454+0.000890560.99910945
ENST00000311967ENST00000435494NRF1chr7129297414+STRIP2chr7129091454+0.0027597360.9972403
ENST00000223190ENST00000249344NRF1chr7129297414+STRIP2chr7129091454+0.000890560.99910945
ENST00000223190ENST00000435494NRF1chr7129297414+STRIP2chr7129091454+0.0027597360.9972403
ENST00000393230ENST00000249344NRF1chr7129297414+STRIP2chr7129091454+0.000738590.99926144
ENST00000393230ENST00000435494NRF1chr7129297414+STRIP2chr7129091454+0.0020931110.9979069
ENST00000393231ENST00000249344NRF1chr7129297414+STRIP2chr7129091454+0.0007975890.99920243
ENST00000393231ENST00000435494NRF1chr7129297414+STRIP2chr7129091454+0.0024173120.9975827

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 NRF1-STRIP2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
NRF1chr7129297414STRIP2chr712909145422474TAADEVTAHLAAAVQGKEWLELEEDA
NRF1chr7129297414STRIP2chr712909145430174TAADEVTAHLAAAVQGKEWLELEEDA
NRF1chr7129297414STRIP2chr712909145433374TAADEVTAHLAAAVQGKEWLELEEDA
NRF1chr7129297414STRIP2chr712909145434074TAADEVTAHLAAAVQGKEWLELEEDA

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Potential FusionNeoAntigen Information of NRF1-STRIP2 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.
NRF1-STRIP2_129297414_129091454.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)
NRF1-STRIP2chr7129297414chr7129091454301HLA-B51:01TAHLAAAV0.99920.9383614
NRF1-STRIP2chr7129297414chr7129091454301HLA-B57:01AAAVQGKEW0.99920.99321019
NRF1-STRIP2chr7129297414chr7129091454301HLA-B58:01AAAVQGKEW0.99720.991019
NRF1-STRIP2chr7129297414chr7129091454301HLA-B58:02AAAVQGKEW0.99680.9851019
NRF1-STRIP2chr7129297414chr7129091454301HLA-B15:17AAAVQGKEW0.99160.97061019
NRF1-STRIP2chr7129297414chr7129091454301HLA-B57:03AAAVQGKEW0.97820.99711019
NRF1-STRIP2chr7129297414chr7129091454301HLA-B53:01AAAVQGKEW0.91210.87171019
NRF1-STRIP2chr7129297414chr7129091454301HLA-B57:01LAAAVQGKEW0.99990.9924919
NRF1-STRIP2chr7129297414chr7129091454301HLA-B58:02LAAAVQGKEW0.99940.9839919
NRF1-STRIP2chr7129297414chr7129091454301HLA-B58:01LAAAVQGKEW0.9990.988919
NRF1-STRIP2chr7129297414chr7129091454301HLA-B57:03LAAAVQGKEW0.99210.9975919
NRF1-STRIP2chr7129297414chr7129091454301HLA-B44:08AAAVQGKEW0.57980.84721019
NRF1-STRIP2chr7129297414chr7129091454301HLA-B51:14TAHLAAAV0.99920.9134614
NRF1-STRIP2chr7129297414chr7129091454301HLA-B51:13TAHLAAAV0.99910.8838614
NRF1-STRIP2chr7129297414chr7129091454301HLA-B51:21TAHLAAAV0.99820.9182614
NRF1-STRIP2chr7129297414chr7129091454301HLA-B57:10AAAVQGKEW0.99920.99321019
NRF1-STRIP2chr7129297414chr7129091454301HLA-B57:04AAAVQGKEW0.99850.84081019
NRF1-STRIP2chr7129297414chr7129091454301HLA-B58:06AAAVQGKEW0.99660.9811019
NRF1-STRIP2chr7129297414chr7129091454301HLA-A68:02VTAHLAAAV0.99310.7426514
NRF1-STRIP2chr7129297414chr7129091454301HLA-A69:01VTAHLAAAV0.98830.7298514
NRF1-STRIP2chr7129297414chr7129091454301HLA-B57:02AAAVQGKEW0.98190.98271019
NRF1-STRIP2chr7129297414chr7129091454301HLA-B15:13AAAVQGKEW0.97510.96781019
NRF1-STRIP2chr7129297414chr7129091454301HLA-B35:13AAVQGKEWL0.69970.95211120
NRF1-STRIP2chr7129297414chr7129091454301HLA-B15:24AAAVQGKEW0.420.98521019
NRF1-STRIP2chr7129297414chr7129091454301HLA-B57:10LAAAVQGKEW0.99990.9924919
NRF1-STRIP2chr7129297414chr7129091454301HLA-B57:04LAAAVQGKEW0.99970.8783919
NRF1-STRIP2chr7129297414chr7129091454301HLA-A68:02EVTAHLAAAV0.99920.8336414
NRF1-STRIP2chr7129297414chr7129091454301HLA-B58:06LAAAVQGKEW0.99890.9807919
NRF1-STRIP2chr7129297414chr7129091454301HLA-B57:02LAAAVQGKEW0.99790.987919
NRF1-STRIP2chr7129297414chr7129091454301HLA-A69:01EVTAHLAAAV0.99780.7797414
NRF1-STRIP2chr7129297414chr7129091454301HLA-B15:13HLAAAVQGKEW0.99930.9713819

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Potential FusionNeoAntigen Information of NRF1-STRIP2 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.
NRF1-STRIP2_129297414_129091454.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)
NRF1-STRIP2chr7129297414chr7129091454301DRB1-0906ADEVTAHLAAAVQGK217

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Fusion breakpoint peptide structures of NRF1-STRIP2

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
9223TAHLAAAVQGKEWLNRF1STRIP2chr7129297414chr7129091454301

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of NRF1-STRIP2

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-B14:023BVN9223TAHLAAAVQGKEWL-7.15543-7.26883
HLA-B14:023BVN9223TAHLAAAVQGKEWL-4.77435-5.80965
HLA-B52:013W399223TAHLAAAVQGKEWL-6.80875-6.92215
HLA-B52:013W399223TAHLAAAVQGKEWL-4.20386-5.23916
HLA-A11:014UQ29223TAHLAAAVQGKEWL-7.5194-8.5547
HLA-A11:014UQ29223TAHLAAAVQGKEWL-6.9601-7.0735
HLA-A24:025HGA9223TAHLAAAVQGKEWL-7.52403-7.63743
HLA-A24:025HGA9223TAHLAAAVQGKEWL-5.82433-6.85963
HLA-B27:056PYJ9223TAHLAAAVQGKEWL-3.28285-4.31815
HLA-B44:053DX89223TAHLAAAVQGKEWL-5.91172-6.94702
HLA-B44:053DX89223TAHLAAAVQGKEWL-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of NRF1-STRIP2

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
NRF1-STRIP2chr7129297414chr71290914541019AAAVQGKEWCAGCTGCAGTGCAGGGCAAGGAATGGC
NRF1-STRIP2chr7129297414chr71290914541120AAVQGKEWLCTGCAGTGCAGGGCAAGGAATGGCTGG
NRF1-STRIP2chr7129297414chr7129091454414EVTAHLAAAVAGGTGACAGCTCATCTGGCAGCTGCAGTGC
NRF1-STRIP2chr7129297414chr7129091454514VTAHLAAAVTGACAGCTCATCTGGCAGCTGCAGTGC
NRF1-STRIP2chr7129297414chr7129091454614TAHLAAAVCAGCTCATCTGGCAGCTGCAGTGC
NRF1-STRIP2chr7129297414chr7129091454819HLAAAVQGKEWATCTGGCAGCTGCAGTGCAGGGCAAGGAATGGC
NRF1-STRIP2chr7129297414chr7129091454919LAAAVQGKEWTGGCAGCTGCAGTGCAGGGCAAGGAATGGC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
NRF1-STRIP2chr7129297414chr7129091454217ADEVTAHLAAAVQGKCTGATGAGGTGACAGCTCATCTGGCAGCTGCAGTGCAGGGCAAGG

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Information of the samples that have these potential fusion neoantigens of NRF1-STRIP2

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
BRCANRF1-STRIP2chr7129297414ENST00000223190chr7129091454ENST00000249344TCGA-D8-A140-01A

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Potential target of CAR-T therapy development for NRF1-STRIP2

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 NRF1-STRIP2

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 NRF1-STRIP2

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