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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:ABR-SMG6

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ABR-SMG6
FusionPDB ID: 561
FusionGDB2.0 ID: 561
HgeneTgene
Gene symbol

ABR

SMG6

Gene ID

29

23293

Gene nameABR activator of RhoGEF and GTPaseSMG6 nonsense mediated mRNA decay factor
SynonymsMDBC17orf31|EST1A|SMG-6|hSMG5/7a
Cytomap

17p13.3

17p13.3

Type of geneprotein-codingprotein-coding
Descriptionactive breakpoint cluster region-related proteinABR, RhoGEF and GTPase activating proteinactive BCR-relatedtelomerase-binding protein EST1AEST1 telomerase component homolog Aever shorter telomeres 1Asmg-6 homolog, nonsense mediated mRNA decay factortelomerase subunit EST1A
Modification date2020031320200320
UniProtAcc

Q15018

Main function of 5'-partner protein: FUNCTION: Component of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked polyubiquitin, leaving the last ubiquitin chain attached to its substrates (PubMed:19214193, PubMed:20032457, PubMed:20656690, PubMed:24075985). May act as a central scaffold protein that assembles the various components of the BRISC complex and retains them in the cytoplasm (PubMed:20656690). Plays a role in regulating the onset of apoptosis via its role in modulating 'Lys-63'-linked ubiquitination of target proteins (By similarity). Required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating NUMA1 (PubMed:26195665). Plays a role in interferon signaling via its role in the deubiquitination of the interferon receptor IFNAR1; deubiquitination increases IFNAR1 activities by enhancing its stability and cell surface expression (PubMed:24075985, PubMed:26344097). Down-regulates the response to bacterial lipopolysaccharide (LPS) via its role in IFNAR1 deubiquitination (PubMed:24075985). Required for normal induction of p53/TP53 in response to DNA damage (PubMed:25283148). Independent of the BRISC complex, promotes interaction between USP7 and p53/TP53, and thereby promotes deubiquitination of p53/TP53, preventing its degradation and resulting in increased p53/TP53-mediated transcription regulation and p53/TP53-dependent apoptosis in response to DNA damage (PubMed:25283148). {ECO:0000250|UniProtKB:Q3TCJ1, ECO:0000269|PubMed:19214193, ECO:0000269|PubMed:20032457, ECO:0000269|PubMed:20656690, ECO:0000269|PubMed:24075985, ECO:0000269|PubMed:25283148}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000291107, ENST00000302538, 
ENST00000536794, ENST00000544583, 
ENST00000574437, ENST00000543210, 
ENST00000572441, ENST00000573895, 
ENST00000573166, ENST00000263073, 
ENST00000354901, ENST00000536871, 
ENST00000544865, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score23 X 15 X 14=483021 X 16 X 8=2688
# samples 3622
** MAII scorelog2(36/4830*10)=-3.74595437739346
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(22/2688*10)=-3.6109577092541
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ABR [Title/Abstract] AND SMG6 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ABR [Title/Abstract] AND SMG6 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ABR(953289)-SMG6(1989195), # samples:1
Anticipated loss of major functional domain due to fusion event.ABR-SMG6 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.
ABR-SMG6 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.
ABR-SMG6 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.
ABR-SMG6 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.
ABR-SMG6 seems lost the major protein functional domain in Hgene partner, which is a kinase due to the frame-shifted ORF.
ABR-SMG6 seems lost the major protein functional domain in Tgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
ABR-SMG6 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
HgeneABR

GO:0090630

activation of GTPase activity

7479768

TgeneSMG6

GO:1904354

negative regulation of telomere capping

12676087



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/chr17:953289/chr17:1989195)
- 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 ABR (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 SMG6 (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)
ENST00000302538ABRchr17953289-ENST00000544865SMG6chr171989195-449419381472840897
ENST00000302538ABRchr17953289-ENST00000263073SMG6chr171989195-449019381472840897
ENST00000302538ABRchr17953289-ENST00000354901SMG6chr171989195-448319381472840897
ENST00000302538ABRchr17953289-ENST00000536871SMG6chr171989195-292819381472840897
ENST00000574437ABRchr17953289-ENST00000544865SMG6chr171989195-467421181233020965
ENST00000574437ABRchr17953289-ENST00000263073SMG6chr171989195-467021181233020965
ENST00000574437ABRchr17953289-ENST00000354901SMG6chr171989195-466321181233020965
ENST00000574437ABRchr17953289-ENST00000536871SMG6chr171989195-310821181233020965
ENST00000291107ABRchr17953289-ENST00000544865SMG6chr171989195-42681712322614860
ENST00000291107ABRchr17953289-ENST00000263073SMG6chr171989195-42641712322614860
ENST00000291107ABRchr17953289-ENST00000354901SMG6chr171989195-42571712322614860
ENST00000291107ABRchr17953289-ENST00000536871SMG6chr171989195-27021712322614860
ENST00000536794ABRchr17953289-ENST00000544865SMG6chr171989195-398014241402326728
ENST00000536794ABRchr17953289-ENST00000263073SMG6chr171989195-397614241402326728
ENST00000536794ABRchr17953289-ENST00000354901SMG6chr171989195-396914241402326728
ENST00000536794ABRchr17953289-ENST00000536871SMG6chr171989195-241414241402326728

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
ENST00000302538ENST00000544865ABRchr17953289-SMG6chr171989195-0.0012332930.9987668
ENST00000302538ENST00000263073ABRchr17953289-SMG6chr171989195-0.0012390130.99876106
ENST00000302538ENST00000354901ABRchr17953289-SMG6chr171989195-0.0012287210.99877125
ENST00000302538ENST00000536871ABRchr17953289-SMG6chr171989195-0.0030254350.9969746
ENST00000574437ENST00000544865ABRchr17953289-SMG6chr171989195-0.0019898420.9980102
ENST00000574437ENST00000263073ABRchr17953289-SMG6chr171989195-0.0020007960.99799913
ENST00000574437ENST00000354901ABRchr17953289-SMG6chr171989195-0.0019861830.99801385
ENST00000574437ENST00000536871ABRchr17953289-SMG6chr171989195-0.0044333930.99556655
ENST00000291107ENST00000544865ABRchr17953289-SMG6chr171989195-0.0026831270.9973169
ENST00000291107ENST00000263073ABRchr17953289-SMG6chr171989195-0.0026940260.997306
ENST00000291107ENST00000354901ABRchr17953289-SMG6chr171989195-0.0026732260.99732673
ENST00000291107ENST00000536871ABRchr17953289-SMG6chr171989195-0.0060711050.9939289
ENST00000536794ENST00000544865ABRchr17953289-SMG6chr171989195-0.0072966030.99270344
ENST00000536794ENST00000263073ABRchr17953289-SMG6chr171989195-0.0073414040.99265856
ENST00000536794ENST00000354901ABRchr17953289-SMG6chr171989195-0.0072782450.99272174
ENST00000536794ENST00000536871ABRchr17953289-SMG6chr171989195-0.0152464250.9847536

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 ABR-SMG6

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ABRchr17953289SMG6chr1719891951424428EIVDKIMGKGQIQVIAADCKRVTVLK
ABRchr17953289SMG6chr1719891951712560EIVDKIMGKGQIQVIAADCKRVTVLK
ABRchr17953289SMG6chr1719891951938597EIVDKIMGKGQIQVIAADCKRVTVLK
ABRchr17953289SMG6chr1719891952118665EIVDKIMGKGQIQVIAADCKRVTVLK

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Potential FusionNeoAntigen Information of ABR-SMG6 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.
ABR-SMG6_953289_1989195.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)
ABR-SMG6chr17953289chr1719891951712HLA-A02:13IMGKGQIQV0.99640.5493514
ABR-SMG6chr17953289chr1719891951712HLA-A02:04IMGKGQIQV0.99290.7811514
ABR-SMG6chr17953289chr1719891951712HLA-A02:17IMGKGQIQV0.98610.7712514
ABR-SMG6chr17953289chr1719891951712HLA-A02:38IMGKGQIQV0.98430.5993514
ABR-SMG6chr17953289chr1719891951712HLA-B13:02IMGKGQIQV0.11630.9035514
ABR-SMG6chr17953289chr1719891951712HLA-A02:13KIMGKGQIQV0.9980.5899414
ABR-SMG6chr17953289chr1719891951712HLA-A02:11KIMGKGQIQV0.99780.5663414
ABR-SMG6chr17953289chr1719891951712HLA-A02:60KIMGKGQIQV0.99770.5514414
ABR-SMG6chr17953289chr1719891951712HLA-A02:24KIMGKGQIQV0.99760.5269414
ABR-SMG6chr17953289chr1719891951712HLA-A02:30KIMGKGQIQV0.99760.5269414
ABR-SMG6chr17953289chr1719891951712HLA-A02:67KIMGKGQIQV0.99760.5269414
ABR-SMG6chr17953289chr1719891951712HLA-A02:27KIMGKGQIQV0.99750.5103414
ABR-SMG6chr17953289chr1719891951712HLA-A02:21KIMGKGQIQV0.99670.6226414
ABR-SMG6chr17953289chr1719891951712HLA-A02:38KIMGKGQIQV0.99410.5824414
ABR-SMG6chr17953289chr1719891951712HLA-A02:35KIMGKGQIQV0.95940.5368414
ABR-SMG6chr17953289chr1719891951712HLA-A02:29KIMGKGQIQV0.95850.5273414
ABR-SMG6chr17953289chr1719891951712HLA-A02:20KIMGKGQIQV0.92510.5334414
ABR-SMG6chr17953289chr1719891951712HLA-A02:01KIMGKGQIQV0.99760.5269414
ABR-SMG6chr17953289chr1719891951712HLA-A02:03IMGKGQIQV0.99750.6014514
ABR-SMG6chr17953289chr1719891951712HLA-A02:03KIMGKGQIQV0.99830.6605414
ABR-SMG6chr17953289chr1719891951712HLA-A02:14KIMGKGQIQV0.99680.6139414
ABR-SMG6chr17953289chr1719891951712HLA-A02:06KIMGKGQIQV0.99670.6226414

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Potential FusionNeoAntigen Information of ABR-SMG6 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 ABR-SMG6

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
5913MGKGQIQVIAADCKABRSMG6chr17953289chr1719891951712

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ABR-SMG6

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-B14:023BVN5913MGKGQIQVIAADCK-7.4838-7.5956
HLA-B14:023BVN5913MGKGQIQVIAADCK-3.16066-4.20376
HLA-B52:013W395913MGKGQIQVIAADCK-6.93679-7.04859
HLA-B52:013W395913MGKGQIQVIAADCK-6.10064-7.14374
HLA-A11:014UQ25913MGKGQIQVIAADCK-7.21307-7.32487
HLA-A24:025HGA5913MGKGQIQVIAADCK-6.56769-6.67949
HLA-A24:025HGA5913MGKGQIQVIAADCK-4.65311-5.69621
HLA-B44:053DX85913MGKGQIQVIAADCK-6.68002-6.79182
HLA-B44:053DX85913MGKGQIQVIAADCK-3.22493-4.26803

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Vaccine Design for the FusionNeoAntigens of ABR-SMG6

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
ABR-SMG6chr17953289chr171989195414KIMGKGQIQVAAGATCATGGGCAAAGGACAGATCCAGGTT
ABR-SMG6chr17953289chr171989195514IMGKGQIQVATCATGGGCAAAGGACAGATCCAGGTT

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 ABR-SMG6

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
OVABR-SMG6chr17953289ENST00000291107chr171989195ENST00000263073TCGA-61-2012

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Potential target of CAR-T therapy development for ABR-SMG6

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 ABR-SMG6

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 ABR-SMG6

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