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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:AS3MT-SUFU

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: AS3MT-SUFU
FusionPDB ID: 6929
FusionGDB2.0 ID: 6929
HgeneTgene
Gene symbol

AS3MT

SUFU

Gene ID

57412

51684

Gene namearsenite methyltransferaseSUFU negative regulator of hedgehog signaling
SynonymsCYT19JBTS32|PRO1280|SUFUH|SUFUXL
Cytomap

10q24.32

10q24.32

Type of geneprotein-codingprotein-coding
Descriptionarsenite methyltransferaseS-adenosyl-L-methionine:arsenic(III) methyltransferaseS-adenosylmethionine:arsenic (III) methyltransferasearsenic (+3 oxidation state) methyltransferasemethylarsonite methyltransferasemethyltransferase cyt19suppressor of fused homolog
Modification date2020032920200313
UniProtAcc

Q9HBK9

Main function of 5'-partner protein: FUNCTION: Catalyzes the transfer of a methyl group from AdoMet to trivalent arsenicals producing methylated and dimethylated arsenicals (PubMed:16407288, PubMed:25997655). It methylates arsenite to form methylarsonate, Me-AsO(3)H(2), which is reduced by methylarsonate reductase to methylarsonite, Me-As(OH)2 (PubMed:16407288, PubMed:25997655). Methylarsonite is also a substrate and it is converted into the much less toxic compound dimethylarsinate (cacodylate), Me(2)As(O)-OH (PubMed:16407288, PubMed:25997655). {ECO:0000269|PubMed:16407288, ECO:0000269|PubMed:25997655}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000369880, ENST00000471000, 
ENST00000369899, ENST00000369902, 
ENST00000423559, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score3 X 2 X 3=188 X 8 X 8=512
# samples 312
** MAII scorelog2(3/18*10)=0.736965594166206
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
log2(12/512*10)=-2.09310940439148
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: AS3MT [Title/Abstract] AND SUFU [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: AS3MT [Title/Abstract] AND SUFU [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)AS3MT(104650435)-SUFU(104356897), # samples:3
Anticipated loss of major functional domain due to fusion event.AS3MT-SUFU 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.
AS3MT-SUFU 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.
* 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
HgeneAS3MT

GO:0009404

toxin metabolic process

25997655

HgeneAS3MT

GO:0018872

arsonoacetate metabolic process

25997655

HgeneAS3MT

GO:0032259

methylation

25997655

TgeneSUFU

GO:0000122

negative regulation of transcription by RNA polymerase II

10564661



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/chr10:104650435/chr10:104356897)
- 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 AS3MT (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 SUFU (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)
ENST00000369880AS3MTchr10104650435+ENST00000369902SUFUchr10104356897+51761097771795572
ENST00000369880AS3MTchr10104650435+ENST00000369899SUFUchr10104356897+20341097771642521
ENST00000369880AS3MTchr10104650435+ENST00000423559SUFUchr10104356897+28681097771786569

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
ENST00000369880ENST00000369902AS3MTchr10104650435+SUFUchr10104356897+0.0032451120.9967548
ENST00000369880ENST00000369899AS3MTchr10104650435+SUFUchr10104356897+0.008129160.9918709
ENST00000369880ENST00000423559AS3MTchr10104650435+SUFUchr10104356897+0.0025166990.9974833

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 AS3MT-SUFU

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
AS3MTchr10104650435SUFUchr101043568971097340LPTSGGCSALELKERVDKGIETDGSN

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Potential FusionNeoAntigen Information of AS3MT-SUFU 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.
AS3MT-SUFU_104650435_104356897.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)
AS3MT-SUFUchr10104650435chr101043568971097HLA-B52:01SALELKERV0.99280.9777716
AS3MT-SUFUchr10104650435chr101043568971097HLA-C06:03SALELKERV0.97460.9911716
AS3MT-SUFUchr10104650435chr101043568971097HLA-B51:09SALELKERV0.98110.527716

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Potential FusionNeoAntigen Information of AS3MT-SUFU 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 AS3MT-SUFU

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
928CSALELKERVDKGIAS3MTSUFUchr10104650435chr101043568971097

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of AS3MT-SUFU

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-B14:023BVN928CSALELKERVDKGI-7.9962-8.1096
HLA-B14:023BVN928CSALELKERVDKGI-5.70842-6.74372
HLA-B52:013W39928CSALELKERVDKGI-6.83737-6.95077
HLA-B52:013W39928CSALELKERVDKGI-4.4836-5.5189
HLA-A11:014UQ2928CSALELKERVDKGI-10.0067-10.1201
HLA-A11:014UQ2928CSALELKERVDKGI-9.03915-10.0745
HLA-A24:025HGA928CSALELKERVDKGI-6.56204-6.67544
HLA-A24:025HGA928CSALELKERVDKGI-5.42271-6.45801
HLA-B44:053DX8928CSALELKERVDKGI-7.85648-8.89178
HLA-B44:053DX8928CSALELKERVDKGI-5.3978-5.5112
HLA-A02:016TDR928CSALELKERVDKGI-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of AS3MT-SUFU

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
AS3MT-SUFUchr10104650435chr10104356897716SALELKERVTCTGCTTTGGAGTTAAAGGAGAGAGTT

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 AS3MT-SUFU

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
ACCAS3MT-SUFUchr10104650435ENST00000369880chr10104356897ENST00000369899TCGA-OR-A5J7-01A

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Potential target of CAR-T therapy development for AS3MT-SUFU

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 AS3MT-SUFU

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 AS3MT-SUFU

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