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Center for Computational Systems Medicine level3
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Fusion Gene Summary

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Fusion Gene Sample Information

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Fusion ORF Analysis

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Fusion Amino Acid Sequences

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Fusion Protein Functional Features

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Fusion Protein Structure

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pLDDT scores

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Ramachandran Plot of Fusion Protein Structure

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Potential Active Site Information

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Potentially Interacting Small Molecules through Virtual Screening

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Biochemical Features of Small Molecules with ADME

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Drug Toxicity Information

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Fusion Protein-Protein Interaction

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Related drugs with this fusion protein

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Related disease with this fusion protein

Fusion Protein:SS18-SSX7

Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: SS18-SSX7
FusionPDB ID: 86687
FusionGDB2.0 ID: 86687
HgeneTgene
Gene symbol

SS18

SSX7

Gene ID

6760

280658

Gene nameSS18 subunit of BAF chromatin remodeling complex
SynonymsSSXT|SYT
Cytomap

18q11.2

Type of geneprotein-coding
Descriptionprotein SSXTSS18, nBAF chromatin remodeling complex subunitsynovial sarcoma translocated to X chromosome proteinsynovial sarcoma translocation, chromosome 18synovial sarcoma, translocated to X chromosome
Modification date20200329
UniProtAcc

O75177

Q7RTT5

Ensembl transtripts involved in fusion geneENST idsENST00000539849, ENST00000542420, 
ENST00000542743, ENST00000269137, 
ENST00000415083, ENST00000545952, 
ENST00000585241, 
ENST00000298181, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score24 X 33 X 8=63361 X 1 X 1=1
# samples 381
** MAII scorelog2(38/6336*10)=-4.05950101174866
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(1/1*10)=3.32192809488736
Context (manual curation of fusion genes in FusionPDB)

PubMed: SS18 [Title/Abstract] AND SSX7 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)
Anticipated loss of major functional domain due to fusion event.SS18-SSX7 seems lost the major protein functional domain in Hgene partner, which is a CGC 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
HgeneSS18

GO:0045944

positive regulation of transcription by RNA polymerase II

15919756


check buttonFusion gene breakpoints across SS18 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

check buttonFusion gene breakpoints across SSX7 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.


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Fusion Gene Sample Information

check buttonFusion gene information from FusionGDB2.0.
check button Fusion gene information from two resources (ChiTars 5.0 and ChimerDB 4.0)
* All genome coordinats were lifted-over on hg19.
* Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser.
SourceDiseaseSampleHgeneHchrHbpHstrandTgeneTchrTbpTstrand
ChimerKB3..SS18chr18

23612363

-SSX7chrX

52677446

-


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Fusion ORF Analysis


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)
ENST00000415083SS18chr1823612363-ENST00000298181SSX7chrX52677446-21081286561522488
ENST00000269137SS18chr1823612363-ENST00000298181SSX7chrX52677446-229114691611705514
ENST00000545952SS18chr1823612363-ENST00000298181SSX7chrX52677446-210612843031520405

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

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Fusion Amino Acid Sequences


check button For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among the all predicted ones.
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

>86687_86687_1_SS18-SSX7_SS18_chr18_23612363_ENST00000269137_SSX7_chrX_52677446_ENST00000298181_length(amino acids)=514AA_BP=436
MARVPPSGLPRRPSAWPRSIPPPRIPEVVQPERPASLPQFAVHPERSGLADSGDGGNMSVAFAAPRQRGKGEITPAAIQKMLDDNNHLIQ
CIMDSQNKGKTSECSQYQQMLHTNLVYLATIADSNQNMQSLLPAPPTQNMPMGPGGMNQSGPPPPPRSHNMPSDGMVGGGPPAPHMQNQM
NGQMPGPNHMPMQGPGPNQLNMTNSSMNMPSSSHGSMGGYNHSVPSSQSMPVQNQMTMSQGQPMGNYGPRPNMSMQPNQGPMMHQQPPSQ
QYNMPQGGGQHYQGQQPPMGMMGQVNQGNHMMGQRQIPPYRPPQQGPPQQYSGQEDYYGDQYSHGGQGPPEGMNQQYYPDGNSQYGQQQD
AYQGPPPQQGYPPQQQQYPGQQGYPGQQQGYGPSQGGPGPQYPNYPQGQGQQYGGYRPTQPGPPQPPQQRPYGYDQIMPKKPAEEGNDSK

--------------------------------------------------------------

>86687_86687_2_SS18-SSX7_SS18_chr18_23612363_ENST00000415083_SSX7_chrX_52677446_ENST00000298181_length(amino acids)=488AA_BP=410
MSVAFAAPRQRGKGEITPAAIQKMLDDNNHLIQCIMDSQNKGKTSECSQYQQMLHTNLVYLATIADSNQNMQSLLPAPPTQNMPMGPGGM
NQSGPPPPPRSHNMPSDGMVGGGPPAPHMQNQMNGQMPGPNHMPMQGPGPNQLNMTNSSMNMPSSSHGSMGGYNHSVPSSQSMPVQNQMT
MSQGQPMGNYGPRPNMSMQPNQGPMMHQQPPSQQYNMPQGGGQHYQGQQPPMGMMGQVNQGNHMMGQRQIPPYRPPQQGPPQQYSGQEDY
YGDQYSHGGQGPPEGMNQQYYPDGHNDYGYQQPSYPEQGYDRPYEDSSQHYYEGGNSQYGQQQDAYQGPPPQQGYPPQQQQYPGQQGYPG
QQQGYGPSQGGPGPQYPNYPQGQGQQYGGYRPTQPGPPQPPQQRPYGYDQIMPKKPAEEGNDSKGVPEASGSQNDGKHLCPPGKPSTSEK

--------------------------------------------------------------

>86687_86687_3_SS18-SSX7_SS18_chr18_23612363_ENST00000545952_SSX7_chrX_52677446_ENST00000298181_length(amino acids)=405AA_BP=327
MLHTNLVYLATIADSNQNMQSLLPAPPTQNMPMGPGGMNQSGPPPPPRSHNMPSDGMVGGGPPAPHMQNQMNGQMPGPNHMPMQGPGPNQ
LNMTNSSMNMPSSSHGSMGGYNHSVPSSQSMPVQNQMTMSQGQPMGNYGPRPNMSMQPNQGPMMHQQPPSQQYNMPQGGGQHYQGQQPPM
GMMGQVNQGNHMMGQRQIPPYRPPQQGPPQQYSGQEDYYGDQYSHGGQGPPEGMNQQYYPDGNSQYGQQQDAYQGPPPQQGYPPQQQQYP
GQQGYPGQQQGYGPSQGGPGPQYPNYPQGQGQQYGGYRPTQPGPPQPPQQRPYGYDQIMPKKPAEEGNDSKGVPEASGSQNDGKHLCPPG

--------------------------------------------------------------

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Fusion Protein Functional Features


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/chr18:/chrX:)
- 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 buttonMain function of each fusion partner protein. (from UniProt)
HgeneTgene
SS18

O75177

SSX7

Q7RTT5

FUNCTION: Transcriptional activator which is required for calcium-dependent dendritic growth and branching in cortical neurons. Recruits CREB-binding protein (CREBBP) to nuclear bodies. Component of the CREST-BRG1 complex, a multiprotein complex that regulates promoter activation by orchestrating a calcium-dependent release of a repressor complex and a recruitment of an activator complex. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex. At the same time, there is increased recruitment of CREBBP to the promoter by a CREST-dependent mechanism, which leads to transcriptional activation. The CREST-BRG1 complex also binds to the NR2B promoter, and activity-dependent induction of NR2B expression involves a release of HDAC1 and recruitment of CREBBP (By similarity). {ECO:0000250}.FUNCTION: Could act as a modulator of transcription.

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, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at

download page

* Minus value of BPloci means that the break pointn is located before the CDS.
- Retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

- Not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note


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Fusion Protein Structures

check button PDB and CIF files of the predicted fusion proteins
* Here we show the 3D structure of the fusion proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format.
Fusion protein PDB link (fusion AA seq ID in FusionPDB)HgeneHchrHbpHstrandTgeneTchrTbpTstrandAA seqLen(AA seq)
PDB file (166) >>>166.pdbFusion protein BP residue: 327
CIF file (166) >>>166.cif
SS18chr1823612363-SSX7chrX52677446-
MLHTNLVYLATIADSNQNMQSLLPAPPTQNMPMGPGGMNQSGPPPPPRSH
NMPSDGMVGGGPPAPHMQNQMNGQMPGPNHMPMQGPGPNQLNMTNSSMNM
PSSSHGSMGGYNHSVPSSQSMPVQNQMTMSQGQPMGNYGPRPNMSMQPNQ
GPMMHQQPPSQQYNMPQGGGQHYQGQQPPMGMMGQVNQGNHMMGQRQIPP
YRPPQQGPPQQYSGQEDYYGDQYSHGGQGPPEGMNQQYYPDGNSQYGQQQ
DAYQGPPPQQGYPPQQQQYPGQQGYPGQQQGYGPSQGGPGPQYPNYPQGQ
GQQYGGYRPTQPGPPQPPQQRPYGYDQIMPKKPAEEGNDSKGVPEASGSQ
NDGKHLCPPGKPSTSEKINKTSGPKRGKHAWTHRLRERKQLVIYEEISDP
405
3D view using mol* of 166 (AA BP:327)
PDB file (279) >>>279.pdbFusion protein BP residue: 410
CIF file (279) >>>279.cif
SS18chr1823612363-SSX7chrX52677446-
MSVAFAAPRQRGKGEITPAAIQKMLDDNNHLIQCIMDSQNKGKTSECSQY
QQMLHTNLVYLATIADSNQNMQSLLPAPPTQNMPMGPGGMNQSGPPPPPR
SHNMPSDGMVGGGPPAPHMQNQMNGQMPGPNHMPMQGPGPNQLNMTNSSM
NMPSSSHGSMGGYNHSVPSSQSMPVQNQMTMSQGQPMGNYGPRPNMSMQP
NQGPMMHQQPPSQQYNMPQGGGQHYQGQQPPMGMMGQVNQGNHMMGQRQI
PPYRPPQQGPPQQYSGQEDYYGDQYSHGGQGPPEGMNQQYYPDGHNDYGY
QQPSYPEQGYDRPYEDSSQHYYEGGNSQYGQQQDAYQGPPPQQGYPPQQQ
QYPGQQGYPGQQQGYGPSQGGPGPQYPNYPQGQGQQYGGYRPTQPGPPQP
PQQRPYGYDQIMPKKPAEEGNDSKGVPEASGSQNDGKHLCPPGKPSTSEK
488
3D view using mol* of 279 (AA BP:410)
PDB file (323) >>>323.pdbFusion protein BP residue: 436
CIF file (323) >>>323.cif
SS18chr1823612363-SSX7chrX52677446-
MARVPPSGLPRRPSAWPRSIPPPRIPEVVQPERPASLPQFAVHPERSGLA
DSGDGGNMSVAFAAPRQRGKGEITPAAIQKMLDDNNHLIQCIMDSQNKGK
TSECSQYQQMLHTNLVYLATIADSNQNMQSLLPAPPTQNMPMGPGGMNQS
GPPPPPRSHNMPSDGMVGGGPPAPHMQNQMNGQMPGPNHMPMQGPGPNQL
NMTNSSMNMPSSSHGSMGGYNHSVPSSQSMPVQNQMTMSQGQPMGNYGPR
PNMSMQPNQGPMMHQQPPSQQYNMPQGGGQHYQGQQPPMGMMGQVNQGNH
MMGQRQIPPYRPPQQGPPQQYSGQEDYYGDQYSHGGQGPPEGMNQQYYPD
GNSQYGQQQDAYQGPPPQQGYPPQQQQYPGQQGYPGQQQGYGPSQGGPGP
QYPNYPQGQGQQYGGYRPTQPGPPQPPQQRPYGYDQIMPKKPAEEGNDSK
GVPEASGSQNDGKHLCPPGKPSTSEKINKTSGPKRGKHAWTHRLRERKQL
514
3D view using mol* of 323 (AA BP:436)


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pLDDT score distribution

check button pLDDT score distribution of the predicted wild-type structures of two partner proteins from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.
SS18_pLDDT.png
all structure
all structure

all structure

check button pLDDT score distribution of the predicted fusion protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.
SS18_SSX7_166_PAE.png (AA BP:327)
all structure
SS18_SSX7_166_pLDDT.png (AA BP:327)
all structure
SS18_SSX7_166_pLDDT_and_active_sites.png (AA BP:327)
all structure
SS18_SSX7_166_violinplot.png (AA BP:327)
all structure
SS18_SSX7_279_pLDDT.png (AA BP:410)
all structure
SS18_SSX7_279_pLDDT_and_active_sites.png (AA BP:410)
all structure
SS18_SSX7_279_violinplot.png (AA BP:410)
all structure
SS18_SSX7_323_pLDDT.png (AA BP:436)
all structure
SS18_SSX7_323_pLDDT_and_active_sites.png (AA BP:436)
all structure
SS18_SSX7_323_violinplot.png (AA BP:436)
all structure


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Ramachandran Plot of Fusion Protein Structure


check button Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this fusion protein peptide.
Fusion AA seq ID in FusionPDB and their Ramachandran plots
SS18_SSX7_166.png
all structure
SS18_SSX7_279.png
all structure
SS18_SSX7_323.png
all structure

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Potential Active Site Information


check button The potential binding sites of these fusion proteins were identified using SiteMap, a module of the Schrodinger suite.
Fusion AA seq ID in FusionPDBSite scoreSizeD scoreVolumeExposureEnclosureContactPhobicPhilicBalanceDon/AccResidues
1660.29180.18210.9760.8460.4240.5710.0381.0390.0360.676Chain A: 220,221,222,223,224,225
2790.991081.049329.6230.6880.6090.80.6190.7860.7870.99Chain A: 5,6,7,8,9,11,12,13,14,15,16,17,20,21,23,2
4,27,31,52,53,55,56,57,59,60,61,63,64
3230.741370.72123.1370.5980.660.9071.2870.7591.6960.913Chain A: 62,65,68,112,113,116,117,120,121

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Potentially Interacting Small Molecules through Virtual Screening


check button The FDA-approved small molecule library molecules were subjected to virtual screening using the Glide.
Fusion AA seq ID in FusionPDBZINC IDDrugBank IDDrug nameDocking scoreGlide gscore

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check button Drug information from DrugBank of the top 20 interacting small molecules.
ZINC IDDrugBank IDDrug nameDrug typeSMILESDrug group

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Biochemical Features of Small Molecules


check button ADME (Absorption, Distribution, Metabolism, and Excretion) of drugs using QikProp(v3.9)
ZINC IDmol_MWdipoleSASAFOSAFISAPISAWPSAvolumedonorHBaccptHBIPHuman Oral AbsorptionPercent Human Oral AbsorptionRule Of FiveRule Of Three


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Drug Toxicity Information


check button Toxicity information of individual drugs using eToxPred
ZINC IDSmileSurface AccessibilityToxicity


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Fusion Protein-Protein Interaction


check button Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in

ChiPPI page.


check button Protein-protein interactors with each fusion partner protein in wild-type from validated records (BIOGRID-3.4.160)
GenePPI interactors
SS18SMARCA2, SMARCB1, EP300, MLLT10, GRB2, Bcl7b, SMARCD1, RBM14, YWHAG, ELAVL1, CUL3, CST11, ATF2, TLE1, SMARCA5, HDAC1, HDAC2, EED, SUZ12, EZH2, SS18, NFKBID, DPF3, DPF2, SMARCE1, ARID1B, ARID1A, PHF10, SMARCC2, SMARCC1, GLTSCR1, SMARCD3, SMARCD2, SMARCA4, ARID2, DPF1, ACTL6A, ACTL6B, BCL7A, BCL7C, BCL7B, BRD9, CDKN1A, NEFM, RAB5C, SYNCRIP, Wash, FUS, DDIT3, FLI1, nsp13ab, BRD3, NR3C1, SS18L1, BRD7, PBRM1, ACTC1, STK11IP, DDX58, UBQLN2, PTPRR, T, ELF5, ERG, ETV4, FOS, GATA2, GCM1, HNF4A, IRF1, IRF4, KLF3, KLF5, LHX2, MYOD1, PAX7, SOX17, SOX2, SP7,


check button Protein-protein interactors based on sequence similarity (STRING)
GeneSTRING network
SS18all structure
SSX7all structure


check button - Retained interactions in fusion protein (protein functional feature from UniProt).
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenStill interaction with


check button - Lost interactions due to fusion (protein functional feature from UniProt).
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


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Related Drugs to SS18-SSX7


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 SS18-SSX7


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
HgeneSS18C0039101synovial sarcoma2CTD_human;ORPHANET