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Center for Computational Systems Medicine level2
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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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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:NUP188-POLR2A

Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NUP188-POLR2A
FusionPDB ID: 61009
FusionGDB2.0 ID: 61009
HgeneTgene
Gene symbol

NUP188

POLR2A

Gene ID

23511

5430

Gene namenucleoporin 188RNA polymerase II subunit A
SynonymsKIAA0169|SANDSTEF|hNup188NEDHIB|POLR2|POLRA|RPB1|RPBh1|RPO2|RPOL2|RpIILS|hRPB220|hsRPB1
Cytomap

9q34.11

17p13.1

Type of geneprotein-codingprotein-coding
Descriptionnucleoporin NUP188 homolognucleoporin 188kDaDNA-directed RNA polymerase II subunit RPB1DNA-directed RNA polymerase II largest subunit, RNA polymerase II 220 kd subunitDNA-directed RNA polymerase II subunit ADNA-directed RNA polymerase III largest subunitRNA polymerase II subunit B1RNA-directed
Modification date2020031420200327
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000372577, ENST00000550219, 
ENST00000572844, ENST00000322644, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score11 X 12 X 8=10567 X 7 X 2=98
# samples 147
** MAII scorelog2(14/1056*10)=-2.91511110241349
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(7/98*10)=-0.485426827170242
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)

PubMed: NUP188 [Title/Abstract] AND POLR2A [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NUP188(131768868)-POLR2A(7407022), # samples:2
Anticipated loss of major functional domain due to fusion event.NUP188-POLR2A 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.
NUP188-POLR2A 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
TgenePOLR2A

GO:0006366

transcription by RNA polymerase II

9852112

TgenePOLR2A

GO:0033120

positive regulation of RNA splicing

21536736


check buttonFusion gene breakpoints across NUP188 (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 POLR2A (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 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
ChiTaRS5.0N/ABE819347NUP188chr9

131768868

+POLR2Achr17

7407022

+
ChiTaRS5.0N/ABE819348NUP188chr9

131768868

+POLR2Achr17

7407022

+


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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)
ENST00000372577NUP188chr9131768868+ENST00000322644POLR2Achr177407022+879956012151411706

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
ENST00000372577ENST00000322644NUP188chr9131768868+POLR2Achr177407022+0.0009531070.99904686

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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

>61009_61009_1_NUP188-POLR2A_NUP188_chr9_131768868_ENST00000372577_POLR2A_chr17_7407022_ENST00000322644_length(amino acids)=1706AA_BP=
MAAAAGGPCVRSSRELWTILLGRSALRELSQIEAELNKHWRRLLEGLSYYKPPSPSSAEKVKANKDVASPLKELGLRISKFLGLDEEQSV
QLLQCYLQEDYRGTRDSVKTVLQDERQSQALILKIADYYYEERTCILRCVLHLLTYFQDERHPYRVEYADCVDKLEKELVSKYRQQFEEL
YKTEAPTWETHGNLMTERQVSRWFVQCLREQSMLLEIIFLYYAYFEMAPSDLLVLTKMFKEQGFGSRQTNRHLVDETMDPFVDRIGYFSA
LILVEGMDIESLHKCALDDRRELHQFAQDGLICQDMDCLMLTFGDIPHHAPVLLAWALLRHTLNPEETSSVVRKIGGTAIQLNVFQYLTR
LLQSLASGGNDCTTSTACMCVYGLLSFVLTSLELHTLGNQQDIIDTACEVLADPSLPELFWGTEPTSGLGIILDSVCGMFPHLLSPLLQL
LRALVSGKSTAKKVYSFLDKMSFYNELYKHKPHDVISHEDGTLWRRQTPKLLYPLGGQTNLRIPQGTVGQVMLDDRAYLVRWEYSYSSWT
LFTCEIEMLLHVVSTADVIQHCQRVKPIIDLVHKVISTDLSIADCLLPITSRIYMLLQRLTTVISPPVDVIASCVNCLTVLAARNPAKVW
TDLRHTGFLPFVAHPVSSLSQMISAEGMNAGGYGNLLMNSEQPQGEYGVTIAFLRLITTLVKGQLGSTQSQGLVPCVMFVLKEMLPSYHK
WRYNSHGVREQIGCLILELIHAILNLCHETDLHSSHTPSLQFLCICSLAYTEAGQTVINIMGIGVDTIDMVMAAQPRSDGAEGQGQGQLL
IKTVKLAFSVTNNVIRLKPPSNVVSPLEQALSQHGAHGNNLIAVLAKYIYHKHDPALPRLAIQLLKRLATVAPMSVYACLGNDAAAIRDA
FLTRLQSKIEDMRIKVMILEFLTVAVETQPGLIELFLNLEVKDGSDGSKEFSLGMWSCLHAVLELIDSQQQDRYWCPPLLHRAAIAFLHA
LWQDRRDSAMLVLRTKPKFWENLTSPLFGTLSPPSETSEPSILETCALIMKIICLEIYYVVKGSLDQSLKDTLKKFSIEKRFAYWSGYVK
SLAVHVAETEGSSCTSLLEYQMLVSAWRMLLIIATTHADIMHLTDSVVRRQLFLDVLDGTKALLLVPASVNCLRLGSMKCTLLLILLRQW
KRELGSVDEILGPLTEILEGVLQADQQLMEKTKAKVFSAFITVLQMKEMKVSDIPQYSQLVLNVCETLQEEVIALFDQTRHSLALGSATE
DKDSMETDDCSRSRHRDQRDGVCVLGLHLAKELCEVDEDGDSWLQVTRRLPILPTLLTTLEVSLRMKQNLHFTEATLHLLLTLARTQQGA
TAVAGAGITQSICLPLLSVYQLSTNGTAQTPSASRKSLDAPSWPGVYRLSMSLMEQLLKTLRYNFLPEALDFVGVHQERTLQCLNAVRTV
QSLACLEEADHTVGFILQLSNFMKEWHFHLPQLMRDIQVNLGYLCQACTSLLHSRKMLQHYLQNKNGDGLPSAVAQRVQRPPSAASAAPS
SSKQPAADTEASEQQALHTVQYGLLKILSKTLAALRHFTPDVCQILLDQSLDLAEYNFLFALSFTTPTFDSEVAPSFGTLLATVNVALNM

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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/chr9:131768868/chr17:7407022)
- 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
..
FUNCTION: Might normally function as a transcriptional repressor. EWS-fusion-proteins (EFPS) may play a role in the tumorigenic process. They may disturb gene expression by mimicking, or interfering with the normal function of CTD-POLII within the transcription initiation complex. They may also contribute to an aberrant activation of the fusion protein target genes.FUNCTION: Might normally function as a transcriptional repressor. EWS-fusion-proteins (EFPS) may play a role in the tumorigenic process. They may disturb gene expression by mimicking, or interfering with the normal function of CTD-POLII within the transcription initiation complex. They may also contribute to an aberrant activation of the fusion protein target genes.

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
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291593_196001971.0RegionNote=C-terminal domain (CTD)%3B 52 X 7 AA approximate tandem repeats of Y-[ST]-P-[STQ]-[ST]-P-[SRTEVKGN]
TgenePOLR2Achr9:131768868chr17:7407022ENST00000322644029833_84501971.0RegionNote=Bridging helix
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291593_159901971.0RepeatNote=1
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291600_160601971.0RepeatNote=2%3B approximate
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291608_161401971.0RepeatNote=3
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291615_162101971.0RepeatNote=4
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291622_162801971.0RepeatNote=5
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291629_163501971.0RepeatNote=6
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291636_164201971.0RepeatNote=7
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291643_164901971.0RepeatNote=8
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291650_165601971.0RepeatNote=9
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291657_166301971.0RepeatNote=10
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291664_167001971.0RepeatNote=11
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291671_167701971.0RepeatNote=12
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291678_168401971.0RepeatNote=13
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291685_169101971.0RepeatNote=14
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291692_169801971.0RepeatNote=15
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291699_170501971.0RepeatNote=16
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291706_171201971.0RepeatNote=17
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291713_171901971.0RepeatNote=18
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291720_172601971.0RepeatNote=19
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291727_173301971.0RepeatNote=20
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291734_174001971.0RepeatNote=21
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291741_174701971.0RepeatNote=22
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291748_175401971.0RepeatNote=23
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291755_176101971.0RepeatNote=24
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291762_176801971.0RepeatNote=25
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291769_177501971.0RepeatNote=26
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291776_178201971.0RepeatNote=27
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291783_178901971.0RepeatNote=28
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291790_179601971.0RepeatNote=29
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291797_180301971.0RepeatNote=30
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291804_181001971.0RepeatNote=31
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291811_181701971.0RepeatNote=32
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291818_182401971.0RepeatNote=33
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291825_183101971.0RepeatNote=34
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291832_183801971.0RepeatNote=35
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291839_184501971.0RepeatNote=36
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291846_185201971.0RepeatNote=37
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291853_185901971.0RepeatNote=38
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291860_186601971.0RepeatNote=39
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291867_187301971.0RepeatNote=40
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291874_188001971.0RepeatNote=41
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291881_188701971.0RepeatNote=42
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291888_189401971.0RepeatNote=43
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291895_190101971.0RepeatNote=44
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291902_190801971.0RepeatNote=45
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291909_191501971.0RepeatNote=46
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291916_192201971.0RepeatNote=47
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291923_192901971.0RepeatNote=48
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291930_193601971.0RepeatNote=49
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291940_194601971.0RepeatNote=50
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291947_195301971.0RepeatNote=51%3B approximate
TgenePOLR2Achr9:131768868chr17:7407022ENST000003226440291954_196001971.0RepeatNote=52%3B approximate

- 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)


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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.
NUP188_pLDDT.png
all structure
all structure
POLR2A_pLDDT.png
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.


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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

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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


check button Protein-protein interactors based on sequence similarity (STRING)
GeneSTRING network
NUP188
POLR2A


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 NUP188-POLR2A


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 NUP188-POLR2A


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