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Center for Computational Systems Medicine
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Fusion Gene Summary

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Fusion Gene ORF analysis

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Fusion Genomic Features

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Fusion Protein Features

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Fusion Gene Sequence

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Fusion Gene PPI analysis

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Related Drugs

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Related Diseases

Fusion gene:PAH-METAP2 (FusionGDB2 ID:HG5053TG10988)

Fusion Gene Summary for PAH-METAP2

check button Fusion gene summary
Fusion gene informationFusion gene name: PAH-METAP2
Fusion gene ID: hg5053tg10988
HgeneTgene
Gene symbol

PAH

METAP2

Gene ID

5053

10988

Gene namephenylalanine hydroxylasemethionyl aminopeptidase 2
SynonymsPH|PKU|PKU1MAP2|MNPEP|p67eIF2
Cytomap('PAH')('METAP2')

12q23.2

12q22

Type of geneprotein-codingprotein-coding
Descriptionphenylalanine-4-hydroxylasephe-4-monooxygenasephenylalanine 4-monooxygenasemethionine aminopeptidase 2eIF-2-associated p67 homologinitiation factor 2-associated 67 kDa glycoproteinpeptidase M 2testicular tissue protein Li 17
Modification date2020031320200313
UniProtAcc..
Ensembl transtripts involved in fusion geneENST00000551988, ENST00000307000, 
ENST00000553106, 
Fusion gene scores* DoF score5 X 4 X 4=806 X 6 X 3=108
# samples 56
** MAII scorelog2(5/80*10)=-0.678071905112638
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(6/108*10)=-0.84799690655495
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: PAH [Title/Abstract] AND METAP2 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointPAH(103288513)-METAP2(95906577), # samples:3
Anticipated loss of major functional domain due to fusion event.PAH-METAP2 seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
PAH-METAP2 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
PAH-METAP2 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target 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
TgeneMETAP2

GO:0016485

protein processing

8858118

TgeneMETAP2

GO:0018206

peptidyl-methionine modification

8858118

TgeneMETAP2

GO:0031365

N-terminal protein amino acid modification

8858118



check button Fusion gene information
* 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
ChimerDB4ACCTCGA-OR-A5JA-01APAHchr12

103288513

-METAP2chr12

95906577

+


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Fusion Gene ORF analysis for PAH-METAP2

check button Open reading frame (ORF) analsis of fusion genes based on Ensembl gene isoform structure.
* Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser.
ORFHenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrand
5UTR-3CDSENST00000551988ENST00000261220PAHchr12

103288513

-METAP2chr12

95906577

+
5UTR-3CDSENST00000551988ENST00000323666PAHchr12

103288513

-METAP2chr12

95906577

+
5UTR-3CDSENST00000551988ENST00000546753PAHchr12

103288513

-METAP2chr12

95906577

+
5UTR-3CDSENST00000551988ENST00000550777PAHchr12

103288513

-METAP2chr12

95906577

+
5UTR-3CDSENST00000551988ENST00000551840PAHchr12

103288513

-METAP2chr12

95906577

+
Frame-shiftENST00000307000ENST00000261220PAHchr12

103288513

-METAP2chr12

95906577

+
Frame-shiftENST00000307000ENST00000323666PAHchr12

103288513

-METAP2chr12

95906577

+
Frame-shiftENST00000307000ENST00000546753PAHchr12

103288513

-METAP2chr12

95906577

+
Frame-shiftENST00000307000ENST00000550777PAHchr12

103288513

-METAP2chr12

95906577

+
Frame-shiftENST00000307000ENST00000551840PAHchr12

103288513

-METAP2chr12

95906577

+
Frame-shiftENST00000553106ENST00000261220PAHchr12

103288513

-METAP2chr12

95906577

+
Frame-shiftENST00000553106ENST00000323666PAHchr12

103288513

-METAP2chr12

95906577

+
Frame-shiftENST00000553106ENST00000546753PAHchr12

103288513

-METAP2chr12

95906577

+
Frame-shiftENST00000553106ENST00000550777PAHchr12

103288513

-METAP2chr12

95906577

+
Frame-shiftENST00000553106ENST00000551840PAHchr12

103288513

-METAP2chr12

95906577

+

check buttonORFfinder result based on the fusion transcript sequence of in-frame fusion genes.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)
BP loci
(transcript)
Predicted start
(transcript)
Predicted stop
(transcript)
Seq length
(amino acids)

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 Genomic Features for PAH-METAP2


check buttonFusionAI prediction of the potential fusion gene breakpoint based on the pre-mature RNA sequence context (+/- 5kb of individual partner genes, total 20kb length sequence). FusionAI is a fusion gene breakpoint classifier based on convolutional neural network by comparing the fusion positive and negative sequence context of ~ 20K fusion gene data. From here, we can have the relative potentency of the 20K genomic sequence how individual sequnce will be likely used as the gene fusion breakpoints.
HgeneHchrHbpHstrandTgeneTchrTbpTstrand1-pp (fusion gene breakpoint)
PAHchr12103288512-METAP2chr1295906576+0.0317883640.96821165
PAHchr12103288512-METAP2chr1295906576+0.0317883640.96821165


check buttonDistribution of 44 human genomic features loci across 20kb length fusion breakpoint regions that are ovelapped with the top 1% feature importance score regions. More details are in help page.
genomic feature of top 1%

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Fusion Protein Features for PAH-METAP2


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/:103288513/:95906577)
- 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: 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: 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}.

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.
- In-frame and retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

- In-frame and not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note


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Fusion Gene Sequence for PAH-METAP2


check button For in-frame fusion transcripts, we provide the fusion transcript sequences and fusion amino acid sequences. To have fusion amino acid sequence, we ran ORFfinder and chose the longest ORF among the all predicted ones.

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Fusion Gene PPI Analysis for PAH-METAP2


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 (BIOGRID-3.4.160)
HgeneHgene's interactorsTgeneTgene's interactors


check button - Retained PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenStill interaction with


check button - Lost PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


check button - Retained PPIs, but lost function due to frame-shift fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


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Related Drugs for PAH-METAP2


check button Drugs targeting genes involved in this fusion gene.
(DrugBank Version 5.1.8 2021-05-08)
PartnerGeneUniProtAccDrugBank IDDrug nameDrug activityDrug typeDrug status

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Related Diseases for PAH-METAP2


check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource
HgenePAHC0751434Classical phenylketonuria47CTD_human;GENOMICS_ENGLAND;UNIPROT
HgenePAHC0036341Schizophrenia2PSYGENET
HgenePAHC0019193Hepatitis, Toxic1CTD_human
HgenePAHC0031485Phenylketonurias1CTD_human;GENOMICS_ENGLAND
HgenePAHC0033975Psychotic Disorders1PSYGENET
HgenePAHC0085547Phenylketonuria, Maternal1ORPHANET
HgenePAHC0860207Drug-Induced Liver Disease1CTD_human
HgenePAHC1262760Hepatitis, Drug-Induced1CTD_human
HgenePAHC1510586Autism Spectrum Disorders1CTD_human
HgenePAHC3658290Drug-Induced Acute Liver Injury1CTD_human
HgenePAHC4277682Chemical and Drug Induced Liver Injury1CTD_human
HgenePAHC4279912Chemically-Induced Liver Toxicity1CTD_human