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Center for Computational Systems Medicine level1
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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-Protein Interaction

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Related drugs with this fusion protein

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Related disease with this fusion protein

Fusion Protein:GLS-DIS3L2

Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: GLS-DIS3L2
FusionPDB ID: 33354
FusionGDB2.0 ID: 33354
HgeneTgene
Gene symbol

GLS

DIS3L2

Gene ID

27165

129563

Gene nameglutaminase 2DIS3 like 3'-5' exoribonuclease 2
SynonymsGA|GLS|LGA|hLGAFAM6A|PRLMNS|hDIS3L2
Cytomap

12q13.3

2q37.1

Type of geneprotein-codingprotein-coding
Descriptionglutaminase liver isoform, mitochondrialL-glutamine amidohydrolasebreast cell glutaminaseglutaminase 2 (liver, mitochondrial)glutaminase Iphosphate-activated glutaminasephosphate-dependent glutaminaseDIS3-like exonuclease 2DIS3 mitotic control homolog-like 2family with sequence similarity 6, member A
Modification date2020031320200313
UniProtAcc

Q9UI32

Q8IYB7

Ensembl transtripts involved in fusion geneENST idsENST00000320717, ENST00000338435, 
ENST00000409215, ENST00000409428, 
ENST00000409626, ENST00000471443, 
ENST00000409307, ENST00000409401, 
ENST00000470087, ENST00000360410, 
ENST00000273009, ENST00000325385, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score8 X 8 X 6=3848 X 8 X 6=384
# samples 109
** MAII scorelog2(10/384*10)=-1.94110631094643
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(9/384*10)=-2.09310940439148
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)

PubMed: GLS [Title/Abstract] AND DIS3L2 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)GLS(191746196)-DIS3L2(233028169), # samples:1
Anticipated loss of major functional domain due to fusion event.GLS-DIS3L2 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.
GLS-DIS3L2 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.
GLS-DIS3L2 seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
GLS-DIS3L2 seems lost the major protein functional domain in Hgene 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
TgeneDIS3L2

GO:0010587

miRNA catabolic process

24141620


check buttonFusion gene breakpoints across GLS (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 DIS3L2 (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
ChimerDB4Non-CancerTCGA-HU-A4GC-11AGLSchr2

191746196

+DIS3L2chr2

233028169

+


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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)
ENST00000320717GLSchr2191746196+ENST00000273009DIS3L2chr2233028169+22816442581505415
ENST00000320717GLSchr2191746196+ENST00000325385DIS3L2chr2233028169+29196442582351697
ENST00000338435GLSchr2191746196+ENST00000273009DIS3L2chr2233028169+22746372511498415
ENST00000338435GLSchr2191746196+ENST00000325385DIS3L2chr2233028169+29126372512344697

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
ENST00000320717ENST00000273009GLSchr2191746196+DIS3L2chr2233028169+0.0389668230.9610332
ENST00000320717ENST00000325385GLSchr2191746196+DIS3L2chr2233028169+0.0209017750.9790982
ENST00000338435ENST00000273009GLSchr2191746196+DIS3L2chr2233028169+0.0387583080.96124166
ENST00000338435ENST00000325385GLSchr2191746196+DIS3L2chr2233028169+0.021028080.97897196

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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

>33354_33354_1_GLS-DIS3L2_GLS_chr2_191746196_ENST00000320717_DIS3L2_chr2_233028169_ENST00000273009_length(amino acids)=415AA_BP=129
MMRLRGSGMLRDLLLRSPAGVSATLRRAQPLVTLCRRPRGGGRPAAGPAAAARLHPWWGGGGWPAEPLARGLSSSPSEILQELGKGSTHP
QPGVSPPAAPAAPGPKDGPGETDAFGNSEGKELVASGEKQLAKSLGQAGEIEPETEGILTEYGVDFSDFSSEVLECLPQGLPWTIPPEEF
SKRRDLRKDCIFTIDPSTARDLDDALSCKPLADGNFKVGVHIADVSYFVPEGSDLDKVAAERATSVYLVQKVVPMLPRLLCEELCSLNPM
SDKLTFSVIWTLTPEGKILDEWFGRTIIRSCTKLSYEHAQSMIESPTEKIPAKELPPISPEHSSEEVHQQNADKDGAAHLQASHSPSAED

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

>33354_33354_2_GLS-DIS3L2_GLS_chr2_191746196_ENST00000320717_DIS3L2_chr2_233028169_ENST00000325385_length(amino acids)=697AA_BP=129
MMRLRGSGMLRDLLLRSPAGVSATLRRAQPLVTLCRRPRGGGRPAAGPAAAARLHPWWGGGGWPAEPLARGLSSSPSEILQELGKGSTHP
QPGVSPPAAPAAPGPKDGPGETDAFGNSEGKELVASGEKQLAKSLGQAGEIEPETEGILTEYGVDFSDFSSEVLECLPQGLPWTIPPEEF
SKRRDLRKDCIFTIDPSTARDLDDALSCKPLADGNFKVGVHIADVSYFVPEGSDLDKVAAERATSVYLVQKVVPMLPRLLCEELCSLNPM
SDKLTFSVIWTLTPEGKILDEWFGRTIIRSCTKLSYEHAQSMIESPTEKIPAKELPPISPEHSSEEVHQAVLNLHGIAKQLRQQRFVDGA
LRLDQLKLAFTLDHETGLPQGCHIYEYRESNKLVEEFMLLANMAVAHKIHRAFPEQALLRRHPPPQTRMLSDLVEFCDQMGLPVDFSSAG
ALNKSLTQTFGDDKYSLARKEVLTNMCSRPMQMALYFCSGLLQDPAQFRHYALNVPLYTHFTSPIRRFADVLVHRLLAAALGYRERLDMA
PDTLQKQADHCNDRRMASKRVQELSTSLFFAVLVKESGPLESEAMVMGILKQAFDVLVLRYGVQKRIYCNALALRSHHFQKVGKKPELTL

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

>33354_33354_3_GLS-DIS3L2_GLS_chr2_191746196_ENST00000338435_DIS3L2_chr2_233028169_ENST00000273009_length(amino acids)=415AA_BP=129
MMRLRGSGMLRDLLLRSPAGVSATLRRAQPLVTLCRRPRGGGRPAAGPAAAARLHPWWGGGGWPAEPLARGLSSSPSEILQELGKGSTHP
QPGVSPPAAPAAPGPKDGPGETDAFGNSEGKELVASGEKQLAKSLGQAGEIEPETEGILTEYGVDFSDFSSEVLECLPQGLPWTIPPEEF
SKRRDLRKDCIFTIDPSTARDLDDALSCKPLADGNFKVGVHIADVSYFVPEGSDLDKVAAERATSVYLVQKVVPMLPRLLCEELCSLNPM
SDKLTFSVIWTLTPEGKILDEWFGRTIIRSCTKLSYEHAQSMIESPTEKIPAKELPPISPEHSSEEVHQQNADKDGAAHLQASHSPSAED

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

>33354_33354_4_GLS-DIS3L2_GLS_chr2_191746196_ENST00000338435_DIS3L2_chr2_233028169_ENST00000325385_length(amino acids)=697AA_BP=129
MMRLRGSGMLRDLLLRSPAGVSATLRRAQPLVTLCRRPRGGGRPAAGPAAAARLHPWWGGGGWPAEPLARGLSSSPSEILQELGKGSTHP
QPGVSPPAAPAAPGPKDGPGETDAFGNSEGKELVASGEKQLAKSLGQAGEIEPETEGILTEYGVDFSDFSSEVLECLPQGLPWTIPPEEF
SKRRDLRKDCIFTIDPSTARDLDDALSCKPLADGNFKVGVHIADVSYFVPEGSDLDKVAAERATSVYLVQKVVPMLPRLLCEELCSLNPM
SDKLTFSVIWTLTPEGKILDEWFGRTIIRSCTKLSYEHAQSMIESPTEKIPAKELPPISPEHSSEEVHQAVLNLHGIAKQLRQQRFVDGA
LRLDQLKLAFTLDHETGLPQGCHIYEYRESNKLVEEFMLLANMAVAHKIHRAFPEQALLRRHPPPQTRMLSDLVEFCDQMGLPVDFSSAG
ALNKSLTQTFGDDKYSLARKEVLTNMCSRPMQMALYFCSGLLQDPAQFRHYALNVPLYTHFTSPIRRFADVLVHRLLAAALGYRERLDMA
PDTLQKQADHCNDRRMASKRVQELSTSLFFAVLVKESGPLESEAMVMGILKQAFDVLVLRYGVQKRIYCNALALRSHHFQKVGKKPELTL

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

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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/chr2:191746196/chr2:233028169)
- 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
GLS

Q9UI32

DIS3L2

Q8IYB7

FUNCTION: Plays an important role in the regulation of glutamine catabolism. Promotes mitochondrial respiration and increases ATP generation in cells by catalyzing the synthesis of glutamate and alpha-ketoglutarate. Increases cellular anti-oxidant function via NADH and glutathione production. May play a role in preventing tumor proliferation. {ECO:0000269|PubMed:20378837}.FUNCTION: 3'-5'-exoribonuclease that specifically recognizes RNAs polyuridylated at their 3' end and mediates their degradation. Component of an exosome-independent RNA degradation pathway that mediates degradation of both mRNAs and miRNAs that have been polyuridylated by a terminal uridylyltransferase, such as ZCCHC11/TUT4. Mediates degradation of cytoplasmic mRNAs that have been deadenylated and subsequently uridylated at their 3'. Mediates degradation of uridylated pre-let-7 miRNAs, contributing to the maintenance of embryonic stem (ES) cells. Essential for correct mitosis, and negatively regulates cell proliferation. {ECO:0000255|HAMAP-Rule:MF_03045, ECO:0000269|PubMed:23756462, ECO:0000269|PubMed:24141620}.

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
HgeneGLSchr2:191746196chr2:233028169ENST00000320717+118315_322128.66666666666666670.0RegionHighly mobile activation loop
HgeneGLSchr2:191746196chr2:233028169ENST00000338435+115315_322128.66666666666666599.0RegionHighly mobile activation loop
HgeneGLSchr2:191746196chr2:233028169ENST00000320717+118585_614128.66666666666666670.0RepeatNote=ANK 1
HgeneGLSchr2:191746196chr2:233028169ENST00000320717+118619_648128.66666666666666670.0RepeatNote=ANK 2
HgeneGLSchr2:191746196chr2:233028169ENST00000338435+115585_614128.66666666666666599.0RepeatNote=ANK 1
HgeneGLSchr2:191746196chr2:233028169ENST00000338435+115619_648128.66666666666666599.0RepeatNote=ANK 2


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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
GLS
DIS3L2


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 GLS-DIS3L2


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 GLS-DIS3L2


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