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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:GMDS-PDE8B

Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: GMDS-PDE8B
FusionPDB ID: 33469
FusionGDB2.0 ID: 33469
HgeneTgene
Gene symbol

GMDS

PDE8B

Gene ID

2762

8622

Gene nameGDP-mannose 4,6-dehydratasephosphodiesterase 8B
SynonymsGMD|SDR3E1ADSD|PPNAD3
Cytomap

6p25.3

5q13.3

Type of geneprotein-codingprotein-coding
DescriptionGDP-mannose 4,6 dehydrataseGDP-D-mannose dehydrataseshort chain dehydrogenase/reductase family 3E, member 1high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B3',5' cyclic nucleotide phosphodiesterase 8Bcell proliferation-inducing gene 22 protein
Modification date2020031320200313
UniProtAcc

O60547

O95263

Ensembl transtripts involved in fusion geneENST idsENST00000380815, ENST00000467288, 
ENST00000530927, 
ENST00000264917, 
ENST00000333194, ENST00000342343, 
ENST00000340978, ENST00000346042, 
ENST00000505283, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score28 X 19 X 15=79803 X 3 X 2=18
# samples 323
** MAII scorelog2(32/7980*10)=-4.64024493622235
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(3/18*10)=0.736965594166206
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Context (manual curation of fusion genes in FusionPDB)

PubMed: GMDS [Title/Abstract] AND PDE8B [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.GMDS-PDE8B seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
GMDS-PDE8B seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
GMDS-PDE8B seems lost the major protein functional domain in Tgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
GMDS-PDE8B seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
GMDS-PDE8B 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
HgeneGMDS

GO:0019673

GDP-mannose metabolic process

9525924

HgeneGMDS

GO:0042351

'de novo' GDP-L-fucose biosynthetic process

9525924


check buttonFusion gene breakpoints across GMDS (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 PDE8B (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..GMDSchr6

2245554

-PDE8Bchr5

76722269

+


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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)
ENST00000380815GMDSchr62245554-ENST00000340978PDE8Bchr576722269+134637238481147
ENST00000380815GMDSchr62245554-ENST00000346042PDE8Bchr576722269+134637238481147
ENST00000380815GMDSchr62245554-ENST00000505283PDE8Bchr576722269+212337238481147

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

>33469_33469_1_GMDS-PDE8B_GMDS_chr6_2245554_ENST00000380815_PDE8B_chr5_76722269_ENST00000340978_length(amino acids)=147AA_BP=111
MLGPSGPPWPARPAPGPPCTASRAPLSDCGGRSRGALSLPARSLERRFVLHTPAFLPAPRLPSAALRPAADRTPAAGHGTRTGTLPQRPG

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

>33469_33469_2_GMDS-PDE8B_GMDS_chr6_2245554_ENST00000380815_PDE8B_chr5_76722269_ENST00000346042_length(amino acids)=147AA_BP=111
MLGPSGPPWPARPAPGPPCTASRAPLSDCGGRSRGALSLPARSLERRFVLHTPAFLPAPRLPSAALRPAADRTPAAGHGTRTGTLPQRPG

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

>33469_33469_3_GMDS-PDE8B_GMDS_chr6_2245554_ENST00000380815_PDE8B_chr5_76722269_ENST00000505283_length(amino acids)=147AA_BP=111
MLGPSGPPWPARPAPGPPCTASRAPLSDCGGRSRGALSLPARSLERRFVLHTPAFLPAPRLPSAALRPAADRTPAAGHGTRTGTLPQRPG

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

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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/chr6:/chr5:)
- 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
GMDS

O60547

PDE8B

O95263

FUNCTION: Catalyzes the conversion of GDP-D-mannose to GDP-4-dehydro-6-deoxy-D-mannose. {ECO:0000269|PubMed:9525924}.FUNCTION: Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in specific signaling in the thyroid gland.

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 (10) >>>10.pdbFusion protein BP residue: 111
CIF file (10) >>>10.cif
GMDSchr62245554-PDE8Bchr576722269+
MLGPSGPPWPARPAPGPPCTASRAPLSDCGGRSRGALSLPARSLERRFVL
HTPAFLPAPRLPSAALRPAADRTPAAGHGTRTGTLPQRPGLRGRRDGQAQ
147
3D view using mol* of 10 (AA BP:111)


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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.
GMDS_pLDDT.png
all structure
all structure
PDE8B_pLDDT.png
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.
GMDS_PDE8B_10_pLDDT.png (AA BP:111)
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
GMDS_PDE8B_10.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

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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
GMDSGMDS, TNKS, BLVRB, BAG3, ATIC, CAPN2, CTH, NSFL1C, PTMA, RAP1GDS1, TATDN1, WDYHV1, RNF166, MAT2B, RAB2A, TTC5, NDUFA9, PSMG4, CCDC22, SKA1, Ddb1, Kif2a, Smad3, Rab5c, Tnks, Shoc2, Tnks2, NF2, FBXW7, TNKS2, HIF1AN, NPHP3, ORF17.5, TAE1, TRIM14, EGLN3, EFTUD2, AAR2, PIH1D1, RBX1, BMH2, BMH1, KCNAB3, PLEKHA4, HSPA1B, HSPA8, PAGE4, PPP1R12B, CHD1L, SPRTN,


check button Protein-protein interactors based on sequence similarity (STRING)
GeneSTRING network
GMDSall structure
PDE8Ball 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 GMDS-PDE8B


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 GMDS-PDE8B


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
TgenePDE8BC3280094PIGMENTED NODULAR ADRENOCORTICAL DISEASE, PRIMARY, 32CTD_human;GENOMICS_ENGLAND;UNIPROT
TgenePDE8BC0001627Congenital adrenal hyperplasia1CTD_human
TgenePDE8BC0004782Basal Ganglia Diseases1CTD_human
TgenePDE8BC0013362Dysarthria1CTD_human
TgenePDE8BC0015371Extrapyramidal Disorders1CTD_human
TgenePDE8BC0026837Muscle Rigidity1CTD_human
TgenePDE8BC0151564Cogwheel Rigidity1CTD_human
TgenePDE8BC0231519Gegenhalten1CTD_human
TgenePDE8BC0233608Catatonic Rigidity1CTD_human
TgenePDE8BC0239325Extensor Rigidity1CTD_human
TgenePDE8BC0240952Dysarthria, Scanning1CTD_human
TgenePDE8BC0270715Degenerative Diseases, Central Nervous System1CTD_human
TgenePDE8BC0277821Extrapyramidal Rigidity1CTD_human
TgenePDE8BC0454596Dysarthria, Spastic1CTD_human
TgenePDE8BC0454597Dysarthria, Flaccid1CTD_human
TgenePDE8BC0454598Dysarthria, Mixed1CTD_human
TgenePDE8BC0524851Neurodegenerative Disorders1CTD_human
TgenePDE8BC0750951Lenticulostriate Disorders1CTD_human
TgenePDE8BC0751733Degenerative Diseases, Spinal Cord1CTD_human
TgenePDE8BC1320474Nuchal Rigidity1CTD_human
TgenePDE8BC1563666Dysarthria, Guttural1CTD_human
TgenePDE8BC1836694Striatal Degeneration, Autosomal Dominant1CTD_human;ORPHANET
TgenePDE8BC4304832Primary pigmented nodular adrenocortical disease1ORPHANET