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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:CDK8-ATP8A2

Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CDK8-ATP8A2
FusionPDB ID: 15310
FusionGDB2.0 ID: 15310
HgeneTgene
Gene symbol

CDK8

ATP8A2

Gene ID

1024

51761

Gene namecyclin dependent kinase 8ATPase phospholipid transporting 8A2
SynonymsIDDHBA|K35ATP|ATPIB|CAMRQ4|IB|ML-1
Cytomap

13q12.13

13q12.13

Type of geneprotein-codingprotein-coding
Descriptioncyclin-dependent kinase 8CDK8 protein kinasecell division protein kinase 8mediator complex subunit CDK8mediator of RNA polymerase II transcription subunit CDK8protein kinase K35phospholipid-transporting ATPase IBATPase, aminophospholipid transporter, class I, type 8A, member 2ATPase, aminophospholipid transporter-like, class I, type 8A, member 2P4-ATPase flippase complex alpha subunit ATP8A2probable phospholipid-transporting
Modification date2020031320200329
UniProtAcc

P49336

Q9NTI2

Ensembl transtripts involved in fusion geneENST idsENST00000381527, ENST00000536792, 
ENST00000480323, 
ENST00000491840, 
ENST00000255283, ENST00000381655, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score8 X 5 X 6=24013 X 13 X 7=1183
# samples 915
** MAII scorelog2(9/240*10)=-1.41503749927884
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(15/1183*10)=-2.97941566784391
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)

PubMed: CDK8 [Title/Abstract] AND ATP8A2 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CDK8(26928017)-ATP8A2(26402256), # samples:2
Anticipated loss of major functional domain due to fusion event.CDK8-ATP8A2 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.
CDK8-ATP8A2 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.
CDK8-ATP8A2 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.
CDK8-ATP8A2 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

check buttonFusion gene breakpoints across CDK8 (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 ATP8A2 (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
ChimerDB4ESCATCGA-L5-A8NW-01ACDK8chr13

26928017

+ATP8A2chr13

26402256

+
ChimerDB4ESCATCGA-L5-A8NWCDK8chr13

26928017

+ATP8A2chr13

26402255

+
ChimerDB4ESCATCGA-L5-A8NWCDK8chr13

26928017

+ATP8A2chr13

26402256

+


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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)
ENST00000381527CDK8chr1326928017+ENST00000381655ATP8A2chr1326402256+77139595031846447
ENST00000536792CDK8chr1326928017+ENST00000381655ATP8A2chr1326402256+721045601343447
ENST00000381527CDK8chr1326928017+ENST00000381655ATP8A2chr1326402255+77139595031846447
ENST00000536792CDK8chr1326928017+ENST00000381655ATP8A2chr1326402255+721045601343447

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
ENST00000381527ENST00000381655CDK8chr1326928017+ATP8A2chr1326402256+0.0010044590.9989956
ENST00000536792ENST00000381655CDK8chr1326928017+ATP8A2chr1326402256+0.0008556810.9991443
ENST00000381527ENST00000381655CDK8chr1326928017+ATP8A2chr1326402255+0.0010044590.9989956
ENST00000536792ENST00000381655CDK8chr1326928017+ATP8A2chr1326402255+0.0008556810.9991443

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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

>15310_15310_1_CDK8-ATP8A2_CDK8_chr13_26928017_ENST00000381527_ATP8A2_chr13_26402255_ENST00000381655_length(amino acids)=447AA_BP=152
MDYDFKVKLSSERERVEDLFEYEGCKVGRGTYGHVYKAKRKDGKDDKDYALKQIEGTGISMSACREIALLRELKHPNVISLQKVFLSHAD
RKVWLLFDYAEHDLWHIIKFHRASKANKKPVQLPRGMVKSLLYQILDGIHYLHANWVLHRDLLWFAFVNGFSGQILFERWCIGLYNVIFT
ALPPFTLGIFERSCTQESMLRFPQLYKITQNGEGFNTKVFWGHCINALVHSLILFWFPMKALEHDTVLTSGHATDYLFVGNIVYTYVVVT
VCLKAGLETTAWTKFSHLAVWGSMLTWLVFFGIYSTIWPTIPIAPDMRGQATMVLSSAHFWLGLFLVPTACLIEDVAWRAAKHTCKKTLL

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

>15310_15310_2_CDK8-ATP8A2_CDK8_chr13_26928017_ENST00000381527_ATP8A2_chr13_26402256_ENST00000381655_length(amino acids)=447AA_BP=152
MDYDFKVKLSSERERVEDLFEYEGCKVGRGTYGHVYKAKRKDGKDDKDYALKQIEGTGISMSACREIALLRELKHPNVISLQKVFLSHAD
RKVWLLFDYAEHDLWHIIKFHRASKANKKPVQLPRGMVKSLLYQILDGIHYLHANWVLHRDLLWFAFVNGFSGQILFERWCIGLYNVIFT
ALPPFTLGIFERSCTQESMLRFPQLYKITQNGEGFNTKVFWGHCINALVHSLILFWFPMKALEHDTVLTSGHATDYLFVGNIVYTYVVVT
VCLKAGLETTAWTKFSHLAVWGSMLTWLVFFGIYSTIWPTIPIAPDMRGQATMVLSSAHFWLGLFLVPTACLIEDVAWRAAKHTCKKTLL

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

>15310_15310_3_CDK8-ATP8A2_CDK8_chr13_26928017_ENST00000536792_ATP8A2_chr13_26402255_ENST00000381655_length(amino acids)=447AA_BP=152
MDYDFKVKLSSERERVEDLFEYEGCKVGRGTYGHVYKAKRKDGKDDKDYALKQIEGTGISMSACREIALLRELKHPNVISLQKVFLSHAD
RKVWLLFDYAEHDLWHIIKFHRASKANKKPVQLPRGMVKSLLYQILDGIHYLHANWVLHRDLLWFAFVNGFSGQILFERWCIGLYNVIFT
ALPPFTLGIFERSCTQESMLRFPQLYKITQNGEGFNTKVFWGHCINALVHSLILFWFPMKALEHDTVLTSGHATDYLFVGNIVYTYVVVT
VCLKAGLETTAWTKFSHLAVWGSMLTWLVFFGIYSTIWPTIPIAPDMRGQATMVLSSAHFWLGLFLVPTACLIEDVAWRAAKHTCKKTLL

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

>15310_15310_4_CDK8-ATP8A2_CDK8_chr13_26928017_ENST00000536792_ATP8A2_chr13_26402256_ENST00000381655_length(amino acids)=447AA_BP=152
MDYDFKVKLSSERERVEDLFEYEGCKVGRGTYGHVYKAKRKDGKDDKDYALKQIEGTGISMSACREIALLRELKHPNVISLQKVFLSHAD
RKVWLLFDYAEHDLWHIIKFHRASKANKKPVQLPRGMVKSLLYQILDGIHYLHANWVLHRDLLWFAFVNGFSGQILFERWCIGLYNVIFT
ALPPFTLGIFERSCTQESMLRFPQLYKITQNGEGFNTKVFWGHCINALVHSLILFWFPMKALEHDTVLTSGHATDYLFVGNIVYTYVVVT
VCLKAGLETTAWTKFSHLAVWGSMLTWLVFFGIYSTIWPTIPIAPDMRGQATMVLSSAHFWLGLFLVPTACLIEDVAWRAAKHTCKKTLL

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

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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/chr13:26928017/chr13:26402256)
- 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
CDK8

P49336

ATP8A2

Q9NTI2

FUNCTION: Component of the Mediator complex, a coactivator involved in regulated gene transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional pre-initiation complex with RNA polymerase II and the general transcription factors. Phosphorylates the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAp II), which may inhibit the formation of a transcription initiation complex. Phosphorylates CCNH leading to down-regulation of the TFIIH complex and transcriptional repression. Recruited through interaction with MAML1 to hyperphosphorylate the intracellular domain of NOTCH, leading to its degradation. {ECO:0000269|PubMed:10993082, ECO:0000269|PubMed:15546612, ECO:0000269|PubMed:30905399}.FUNCTION: Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and ensures the maintenance of asymmetric distribution of phospholipids. Phospholipid translocation seems also to be implicated in vesicle formation and in uptake of lipid signaling molecules. Reconstituted to liposomes, the ATP8A2:TMEM30A flippase complex predominantly transports phosphatidylserine (PS) and to a lesser extent phosphatidylethanolamine (PE). Phospholipid translocation is not associated with a countertransport of an inorganic ion or other charged substrate from the cytoplasmic side toward the exoplasm in connection with the phosphorylation from ATP. ATP8A2:TMEM30A may be involved in regulation of neurite outgrowth. Proposed to function in the generation and maintenance of phospholipid asymmetry in photoreceptor disk membranes and neuronal axon membranes. May be involved in vesicle trafficking in neuronal cells. Required for normal visual and auditory function; involved in photoreceptor and inner ear spiral ganglion cell survival. {ECO:0000250|UniProtKB:C7EXK4}.

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
HgeneCDK8chr13:26928017chr13:26402255ENST00000381527+41327_35152.0465.0Nucleotide bindingATP
HgeneCDK8chr13:26928017chr13:26402256ENST00000381527+41327_35152.0465.0Nucleotide bindingATP
TgeneATP8A2chr13:26928017chr13:26402255ENST0000038165526371019_1028893.01189.0Topological domainCytoplasmic
TgeneATP8A2chr13:26928017chr13:26402255ENST0000038165526371050_1063893.01189.0Topological domainExtracellular
TgeneATP8A2chr13:26928017chr13:26402255ENST0000038165526371085_1188893.01189.0Topological domainCytoplasmic
TgeneATP8A2chr13:26928017chr13:26402255ENST000003816552637909_910893.01189.0Topological domainExtracellular
TgeneATP8A2chr13:26928017chr13:26402255ENST000003816552637932_959893.01189.0Topological domainCytoplasmic
TgeneATP8A2chr13:26928017chr13:26402255ENST000003816552637981_997893.01189.0Topological domainExtracellular
TgeneATP8A2chr13:26928017chr13:26402256ENST0000038165526371019_1028893.01189.0Topological domainCytoplasmic
TgeneATP8A2chr13:26928017chr13:26402256ENST0000038165526371050_1063893.01189.0Topological domainExtracellular
TgeneATP8A2chr13:26928017chr13:26402256ENST0000038165526371085_1188893.01189.0Topological domainCytoplasmic
TgeneATP8A2chr13:26928017chr13:26402256ENST000003816552637909_910893.01189.0Topological domainExtracellular
TgeneATP8A2chr13:26928017chr13:26402256ENST000003816552637932_959893.01189.0Topological domainCytoplasmic
TgeneATP8A2chr13:26928017chr13:26402256ENST000003816552637981_997893.01189.0Topological domainExtracellular
TgeneATP8A2chr13:26928017chr13:26402255ENST0000038165526371029_1049893.01189.0TransmembraneHelical
TgeneATP8A2chr13:26928017chr13:26402255ENST0000038165526371064_1084893.01189.0TransmembraneHelical
TgeneATP8A2chr13:26928017chr13:26402255ENST000003816552637911_931893.01189.0TransmembraneHelical
TgeneATP8A2chr13:26928017chr13:26402255ENST000003816552637960_980893.01189.0TransmembraneHelical
TgeneATP8A2chr13:26928017chr13:26402255ENST000003816552637998_1018893.01189.0TransmembraneHelical
TgeneATP8A2chr13:26928017chr13:26402256ENST0000038165526371029_1049893.01189.0TransmembraneHelical
TgeneATP8A2chr13:26928017chr13:26402256ENST0000038165526371064_1084893.01189.0TransmembraneHelical
TgeneATP8A2chr13:26928017chr13:26402256ENST000003816552637911_931893.01189.0TransmembraneHelical
TgeneATP8A2chr13:26928017chr13:26402256ENST000003816552637960_980893.01189.0TransmembraneHelical
TgeneATP8A2chr13:26928017chr13:26402256ENST000003816552637998_1018893.01189.0TransmembraneHelical

- Not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneCDK8chr13:26928017chr13:26402255ENST00000381527+413373_377152.0465.0Compositional biasNote=Poly-Gln
HgeneCDK8chr13:26928017chr13:26402256ENST00000381527+413373_377152.0465.0Compositional biasNote=Poly-Gln
HgeneCDK8chr13:26928017chr13:26402255ENST00000381527+41321_335152.0465.0DomainProtein kinase
HgeneCDK8chr13:26928017chr13:26402256ENST00000381527+41321_335152.0465.0DomainProtein kinase
TgeneATP8A2chr13:26928017chr13:26402255ENST000003816552637116_119893.01189.0Topological domainExtracellular
TgeneATP8A2chr13:26928017chr13:26402255ENST000003816552637141_316893.01189.0Topological domainCytoplasmic
TgeneATP8A2chr13:26928017chr13:26402255ENST0000038165526371_94893.01189.0Topological domainCytoplasmic
TgeneATP8A2chr13:26928017chr13:26402255ENST000003816552637338_364893.01189.0Topological domainExtracellular
TgeneATP8A2chr13:26928017chr13:26402255ENST000003816552637386_887893.01189.0Topological domainCytoplasmic
TgeneATP8A2chr13:26928017chr13:26402256ENST000003816552637116_119893.01189.0Topological domainExtracellular
TgeneATP8A2chr13:26928017chr13:26402256ENST000003816552637141_316893.01189.0Topological domainCytoplasmic
TgeneATP8A2chr13:26928017chr13:26402256ENST0000038165526371_94893.01189.0Topological domainCytoplasmic
TgeneATP8A2chr13:26928017chr13:26402256ENST000003816552637338_364893.01189.0Topological domainExtracellular
TgeneATP8A2chr13:26928017chr13:26402256ENST000003816552637386_887893.01189.0Topological domainCytoplasmic
TgeneATP8A2chr13:26928017chr13:26402255ENST000003816552637120_140893.01189.0TransmembraneHelical
TgeneATP8A2chr13:26928017chr13:26402255ENST000003816552637317_337893.01189.0TransmembraneHelical
TgeneATP8A2chr13:26928017chr13:26402255ENST000003816552637365_385893.01189.0TransmembraneHelical
TgeneATP8A2chr13:26928017chr13:26402255ENST000003816552637888_908893.01189.0TransmembraneHelical
TgeneATP8A2chr13:26928017chr13:26402255ENST00000381655263795_115893.01189.0TransmembraneHelical
TgeneATP8A2chr13:26928017chr13:26402256ENST000003816552637120_140893.01189.0TransmembraneHelical
TgeneATP8A2chr13:26928017chr13:26402256ENST000003816552637317_337893.01189.0TransmembraneHelical
TgeneATP8A2chr13:26928017chr13:26402256ENST000003816552637365_385893.01189.0TransmembraneHelical
TgeneATP8A2chr13:26928017chr13:26402256ENST000003816552637888_908893.01189.0TransmembraneHelical
TgeneATP8A2chr13:26928017chr13:26402256ENST00000381655263795_115893.01189.0TransmembraneHelical


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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 >>>935_CDK8_26928017_ATP8A2_26402256_935_CDK8_26928017_ATP8A2_26402256_ranked_0.pdbCDK82692801726928017ENST00000381655ATP8A2chr1326402256+
MDYDFKVKLSSERERVEDLFEYEGCKVGRGTYGHVYKAKRKDGKDDKDYALKQIEGTGISMSACREIALLRELKHPNVISLQKVFLSHAD
RKVWLLFDYAEHDLWHIIKFHRASKANKKPVQLPRGMVKSLLYQILDGIHYLHANWVLHRDLLWFAFVNGFSGQILFERWCIGLYNVIFT
ALPPFTLGIFERSCTQESMLRFPQLYKITQNGEGFNTKVFWGHCINALVHSLILFWFPMKALEHDTVLTSGHATDYLFVGNIVYTYVVVT
VCLKAGLETTAWTKFSHLAVWGSMLTWLVFFGIYSTIWPTIPIAPDMRGQATMVLSSAHFWLGLFLVPTACLIEDVAWRAAKHTCKKTLL
447


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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.
CDK8_pLDDT.png
all structure
all structure
ATP8A2_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.
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

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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
CDK8
ATP8A2


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 CDK8-ATP8A2


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 CDK8-ATP8A2


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