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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:DDT-ACPP

Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: DDT-ACPP
FusionPDB ID: 21853
FusionGDB2.0 ID: 21860
HgeneTgene
Gene symbol

DDT

ACPP

Gene ID

100037417

55

Gene nameD-dopachrome tautomerase likeacid phosphatase 3
SynonymsDDT|KB-226F1.25'-NT|ACP-3|ACPP|TM-PAP
Cytomap

22q11.23

3q22.1

Type of geneprotein-codingprotein-coding
DescriptionD-dopachrome decarboxylase-like proteinD-dopachrome decarboxylaseD-dopachrome tautomerase-like proteinPhenylpyruvate tautomerase IIprostatic acid phosphataseTMPaseacid phosphatase, prostateecto-5'-nucleotidaseprostatic acid phosphotasethiamine monophosphatase
Modification date2020031320200313
UniProtAcc

A6NHG4

.
Ensembl transtripts involved in fusion geneENST idsENST00000350608, ENST00000398344, 
ENST00000403754, ENST00000404092, 
ENST00000430101, 
ENST00000489084, 
ENST00000336375, ENST00000351273, 
ENST00000475741, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score10 X 3 X 6=18016 X 8 X 2=256
# samples 1016
** MAII scorelog2(10/180*10)=-0.84799690655495
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(16/256*10)=-0.678071905112638
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)

PubMed: DDT [Title/Abstract] AND ACPP [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)DDT(24315957)-ACPP(132075530), # samples:2
Anticipated loss of major functional domain due to fusion event.DDT-ACPP seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
DDT-ACPP seems lost the major protein functional domain in Tgene partner, which is a cell metabolism gene 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
TgeneACPP

GO:0046085

adenosine metabolic process

18940592


check buttonFusion gene breakpoints across DDT (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 ACPP (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
ChimerDB4PRADTCGA-EJ-A7NH-01ADDTchr22

24315957

-ACPPchr3

132075530

+
ChimerDB4PRADTCGA-EJ-A7NHDDTchr22

24315957

-ACPPchr3

132075530

+


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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)
ENST00000398344DDTchr2224315957-ENST00000351273ACPPchr3132075530+1219454116742208
ENST00000350608DDTchr2224315957-ENST00000475741ACPPchr3132075530+734412119604161
ENST00000404092DDTchr2224315957-ENST00000475741ACPPchr3132075530+88155968751227
ENST00000403754DDTchr2224315957-ENST00000351273ACPPchr3132075530+109432936617193
ENST00000430101DDTchr2224315957-ENST00000351273ACPPchr3132075530+109432936617193

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
ENST00000398344ENST00000351273DDTchr2224315957-ACPPchr3132075530+0.0269939420.973006
ENST00000350608ENST00000475741DDTchr2224315957-ACPPchr3132075530+0.0212120170.97878796
ENST00000404092ENST00000475741DDTchr2224315957-ACPPchr3132075530+0.0086555030.99134445
ENST00000403754ENST00000351273DDTchr2224315957-ACPPchr3132075530+0.0328224970.9671775
ENST00000430101ENST00000351273DDTchr2224315957-ACPPchr3132075530+0.0328224970.9671775

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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

>21853_21853_1_DDT-ACPP_DDT_chr22_24315957_ENST00000350608_ACPP_chr3_132075530_ENST00000475741_length(amino acids)=161AA_BP=97
MPAMPFLELDTNLPANRVPAGLEKRLCAAAASILGKPADRVNVTVRPGLAMALSGSTEPCAQLSISSIGVVGTAEDNRSHSAHFFEFLTK

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

>21853_21853_2_DDT-ACPP_DDT_chr22_24315957_ENST00000398344_ACPP_chr3_132075530_ENST00000351273_length(amino acids)=208AA_BP=112
MGTPSFSSARAVSVPLPAMPFLELDTNLPANRVPAGLEKRLCAAAASILGKPADRVNVTVRPGLAMALSGSTEPCAQLSISSIGVVGTAE
DNRSHSAHFFEFLTKELALGQDREYFVEMYYRNETQHEPYPLMLPGCSPSCPLERFAELVGPVIPQDWSTECMTTNSHQVLKVIFAVAFC

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

>21853_21853_3_DDT-ACPP_DDT_chr22_24315957_ENST00000403754_ACPP_chr3_132075530_ENST00000351273_length(amino acids)=193AA_BP=97
MPAMPFLELDTNLPANRVPAGLEKRLCAAAASILGKPADRVNVTVRPGLAMALSGSTEPCAQLSISSIGVVGTAEDNRSHSAHFFEFLTK
ELALGQDREYFVEMYYRNETQHEPYPLMLPGCSPSCPLERFAELVGPVIPQDWSTECMTTNSHQVLKVIFAVAFCLISAVLMVLLFIHIR

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

>21853_21853_4_DDT-ACPP_DDT_chr22_24315957_ENST00000404092_ACPP_chr3_132075530_ENST00000475741_length(amino acids)=227AA_BP=163
MAAESLKADPRWQHGAQHVEAAVREDLFQEALPAVLKAKDLPPVEPAVKENLKTLMQLFLLAVSVPLPAMPFLELDTNLPANRVPAGLEK
RLCAAAASILGKPADRVNVTVRPGLAMALSGSTEPCAQLSISSIGVVGTAEDNRSHSAHFFEFLTKELALGQDREYFVEMYYRNETQHEP

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

>21853_21853_5_DDT-ACPP_DDT_chr22_24315957_ENST00000430101_ACPP_chr3_132075530_ENST00000351273_length(amino acids)=193AA_BP=97
MPAMPFLELDTNLPANRVPAGLEKRLCAAAASILGKPADRVNVTVRPGLAMALSGSTEPCAQLSISSIGVVGTAEDNRSHSAHFFEFLTK
ELALGQDREYFVEMYYRNETQHEPYPLMLPGCSPSCPLERFAELVGPVIPQDWSTECMTTNSHQVLKVIFAVAFCLISAVLMVLLFIHIR

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

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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/chr22:24315957/chr3:132075530)
- 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
DDT

A6NHG4

.
FUNCTION: May have lyase activity. {ECO:0000305}.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

- 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 >>>347_DDT_24315957_ACPP_132075530_ranked_0.pdbDDT2431595724315957ENST00000351273ACPPchr3132075530+
MAAESLKADPRWQHGAQHVEAAVREDLFQEALPAVLKAKDLPPVEPAVKENLKTLMQLFLLAVSVPLPAMPFLELDTNLPANRVPAGLEK
RLCAAAASILGKPADRVNVTVRPGLAMALSGSTEPCAQLSISSIGVVGTAEDNRSHSAHFFEFLTKELALGQDREYFVEMYYRNETQHEP
227


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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.
DDT_pLDDT.png
all structure
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
DDT
ACPP


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 DDT-ACPP


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 DDT-ACPP


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