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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:WDR48-HERC2

Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: WDR48-HERC2
FusionPDB ID: 99012
FusionGDB2.0 ID: 99012
HgeneTgene
Gene symbol

WDR48

HERC2

Gene ID

57599

8924

Gene nameWD repeat domain 48HECT and RLD domain containing E3 ubiquitin protein ligase 2
SynonymsP80|SPG60|UAF1D15F37S1|MRT38|SHEP1|jdf2|p528
Cytomap

3p22.2

15q13.1

Type of geneprotein-codingprotein-coding
DescriptionWD repeat-containing protein 48USP1 associated factor 1WD repeat endosomal proteintesticular tissue protein Li 224E3 ubiquitin-protein ligase HERC2HECT-type E3 ubiquitin transferase HERC2hect domain and RCC1-like domain-containing protein 2hect domain and RLD 2probable E3 ubiquitin-protein ligase HERC2
Modification date2020031320200313
UniProtAcc.

O95714

Ensembl transtripts involved in fusion geneENST idsENST00000302313, ENST00000544962, 
ENST00000396258, ENST00000418020, 
ENST00000466405, 
ENST00000563945, 
ENST00000261609, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score5 X 4 X 2=407 X 8 X 4=224
# samples 58
** MAII scorelog2(5/40*10)=0.321928094887362
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
log2(8/224*10)=-1.48542682717024
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)

PubMed: WDR48 [Title/Abstract] AND HERC2 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)WDR48(39093564)-HERC2(28397976), # samples:2
Anticipated loss of major functional domain due to fusion event.WDR48-HERC2 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.
WDR48-HERC2 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.
WDR48-HERC2 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.
WDR48-HERC2 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
HgeneWDR48

GO:0016579

protein deubiquitination

18082604|19075014|24145035

TgeneHERC2

GO:0006974

cellular response to DNA damage stimulus

22508508

TgeneHERC2

GO:0016567

protein ubiquitination

20304803


check buttonFusion gene breakpoints across WDR48 (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 HERC2 (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
ChimerDB4BLCATCGA-XF-AAMG-01AWDR48chr3

39093564

+HERC2chr15

28397976

-
ChimerDB4BLCATCGA-XF-AAMGWDR48chr3

39093564

+HERC2chr15

28397976

-


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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)
ENST00000302313WDR48chr339093564+ENST00000261609HERC2chr1528397976-4558762838341268
ENST00000544962WDR48chr339093564+ENST00000261609HERC2chr1528397976-4540581038161268

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
ENST00000302313ENST00000261609WDR48chr339093564+HERC2chr1528397976-0.0007169210.99928313
ENST00000544962ENST00000261609WDR48chr339093564+HERC2chr1528397976-0.0007215620.9992785

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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

>99012_99012_1_WDR48-HERC2_WDR48_chr3_39093564_ENST00000302313_HERC2_chr15_28397976_ENST00000261609_length(amino acids)=1268AA_BP=599
MAAHHRQNTAGRRKVQVADMLLELCVTELEDVATDSQSGRLSSQPVVVESSHPYTDDTSTSGTVKIPGAEGLRVEFDRQCSTERRHDPLT
VMDGVNRIVSVRSGREWSDWSSELRIPGDELKWKFISDGSVNGWGWRFTVYPIMPAAGPKELLSDRCVLSCPSMDLVTCLLDFRLNLASN
RSIVPRLAASLAACAQLSALAASHRMWALQRLRKLLTTEFGQSININRLLGENDGETRALSFTGSALAALVKGLPEALQRQFEYEDPIVR
GGKQLLHSPFFKVLVALACDLELDTLPCCAETHKWAWFRRYCMASRVAVALDKRTPLPRLFLDEVAKKIRELMADSENMDVLHESHDIFK
REQDEQLVQWMNRRPDDWTLSAGGSGTIYGWGHNHRGQLGGIEGAKVKVPTPCEALATLRPVQLIGGEQTLFAVTADGKLYATGYGAGGR
LGIGGTESVSTPTLLESIQHVFIKKVAVNSGGKHCLALSSEGEVYSWGEAEDGKLGHGNRSPCDRPRVIESLRGIEVVDVAAGGAHSACV
TAAGDLYTWGKGRYGRLGHSDSEDQLKPKLVEALQGHRVVDIACGSGDAQTLCLTDDDTVWSWGDGDYGKLGRGGSDGCKVPMKIDSLTG
LGVVKVECGSQFSVALTKSGAVYTWGKGDYHRLGHGSDDHVRRPRQVQGLQGKKVIAIATGSLHCVCCTEDGEVYTWGDNDEGQLGDGTT
NAIQRPRLVAALQGKKVNRVACGSAHTLAWSTSKPASAGKLPAQVPMEYNHLQEIPIIALRNRLLLLHHLSELFCPCIPMFDLEGSLDET
GLGPSVGFDTLRGILISQGKEAAFRKVVQATMVRDRQHGPVVELNRIQVKRSRSKGGLAGPDGTKSVFGQMCAKMSSFGPDSLLLPHRVW
KVKFVGESVDDCGGGYSESIAEICEELQNGLTPLLIVTPNGRDESGANRDCYLLSPAARAPVHSSMFRFLGVLLGIAIRTGSPLSLNLAE
PVWKQLAGMSLTIADLSEVDKDFIPGLMYIRDNEATSEEFEAMSLPFTVPSASGQDIQLSSKHTHITLDNRAEYVRLAINYRLHEFDEQV
AAVREGMARVVPVPLLSLFTGYELETMVCGSPDIPLHLLKSVATYKGIEPSASLIQWFWEVMESFSNTERSLFLRFVWGRTRLPRTIADF
RGRDFVIQVLDKYNPPDHFLPESYTCFFLLKLPRYSCKQVLEEKLKYAIHFCKSIDTDDYARIALTGEPAADDSSDDSDNEDVDSFASDS

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>99012_99012_2_WDR48-HERC2_WDR48_chr3_39093564_ENST00000544962_HERC2_chr15_28397976_ENST00000261609_length(amino acids)=1268AA_BP=599
MAAHHRQNTAGRRKVQVADMLLELCVTELEDVATDSQSGRLSSQPVVVESSHPYTDDTSTSGTVKIPGAEGLRVEFDRQCSTERRHDPLT
VMDGVNRIVSVRSGREWSDWSSELRIPGDELKWKFISDGSVNGWGWRFTVYPIMPAAGPKELLSDRCVLSCPSMDLVTCLLDFRLNLASN
RSIVPRLAASLAACAQLSALAASHRMWALQRLRKLLTTEFGQSININRLLGENDGETRALSFTGSALAALVKGLPEALQRQFEYEDPIVR
GGKQLLHSPFFKVLVALACDLELDTLPCCAETHKWAWFRRYCMASRVAVALDKRTPLPRLFLDEVAKKIRELMADSENMDVLHESHDIFK
REQDEQLVQWMNRRPDDWTLSAGGSGTIYGWGHNHRGQLGGIEGAKVKVPTPCEALATLRPVQLIGGEQTLFAVTADGKLYATGYGAGGR
LGIGGTESVSTPTLLESIQHVFIKKVAVNSGGKHCLALSSEGEVYSWGEAEDGKLGHGNRSPCDRPRVIESLRGIEVVDVAAGGAHSACV
TAAGDLYTWGKGRYGRLGHSDSEDQLKPKLVEALQGHRVVDIACGSGDAQTLCLTDDDTVWSWGDGDYGKLGRGGSDGCKVPMKIDSLTG
LGVVKVECGSQFSVALTKSGAVYTWGKGDYHRLGHGSDDHVRRPRQVQGLQGKKVIAIATGSLHCVCCTEDGEVYTWGDNDEGQLGDGTT
NAIQRPRLVAALQGKKVNRVACGSAHTLAWSTSKPASAGKLPAQVPMEYNHLQEIPIIALRNRLLLLHHLSELFCPCIPMFDLEGSLDET
GLGPSVGFDTLRGILISQGKEAAFRKVVQATMVRDRQHGPVVELNRIQVKRSRSKGGLAGPDGTKSVFGQMCAKMSSFGPDSLLLPHRVW
KVKFVGESVDDCGGGYSESIAEICEELQNGLTPLLIVTPNGRDESGANRDCYLLSPAARAPVHSSMFRFLGVLLGIAIRTGSPLSLNLAE
PVWKQLAGMSLTIADLSEVDKDFIPGLMYIRDNEATSEEFEAMSLPFTVPSASGQDIQLSSKHTHITLDNRAEYVRLAINYRLHEFDEQV
AAVREGMARVVPVPLLSLFTGYELETMVCGSPDIPLHLLKSVATYKGIEPSASLIQWFWEVMESFSNTERSLFLRFVWGRTRLPRTIADF
RGRDFVIQVLDKYNPPDHFLPESYTCFFLLKLPRYSCKQVLEEKLKYAIHFCKSIDTDDYARIALTGEPAADDSSDDSDNEDVDSFASDS

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

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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/chr3:39093564/chr15:28397976)
- 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
.HERC2

O95714

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.FUNCTION: E3 ubiquitin-protein ligase that regulates ubiquitin-dependent retention of repair proteins on damaged chromosomes. Recruited to sites of DNA damage in response to ionizing radiation (IR) and facilitates the assembly of UBE2N and RNF8 promoting DNA damage-induced formation of 'Lys-63'-linked ubiquitin chains. Acts as a mediator of binding specificity between UBE2N and RNF8. Involved in the maintenance of RNF168 levels. E3 ubiquitin-protein ligase that promotes the ubiquitination and proteasomal degradation of XPA which influences the circadian oscillation of DNA excision repair activity. By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway (PubMed:26692333). {ECO:0000269|PubMed:20023648, ECO:0000269|PubMed:20304803, ECO:0000269|PubMed:22508508, ECO:0000269|PubMed:26692333}.

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
TgeneHERC2chr3:39093564chr15:28397976ENST0000026160968934457_47943582.04835.0DomainHECT
TgeneHERC2chr3:39093564chr15:28397976ENST0000026160968933951_40023582.04835.0RepeatRCC1 3-1
TgeneHERC2chr3:39093564chr15:28397976ENST0000026160968934004_40563582.04835.0RepeatRCC1 3-2
TgeneHERC2chr3:39093564chr15:28397976ENST0000026160968934058_41083582.04835.0RepeatRCC1 3-3
TgeneHERC2chr3:39093564chr15:28397976ENST0000026160968934110_41623582.04835.0RepeatRCC1 3-4
TgeneHERC2chr3:39093564chr15:28397976ENST0000026160968934164_42143582.04835.0RepeatRCC1 3-5
TgeneHERC2chr3:39093564chr15:28397976ENST0000026160968934216_42663582.04835.0RepeatRCC1 3-6
TgeneHERC2chr3:39093564chr15:28397976ENST0000026160968934268_43183582.04835.0RepeatRCC1 3-7

- Not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneWDR48chr3:39093564chr15:28397976ENST00000302313+119115_15416.0678.0RepeatNote=WD 3
HgeneWDR48chr3:39093564chr15:28397976ENST00000302313+119166_20516.0678.0RepeatNote=WD 4
HgeneWDR48chr3:39093564chr15:28397976ENST00000302313+119208_24716.0678.0RepeatNote=WD 5
HgeneWDR48chr3:39093564chr15:28397976ENST00000302313+119250_28916.0678.0RepeatNote=WD 6
HgeneWDR48chr3:39093564chr15:28397976ENST00000302313+11928_6716.0678.0RepeatNote=WD 1
HgeneWDR48chr3:39093564chr15:28397976ENST00000302313+119292_33416.0678.0RepeatNote=WD 7
HgeneWDR48chr3:39093564chr15:28397976ENST00000302313+119358_39716.0678.0RepeatNote=WD 8
HgeneWDR48chr3:39093564chr15:28397976ENST00000302313+11973_11216.0678.0RepeatNote=WD 2
HgeneWDR48chr3:39093564chr15:28397976ENST00000396258+118115_1540596.0RepeatNote=WD 3
HgeneWDR48chr3:39093564chr15:28397976ENST00000396258+118166_2050596.0RepeatNote=WD 4
HgeneWDR48chr3:39093564chr15:28397976ENST00000396258+118208_2470596.0RepeatNote=WD 5
HgeneWDR48chr3:39093564chr15:28397976ENST00000396258+118250_2890596.0RepeatNote=WD 6
HgeneWDR48chr3:39093564chr15:28397976ENST00000396258+11828_670596.0RepeatNote=WD 1
HgeneWDR48chr3:39093564chr15:28397976ENST00000396258+118292_3340596.0RepeatNote=WD 7
HgeneWDR48chr3:39093564chr15:28397976ENST00000396258+118358_3970596.0RepeatNote=WD 8
HgeneWDR48chr3:39093564chr15:28397976ENST00000396258+11873_1120596.0RepeatNote=WD 2
HgeneWDR48chr3:39093564chr15:28397976ENST00000544962+111115_15416.0403.0RepeatNote=WD 3
HgeneWDR48chr3:39093564chr15:28397976ENST00000544962+111166_20516.0403.0RepeatNote=WD 4
HgeneWDR48chr3:39093564chr15:28397976ENST00000544962+111208_24716.0403.0RepeatNote=WD 5
HgeneWDR48chr3:39093564chr15:28397976ENST00000544962+111250_28916.0403.0RepeatNote=WD 6
HgeneWDR48chr3:39093564chr15:28397976ENST00000544962+11128_6716.0403.0RepeatNote=WD 1
HgeneWDR48chr3:39093564chr15:28397976ENST00000544962+111292_33416.0403.0RepeatNote=WD 7
HgeneWDR48chr3:39093564chr15:28397976ENST00000544962+111358_39716.0403.0RepeatNote=WD 8
HgeneWDR48chr3:39093564chr15:28397976ENST00000544962+11173_11216.0403.0RepeatNote=WD 2
TgeneHERC2chr3:39093564chr15:28397976ENST000002616096893948_9803582.04835.0Coiled coilOntology_term=ECO:0000255
TgeneHERC2chr3:39093564chr15:28397976ENST0000026160968931207_12833582.04835.0DomainCytochrome b5 heme-binding
TgeneHERC2chr3:39093564chr15:28397976ENST0000026160968931859_19323582.04835.0DomainMIB/HERC2
TgeneHERC2chr3:39093564chr15:28397976ENST0000026160968932759_29363582.04835.0DomainDOC
TgeneHERC2chr3:39093564chr15:28397976ENST0000026160968932958_30093582.04835.0RepeatRCC1 2-1
TgeneHERC2chr3:39093564chr15:28397976ENST0000026160968933010_30643582.04835.0RepeatRCC1 2-2
TgeneHERC2chr3:39093564chr15:28397976ENST0000026160968933065_31163582.04835.0RepeatRCC1 2-3
TgeneHERC2chr3:39093564chr15:28397976ENST0000026160968933118_31683582.04835.0RepeatRCC1 2-4
TgeneHERC2chr3:39093564chr15:28397976ENST0000026160968933171_32223582.04835.0RepeatRCC1 2-5
TgeneHERC2chr3:39093564chr15:28397976ENST0000026160968933224_32743582.04835.0RepeatRCC1 2-6
TgeneHERC2chr3:39093564chr15:28397976ENST0000026160968933275_33263582.04835.0RepeatRCC1 2-7
TgeneHERC2chr3:39093564chr15:28397976ENST000002616096893415_4613582.04835.0RepeatRCC1 1-1
TgeneHERC2chr3:39093564chr15:28397976ENST000002616096893462_5123582.04835.0RepeatRCC1 1-2
TgeneHERC2chr3:39093564chr15:28397976ENST000002616096893513_5683582.04835.0RepeatRCC1 1-3
TgeneHERC2chr3:39093564chr15:28397976ENST000002616096893569_6203582.04835.0RepeatRCC1 1-4
TgeneHERC2chr3:39093564chr15:28397976ENST000002616096893623_6743582.04835.0RepeatRCC1 1-5
TgeneHERC2chr3:39093564chr15:28397976ENST000002616096893675_7263582.04835.0RepeatRCC1 1-6
TgeneHERC2chr3:39093564chr15:28397976ENST000002616096893728_7783582.04835.0RepeatRCC1 1-7
TgeneHERC2chr3:39093564chr15:28397976ENST0000026160968932702_27493582.04835.0Zinc fingerZZ-type


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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)


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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.
WDR48_pLDDT.png
all structure
all structure
HERC2_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.


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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
WDR48
HERC2


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 WDR48-HERC2


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 WDR48-HERC2


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