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Center for Computational Systems Medicine
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Fusion Gene Summary

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Fusion Gene ORF analysis

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Fusion Genomic Features

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Fusion Protein Features

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Fusion Gene Sequence

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Fusion Gene PPI analysis

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Related Drugs

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Related Diseases

Fusion gene:CUL3-RWDD3 (FusionGDB2 ID:20669)

Fusion Gene Summary for CUL3-RWDD3

check button Fusion gene summary
Fusion gene informationFusion gene name: CUL3-RWDD3
Fusion gene ID: 20669
HgeneTgene
Gene symbol

CUL3

RWDD3

Gene ID

8452

25950

Gene namecullin 3RWD domain containing 3
SynonymsCUL-3|PHA2ERSUME
Cytomap

2q36.2

1p21.3

Type of geneprotein-codingprotein-coding
Descriptioncullin-3RWD domain-containing protein 3RWD domain-containing sumoylation enhancerRWD-containing sumoylation enhancer
Modification date2020032720200320
UniProtAcc

Q13618

.
Ensembl transtripts involved in fusion geneENST00000264414, ENST00000344951, 
ENST00000409096, ENST00000409777, 
ENST00000432260, 		ENST00000370202, 
ENST00000429514, ENST00000263893, 
ENST00000495272, 
Fusion gene scores* DoF score12 X 12 X 7=10082 X 2 X 2=8
# samples 142
** MAII scorelog2(14/1008*10)=-2.84799690655495
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(2/8*10)=1.32192809488736
Context

PubMed: CUL3 [Title/Abstract] AND RWDD3 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointCUL3(225449660)-RWDD3(95712311), # samples:1
Anticipated loss of major functional domain due to fusion event.CUL3-RWDD3 seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF.
CUL3-RWDD3 seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor 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
HgeneCUL3

GO:0000209

protein polyubiquitination

19261606

HgeneCUL3

GO:0006511

ubiquitin-dependent protein catabolic process

25401743|27561354

HgeneCUL3

GO:0006513

protein monoubiquitination

22358839

HgeneCUL3

GO:0006888

ER to Golgi vesicle-mediated transport

22358839

HgeneCUL3

GO:0016567

protein ubiquitination

17543862|19782033|19995937|20389280|23213400

HgeneCUL3

GO:0031145

anaphase-promoting complex-dependent catabolic process

10500095

HgeneCUL3

GO:0043161

proteasome-mediated ubiquitin-dependent protein catabolic process

19261606|19782033|20389280

HgeneCUL3

GO:0071630

nuclear protein quality control by the ubiquitin-proteasome system

27561354

TgeneRWDD3

GO:0032088

negative regulation of NF-kappaB transcription factor activity

23469069

TgeneRWDD3

GO:0033235

positive regulation of protein sumoylation

23469069

TgeneRWDD3

GO:1902073

positive regulation of hypoxia-inducible factor-1alpha signaling pathway

23469069


check buttonFusion gene breakpoints across CUL3 (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 RWDD3 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

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
ChimerDB4STADTCGA-BR-8364CUL3chr2

225449660

-RWDD3chr1

95712311

+


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Fusion Gene ORF analysis for CUL3-RWDD3

check button Open reading frame (ORF) analsis of fusion genes based on Ensembl gene isoform structure.
* Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser.
ORFHenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrand
Frame-shiftENST00000264414ENST00000370202CUL3chr2

225449660

-RWDD3chr1

95712311

+
5CDS-intronENST00000264414ENST00000429514CUL3chr2

225449660

-RWDD3chr1

95712311

+
5CDS-3UTRENST00000264414ENST00000263893CUL3chr2

225449660

-RWDD3chr1

95712311

+
5CDS-3UTRENST00000264414ENST00000495272CUL3chr2

225449660

-RWDD3chr1

95712311

+
Frame-shiftENST00000344951ENST00000370202CUL3chr2

225449660

-RWDD3chr1

95712311

+
5CDS-intronENST00000344951ENST00000429514CUL3chr2

225449660

-RWDD3chr1

95712311

+
5CDS-3UTRENST00000344951ENST00000263893CUL3chr2

225449660

-RWDD3chr1

95712311

+
5CDS-3UTRENST00000344951ENST00000495272CUL3chr2

225449660

-RWDD3chr1

95712311

+
intron-3CDSENST00000409096ENST00000370202CUL3chr2

225449660

-RWDD3chr1

95712311

+
intron-intronENST00000409096ENST00000429514CUL3chr2

225449660

-RWDD3chr1

95712311

+
intron-3UTRENST00000409096ENST00000263893CUL3chr2

225449660

-RWDD3chr1

95712311

+
intron-3UTRENST00000409096ENST00000495272CUL3chr2

225449660

-RWDD3chr1

95712311

+
intron-3CDSENST00000409777ENST00000370202CUL3chr2

225449660

-RWDD3chr1

95712311

+
intron-intronENST00000409777ENST00000429514CUL3chr2

225449660

-RWDD3chr1

95712311

+
intron-3UTRENST00000409777ENST00000263893CUL3chr2

225449660

-RWDD3chr1

95712311

+
intron-3UTRENST00000409777ENST00000495272CUL3chr2

225449660

-RWDD3chr1

95712311

+
intron-3CDSENST00000432260ENST00000370202CUL3chr2

225449660

-RWDD3chr1

95712311

+
intron-intronENST00000432260ENST00000429514CUL3chr2

225449660

-RWDD3chr1

95712311

+
intron-3UTRENST00000432260ENST00000263893CUL3chr2

225449660

-RWDD3chr1

95712311

+
intron-3UTRENST00000432260ENST00000495272CUL3chr2

225449660

-RWDD3chr1

95712311

+

check buttonORFfinder result based on the fusion transcript sequence of in-frame fusion genes.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)		BP loci
(transcript)		Predicted start
(transcript)		Predicted stop
(transcript)		Seq length
(amino acids)

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 Genomic Features for CUL3-RWDD3


check buttonFusionAI prediction of the potential fusion gene breakpoint based on the pre-mature RNA sequence context (+/- 5kb of individual partner genes, total 20kb length sequence). FusionAI is a fusion gene breakpoint classifier based on convolutional neural network by comparing the fusion positive and negative sequence context of ~ 20K fusion gene data. From here, we can have the relative potentency of the 20K genomic sequence how individual sequnce will be likely used as the gene fusion breakpoints.
HgeneHchrHbpHstrandTgeneTchrTbpTstrand1-pp (fusion gene breakpoint)
CUL3chr2225449660-RWDD3chr195712311+7.00E-080.9999999
CUL3chr2225449660-RWDD3chr195712311+7.00E-080.9999999

check buttonDistribution of 44 human genomic features loci across 20kb length fusion breakpoint regions. We integrated a total of 44 different types of human genomic feature loci information across five big categories including virus integration sites, repeats, structural variants, chromatin states, and gene expression regulation. More details are in help page.

check buttonDistribution of 44 human genomic features loci across 20kb length fusion breakpoint regions that are ovelapped with the top 1% feature importance score regions. More details are in help page.

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Fusion Protein Features for CUL3-RWDD3


check button Go to

FGviewer for the breakpoints of :-:

.
- FGviewer provides the online visualization of the retention search of the protein functional features across DNA, RNA, protein, and pathological levels.
FGviewer

check buttonMain function of each fusion partner protein. (from UniProt)
HgeneTgene
CUL3

Q13618

.
FUNCTION: Core component of multiple cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. BCR complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins (PubMed:27565346). As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1. The functional specificity of the BCR complex depends on the BTB domain-containing protein as the substrate recognition component. BCR(KLHL42) is involved in ubiquitination of KATNA1. BCR(SPOP) is involved in ubiquitination of BMI1/PCGF4, BRMS1, MACROH2A1 and DAXX, GLI2 and GLI3. Can also form a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex containing homodimeric SPOPL or the heterodimer formed by SPOP and SPOPL; these complexes have lower ubiquitin ligase activity. BCR(KLHL9-KLHL13) controls the dynamic behavior of AURKB on mitotic chromosomes and thereby coordinates faithful mitotic progression and completion of cytokinesis. BCR(KLHL12) is involved in ER-Golgi transport by regulating the size of COPII coats, thereby playing a key role in collagen export, which is required for embryonic stem (ES) cells division: BCR(KLHL12) acts by mediating monoubiquitination of SEC31 (SEC31A or SEC31B) (PubMed:22358839, PubMed:27716508). BCR(KLHL3) acts as a regulator of ion transport in the distal nephron; by mediating ubiquitination of WNK4 (PubMed:23387299, PubMed:23453970, PubMed:23576762). The BCR(KLHL20) E3 ubiquitin ligase complex is involved in interferon response and anterograde Golgi to endosome transport: it mediates both ubiquitination leading to degradation and 'Lys-33'-linked ubiquitination (PubMed:20389280, PubMed:21840486, PubMed:21670212, PubMed:24768539). The BCR(KLHL21) E3 ubiquitin ligase complex regulates localization of the chromosomal passenger complex (CPC) from chromosomes to the spindle midzone in anaphase and mediates the ubiquitination of AURKB (PubMed:19995937). The BCR(KLHL22) ubiquitin ligase complex mediates monoubiquitination of PLK1, leading to PLK1 dissociation from phosphoreceptor proteins and subsequent removal from kinetochores, allowing silencing of the spindle assembly checkpoint (SAC) and chromosome segregation (PubMed:23455478). The BCR(KLHL22) ubiquitin ligase complex is also responsible for the amino acid-stimulated 'Lys-48' polyubiquitination and proteasomal degradation of DEPDC5. Through the degradation of DEPDC5, releases the GATOR1 complex-mediated inhibition of the TORC1 pathway (PubMed:29769719). The BCR(KLHL25) ubiquitin ligase complex is involved in translational homeostasis by mediating ubiquitination and subsequent degradation of hypophosphorylated EIF4EBP1 (4E-BP1) (PubMed:22578813). The BCR(KBTBD8) complex acts by mediating monoubiquitination of NOLC1 and TCOF1, leading to remodel the translational program of differentiating cells in favor of neural crest specification (PubMed:26399832). Involved in ubiquitination of cyclin E and of cyclin D1 (in vitro) thus involved in regulation of G1/S transition. Involved in the ubiquitination of KEAP1, ENC1 and KLHL41 (PubMed:15983046). In concert with ATF2 and RBX1, promotes degradation of KAT5 thereby attenuating its ability to acetylate and activate ATM. The BCR(KCTD17) E3 ubiquitin ligase complex mediates ubiquitination and degradation of TCHP, a down-regulator of cilium assembly, thereby inducing ciliogenesis (PubMed:25270598). The BCR(KLHL24) E3 ubiquitin ligase complex mediates ubiquitination of KRT14, controls KRT14 levels during keratinocytes differentiation, and is essential for skin integrity (PubMed:27798626). The BCR(KLHL18) E3 ubiquitin ligase complex mediates the ubiquitination of AURKA leading to its activation at the centrosome which is required for initiating mitotic entry (PubMed:23213400). The BCR(KEAP1) E3 ubiquitin ligase complex acts as a key sensor of oxidative and electrophilic stress by mediating ubiquitination and degradation of NFE2L2/NRF2, a transcription factor regulating expression of many cytoprotective genes (PubMed:15601839, PubMed:16006525). {ECO:0000269|PubMed:10500095, ECO:0000269|PubMed:11311237, ECO:0000269|PubMed:15601839, ECO:0000269|PubMed:15897469, ECO:0000269|PubMed:15983046, ECO:0000269|PubMed:16006525, ECO:0000269|PubMed:16524876, ECO:0000269|PubMed:17543862, ECO:0000269|PubMed:18397884, ECO:0000269|PubMed:19261606, ECO:0000269|PubMed:19995937, ECO:0000269|PubMed:20389280, ECO:0000269|PubMed:21670212, ECO:0000269|PubMed:21840486, ECO:0000269|PubMed:22085717, ECO:0000269|PubMed:22358839, ECO:0000269|PubMed:22578813, ECO:0000269|PubMed:22632832, ECO:0000269|PubMed:23213400, ECO:0000269|PubMed:23387299, ECO:0000269|PubMed:23453970, ECO:0000269|PubMed:23455478, ECO:0000269|PubMed:23576762, ECO:0000269|PubMed:24768539, ECO:0000269|PubMed:25270598, ECO:0000269|PubMed:26399832, ECO:0000269|PubMed:27565346, ECO:0000269|PubMed:27716508, ECO:0000269|PubMed:27798626, ECO:0000269|PubMed:29769719}.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.
- In-frame and retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

- In-frame and not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note


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Fusion Gene Sequence for CUL3-RWDD3


check button For in-frame fusion transcripts, we provide the fusion transcript sequences and fusion amino acid sequences. To have fusion amino acid sequence, we ran ORFfinder and chose the longest ORF among the all predicted ones.

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Fusion Gene PPI Analysis for CUL3-RWDD3


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 (BIOGRID-3.4.160)
HgeneHgene's interactorsTgeneTgene's interactors


check button - Retained PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenStill interaction with


check button - Lost PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


check button - Retained PPIs, but lost function due to frame-shift fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


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Related Drugs for CUL3-RWDD3


check button Drugs targeting genes involved in this fusion gene.
(DrugBank Version 5.1.8 2021-05-08)
PartnerGeneUniProtAccDrugBank IDDrug nameDrug activityDrug typeDrug status

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Related Diseases for CUL3-RWDD3


check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource
HgeneCUL3C0025202melanoma1CTD_human
HgeneCUL3C0033578Prostatic Neoplasms1CTD_human
HgeneCUL3C0376358Malignant neoplasm of prostate1CTD_human
HgeneCUL3C1535926Neurodevelopmental Disorders1CTD_human
HgeneCUL3C3469606PSEUDOHYPOALDOSTERONISM, TYPE IIE1CTD_human;GENOMICS_ENGLAND;UNIPROT