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Center for Computational Systems Medicine
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Fusion Gene Summary

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Fusion Gene Breakpoints

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Tumorigenic MoA (Mechanism of Action) Scenarios of Fusion Geness

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Fusion Genomic Features

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Fusion Gene ORF Annotations

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Fusion Protein Retained/Non-Retained Functional Features

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Fusion Transcript Sequences

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Fusion Protein Sequences

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Personalized Fusion Protein Sequences

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Fusion Gene Expressed Samples

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Related Drugs

Fusion gene:CUL3_RWDD3 (FusionGDB2 ID:HG8452TG25950)

Fusion Gene Summary for CUL3_RWDD3

check button Fusion gene summary
Fusion gene informationFusion gene name: CUL3_RWDD3
Fusion gene ID: hg8452tg25950
HgeneTgene
Gene symbol

CUL3

RWDD3

Gene ID

8452

25950

Gene namecullin 3RWD domain containing 3
SynonymsCUL-3|NEDAUS|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 date2024040720240305
UniProtAcc..
Ensembl transtripts involved in fusion gene
Fusion gene scores* DoF score* DoF score (Degree of Frequency) = # partners X # break points X # disease types
21 X 22 X 16=7392
* DoF score (Degree of Frequency) = # partners X # break points X # disease types
1 X 7 X 5=35
# samples 39114
** MAII score** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10)
log2(39/7392*10)=-4.24441872766645
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10)
log2(114/35*10)=5.02553509210714
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Context

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

Most frequent breakpoint


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Fusion Gene Breakpoints for CUL3_RWDD3


check button RNA-seq based exon junction arranged fusion gene breakpoints from 8 resources (TCGA, CCLE, cBioPortal, GenBank, ChimerDB, ChimerKB, ChildHoodFusions, and GTEx). For the expressed sample information, go to Fusion Gene Sample section.
HgeneHchrHbpTgeneTchrTbp
CUL3chr2225449660RWDD3chr1225449660


check button DNA-seq based exon junction arranged fusion gene breakpoints from dbVar. For the expressed sample information, go to Fusion Gene Sample section.
HgeneHchrHbpTgeneTchrTbpSV type


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Tumorigenic MoA (Mechanism of Action) Scenarios of Fusion Genes for CUL3_RWDD3


check button To generate these tumorigenic scenario annotations, we implemented a deduction-first, retrieval-later computational framework. The pipeline first applies rule-guided reasoning across ten core mechanistic categories (M1–M10) derived from fusion gene biology to infer candidate mechanisms, tumorigenic scenarios, targeting points, and targeting backgrounds. To ensure empirical accountability, a governed Python workflow retrieves literature candidates via NCBI E-utilities and Europe PMC using tiered searches. Using JSON Schema-constrained LLM evidence judges (GPT-5.6 Luna and Terra), retrieved articles are evaluated for specificity and confidence without de novo PMID generation. This produces two distinct versions: a strict version restricted to high- or medium-confidence fusion-specific evidence, and an extended version incorporating broader gene-, pathway-, and contextual evidence.
* We have 10 tumorigenic mechanism categories of fusion genes as shown below.
Constitutively Active Kinases, Catalytic Domain Dysregulation, & Transmembrane Ligand FusionsAberrant Chimeric Transcription Factor / Fusion Transcription Factor ActivityEpigenetic Reprogramming / Histone Modifier DysregulationChromatin Remodeling DysregulationCondensate-Driven Transcriptional Rewiring / LLPPromoter / Enhancer HijackingDominant-Negative AntagonismCell Cycle / Checkpoint Bypass / RNA Processing DysregulationSubcellular Mislocalization / Spatial DysregulationNuclear Body / Sub-organellar Architecture Disruption & Differentiation Blockade

* Strict version: Restricted to high- or medium-confidence fusion-specific evidence.
Fusion Gene NameMechanism CategoryMechanism PubMedTumorigenic ScenariosTumorigenic Scenario PubMedTargeting PointsTargeting PubMedMechanism BackgroundMechanism Background PubMed

* Extended version: Includes all strict-level fusion evidence plus broader gene-, pathway-, and low-confidence contextual evidence.
Fusion Gene NameMechanism CategoryMechanism PubMedTumorigenic ScenariosTumorigenic Scenario PubMedTargeting PointsTargeting PubMedMechanism BackgroundMechanism Background PubMed

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

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

14528312|19261606

HgeneCUL3

GO:0006511

ubiquitin-dependent protein catabolic process

25401743

HgeneCUL3

GO:0006511

ubiquitin-dependent protein catabolic process

27561354

HgeneCUL3

GO:0006513

protein monoubiquitination

22358839

HgeneCUL3

GO:0006888

endoplasmic reticulum 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:0032480

negative regulation of type I interferon production

36394357

HgeneCUL3

GO:0043161

proteasome-mediated ubiquitin-dependent protein catabolic process

19261606|19782033|20389280|23453970|29769719

HgeneCUL3

GO:0051865

protein autoubiquitination

14528312

HgeneCUL3

GO:0070936

protein K48-linked ubiquitination

25684205

HgeneCUL3

GO:0071230

cellular response to amino acid stimulus

29769719

HgeneCUL3

GO:0071630

nuclear protein quality control by the ubiquitin-proteasome system

27561354

HgeneCUL3

GO:1904263

positive regulation of TORC1 signaling

29769719

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


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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) of In-frame fusion genes. 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)


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) of 5UTR-3CSD fusion genes (N-truncated cases).
HgeneHchrHbpHstrandTgeneTchrTbpTstrand1-pp (fusion gene breakpoint)

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) of 5CDS-3UTR fusion genes (C-truncated cases).
HgeneHchrHbpHstrandTgeneTchrTbpTstrand1-pp (fusion gene breakpoint)

check buttonDistribution of six genomic regulatory feature tracks across a ±5 kb window centered on the fusion breakpoints. We input the breakpoint sequences into AlphaGenome and obtained predicted genome tracks at single-base-pair resolution for each modality by running a single forward pass over the reference sequence. Specifically, for each breakpoint, AlphaGenome processed and returned predicted track data across diverse modalities, which were then averaged across all tracks within each output type and visualized across the ±5 kb window. The left panel shows the 5'-gene breakpoint ±5 kb area, and the right panel shows the 3'-gene breakpoint area, with tracks grouped by category: chromatin accessibility (DNase-seq, ATAC-seq), active transcription (RNA-seq, CAGE), and chromatin binding (ChIP-Histone, ChIP-TF).

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Fusion Gene ORF Annotations 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

check buttonORFfinder Result Based On The Fusion Transcript Sequences of the In-frame Fusion Genes.
HenstTenstHgeneHchrHbpTgeneTchrTbpSeq length
(transcript)
Seq length
(peptide)

check buttonORFfinder Result Based On The Fusion Transcript Sequences of the 5UTR-3CDS Fusion Genes for N-Truncated Protein Search.
HenstTenstHgeneHchrHbpTgeneTchrTbpSeq length
(transcript)
Seq length
(peptide)

check buttonORFfinder Result Based On The Fusion Transcript Sequences of the 5CDS-3UTR Fusion Genes for C-Truncated Protein Search.
HenstTenstHgeneHchrHbpTgeneTchrTbpSeq length
(transcript)
Seq length
(peptide)

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.
HenstTenstHgeneHchrHbpTgeneTchrTbpNo-coding scoreCoding score

check buttonDeepORF Prediction of The Coding Potential Based on The Fusion Transcript Sequence of 5UTR-3CDS Fusion Genes (Potential N-Truncated Proteins).
HenstTenstHgeneHchrHbpTgeneTchrTbpNo-coding scoreCoding score

check buttonDeepORF Prediction of The Coding Potential Based on The Fusion Transcript Sequence of 5CDS-3UTR Fusion Genes (Potential C-Truncated Proteins).
HenstTenstHgeneHchrHbpTgeneTchrTbpNo-coding scoreCoding score

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Fusion Protein Retained/Non-Retained Functional Features for CUL3_RWDD3

check buttonProtein Level Annotation from FGviewer
* Retention 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.
fgviewer annotation
- In-frame and retained protein feature among the 13 regional features (visualization across fusion protein length).
No matching images found for ${hg}_${tg}.

- In-frame and retained protein feature among the 13 regional features (texts).
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


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


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


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Fusion Transcript Sequence for CUL3_RWDD3

check button In-frame Fusion Transcript Sequences.

check button N-Truncated Transcript (5UTR-3CDS) Sequences

check button C-Truncated Transcript (5CDS-3UTR) Sequences

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Fusion Protein Sequence for CUL3_RWDD3

check button In-frame Fusion Protein Sequences.

check button N-Truncated Protein (5UTR-3CDS) Sequences

check button C-Truncated Protein (5CDS-3UTR) Sequences

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Personalized Fusion Protein Sequence for CUL3_RWDD3


check button TCGA Kinase/DNA-binding Domain Mutated Fusion Protein Sequences
NumGene GroupDomain LociFusion Protein IDFusion Gene NamePartnerMutated Residue in WT ProteinSeq. LengthMutated Residue in Fusion Protein

check button CCLE Kinase/DNA-binding Domain Mutated Fusion Protein Sequences

NumGene GroupDomain LociFusion Protein IDFusion Gene NamePartnerMutated Residue in WT ProteinSeq. LengthMutated Residue in Fusion Protein

check button TCGA All Mutated Fusion Protein Sequences


Fusion Protein IDSample IDMutated PartnerAAchange in WTSeq. LengthAAchange in Fusion

check button CCLE All Mutated Fusion Protein Sequences


Fusion Protein IDSample IDMutated PartnerAAchange in WTSeq. LengthAAchange in Fusion

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Fusion Gene Exprssed Samples for CUL3_RWDD3


check buttonRNA-seq based fusion gene expressed samples.
SourceStudyDiseaseSampleHgeneHchrHbpHstrandTgeneTchrTbpTstrand
ChimerDBSTADTCGA-BR-8364CUL3

chr2

225449660-RWDD3

chr1

225449660

+

check buttonDNA-seq based fusion gene expressed samples.
SourceStudyDiseaseSampleHgeneHchrHbpHstrandTgeneTchrTbpTstrandSV type


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Related Drugs for CUL3_RWDD3


check button PubMed Abstract Search With ['A-B' AND 'drug'], ['A::B' AND 'drug']
* For more details on the Studied, Reported, Approved Drugs targeting this fusion gene, Go to FusionPub.
PMIDFusion Gene NameDrugStudy Title

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