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	Fusion Gene Summary
	Fusion Gene Breakpoints
	Tumorigenic MoA (Mechanism of Action) Scenarios of Fusion Geness
	Fusion Genomic Features
	Fusion Gene ORF Annotations
	Fusion Protein Retained/Non-Retained Functional Features
	Fusion Transcript Sequences
	Fusion Protein Sequences
	Personalized Fusion Protein Sequences
	Fusion Gene Expressed Samples
	Related Drugs

Fusion gene:NCL_CLU (FusionGDB2 ID:HG4691TG1191)

Fusion Gene Summary for NCL_CLU

Fusion gene summary

Fusion gene information	Fusion gene name: NCL_CLU
	Fusion gene ID: hg4691tg1191
		Hgene	Tgene
	Gene symbol	NCL	CLU
	Gene ID	4691	1191
	Gene name	nucleolin	clusterin
	Synonyms	C23|Nsr1	AAG4|APO-J|APOJ|CLI|CLU1|CLU2|KUB1|NA1/NA2|SGP-2|SGP2|SP-40|TRPM-2|TRPM2
	Cytomap	2q37.1	8p21.1
	Type of gene	protein-coding	protein-coding
	Description	nucleolin	clusterinaging-associated protein 4apolipoprotein Jcomplement cytolysis inhibitorcomplement lysis inhibitorcomplement-associated protein SP-40,40epididymis secretory sperm binding proteinku70-binding protein 1sulfated glycoprotein 2testosterone-r
	Modification date	20240411	20240305
	UniProtAcc	P19338	P10909
	Ensembl transtripts involved in fusion gene	ENST00000322723,
Fusion gene scores	* DoF score	* DoF score (Degree of Frequency) = # partners X # break points X # disease types 24 X 20 X 28=13440	* DoF score (Degree of Frequency) = # partners X # break points X # disease types 10 X 21 X 18=3780
	# samples	42	30
	** MAII score	** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10) log2(42/13440*10)=-5 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(30/3780*10)=-3.65535182861255 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0
Context	PubMed: NCL [Title/Abstract] AND CLU [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint	NCL(232326250)-CLU(27464041), # samples:1

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Fusion Gene Breakpoints for NCL_CLU

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.

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

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

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 Fusions	Aberrant Chimeric Transcription Factor / Fusion Transcription Factor Activity	Epigenetic Reprogramming / Histone Modifier Dysregulation	Chromatin Remodeling Dysregulation	Condensate-Driven Transcriptional Rewiring / LLP	Promoter / Enhancer Hijacking	Dominant-Negative Antagonism	Cell Cycle / Checkpoint Bypass / RNA Processing Dysregulation	Subcellular Mislocalization / Spatial Dysregulation	Nuclear Body / Sub-organellar Architecture Disruption & Differentiation Blockade

* Strict version: Restricted to high- or medium-confidence fusion-specific evidence.

Fusion Gene Name

Mechanism Category

Mechanism PubMed

Tumorigenic Scenarios

Tumorigenic Scenario PubMed

Targeting Points

Targeting PubMed

Mechanism Background

Mechanism Background PubMed

* Extended version: Includes all strict-level fusion evidence plus broader gene-, pathway-, and low-confidence contextual evidence.

Fusion Gene Name

Mechanism Category

Mechanism PubMed

Tumorigenic Scenarios

Tumorigenic Scenario PubMed

Targeting Points

Targeting PubMed

Mechanism Background

Mechanism Background PubMed

Main function of each fusion partner protein. (from UniProt)

Hgene	Tgene
NCL P19338	CLU P10909

Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez

Partner	Gene	GO ID	GO term	PubMed ID
Hgene	NCL	GO:0001525	angiogenesis	16403913
Tgene	CLU	GO:0000902	cell morphogenesis	15857407
Tgene	CLU	GO:0001774	microglial cell activation	15857407
Tgene	CLU	GO:0017038	protein import	24446231
Tgene	CLU	GO:0031333	negative regulation of protein-containing complex assembly	22179788|23106396
Tgene	CLU	GO:0031334	positive regulation of protein-containing complex assembly	22179788
Tgene	CLU	GO:0032760	positive regulation of tumor necrosis factor production	15857407
Tgene	CLU	GO:0045429	positive regulation of nitric oxide biosynthetic process	15857407
Tgene	CLU	GO:0050821	protein stabilization	11123922|12176985
Tgene	CLU	GO:0051131	chaperone-mediated protein complex assembly	17412999
Tgene	CLU	GO:0051788	response to misfolded protein	19996109
Tgene	CLU	GO:0061077	chaperone-mediated protein folding	11123922
Tgene	CLU	GO:0061518	microglial cell proliferation	15857407
Tgene	CLU	GO:0061740	protein targeting to lysosome involved in chaperone-mediated autophagy	9228033
Tgene	CLU	GO:1900221	regulation of amyloid-beta clearance	24446231
Tgene	CLU	GO:1902430	negative regulation of amyloid-beta formation	12047389|17412999
Tgene	CLU	GO:1905907	negative regulation of amyloid fibril formation	22179788

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Fusion Genomic Features for NCL_CLU

FusionAI 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.

Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand	1-p	p (fusion gene breakpoint)
NCL	chr2	232326250	-	CLU	chr8	27464041	-	1.22e-14	1.00e+00

FusionAI 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).

Hgene

Hchr

Hbp

Hstrand

Tgene

Tchr

Tbp

Tstrand

1-p

p (fusion gene breakpoint)

FusionAI 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).

Hgene

Hchr

Hbp

Hstrand

Tgene

Tchr

Tbp

Tstrand

1-p

p (fusion gene breakpoint)

Distribution 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 NCL_CLU

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.

ORFfinder Result Based On The Fusion Transcript Sequences of the In-frame Fusion Genes.

ORFfinder Result Based On The Fusion Transcript Sequences of the 5UTR-3CDS Fusion Genes for N-Truncated Protein Search.

ORFfinder Result Based On The Fusion Transcript Sequences of the 5CDS-3UTR Fusion Genes for C-Truncated Protein Search.

DeepORF 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.

DeepORF Prediction of The Coding Potential Based on The Fusion Transcript Sequence of 5UTR-3CDS Fusion Genes (Potential N-Truncated Proteins).

DeepORF Prediction of The Coding Potential Based on The Fusion Transcript Sequence of 5CDS-3UTR Fusion Genes (Potential C-Truncated Proteins).

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Fusion Protein Retained/Non-Retained Functional Features for NCL_CLU

Protein 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.

- In-frame and retained protein feature among the 13 regional features (visualization across fusion protein length).

- In-frame and not-retained protein feature among the 13 regional features.

- Retained PPIs in in-frame fusion.

Partner

Hgene

Hbp

Tgene

Tbp

ENST

UniProt

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Still interaction with

- Lost PPIs in in-frame fusion.

Partner

Hgene

Hbp

Tgene

Tbp

ENST

UniProt

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Interaction lost with

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Fusion Transcript Sequence for NCL_CLU

In-frame Fusion Transcript Sequences.

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

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

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Fusion Protein Sequence for NCL_CLU

In-frame Fusion Protein Sequences.

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

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

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Personalized Fusion Protein Sequence for NCL_CLU

TCGA Kinase/DNA-binding Domain Mutated Fusion Protein Sequences

CCLE Kinase/DNA-binding Domain Mutated Fusion Protein Sequences

TCGA All Mutated Fusion Protein Sequences

CCLE All Mutated Fusion Protein Sequences

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Fusion Gene Exprssed Samples for NCL_CLU

RNA-seq based fusion gene expressed samples.

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Related Drugs for NCL_CLU

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.

Drugs targeting genes involved in this fusion gene. (DrugBank Version 5.1.8 2021-05-08)