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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:NCL-CLU (FusionGDB2 ID:HG4691TG1191)

Fusion Gene Summary for NCL-CLU

check button Fusion gene summary
Fusion gene informationFusion gene name: NCL-CLU
Fusion gene ID: hg4691tg1191
HgeneTgene
Gene symbol

NCL

CLU

Gene ID

4691

1191

Gene namenucleolinclusterin
SynonymsC23|Nsr1AAG4|APO-J|APOJ|CLI|CLU1|CLU2|KUB1|NA1/NA2|SGP-2|SGP2|SP-40|TRPM-2|TRPM2
Cytomap('NCL')('CLU')

2q37.1

8p21.1

Type of geneprotein-codingprotein-coding
Descriptionnucleolinclusterinaging-associated protein 4apolipoprotein Jcomplement cytolysis inhibitorcomplement lysis inhibitorcomplement-associated protein SP-40,40epididymis secretory sperm binding proteinku70-binding protein 1sulfated glycoprotein 2testosterone-r
Modification date2020031320200327
UniProtAcc

P19338

P10909

Ensembl transtripts involved in fusion geneENST00000322723, 
Fusion gene scores* DoF score25 X 25 X 6=375023 X 24 X 12=6624
# samples 2830
** MAII scorelog2(28/3750*10)=-3.74339186332564
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(30/6624*10)=-4.46466826700344
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 breakpointNCL(232326250)-CLU(27464041), # samples:1
Anticipated loss of major functional domain due to fusion event.NCL-CLU seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF.
NCL-CLU seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
NCL-CLU seems lost the major protein functional domain in Tgene partner, which is a tumor suppressor 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
HgeneNCL

GO:0001525

angiogenesis

16403913

TgeneCLU

GO:0000902

cell morphogenesis

15857407

TgeneCLU

GO:0001774

microglial cell activation

15857407

TgeneCLU

GO:0017038

protein import

24446231

TgeneCLU

GO:0031333

negative regulation of protein complex assembly

22179788|23106396

TgeneCLU

GO:0031334

positive regulation of protein complex assembly

22179788

TgeneCLU

GO:0032760

positive regulation of tumor necrosis factor production

15857407

TgeneCLU

GO:0045429

positive regulation of nitric oxide biosynthetic process

15857407

TgeneCLU

GO:0050821

protein stabilization

11123922|12176985

TgeneCLU

GO:0051131

chaperone-mediated protein complex assembly

17412999

TgeneCLU

GO:0051788

response to misfolded protein

19996109

TgeneCLU

GO:0061077

chaperone-mediated protein folding

11123922

TgeneCLU

GO:0061518

microglial cell proliferation

15857407

TgeneCLU

GO:1900221

regulation of amyloid-beta clearance

24446231

TgeneCLU

GO:1901214

regulation of neuron death

17412999

TgeneCLU

GO:1901216

positive regulation of neuron death

15857407

TgeneCLU

GO:1902430

negative regulation of amyloid-beta formation

12047389|17412999

TgeneCLU

GO:1905907

negative regulation of amyloid fibril formation

22179788



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
ChimerDB4OVTCGA-24-0975NCLchr2

232326250

-CLUchr8

27464041

-


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Fusion Gene ORF analysis for NCL-CLU

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-shiftENST00000322723ENST00000316403NCLchr2

232326250

-CLUchr8

27464041

-
Frame-shiftENST00000322723ENST00000405140NCLchr2

232326250

-CLUchr8

27464041

-
Frame-shiftENST00000322723ENST00000523500NCLchr2

232326250

-CLUchr8

27464041

-
Frame-shiftENST00000322723ENST00000546343NCLchr2

232326250

-CLUchr8

27464041

-
Frame-shiftENST00000322723ENST00000560366NCLchr2

232326250

-CLUchr8

27464041

-

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 NCL-CLU


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)


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Fusion Protein Features for NCL-CLU


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/:232326250/:27464041)
- 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
NCL

P19338

CLU

P10909

FUNCTION: Nucleolin is the major nucleolar protein of growing eukaryotic cells. It is found associated with intranucleolar chromatin and pre-ribosomal particles. It induces chromatin decondensation by binding to histone H1. It is thought to play a role in pre-rRNA transcription and ribosome assembly. May play a role in the process of transcriptional elongation. Binds RNA oligonucleotides with 5'-UUAGGG-3' repeats more tightly than the telomeric single-stranded DNA 5'-TTAGGG-3' repeats. {ECO:0000269|PubMed:10393184}.FUNCTION: [Isoform 1]: Functions as extracellular chaperone that prevents aggregation of non native proteins (PubMed:11123922, PubMed:19535339). Prevents stress-induced aggregation of blood plasma proteins (PubMed:11123922, PubMed:12176985, PubMed:17260971, PubMed:19996109). Inhibits formation of amyloid fibrils by APP, APOC2, B2M, CALCA, CSN3, SNCA and aggregation-prone LYZ variants (in vitro) (PubMed:12047389, PubMed:17412999, PubMed:17407782). Does not require ATP (PubMed:11123922). Maintains partially unfolded proteins in a state appropriate for subsequent refolding by other chaperones, such as HSPA8/HSC70 (PubMed:11123922). Does not refold proteins by itself (PubMed:11123922). Binding to cell surface receptors triggers internalization of the chaperone-client complex and subsequent lysosomal or proteasomal degradation (PubMed:21505792). Protects cells against apoptosis and against cytolysis by complement (PubMed:2780565). Intracellular forms interact with ubiquitin and SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes and promote the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:20068069). Promotes proteasomal degradation of COMMD1 and IKBKB (PubMed:20068069). Modulates NF-kappa-B transcriptional activity (PubMed:12882985). A mitochondrial form suppresses BAX-dependent release of cytochrome c into the cytoplasm and inhibit apoptosis (PubMed:16113678, PubMed:17689225). Plays a role in the regulation of cell proliferation (PubMed:19137541). An intracellular form suppresses stress-induced apoptosis by stabilizing mitochondrial membrane integrity through interaction with HSPA5 (PubMed:22689054). Secreted form does not affect caspase or BAX-mediated intrinsic apoptosis and TNF-induced NF-kappa-B-activity (PubMed:24073260). Secreted form act as an important modulator during neuronal differentiation through interaction with STMN3 (By similarity). Plays a role in the clearance of immune complexes that arise during cell injury (By similarity). {ECO:0000250|UniProtKB:P05371, ECO:0000250|UniProtKB:Q06890, ECO:0000269|PubMed:11123922, ECO:0000269|PubMed:12047389, ECO:0000269|PubMed:12176985, ECO:0000269|PubMed:12882985, ECO:0000269|PubMed:16113678, ECO:0000269|PubMed:17260971, ECO:0000269|PubMed:17407782, ECO:0000269|PubMed:17412999, ECO:0000269|PubMed:17689225, ECO:0000269|PubMed:19137541, ECO:0000269|PubMed:19535339, ECO:0000269|PubMed:19996109, ECO:0000269|PubMed:20068069, ECO:0000269|PubMed:21505792, ECO:0000269|PubMed:22689054, ECO:0000269|PubMed:24073260, ECO:0000269|PubMed:2780565}.; FUNCTION: [Isoform 6]: Does not affect caspase or BAX-mediated intrinsic apoptosis and TNF-induced NF-kappa-B-activity. {ECO:0000269|PubMed:24073260}.; FUNCTION: [Isoform 4]: Does not affect caspase or BAX-mediated intrinsic apoptosis and TNF-induced NF-kappa-B-activity (PubMed:24073260). Promotes cell death through interaction with BCL2L1 that releases and activates BAX (PubMed:21567405). {ECO:0000269|PubMed:21567405, ECO:0000269|PubMed:24073260}.

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 NCL-CLU


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 NCL-CLU


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 NCL-CLU


check button Drugs targeting genes involved in this fusion gene.
(DrugBank Version 5.1.8 2021-05-08)
PartnerGeneUniProtAccDrugBank IDDrug nameDrug activityDrug typeDrug status
TgeneCLUP10909DB14548Zinc sulfate, unspecified formInducerSmall moleculeApproved|Experimental
TgeneCLUP10909DB14548Zinc sulfate, unspecified formInducerSmall moleculeApproved|Experimental
TgeneCLUP10909DB14548Zinc sulfate, unspecified formInducerSmall moleculeApproved|Experimental
TgeneCLUP10909DB14548Zinc sulfate, unspecified formInducerSmall moleculeApproved|Experimental
TgeneCLUP10909DB14548Zinc sulfate, unspecified formInducerSmall moleculeApproved|Experimental
TgeneCLUP10909DB01593ZincSmall moleculeApproved|Investigational
TgeneCLUP10909DB01593ZincSmall moleculeApproved|Investigational
TgeneCLUP10909DB01593ZincSmall moleculeApproved|Investigational
TgeneCLUP10909DB01593ZincSmall moleculeApproved|Investigational
TgeneCLUP10909DB01593ZincSmall moleculeApproved|Investigational
TgeneCLUP10909DB09130CopperSmall moleculeApproved|Investigational
TgeneCLUP10909DB09130CopperSmall moleculeApproved|Investigational
TgeneCLUP10909DB09130CopperSmall moleculeApproved|Investigational
TgeneCLUP10909DB09130CopperSmall moleculeApproved|Investigational
TgeneCLUP10909DB09130CopperSmall moleculeApproved|Investigational
TgeneCLUP10909DB14487Zinc acetateSmall moleculeApproved|Investigational
TgeneCLUP10909DB14487Zinc acetateSmall moleculeApproved|Investigational
TgeneCLUP10909DB14487Zinc acetateSmall moleculeApproved|Investigational
TgeneCLUP10909DB14487Zinc acetateSmall moleculeApproved|Investigational
TgeneCLUP10909DB14487Zinc acetateSmall moleculeApproved|Investigational
TgeneCLUP10909DB14533Zinc chlorideInducerSmall moleculeApproved|Investigational
TgeneCLUP10909DB14533Zinc chlorideInducerSmall moleculeApproved|Investigational
TgeneCLUP10909DB14533Zinc chlorideInducerSmall moleculeApproved|Investigational
TgeneCLUP10909DB14533Zinc chlorideInducerSmall moleculeApproved|Investigational
TgeneCLUP10909DB14533Zinc chlorideInducerSmall moleculeApproved|Investigational

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Related Diseases for NCL-CLU


check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource
HgeneNCLC0151744Myocardial Ischemia1CTD_human
HgeneNCLC0152013Adenocarcinoma of lung (disorder)1CTD_human
TgeneC0022660Kidney Failure, Acute6CTD_human
TgeneC1565662Acute Kidney Insufficiency6CTD_human
TgeneC2609414Acute kidney injury6CTD_human
TgeneC0002395Alzheimer's Disease3CTD_human
TgeneC0011265Presenile dementia3CTD_human
TgeneC0022658Kidney Diseases3CTD_human
TgeneC0276496Familial Alzheimer Disease (FAD)3CTD_human
TgeneC0494463Alzheimer Disease, Late Onset3CTD_human
TgeneC0546126Acute Confusional Senile Dementia3CTD_human
TgeneC0750900Alzheimer's Disease, Focal Onset3CTD_human
TgeneC0750901Alzheimer Disease, Early Onset3CTD_human
TgeneC0013221Drug toxicity2CTD_human
TgeneC0029408Degenerative polyarthritis2CTD_human
TgeneC0041755Adverse reaction to drug2CTD_human
TgeneC0086743Osteoarthrosis Deformans2CTD_human
TgeneC0019193Hepatitis, Toxic1CTD_human
TgeneC0022333Jacksonian Seizure1CTD_human
TgeneC0024141Lupus Erythematosus, Systemic1CTD_human
TgeneC0025202melanoma1CTD_human
TgeneC0027686Pathologic Neovascularization1CTD_human
TgeneC0033578Prostatic Neoplasms1CTD_human
TgeneC0036341Schizophrenia1PSYGENET
TgeneC0036572Seizures1CTD_human
TgeneC0087031Juvenile-Onset Still Disease1CTD_human
TgeneC0149958Complex partial seizures1CTD_human
TgeneC0234533Generalized seizures1CTD_human
TgeneC0234535Clonic Seizures1CTD_human
TgeneC0234985Mental deterioration1CTD_human
TgeneC0242380Libman-Sacks Disease1CTD_human
TgeneC0270824Visual seizure1CTD_human
TgeneC0270844Tonic Seizures1CTD_human
TgeneC0270846Epileptic drop attack1CTD_human
TgeneC0333641Atrophic1CTD_human
TgeneC0338656Impaired cognition1CTD_human
TgeneC0376358Malignant neoplasm of prostate1CTD_human
TgeneC0422850Seizures, Somatosensory1CTD_human
TgeneC0422852Seizures, Auditory1CTD_human
TgeneC0422853Olfactory seizure1CTD_human
TgeneC0422854Gustatory seizure1CTD_human
TgeneC0422855Vertiginous seizure1CTD_human
TgeneC0494475Tonic - clonic seizures1CTD_human
TgeneC0751056Non-epileptic convulsion1CTD_human
TgeneC0751110Single Seizure1CTD_human
TgeneC0751123Atonic Absence Seizures1CTD_human
TgeneC0751494Convulsive Seizures1CTD_human
TgeneC0751495Seizures, Focal1CTD_human
TgeneC0751496Seizures, Sensory1CTD_human
TgeneC0860207Drug-Induced Liver Disease1CTD_human
TgeneC1262760Hepatitis, Drug-Induced1CTD_human
TgeneC1270972Mild cognitive disorder1CTD_human
TgeneC1862939AMYOTROPHIC LATERAL SCLEROSIS 11CTD_human
TgeneC1862941Amyotrophic Lateral Sclerosis, Sporadic1CTD_human
TgeneC3495559Juvenile arthritis1CTD_human
TgeneC3495874Nonepileptic Seizures1CTD_human
TgeneC3658290Drug-Induced Acute Liver Injury1CTD_human
TgeneC3714758Juvenile psoriatic arthritis1CTD_human
TgeneC4048158Convulsions1CTD_human
TgeneC4277682Chemical and Drug Induced Liver Injury1CTD_human
TgeneC4279912Chemically-Induced Liver Toxicity1CTD_human
TgeneC4316903Absence Seizures1CTD_human
TgeneC4317109Epileptic Seizures1CTD_human
TgeneC4317123Myoclonic Seizures1CTD_human
TgeneC4505436Generalized Absence Seizures1CTD_human
TgeneC4551993Amyotrophic Lateral Sclerosis, Familial1CTD_human
TgeneC4552091Polyarthritis, Juvenile, Rheumatoid Factor Negative1CTD_human
TgeneC4704862Polyarthritis, Juvenile, Rheumatoid Factor Positive1CTD_human