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Symbol CLU contributors: mct/npt/pgu/shn - updated : 08-06-2016
HGNC name clusterin
HGNC id 2095
Location 8p21.1      Physical location : 27.454.450 - 27.472.327
Synonym name
  • clusterin (complement lysis inhibitor, SP-40,40, sulfated glycoprotein 2, testosterone-repressed prostate message 2, apolipoprotein J
  • apolipoprotein J
  • complement lysis inhibitor
  • complement cytolysis inhibitor
  • sulfated glycoprotein 2
  • testosterone-repressed prostate message 2
  • aging-associated protein 4
  • complement-associated protein SP-40,40
  • ku70-binding protein 1
  • Synonym symbol(s) APOJ, APO-J, CLI, SGP2, SP40, SP-40, KUPB1, TRPM2, TRPM-2, XIP8, SGP-2, AAG4, KUB1, MGC24903, AAG4, NA1/NA2, KUB1, sCLU
    TYPE functioning gene
    STRUCTURE 14.52 kb     9 Exon(s)    1 Copie(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    text structure
  • region between -218 and -106 bp, contains a particular heat-shock element, named CLE for 'clusterin element', bound by HSF1 (heat-shock factor 1) and HSF2 upon proteasome inhibition
  • a non-canonical E-box (NCE-box) motif in the proximal upstream region within the clusterin promoter is necessary for insulin-stimulated hepatic expression of clusterin via SREBF1
  • MAPPING cloned Y linked N status confirmed
    Map pter - D8S382 - D8S1839 - CLU - D8S1820 - D8S1809 - cen
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 splicing 2877 70 449 - 2010 20028970
  • lacking exon 2
  • coding for the longest product
  • secreted isoform, glycosylated presecretory form (psCLU)
  • has a cytoprotective and chaperone role
  • anti-apoptotic secreted form
  • psCLU form of CLU has regulatory activity on NF-kappaB
  • 8 splicing 2871 - - - -
    transcript variant 4, non-coding RNA.
    9 splicing 3012 - - - -
    transcript variant 3, non-coding RNA
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
     spinal cord    
    Reproductivemale systemtestis   
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier liningretinal pigment epithelium (RPE)  
    SystemCellPubmedSpeciesStageRna symbol
    cell lineage
    cell lines
    at STAGE
    physiological period
    cell cycle     cell cycle
  • C-terminal coiled-coil domain with Ku70 binding activity
  • DeltaCLU domain involved in NF-kappaB pathway regulation
  • secondary structure a CLUSTERIN alpha chain, a CLUSTERIN beta chain
    conjugated GlycoP , LipoP
    mono polymer heteromer , dimer
    interspecies ortholog to Clu, Rattus norvegicus
    ortholog to Clu, Mus musculus
    ortholog to clu, Danio rerio
    ortholog to CLU, Pan troglodytes
  • clusterin family
  • CATEGORY chaperone/stress , antigen , transport carrier
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    basic FUNCTION
  • involved in lipid transport, epithelial cell differentiation, tumorigenesis, and apoptosis
  • potentially involved in spermatogenesis
  • maybe involved in DNA double-strand break repair by end joining (non homologous recombination) V(D)J recombination and apoptosis
  • participating in the terminal complement reaction, serving as a granule constituent in neuronal and endocrine cells
  • recognized as a thyroid autoantigen (70kDa) (G22P1) binding protein
  • playing a protective role against chronic glomerular kidney disease and modifiyng immune complex metabolism and disposal
  • having anti-apoptotic and anti-inflammatory functions in the exocrine pancreas and protective during inflammation of exocrine pancreas
  • may play an important role in hepatocellular metastasis
  • regulates TGF- signaling pathway by modulating the stability of SMAD2/3 proteins
  • limits progression of autoimmune myocarditis and protects the heart from postinflammatory tissue destruction
  • inhibits stress-induced precipitation of a very broad range of structurally divergent protein substrates
  • stabilizes stressed proteins in a state competent for refolding by heat shock protein 70
  • can influence structure, toxicity, and accumulation of the amyloid-beta peptide in brain
  • extracellular chaperone that has been functionally implicated in DNA repair, cell-cycle regulation, apoptotic cell death and tumorigenesis
  • potentially represents the only chaperone that regulates protein stability both extra- and intracellularly
  • chaperone-like role for clusterin in facilitating the degradation of ATP7A, ATP7B
  • new role for intracellular clusterin in mediating Cu-ATPase quality control and hence in the normal maintenance of copper homeostasis, and in promoting cell survival in the context of disease
  • involved in the disposal of oxidized/defected material through diseased red blood cells vesiculation
  • clusterin and COMMD1 represent alternative and independent systems regulating Cu-ATPase quality control, and consequently contributing to the maintenance of copper homeostasis
  • novel function for CLU as an inducer of TNF in macrophages and their chemotactic migration, suggesting that CLU has a tumor-promoting effect
  • can stimulate various chemotactic cytokines, including TNF and play a critical role in macrophage chemotaxis
  • glycosylated intracellular CLU forms may act as a redox sensor under oxidative stress conditions
  • glycoprotein involved in various biological processes, including attenuation of complement activity, sperm maturation, apoptosis, and reverse lipid transport
  • activation of prosurvival autophagy by hypoxia in kidney cells requires CLU expression and may be a key cytoprotective mechanism of CLU in the protection of the kidney from hypoxia/ischemia-mediated injury
  • exhibits characteristics of soluble innate immunity receptors, as assessed by its ability to bind some bacteria strains
  • potentiates the phagocytosis of late apoptotic cells by macrophages
  • facilitates apoptotic cell clearance and prevents apoptotic cell-induced autoimmune responses
  • CELLULAR PROCESS cell life, proliferation/growth
    cell life, cell death/apoptosis
    nucleotide, repair, recombination
    PHYSIOLOGICAL PROCESS inflammation , carcinogenesis
    metabolism lipid/lipoprotein
  • hypothalamic CLU-LRP2 axis is a novel anorexigenic signalling pathway that is tightly coupled with long-form leptin receptor-mediated signalling
  • a component
  • antiparallel disulfide-linked heterodimer
    small molecule
  • Glycoprotein 330, gp330
  • paraoxonase
  • amphiphilic C5b-9 complex
  • complement C7, C8 beta, and the b domain of C9
  • type II TGF beta receptor (RII)
  • amyloid-beta (A beta) plaques
  • Abeta1-40
  • Ku70
  • leptin
  • Bax
  • Hrd1/synoviolin
  • alpha-actinin
  • CLU facilitates exchange of glycosyl phosphatidylinositol-linked SPAM1 between reproductive luminal fluids and sperm membranes
  • wild-type TTR and TTR variants V30M and L55P
  • Chibby
  • ATP7A and ATP7B
  • anti-apoptotic Bcl-2 family proteins
  • COMMD1
  • multifunctional extracellular chaperone clusterin is a cathepsin K-binding protein
  • induce the expression of MMP9 in macrophages, and MMP9 is known to be essential for tumor cell migration and invasion
  • binds to apolipoprotein E receptor 2 (LRP8) and very low density lipoprotein receptor (VLDLR) and is internalized by cells expressing either one of these receptors
  • nuclear CLU expression is regulated by direct binding of HIF1A to HRE sites and is epigenetically controlled by methylation of its promoter region
  • sCLU reduces osteoclastogenesis formation by inhibiting the actions of CSF1, thereby suggesting its protective role in bone erosion
  • cell & other
  • altered elastic fibers in aged human skin
    Other CRM1
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in frontal cortex in Alzheimer disease
    constitutional     --low  
    in glomerular diseases causing nephrotic syndrome
    tumoral     --low  
    in pancreatic cancer in progression, in prostate cancer low-and high-grade,
    constitutional     --over  
    in pancreas during the acute phase of pancreatitis
    tumoral     --over  
    n epithelial ovarian cancer appears to be correlated with increased tumor angiogenesis, consistent with the established role of CLU as an oncogene in the biology of ovarian cancer
  • to Alzheimer disease
  • to Fuchs' corneal dystrophy
  • Variant & Polymorphism other
  • polymorphisms increasing the risk of Alzheimer disease
  • SNPs in CLU, in association with APOE epsilon4 homozygotes associated to familial late-onset Alzheimer disease
  • C allele confers a 1.16 greater odds of developing late-onset AD than the T allele, and carriers of this CLU gene risk variant showed a distinct profile of lower white matter integrity that may increase vulnerability to developing AD later in life
  • variant rs11136000 leading to altered coupling between hippocampus and prefrontal cortex during memory processing, providing a neurogenetic mechanism for CLU-associated risk and protection
  • association of CLU (rs17466684) wih Fuchs' corneal dystrophy
  • Candidate gene candidate to be part of a cellular defence mechanism against neurodegenerative diseases associated with misfolded protein accumulation or decrease in proteasome activity
  • CLU CSF levels could serve as a potential marker for Parkinson disease (PD), dementia with Lewy bodies (DLB), differentiation (Significantly higher CSF clusterin levels were found in PD and lower in DLB)
  • abnormal sCLU expression associated with tumor progression could be a potential diagnostic and prognostic biomarker for hepatocellular carcinoma
  • circulating clusterin level may be a surrogate marker for obesity-associated systemic inflammation
  • seminal clusterin can be considered as a marker for the quick assessment of semen quality in male infertility studies
  • Therapy target
    possibility of using clusterin as a therapeutic agent for TTR amyloidosis
    targeting CLU could represent a promising therapeutic strategy in association with antiestrogen treatment in breast cancer patients
    protects against in vitro amyloid-beta (1-40) neurotoxicity
    may be a therapeutic target to modulate non-caspase-dependent neuronal death following acute brain injury
  • depletion of endogenous nCLU protein using siRNA specific to its truncated mRNA increased clonogenic survival of ionizing radiation (IR)-exposed cells
  • Inflammatory lesions were more diffuse and extensive in apoJ-deficient mice and inflammation was more severe, mice exhibited cardiac function impairment and severe myocardial scarring
  • Clusterin-deficient mice had 50% less brain injury following neonatal hypoxic-ischemic
  • apoE(-/-)/clusterin(-/-) mice had earlier age-dependent Abeta and markedly increased Abeta and amyloid deposition and elevated CSF and brain interstitial fluid Abeta
  • Clu(-/-) mice develop symptoms of autoimmunity, including the generation of anti-dsDNA antibodies, deposition of immunoglobulins and complement components within kidneys, and splenomegaly