CLU

Summary

CLU (clusterin, HGNC:2095) is a protein-coding gene on chromosome 8p21.1, encoding Clusterin (P10909). Functions as extracellular chaperone that prevents aggregation of non native proteins.

The protein encoded by this gene is a secreted chaperone that can under some stress conditions also be found in the cell cytosol. It has been suggested to be involved in several basic biological events such as cell death, tumor progression, and neurodegenerative disorders. Alternate splicing results in both coding and non-coding variants.

Source: NCBI Gene 1191 — RefSeq curated summary.

At a glance

• GWAS associations: 31
• Clinical variants (ClinVar): 48 total
• Phenotypes (HPO): 1
• MANE Select transcript: NM_001831

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2095
Approved symbol	CLU
Name	clusterin
Location	8p21.1
Locus type	gene with protein product
Status	Approved
Aliases	SGP-2, SP-40, TRPM-2, KUB1, CLU1, CLU2
Ensembl gene	ENSG00000120885
Ensembl biotype	protein_coding
OMIM	185430
Entrez	1191

Gene structure

Transcript identifiers

Ensembl transcripts: 67 — 64 protein_coding, 3 retained_intron

ENST00000316403, ENST00000405140, ENST00000518050, ENST00000519472, ENST00000519742, ENST00000520491, ENST00000520796, ENST00000521770, ENST00000522098, ENST00000522238, ENST00000522299, ENST00000522413, ENST00000522502, ENST00000523396, ENST00000523500, ENST00000523589, ENST00000560566, ENST00000877514, ENST00000877515, ENST00000877516, ENST00000877517, ENST00000877518, ENST00000877519, ENST00000877520, ENST00000877521, ENST00000877522, ENST00000877523, ENST00000877524, ENST00000877525, ENST00000877526, ENST00000877527, ENST00000877528, ENST00000877529, ENST00000877530, ENST00000877531, ENST00000877532, ENST00000877533, ENST00000877534, ENST00000877535, ENST00000877536, ENST00000877537, ENST00000877538, ENST00000877539, ENST00000877540, ENST00000877541, ENST00000877542, ENST00000877543, ENST00000877544, ENST00000877545, ENST00000877546, ENST00000877547, ENST00000877548, ENST00000877549, ENST00000877550, ENST00000877551, ENST00000877552, ENST00000877553, ENST00000877554, ENST00000877555, ENST00000877556, ENST00000877557, ENST00000877558, ENST00000912677, ENST00000967026, ENST00000967027, ENST00000967028, ENST00000967029

RefSeq mRNA: 1 — MANE Select: NM_001831 NM_001831

CCDS: CCDS47832

Canonical transcript exons

ENST00000316403 — 9 exons

Exon	Start	End
ENSE00000818629	27598460	27598635
ENSE00001236166	27599780	27600009
ENSE00001817846	27596917	27598250
ENSE00002108249	27614655	27614700
ENSE00003638747	27608938	27609086
ENSE00003639154	27604291	27604395
ENSE00003673710	27610475	27610600
ENSE00003678973	27604924	27605335
ENSE00003786357	27606354	27606524

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 432.7437 / max 9758.2031, expressed in 1704 samples.

FANTOM5 promoters (39 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92505	397.7267	1693
92502	3.7283	495
92482	2.4253	491
92493	2.2432	472
92476	2.2342	650
92480	2.1952	474
92484	2.0901	501
92486	2.0879	422
92469	2.0701	548
92474	1.8534	558

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lateral globus pallidus	UBERON:0002476	99.99	gold quality
calcaneal tendon	UBERON:0003701	99.99	gold quality
paraflocculus	UBERON:0005351	99.99	gold quality
cranial nerve II	UBERON:0000941	99.98	gold quality
palpebral conjunctiva	UBERON:0001812	99.98	gold quality
prefrontal cortex	UBERON:0000451	99.97	gold quality
right uterine tube	UBERON:0001302	99.97	gold quality
Brodmann (1909) area 10	UBERON:0013541	99.97	gold quality
olfactory bulb	UBERON:0002264	99.96	gold quality
middle frontal gyrus	UBERON:0002702	99.96	gold quality
right frontal lobe	UBERON:0002810	99.96	gold quality
left testis	UBERON:0004533	99.96	gold quality
right testis	UBERON:0004534	99.96	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.96	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.96	gold quality
seminal vesicle	UBERON:0000998	99.95	gold quality
nucleus accumbens	UBERON:0001882	99.95	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.95	gold quality
gall bladder	UBERON:0002110	99.95	gold quality
cerebellar hemisphere	UBERON:0002245	99.95	gold quality
caput epididymis	UBERON:0004358	99.95	gold quality
right adrenal gland	UBERON:0001233	99.94	gold quality
right coronary artery	UBERON:0001625	99.94	gold quality
trigeminal ganglion	UBERON:0001675	99.94	gold quality
putamen	UBERON:0001874	99.94	gold quality
amygdala	UBERON:0001876	99.94	gold quality
cerebellum	UBERON:0002037	99.94	gold quality
cerebellar cortex	UBERON:0002129	99.94	gold quality
postcentral gyrus	UBERON:0002581	99.94	gold quality
frontal pole	UBERON:0002795	99.94	gold quality

Single-cell (SCXA)

Detected in 62 experiment(s), a significant marker in 55.

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	23751.81
E-MTAB-8322	yes	16288.67
E-MTAB-7316	yes	13602.31
E-GEOD-81547	yes	13254.32
E-MTAB-9435	yes	11605.84
E-CURD-126	yes	9770.06
E-HCAD-1	yes	8806.75
E-GEOD-137537	yes	7997.67
E-MTAB-5061	yes	7815.51
E-GEOD-180759	yes	7381.16
E-MTAB-10137	yes	6833.54
E-GEOD-135922	yes	6355.54
E-HCAD-36	yes	6311.79
E-MTAB-7407	yes	6123.37
E-ENAD-27	yes	6062.98

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
CCND1	Activation
FOS	Activation
KLF10	Activation

Upstream regulators (CollecTRI, top): AP1, APBB1, APP, AR, CEBPA, ESR2, FOS, FOSL1, FOSL2, FOXL2, GDNF, HSF1, HSF2, JUN, JUNB, JUND, MYB, MYBL2, MYCN, NFIC, NKX3-1, PAX6, PDX1, SP1, SPI1, STAT1, STAT3, TP53, TWIST1, YBX1

miRNA regulators (miRDB)

73 targeting CLU, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981

Literature-anchored findings (GeneRIF, showing 40)

• Clusterin is a holdase-type extracellular chaperone (PMID:10066740)
• Clusterin has a chaperone action like that of the small heat shock proteins (PMID:10694874)
• The chaperone action of clusterin is ATP-independent (PMID:11123922)
• Introduction of clusterin gene into human renal cell carcinoma cells enhances their resistance to cytotoxic chemotherapy through inhibition of apoptosis both in vitro and in vivo (PMID:11714447)
• expression increases early after androgen withdrawal in prostate cancer; protects tumor cells from apoptosis induced by medical castration (PMID:11813210)
• Apo J senescence-related overexpression is proposed to have antiapoptotic rather than antiproliferative effects. (PMID:11892985)
• The chaperone action of clusterin targets slowly aggregating proteins (PMID:11904161)
• Clusterin (SGP-2) transient overexpression decreases proliferation rate of SV40-immortalized human prostate epithelial cells by slowing down cell cycle progression. (PMID:12082621)
• clusterin may modify the formation of alpha-synuclein-positive inclusion bodies such as Lewy bodies and GCIs, through a previously proposed chaperone property of clusterin (PMID:12172907)
• Low pH activates the chaperone action of clusterin (PMID:12176985)
• clusterin is activated in reduced pH (PMID:12176985)
• role during cellular senescence and tumorigenesis [review] (PMID:12200037)
• The overall pool of clusterin is reduced in glomerular diseases causing nephrotic syndrome, with hypercholesterolemia appearing as the unifying feature (PMID:12427144)
• Authors conclude that clusterin is a marker of anaplastic large cell lymphoma and that addition of clusterin to antibody panels designed to distinguish systemic anaplastic large cell lymphoma from classical Hodgkin’s disease is useful. (PMID:12429802)
• synthesis and functional analysis (PMID:12551933)
• Loss of this protein both in serum and tissue correlates with the tumorigenesis of esophageal squamous cell carcinoma via proteomics approaches. (PMID:12679903)
• clusterin may act as a negative regulator of MT6-MMP in vivo (PMID:12860995)
• apolipoprotein J has a role in inhibiting NF-kappaB signaling through stabilization of IkappaBs; this activity may result in suppression of tumor cell motility (PMID:12882985)
• Clusterin is downregulated in CaP in comparison with matched benign controls (PMID:14618611)
• Clusterin is downregulated during prostate cancer onset and progression, and its upregulation has inhibited DNA synthesis and cell cycle progression. (PMID:15033782)
• Data suggest that the N-terminal deletion of clusterin may be essential for its alterations of biogenesis in esophageal squamous cell carcinoma. (PMID:15133840)
• clusterin is involved in 15d-PGJ(2)-induced nodule formation and cell differentiation in vascular smooth muscle cells (PMID:15158456)
• although CLU is essential for cellular homeostasis, it may become highly cytotoxic in certain cellular contexts when it accumulates in high amounts intracellularly either by direct synthesis or by uptake from the extracellular milieu (PMID:15247015)
• Clusterin staining supports a diagnosis of follicular dendritic cell tumor and helps classify them. (PMID:15252304)
• platelet ADP receptor P2Y(12) and clusterin are downregulated in patients with systemic lupus erythematosus (PMID:15304052)
• findings suggest that clusterin may contribute to conferring resistance to oxidative stress-mediated cellular injury on prostate cancer cells, especially in the presence of androgen (PMID:15389725)
• Nuclear clusterin function is proapoptotic in colon cancer when induced by APC or chemotherapy in the context of p21 expression. (PMID:15492264)
• Calcium deprivation causes translocation of a 45kDa CLU isoform to the nucleus in human prostate epithelial cells, leading to inhibition of cell proliferation and caspase-cascade-dependent anoikis. (PMID:15499376)
• The Ectopic overexpression of the secreted form of clusterin/apoliporotein J the sensitivity of HaCaT cells to toxic effects of ropivacaine as demonstrated by DNA fragmentation. (PMID:15538973)
• The role of clusterin & its isoforms in SMC behavior is complex & chronologically regulated in response to microenvironmental changes. Proliferative arrest reduces s-CLU; apoptosis increases n-CLU. (PMID:15591223)
• CLU may become highly cytostatic and/or cytotoxic if it accumulates intracellularly in high amounts (PMID:15649646)
• Data show that ionizing radiation causes stress-induced activation of insulin-like growth factor-1 receptor-Src-Mek-Erk-Egr-1 signaling that regulates the clusterin pro-survival cascade. (PMID:15689620)
• Clusterin mRNA is increased twofold in early exponential phase of cell proliferation followed by downregulation in the subsequent quiescence phase, whereas it is rapidly increased up to twelvefold upon UV-induced apoptosis. (PMID:15791650)
• Antisense oligonucleotide treatment may improve the outcome of radiation therapy for patients with bladder cancer. (PMID:15809754)
• The 866C–>T polymorphism might be associated with preeclampsia and essential hypertension. (PMID:15925890)
• overexpression of cytoplasmic clusterin might be involved in the tumorigenesis and/or progression of colorctal cancers (PMID:15929184)
• Clusterin is strongly expressed in melanoma. Downregulation of clusterin reduces drug-resistance, i.e., reduces melanoma cell survival in response to cytotoxic drugs. Reducing clusterin may be novel tool to overcome drug-resistance in melanoma. (PMID:15955107)
• Taken together, our results suggest that the elevated level of clusterin in human cancers may promote oncogenic transformation and tumour progression by interfering with Bax pro-apoptotic activities. (PMID:16113678)
• the importance of CLU in various physiological functions including tumour growth–review (PMID:16179938)
• following exposure to sub-lethal amounts of iron-ascorbate to induce an increase in reactive oxygen species generation and lipid peroxidation, a time-dependent up-regulation of clusterin protein and mRNA levels was observed in neuroblastoma cells (PMID:16464517)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	clu	ENSDARG00000010434
mus_musculus	Clu	ENSMUSG00000022037
rattus_norvegicus	Clu	ENSRNOG00000016460

Paralogs (1): CLUL1 (ENSG00000079101)

Protein

Protein identifiers

Clusterin — P10909 (reviewed: P10909)

Alternative names: Aging-associated gene 4 protein, Apolipoprotein J, Complement cytolysis inhibitor, Complement-associated protein SP-40,40, Ku70-binding protein 1, NA1/NA2, Sulfated glycoprotein 2, Testosterone-repressed prostate message 2

All UniProt accessions (11): E5RG36, E5RGB0, E5RH61, E5RJD6, E5RJZ5, E7ERK6, E7ETB4, P10909, H0YAS8, H0YC35, H0YLK8

UniProt curated annotations — full annotation on UniProt →

Function. Functions as extracellular chaperone that prevents aggregation of non native proteins. Prevents stress-induced aggregation of blood plasma proteins. Inhibits formation of amyloid fibrils by APP, APOC2, B2M, CALCA, CSN3, SNCA and aggregation-prone LYZ variants (in vitro). Does not require ATP. Maintains partially unfolded proteins in a state appropriate for subsequent refolding by other chaperones, such as HSPA8/HSC70. Does not refold proteins by itself. Binding to cell surface receptors triggers internalization of the chaperone-client complex and subsequent lysosomal or proteasomal degradation. Protects cells against apoptosis and against cytolysis by complement: inhibits assembly of the complement membrane attack complex (MAC) by preventing polymerization of C9 pore component of the MAC complex. 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. Promotes proteasomal degradation of COMMD1 and IKBKB. Modulates NF-kappa-B transcriptional activity. A mitochondrial form suppresses BAX-dependent release of cytochrome c into the cytoplasm and inhibit apoptosis. Plays a role in the regulation of cell proliferation. An intracellular form suppresses stress-induced apoptosis by stabilizing mitochondrial membrane integrity through interaction with HSPA5. Secreted form does not affect caspase or BAX-mediated intrinsic apoptosis and TNF-induced NF-kappa-B-activity. Secreted form act as an important modulator during neuronal differentiation through interaction with STMN3. Plays a role in the clearance of immune complexes that arise during cell injury. Does not affect caspase or BAX-mediated intrinsic apoptosis and TNF-induced NF-kappa-B-activity. Does not affect caspase or BAX-mediated intrinsic apoptosis and TNF-induced NF-kappa-B-activity. Promotes cell death through interaction with BCL2L1 that releases and activates BAX.

Subunit / interactions. Antiparallel disulfide-linked heterodimer of an alpha chain and a beta chain. Self-associates and forms higher oligomers. Interacts with a broad range of misfolded proteins, including APP, APOC2 and LYZ. Slightly acidic pH promotes interaction with misfolded proteins. Forms high-molecular weight oligomers upon interaction with misfolded proteins. Interacts with APOA1, LRP2, CLUAP1 and PON1. Interacts with the complement membrane attack complex. Interacts (via alpha chain) with XRCC6. Interacts with SYVN1, COMMD1, BTRC, CUL1 and with ubiquitin and SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes. Interacts (via alpha chain) with BAX in stressed cells, where BAX undergoes a conformation change leading to association with the mitochondrial membrane. Does not interact with BAX in unstressed cells. Found in a complex with LTF, CLU, EPPIN and SEMG1. Interacts (immaturely glycosylated pre-secreted form) with HSPA5; this interaction promotes CLU stability and facilitates stress-induced CLU retrotranslocation from the secretory pathway to the mitochondria, thereby reducing stress-induced apoptosis by stabilizing mitochondrial membrane integrity. Interacts (isoform 4) with BCL2L1; this interaction releases and activates BAX and promotes cell death. Interacts with TGFBR2 and ACVR1. Interacts (secreted form) with STMN3; this interaction may act as an important modulator during neuronal differentiation. Interacts with VLDLR and LRP8.

Subcellular location. Secreted Cytoplasm Cytoplasm Nucleus. Cytoplasm. Mitochondrion membrane. Cytosol. Microsome. Endoplasmic reticulum. Mitochondrion. Perinuclear region. Cytoplasmic vesicle. Secretory vesicle. Chromaffin granule.

Tissue specificity. Detected in blood plasma, cerebrospinal fluid, milk, seminal plasma and colon mucosa. Detected in the germinal center of colon lymphoid nodules and in colon parasympathetic ganglia of the Auerbach plexus (at protein level). Ubiquitous. Detected in brain, testis, ovary, liver and pancreas, and at lower levels in kidney, heart, spleen and lung.

Post-translational modifications. Proteolytically cleaved on its way through the secretory system, probably within the Golgi lumen. Proteolytic cleavage is not necessary for its chaperone activity. All non-secreted forms are not proteolytically cleaved. Chaperone activity of uncleaved forms is dependent on a non-reducing environment. Polyubiquitinated, leading to proteasomal degradation. Under cellular stress, the intracellular level of cleaved form is reduced due to proteasomal degradation. Extensively glycosylated with sulfated N-linked carbohydrates. About 30% of the protein mass is comprised of complex N-linked carbohydrate. Endoplasmic reticulum (ER) stress induces changes in glycosylation status and increases level of hypoglycosylated forms. Core carbohydrates are essential for chaperone activity. Non-secreted forms are hypoglycosylated or unglycosylated.

Induction. Up-regulated in response to enterovirus 71 (EV71) infection (at protein level). Up-regulated by agents that induce apoptosis, both at mRNA and protein level. Isoform 1 is up-regulated by androgen. Isoform 2 is down-regulated by androgen.

Miscellaneous. Major isoform. Major isoform. Detectable at protein level in stressed and unstressed cells. Minor isoform that has been detected in a breast cancer cell line, but not in any other tissues or cell lines. Not glycosylated. Not detected in unstressed cells. Detectable at low level in stressed cells. Translated from an unconventional translation initiation site CTG. Not glycosylated. Not detected in unstressed cells. Detectable at low level in stressed cells.

Similarity. Belongs to the clusterin family.

Isoforms (6)

UniProt ID	Names	Canonical?
P10909-1	1, 2, CLU35, sCLU	yes
P10909-2	2, 1, CLU34
P10909-3	3
P10909-4	4, nCLU
P10909-5	5, CLU36
P10909-6	6

RefSeq proteins (1): NP_001822* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000753	Clusterin-like	Family
IPR016014	Clusterin_N	Domain
IPR016015	Clusterin_C	Domain
IPR016016	Clusterin	Family
IPR033986	Clusterin_CS	Conserved_site

Pfam: PF01093

UniProt features (68 total): helix 15, mutagenesis site 8, sequence conflict 8, glycosylation site 6, splice variant 6, disulfide bond 5, strand 5, chain 3, sequence variant 3, turn 3, short sequence motif 2, modified residue 2, signal peptide 1, site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7ZET	X-RAY DIFFRACTION	2.8
7ZEU	X-RAY DIFFRACTION	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P10909-F1	77.11	0.39

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 227–228 (cleavage)

Post-translational modifications (2): 133, 396

Disulfide bonds (5): 102–313, 113–305, 116–302, 121–295, 129–285

Glycosylation sites (6): 103, 145, 291, 354, 374, 86

Mutagenesis-validated functional residues (8):

Position	Phenotype
86	decreases molecular mass of beta chain; when associated with q-103 and q-145.
103	decreases molecular mass of beta chain; when associated with q-86 and q-145.
145	decreases molecular mass of beta chain; when associated with q-86 and q-103.
226	does not affect proteolytic cleavage.
227	affects proteolytic cleavage.
291	decreases molecular mass of alpha chain; when associated with q-354 and q-374. decreases secretion; when associated with
354	decreases molecular mass of alpha chain; when associated with q-291 and q-374. decreases secretion; when associated with
374	decreases molecular mass of alpha chain; when associated with q-291 and q-354. decreases secretion; when associated with

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation
R-HSA-166665	Terminal pathway of complement
R-HSA-6803157	Antimicrobial peptides
R-HSA-977606	Regulation of Complement cascade
R-HSA-9920588	Dengue virus activates/modulates innate and adaptive immune responses

MSigDB gene sets: 598 (showing top): GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, WALLACE_PROSTATE_CANCER_RACE_UP, JI_RESPONSE_TO_FSH_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_LYSOSOMAL_TRANSPORT, KANG_FLUOROURACIL_RESISTANCE_UP, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_INFLAMMATORY_RESPONSE, GOCC_SECRETORY_GRANULE, PEREZ_TP63_TARGETS

GO Biological Process (49): cell morphogenesis (GO:0000902), microglial cell activation (GO:0001774), release of cytochrome c from mitochondria (GO:0001836), negative regulation of activation of membrane attack complex (GO:0001971), immune complex clearance (GO:0002434), protein folding (GO:0006457), lipid metabolic process (GO:0006629), complement activation (GO:0006956), complement activation, classical pathway (GO:0006958), response to virus (GO:0009615), positive regulation of gene expression (GO:0010628), protein import (GO:0017038), negative regulation of protein-containing complex assembly (GO:0031333), positive regulation of protein-containing complex assembly (GO:0031334), central nervous system myelin maintenance (GO:0032286), positive regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032436), positive regulation of tumor necrosis factor production (GO:0032760), regulation of cell population proliferation (GO:0042127), regulation of apoptotic process (GO:0042981), positive regulation of apoptotic process (GO:0043065), negative regulation of neuron apoptotic process (GO:0043524), reverse cholesterol transport (GO:0043691), innate immune response (GO:0045087), positive regulation of nitric oxide biosynthetic process (GO:0045429), negative regulation of complement activation (GO:0045916), positive regulation of receptor-mediated endocytosis (GO:0048260), protein stabilization (GO:0050821), obsolete positive regulation of NF-kappaB transcription factor activity (GO:0051092), chaperone-mediated protein complex assembly (GO:0051131), response to misfolded protein (GO:0051788), microglial cell proliferation (GO:0061518), protein targeting to lysosome involved in chaperone-mediated autophagy (GO:0061740), negative regulation of release of cytochrome c from mitochondria (GO:0090201), intrinsic apoptotic signaling pathway (GO:0097193), amyloid-beta clearance (GO:0097242), regulation of amyloid-beta clearance (GO:1900221), positive regulation of amyloid-beta formation (GO:1902004), negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage (GO:1902230), negative regulation of amyloid-beta formation (GO:1902430), regulation of neuronal signal transduction (GO:1902847)

GO Molecular Function (13): amyloid-beta binding (GO:0001540), signaling receptor binding (GO:0005102), ubiquitin protein ligase binding (GO:0031625), protein-containing complex binding (GO:0044877), receptor ligand activity (GO:0048018), tau protein binding (GO:0048156), low-density lipoprotein particle receptor binding (GO:0050750), obsolete unfolded protein binding (GO:0051082), protein-folding chaperone binding (GO:0051087), misfolded protein binding (GO:0051787), protein sequestering activity (GO:0140311), protein carrier activity (GO:0140597), protein binding (GO:0005515)

GO Cellular Component (28): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), cell surface (GO:0009986), platelet alpha granule lumen (GO:0031093), protein-containing complex (GO:0032991), spherical high-density lipoprotein particle (GO:0034366), chromaffin granule (GO:0042583), intracellular membrane-bounded organelle (GO:0043231), synapse (GO:0045202), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), blood microparticle (GO:0072562), neurofibrillary tangle (GO:0097418), apical dendrite (GO:0097440), perinuclear endoplasmic reticulum lumen (GO:0099020), endoplasmic reticulum (GO:0005783), cytoskeleton (GO:0005856), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), mitochondrial membrane (GO:0031966), cell periphery (GO:0071944)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Complement cascade	2
Response to elevated platelet cytosolic Ca2+	1
Innate Immune System	1
Dengue Virus-Host Interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
protein binding	4
cytoplasm	4
intracellular membrane-bounded organelle	3
immune effector process	2
regulation of protein-containing complex assembly	2
protein-containing complex assembly	2
apoptotic process	2
binding	2
intracellular anatomical structure	2
anatomical structure morphogenesis	1
leukocyte activation involved in inflammatory response	1
macrophage activation	1
glial cell activation	1
apoptotic mitochondrial changes	1
apoptotic signaling pathway	1
activation of membrane attack complex	1
regulation of activation of membrane attack complex	1
negative regulation of complement activation	1
cellular process	1
protein maturation	1
primary metabolic process	1
activation of immune response	1
humoral immune response	1
protein activation cascade	1
humoral immune response mediated by circulating immunoglobulin	1
complement activation	1
response to other organism	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
protein transport	1
negative regulation of cellular component organization	1
positive regulation of cellular component biogenesis	1
positive regulation of cellular component organization	1
central nervous system myelination	1
myelin maintenance	1
regulation of proteasomal ubiquitin-dependent protein catabolic process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
positive regulation of proteasomal protein catabolic process	1

Protein interactions and networks

STRING

3594 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLU	APOE	P02649	998
CLU	APOA1	P02647	994
CLU	LRP2	P98164	987
CLU	PON1	P27169	983
CLU	LTF	P02788	980
CLU	TREM2	Q9NZC2	980
CLU	APP	P05067	964
CLU	VTN	P01141	960
CLU	APOD	P05090	935
CLU	PICALM	Q13492	924
CLU	APOA4	P06727	918
CLU	APOC1	P02654	896
CLU	LRP8	Q14114	893
CLU	LEP	P41159	893
CLU	A2M	P01023	890
CLU	APOA2	P02652	890

IntAct

208 interactions, top by confidence:

A	B	Type	Score
CDK19	MED7	psi-mi:“MI:0914”(association)	0.800
APP	CLU	psi-mi:“MI:0407”(direct interaction)	0.680
SNCA	CLU	psi-mi:“MI:0915”(physical association)	0.660
CLU	SNCA	psi-mi:“MI:0403”(colocalization)	0.660
SNCA	APOA1	psi-mi:“MI:0914”(association)	0.620
APP	CLU	psi-mi:“MI:0915”(physical association)	0.560
CLU	ADCYAP1	psi-mi:“MI:0915”(physical association)	0.540
CLU	ADCYAP1	psi-mi:“MI:0403”(colocalization)	0.540
CLU	CANX	psi-mi:“MI:0914”(association)	0.530
EBNA-LP	HAX1	psi-mi:“MI:0914”(association)	0.530
RYK	PCDH7	psi-mi:“MI:0914”(association)	0.530
HLA-DPA1	TYW5	psi-mi:“MI:0914”(association)	0.530
DDX31	IGLL5	psi-mi:“MI:0914”(association)	0.530
FCGRT	GOLIM4	psi-mi:“MI:0914”(association)	0.530
MMP3	APOE	psi-mi:“MI:0914”(association)	0.530
GARRE1	APOD	psi-mi:“MI:0914”(association)	0.530
METTL17	HSPD1	psi-mi:“MI:0914”(association)	0.530
CLU	FOS	psi-mi:“MI:0915”(physical association)	0.520
CLU	PPARG	psi-mi:“MI:0915”(physical association)	0.520
Stag2	PPP1R12A	psi-mi:“MI:0915”(physical association)	0.400
	CD5L	psi-mi:“MI:0915”(physical association)	0.400
	LECT2	psi-mi:“MI:0915”(physical association)	0.400
	GNAT3	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (403): CLU (Reconstituted Complex), CLU (Affinity Capture-MS), CLU (Affinity Capture-MS), CLU (Affinity Capture-MS), CLU (Affinity Capture-MS), CLU (Affinity Capture-MS), CLU (Affinity Capture-MS), CLU (Affinity Capture-MS), CLU (Affinity Capture-MS), CLU (Affinity Capture-MS), CLU (Affinity Capture-MS), CLU (Affinity Capture-MS), CLU (Affinity Capture-MS), CLU (Affinity Capture-MS), CLU (Affinity Capture-MS)

ESM2 similar proteins: A0A096P2H6, A0A0D9S1R4, A0A1B0GTZ2, A4UZ23, A5A777, A6NFE2, B3IXK1, B8VIX3, D3ZNV2, E2RE76, O46617, O70514, O76061, O88452, O97561, P05371, P0DKU6, P0DKW1, P0DKW3, P0DKY3, P10909, P11682, P14018, P15522, P17697, P25473, P55056, P57679, Q06890, Q15846, Q29482, Q29549, Q3ZRW6, Q3ZRW7, Q3ZRW9, Q5CCK0, Q5E9H1, Q5RAT2, Q5U2T4, Q5ZK77

Diamond homologs: P05371, P10909, P14018, P14683, P17697, P17698, P25473, Q06890, Q29482, Q29549, Q9XSC5, Q15846, Q3ZRW6, Q3ZRW7, Q3ZRW9

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
CLU	“up-regulates activity”	SCF-betaTRCP	binding
CLU	“down-regulates quantity by destabilization”	COMMD1	binding
CLU	“down-regulates quantity by destabilization”	IKBKB	binding
CLU	“up-regulates quantity”	LRP2	binding
GDNF	“up-regulates quantity by expression”	CLU	“transcriptional regulation”
MYBL2	“up-regulates quantity by expression”	CLU	“transcriptional regulation”
SYVN1	“down-regulates quantity by destabilization”	CLU	polyubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 219 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of MAPK cascade	7	10.7×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

48 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	14
Benign	9

Top pathogenic / likely-pathogenic (0)

SpliceAI

1326 predictions. Top by Δscore:

Variant	Effect	Δscore
8:27598454:GCTTA:G	donor_loss	1.0000
8:27598455:CTTA:C	donor_loss	1.0000
8:27598456:TTACC:T	donor_loss	1.0000
8:27598457:T:TA	donor_loss	1.0000
8:27598458:A:AC	donor_gain	1.0000
8:27598459:C:CC	donor_gain	1.0000
8:27598459:C:CG	donor_loss	1.0000
8:27598631:GCCAC:G	acceptor_gain	1.0000
8:27598632:CCAC:C	acceptor_gain	1.0000
8:27598632:CCACC:C	acceptor_gain	1.0000
8:27598633:CAC:C	acceptor_gain	1.0000
8:27598633:CACC:C	acceptor_gain	1.0000
8:27598634:AC:A	acceptor_gain	1.0000
8:27598635:CC:C	acceptor_gain	1.0000
8:27598635:CCT:C	acceptor_loss	1.0000
8:27598636:C:CC	acceptor_gain	1.0000
8:27598636:C:T	acceptor_gain	1.0000
8:27598637:T:A	acceptor_loss	1.0000
8:27598640:A:AC	acceptor_gain	1.0000
8:27598640:A:C	acceptor_gain	1.0000
8:27598646:C:CT	acceptor_gain	1.0000
8:27598647:A:T	acceptor_gain	1.0000
8:27599774:GCTCA:G	donor_loss	1.0000
8:27599775:CTCAC:C	donor_loss	1.0000
8:27599776:TCAC:T	donor_loss	1.0000
8:27599777:CACC:C	donor_loss	1.0000
8:27599778:A:AT	donor_loss	1.0000
8:27599779:C:T	donor_loss	1.0000
8:27599800:A:AC	donor_gain	1.0000
8:27599801:C:CC	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000031306 (8:27604862 C>T), RS1000090414 (8:27611289 C>T), RS1000312240 (8:27608099 G>A), RS1000320853 (8:27613817 T>A), RS1000373120 (8:27614124 G>A,C), RS1000466509 (8:27605123 G>A,C), RS1000787999 (8:27600531 C>A,G,T), RS1000861367 (8:27600756 G>A), RS1001014325 (8:27602952 C>A), RS1001090891 (8:27603289 C>T), RS1001092572 (8:27612572 G>T), RS1001440430 (8:27606173 T>C), RS1001478986 (8:27597610 A>G), RS1001528664 (8:27596760 G>A), RS1001604790 (8:27606247 C>T)

Disease associations

OMIM: gene MIM:185430 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): Alzheimer disease (MONDO:0004975)

Orphanet (2): Early-onset autosomal dominant Alzheimer disease (Orphanet:1020), NON RARE IN EUROPE: Alzheimer disease (Orphanet:238616)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0002511	Alzheimer disease

GWAS associations

31 associations (top):

Study	Trait	p-value
GCST000320_9	Panic disorder	7.000000e-07
GCST000479_1	Alzheimer’s disease	9.000000e-10
GCST000480_1	Alzheimer’s disease	6.000000e-10
GCST001026_4	Alzheimer’s disease (late onset)	8.000000e-08
GCST001087_4	Alzheimer’s disease	4.000000e-08
GCST002245_9	Alzheimer’s disease (late onset)	3.000000e-25
GCST002539_72	Schizophrenia	2.000000e-08
GCST002813_6	Alzheimer’s disease in APOE e4+ carriers	3.000000e-09
GCST002817_11	Alzheimer’s disease in APOE e4- carriers	2.000000e-06
GCST004521_193	Autism spectrum disorder or schizophrenia	3.000000e-09
GCST004744_5	Lung adenocarcinoma	9.000000e-06
GCST004749_23	Lung cancer in ever smokers	2.000000e-07
GCST005549_2	Alzheimer’s disease (late onset)	6.000000e-10
GCST006291_5	Spherical equivalent or myopia (age of diagnosis)	1.000000e-08
GCST006803_90	Schizophrenia	8.000000e-12
GCST007319_21	Alzheimer’s disease (late onset)	1.000000e-18
GCST007319_7	Alzheimer’s disease (late onset)	6.000000e-20
GCST007320_4	Alzheimer’s disease or family history of Alzheimer’s disease	3.000000e-19
GCST007320_53	Alzheimer’s disease or family history of Alzheimer’s disease	7.000000e-17
GCST007321_11	Family history of Alzheimer’s disease	6.000000e-08
GCST007321_19	Family history of Alzheimer’s disease	7.000000e-09
GCST007327_206	Smoking status (ever vs never smokers)	7.000000e-22
GCST007826_3	Alzheimer’s disease or fasting insulin levels (pleiotropy)	1.000000e-17
GCST009021_3	Alzheimer’s disease	6.000000e-15
GCST009405_1	Smoking behaviour (cigarettes smoked per day)	6.000000e-13
GCST009407_1	Smoking behaviour (cigarettes smoked per day)	1.000000e-13
GCST009600_146	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	3.000000e-08
GCST010002_272	Refractive error	3.000000e-16
GCST011703_85	Smoking initiation	2.000000e-20
GCST90012877_22	Alzheimer’s disease or family history of Alzheimer’s disease	8.000000e-26

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:1001870	late-onset Alzheimers disease
EFO:0004847	age at onset
EFO:0009268	family history of Alzheimer’s disease
EFO:0004318	smoking behavior
EFO:0006525	cigarettes per day measurement
EFO:0005670	smoking initiation

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D000544	Alzheimer Disease	C10.228.140.380.100; C10.574.945.249; F03.615.400.100

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — Complement system regulators

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
sotevtamab	Binding	8.35	pKd

CTD chemical–gene interactions

150 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases expression, affects binding, decreases reaction (+1 more)	7
bisphenol A	decreases reaction, increases expression, affects expression	4
Estradiol	affects cotreatment, decreases expression	4
Valproic Acid	affects expression, increases expression	4
trichostatin A	affects expression, decreases reaction, increases expression	3
(+)-JQ1 compound	increases expression	3
Copper	decreases export, increases expression, affects binding, affects cotreatment	3
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	3
Tretinoin	affects cotreatment, increases expression, decreases expression	3
Metribolone	increases expression, affects binding, increases reaction, decreases expression, decreases reaction	3
cobaltous chloride	increases expression	2
bicalutamide	decreases reaction, increases expression	2
entinostat	increases expression, affects cotreatment	2
monomethylarsonous acid	increases expression	2
dimethylarsinous acid	increases expression	2
belinostat	increases reaction, increases expression	2
Decitabine	increases expression, increases reaction, affects cotreatment, decreases methylation	2
Arsenic Trioxide	increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Air Pollutants	increases expression, decreases expression, increases abundance	2
Benzo(a)pyrene	affects methylation	2
Cadmium	increases expression, affects binding	2
Calcitriol	increases expression	2
Cisplatin	increases expression, increases reaction, decreases response to substance	2
Doxorubicin	increases expression, decreases response to substance, decreases reaction	2
Lead	affects methylation, affects expression	2
Nickel	affects binding, affects expression, decreases reaction	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Silicon Dioxide	affects secretion, increases expression	2
Smoke	increases expression, increases abundance	2

Cellosaurus cell lines

21 cell lines: 16 transformed cell line, 5 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B7WP	Abcam Raji CLU KO	Cancer cell line	Male
CVCL_B9X8	Abcam THP-1 CLU KO	Cancer cell line	Male
CVCL_C6Z5	Abcam PC-3 CLU KO	Cancer cell line	Male
CVCL_D4BD	HEK293E_Clu WT	Transformed cell line	Female
CVCL_D4BE	HEK293E_Clu TL1	Transformed cell line	Female
CVCL_D4BF	HEK293E_Clu TL2	Transformed cell line	Female
CVCL_D4BG	HEK293E_Clu TL3	Transformed cell line	Female
CVCL_D4BH	HEK293E_Clu TL2+3	Transformed cell line	Female
CVCL_D4BI	HEK293E_Clu TL4	Transformed cell line	Female
CVCL_D4BJ	HEK293E_Clu CC1	Transformed cell line	Female

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00009191	PHASE4	COMPLETED	The Depression in Alzheimer’s Disease Study (DIADS)
NCT00009217	PHASE4	COMPLETED	Treatment of Behavioral Symptoms in Alzheimer’s Disease
NCT00018278	PHASE4	COMPLETED	Electrophysiologic Measures of Treatment Response in Alzheimer Disease
NCT00035204	PHASE4	COMPLETED	A Study of the Effects on Sleep, Attention, and Gastrointestinal Tolerance of Galantamine and Donepezil in Patients With Alzheimer’s Disease
NCT00042172	PHASE4	COMPLETED	Treatment for Early Memory Loss
NCT00046358	PHASE4	COMPLETED	The Effect of Short-Term Statins and NSAIDs on Levels of Beta-Amyloid, a Protein Associated With Alzheimer’s Disease
NCT00104442	PHASE4	COMPLETED	Study of the Effects of Current Drug Treatments on Levels of Certain Brain Chemicals in Alzheimer’s Disease
NCT00120874	PHASE4	COMPLETED	Memantine and Comprehensive, Individualized Management of Alzheimer’s Disease and Caregiver Training
NCT00142324	PHASE4	UNKNOWN	CALM-AD
NCT00165724	PHASE4	COMPLETED	Alzheimer’s Disease Long-term Follow-up Study (ALF Study)
NCT00165750	PHASE4	TERMINATED	Correlation Between Regional Brain Volume and Response to Donepezil Treatment in AD Patients
NCT00202124	PHASE4	COMPLETED	Double Blind Study of Trp01 in Patients With Alzheimer’s Disease
NCT00208819	PHASE4	COMPLETED	A Comparison of Two Standard Therapies in the Management of Dementia With Agitation
NCT00216515	PHASE4	COMPLETED	The Efficacy of Galantamine on the Attention and the Frontal Function of the Patients With Dementia of Alzheimer Type
NCT00230568	PHASE4	COMPLETED	EARTH 413: A Study of Aricept in Hispanic Patients With Mild to Moderate Alzheimer’s Disease (AD)
NCT00234637	PHASE4	COMPLETED	Rivastigmine Monotherapy and Combination Therapy With Memantine in Patients With Moderately Severe Alzheimer’s Disease Who Failed to Benefit From Previous Cholinesterase Inhibitor Treatment
NCT00245206	PHASE4	COMPLETED	Side Effects of Newer Antipsychotics in Older Adults
NCT00254033	PHASE4	COMPLETED	Apathy Associated With Alzheimer’s Disease
NCT00260624	PHASE4	COMPLETED	Escitalopram Treatment of Patients With Agitated Dementia
NCT00303277	PHASE4	COMPLETED	Do HMG CoA Reductase Inhibitors Affect Abeta Levels?
NCT00305903	PHASE4	COMPLETED	Safety and Tolerability of Rivastigmine With Add-on Memantine in Patients With Probable Alzheimer’s Disease
NCT00306124	PHASE4	UNKNOWN	Dopaminergic Enhancement of Learning and Memory in Healthy Adults and Patients With Dementia/Mild Cognitive Impairment
NCT00334906	PHASE4	COMPLETED	Study of Memantine in Assessment of Selected Measures of Volumetric Magnetic Resonance Imaging (MRI) and Cognition in Moderate AD (Alzheimer’s Disease)
NCT00369603	PHASE4	TERMINATED	Functional Brain Imaging of Medication Treatment Response in Mild Alzheimer’s Disease Patients
NCT00375557	PHASE4	WITHDRAWN	Safety and Efficacy of Divalproex and Quetiapine in Elderly Alzheimer’s Dementia Patients
NCT00381381	PHASE4	COMPLETED	The Clinical Response of Choline Acetyltransferase and Apolipoprotein Epsilon Gene Polymorphisms to Donepezil in Alzheimer’s Disease
NCT00385684	PHASE4	COMPLETED	Low-Dose Opiate Therapy for Discomfort in Dementia (L-DOT)
NCT00401167	PHASE4	COMPLETED	Memantine for Agitation and Aggression in Severe Alzheimer’s Disease
NCT00403520	PHASE4	COMPLETED	Hippocampus Study: Comparative Effect of Donepezil 10mg/d and Placebo on Clinical and Radiological Markers
NCT00417482	PHASE4	COMPLETED	Antipsychotic Discontinuation in Alzheimer’s Disease
NCT00443014	PHASE4	COMPLETED	The Dementia Study in Northern Norway
NCT00469456	PHASE4	COMPLETED	Effect of Memantine on Functional Communication in Patients With Alzheimer’s Disease
NCT00476008	PHASE4	COMPLETED	Delaying the Progression of Driving Impairment in Individuals With Mild Alzheimer’s Disease
NCT00477659	PHASE4	COMPLETED	Neural Correlates In Mild Alzheimer’s Disease
NCT00480870	PHASE4	COMPLETED	The Effect of Anticholinesterase Drugs on Sleep in Alzheimer’s Disease Patients
NCT00495820	PHASE4	COMPLETED	Methylphenidate for Apathy in Alzheimer’s Dementia: A Controlled Study
NCT00523666	PHASE4	UNKNOWN	Diffusion Tensor Weighted MRI in Alzheimer’s Disease Modifying Treatment Effects of Galantamine (Reminyl®)
NCT00549601	PHASE4	COMPLETED	Convenience, Tolerability, and Safety of Change in the Administration of Rivastigmine From Capsules to a Transdermal Patch in Patients With Mild to Moderate Alzheimer’s Disease
NCT00551161	PHASE4	COMPLETED	Magnetic Resonance Spectroscopy Study of Memantine in Alzheimer’s Disease
NCT00561392	PHASE4	COMPLETED	Clinical Effectiveness of 10 cm^2 Rivastigmine Patch in Patients With Alzheimer’s Disease