CLU

clusterin, the group of MicroRNA protein coding host genes|Complement system regulators and receptors

Basic information

Region (hg38): 8:27596916-27614700

Previous symbols: [ "CLI", "APOJ" ]

Links

ENSG00000120885 ∙ NCBI:1191 ∙ OMIM:185430 ∙ HGNC:2095 ∙ Uniprot:P10909 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CLU gene.

• not provided (16 variants)
• Alzheimer disease (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CLU gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				7	4	11
missense				1	3	4
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	0	8	7

Variants in CLU

This is a list of pathogenic ClinVar variants found in the CLU region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-27598232-A-G		CLU-related disorder	Likely benign (Oct 23, 2020)
8-27598486-C-A			Likely benign (Jan 31, 2018)
8-27598582-G-A		CLU-related disorder	Likely benign (Jun 21, 2019)
8-27598609-G-A			Benign (Jan 02, 2018)
8-27598613-G-A			Benign (Dec 31, 2019)
8-27599945-G-A			Likely benign (Apr 10, 2018)
8-27599960-G-A			Benign (Dec 31, 2019)
8-27599962-C-T			Benign (Dec 31, 2019)
8-27599990-G-C			Benign (Dec 31, 2019)
8-27604964-A-G		CLU-related disorder	Benign (Oct 17, 2019)
8-27604997-G-A			Likely benign (Dec 31, 2019)
8-27605048-G-A			Likely benign (Jan 02, 2019)
8-27605145-G-A		Alzheimer disease	Likely benign (Oct 10, 2018)
8-27605189-G-A			Likely benign (Oct 03, 2018)
8-27606346-C-G			Benign (Jun 10, 2018)
8-27606389-C-T		CLU-related disorder	Benign/Likely benign (May 11, 2020)
8-27608992-G-A		CLU-related disorder	Likely benign (Jan 01, 2023)
8-27609061-G-A			Benign (Dec 31, 2019)
8-27609064-C-T		CLU-related disorder	Likely benign (Jul 02, 2020)
8-27610497-C-T			Likely benign (Dec 31, 2019)
8-27610512-G-A		CLU-related disorder	Likely benign (Aug 20, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CLU	protein_coding	protein_coding	ENST00000316403	8	18115

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000781	0.983	125728	0	20	125748	0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.796	228	264	0.862	0.0000191	2990
Missense in Polyphen		49	85.375	0.57394		1005
Synonymous	-0.981	123	110	1.12	0.00000835	842
Loss of Function	2.13	10	20.4	0.490	0.00000101	230

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000181	0.000181
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000792	0.0000791
Middle Eastern	0.000163	0.000163
South Asian	0.0000980	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Isoform 1 functions as extracellular chaperone that prevents aggregation of nonnative 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. Secreted isoform 1 protects cells against apoptosis and against cytolysis by complement. Intracellular isoforms 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. Nuclear isoforms promote apoptosis. Mitochondrial isoforms suppress BAX-dependent release of cytochrome c into the cytoplasm and inhibit apoptosis. Plays a role in the regulation of cell proliferation. {ECO:0000269|PubMed:11123922, ECO:0000269|PubMed:12047389, ECO:0000269|PubMed:12176985, ECO:0000269|PubMed:12551933, 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}.
• Pathway: Complement and coagulation cascades - Homo sapiens (human);Dengue-2 Interactions with Complement and Coagulation Cascades;Complement and Coagulation Cascades;Antimicrobial peptides;Innate Immune System;Immune System;Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;Hemostasis;Regulation of Complement cascade;Terminal pathway of complement;Complement cascade;Validated targets of C-MYC transcriptional repression (Consensus)

Recessive Scores

• pRec: 0.837

Intolerance Scores

• rvis_EVS: 0.16
• rvis_percentile_EVS: 64.82

Haploinsufficiency Scores

• pHI: 0.135
• hipred: Y
• hipred_score: 0.827
• ghis: 0.475

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.883

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Clu
• Phenotype: homeostasis/metabolism phenotype; muscle phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; renal/urinary system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: clu
• Affected structure: neuron
• Phenotype tag: abnormal
• Phenotype quality: increased occurrence

Gene ontology

• Biological process: cell morphogenesis;microglial cell activation;release of cytochrome c from mitochondria;platelet degranulation;lipid metabolic process;complement activation;complement activation, classical pathway;response to virus;positive regulation of gene expression;protein import;antimicrobial humoral response;regulation of complement activation;central nervous system myelin maintenance;positive regulation of proteasomal ubiquitin-dependent protein catabolic process;negative regulation of protein homooligomerization;positive regulation of protein homooligomerization;positive regulation of tumor necrosis factor production;reverse cholesterol transport;innate immune response;positive regulation of nitric oxide biosynthetic process;positive regulation of receptor-mediated endocytosis;protein stabilization;positive regulation of NF-kappaB transcription factor activity;chaperone-mediated protein complex assembly;response to misfolded protein;negative regulation of cell death;chaperone-mediated protein folding;microglial cell proliferation;protein targeting to lysosome involved in chaperone-mediated autophagy;chaperone-mediated protein transport involved in chaperone-mediated autophagy;negative regulation of release of cytochrome c from mitochondria;regulation of amyloid-beta clearance;regulation of neuron death;positive regulation of neuron death;positive regulation of amyloid-beta formation;negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage;negative regulation of amyloid-beta formation;regulation of neuronal signal transduction;positive regulation of tau-protein kinase activity;positive regulation of neurofibrillary tangle assembly;negative regulation of response to endoplasmic reticulum stress;negative regulation of cellular response to thapsigargin;negative regulation of cellular response to tunicamycin;negative regulation of amyloid fibril formation;positive regulation of amyloid fibril formation;positive regulation of ubiquitin-dependent protein catabolic process
• Cellular component: extracellular region;extracellular space;nucleus;cytoplasm;mitochondrion;Golgi apparatus;cytosol;cytoskeleton;cell surface;membrane;platelet alpha granule lumen;mitochondrial membrane;protein-containing complex;spherical high-density lipoprotein particle;chromaffin granule;intracellular membrane-bounded organelle;synapse;perinuclear region of cytoplasm;collagen-containing extracellular matrix;extracellular exosome;cell periphery;blood microparticle;neurofibrillary tangle;apical dendrite;perinuclear endoplasmic reticulum lumen
• Molecular function: amyloid-beta binding;protein binding;ATPase activity;ubiquitin protein ligase binding;protein-containing complex binding;tau protein binding;low-density lipoprotein particle receptor binding;chaperone binding;misfolded protein binding