CLU
clusterin, the group of MicroRNA protein coding host genes|Complement system regulators and receptors
Basic information
Region (hg38): 8:27596917-27614700
Previous symbols: [ "CLI", "APOJ" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
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 | 11 | |||||
| missense | 5 | |||||
| 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 | 9 | 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) | ||
| 8-27598608-C-T | Likely benign (Nov 01, 2024) | |||
| 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 (Nov 01, 2024) | ||
| 8-27605189-G-A | Likely benign (Oct 03, 2018) | |||
| 8-27605208-C-T | CLU-related disorder | Likely benign (Aug 30, 2024) | ||
| 8-27606346-C-G | Benign (Jun 10, 2018) | |||
| 8-27606389-C-T | CLU-related disorder | Benign (Dec 31, 2019) | ||
| 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:
| 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:
- 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
- loftool
- 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