CLU

protein-coding

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

Gene summary

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.[provided by RefSeq, May 2011]

Previous symbols:

CLI
APOJ

MANE transcript

NM_001831.4

Inheritance

—

ClinVar variants

U:13B:29

Top phenotype

CLU-related disorder

gnomAD constraint

pLI —, LoF o/e 0.49

Max pathogenic AF

—

Genomic locus

chr8:27,596,917-27,614,700

External References & Databases

Ensembl (ENSG00000120885)

Transcript & Mutation Effects

hg38 • Region Span ~17.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CLU variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 22

not providedTotal: 18

CLU-related disorderTotal: 7

Alzheimer diseaseTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001831.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	18 clinvar	2 clinvar	22
missense			2 clinvar	6 clinvar	3 clinvar	11
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			9 clinvar			9
Total	0	0	13	24	5	42

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 133 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001831.4	RefSeq	NP_001822.3	8	MANE Select
ENST00000316403.15	Ensembl	ENSP00000315130.10	8	MANE Select
ENST00000405140.7	Ensembl	ENSP00000385419.3	8	Standard
ENST00000405140.8	Ensembl	ENSP00000385419.3	8	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
clu	Danio rerio	Structure: neuron Quality: increased occurrence abnormal

Gene / Model

Organism

Observed Phenotype

clu

Danio rerio

Structure: neuron

Quality: increased occurrence

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Complement and coagulation cascades - Homo sapiens (human)
Dengue-2 Interactions with Complement and Coagulation Cascades
Complement and Coagulation Cascades
Antimicrobial peptides
Innate Immune System

Biological Process

cell morphogenesis
microglial cell activation
release of cytochrome c from mitochondria
platelet degranulation
lipid metabolic process

Molecular Function

amyloid-beta binding
protein binding
ATPase activity
ubiquitin protein ligase binding
protein-containing complex binding

Cellular Component

extracellular region
extracellular space
nucleus
cytoplasm
mitochondrion

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000316403
Coding exons: 8
Length: 18115
Individuals with no LoFs: 125728
Homozygous LoFs: 0
Heterozygous LoFs: 20
Defined: 125748
p: 0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.796	228	264	0.862	0.0000191	2990
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00016	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000079	0.000079	rare
South Asian	0.000098	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.837

Intolerance Scores

RVIS EVS: 0.16
RVIS percentile EVS: 64.82

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.883

Gene Damage Prediction

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