APOC3

apolipoprotein C3, the group of Apolipoproteins

Basic information

Region (hg38): 11:116829706-116833072

Links

ENSG00000110245

∙ NCBI:345 ∙ OMIM:107720 ∙ HGNC:610 ∙ Uniprot:P02656 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

cholesterol-ester transfer protein deficiency (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Apolipoprotein C-III deficiency	AD	General	The clinical applicability of Hyperalophalipoproteinemia 2 is unclear, though variants may be related to lower triglyceride levels and protection against cardiovascular disease	Cardiovascular	2914370; 2022742; 16813599; 19074352; 24941081; 24941082; 25225788

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the APOC3 gene.

Cardiovascular_phenotype (39 variants)
not_provided (28 variants)
not_specified (11 variants)
Apolipoprotein_c-III_deficiency (8 variants)
Coronary_heart_disease (4 variants)
APOC3-related_disorder (1 variants)
High_density_lipoprotein_deficiency,_Detroit_type (1 variants)
Apolipoprotein_C-III,_nonglycosylated (1 variants)
Cholesterol-ester_transfer_protein_deficiency (1 variants)
. (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the APOC3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000040.3. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				15 clinvar		15
missense	2 clinvar		25 clinvar	3 clinvar		30
nonsense			1 clinvar			1
start loss	1					1
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar	1 clinvar		2
Total	3	0	28	19	0

Highest pathogenic variant AF is 0.0000266435

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
APOC3	protein_coding	protein_coding	ENST00000227667	3	3367

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0100	0.622	125050	2	528	125580	0.00211

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0576	59	57.8	1.02	0.00000336	634
Missense in Polyphen		13	15.133	0.85903		196
Synonymous	0.310	24	26.0	0.923	0.00000186	197
Loss of Function	0.356	3	3.74	0.801	2.45e-7	34

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00338	0.00336
Ashkenazi Jewish	0.00199	0.00199
East Asian	0.000109	0.000109
Finnish	0.000833	0.000832
European (Non-Finnish)	0.00285	0.00285
Middle Eastern	0.000109	0.000109
South Asian	0.00196	0.00190
Other	0.00326	0.00327

dbNSFP

Source: dbNSFP

Function: FUNCTION: Component of triglyceride-rich very low density lipoproteins (VLDL) and high density lipoproteins (HDL) in plasma (PubMed:18201179, PubMed:22510806). Plays a multifaceted role in triglyceride homeostasis (PubMed:18201179, PubMed:22510806). Intracellularly, promotes hepatic very low density lipoprotein 1 (VLDL1) assembly and secretion; extracellularly, attenuates hydrolysis and clearance of triglyceride-rich lipoproteins (TRLs) (PubMed:18201179, PubMed:22510806). Impairs the lipolysis of TRLs by inhibiting lipoprotein lipase and the hepatic uptake of TRLs by remnant receptors (PubMed:18201179, PubMed:22510806). Formed of several curved helices connected via semiflexible hinges, so that it can wrap tightly around the curved micelle surface and easily adapt to the different diameters of its natural binding partners (PubMed:18408013). {ECO:0000269|PubMed:18408013, ECO:0000303|PubMed:18201179, ECO:0000303|PubMed:22510806}.;
Disease: DISEASE: Hyperalphalipoproteinemia 2 (HALP2) [MIM:614028]: A condition characterized by high levels of high density lipoprotein (HDL) and increased HDL cholesterol levels. {ECO:0000269|PubMed:2022742}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Cholesterol metabolism - Homo sapiens (human);PPAR signaling pathway - Homo sapiens (human);Statin Pathway, Pharmacodynamics;PPAR Alpha Pathway;Nuclear Receptors Meta-Pathway;PPAR signaling pathway;Statin Pathway;Signaling by GPCR;Signal Transduction;Metabolism of fat-soluble vitamins;Chylomicron assembly;Plasma lipoprotein assembly;Chylomicron remodeling;HDL remodeling;Metabolism;Transport of small molecules;Metabolism of vitamins and cofactors;Plasma lipoprotein assembly, remodeling, and clearance;Retinoid metabolism and transport;G alpha (i) signalling events;Plasma lipoprotein remodeling;Visual phototransduction;GPCR downstream signalling (Consensus)

Recessive Scores

pRec: 0.731

Intolerance Scores

loftool: 0.606
rvis_EVS: 0.37
rvis_percentile_EVS: 74.95

Haploinsufficiency Scores

pHI: 0.331
hipred: N
hipred_score: 0.146
ghis: 0.986

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.967

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Apoc3
Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); normal phenotype; growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); homeostasis/metabolism phenotype;

Gene ontology

Biological process: retinoid metabolic process;triglyceride metabolic process;G protein-coupled receptor signaling pathway;negative regulation of triglyceride catabolic process;negative regulation of very-low-density lipoprotein particle remodeling;negative regulation of very-low-density lipoprotein particle clearance;negative regulation of high-density lipoprotein particle clearance;negative regulation of low-density lipoprotein particle clearance;triglyceride catabolic process;regulation of Cdc42 protein signal transduction;cholesterol efflux;phospholipid efflux;chylomicron remodeling;high-density lipoprotein particle remodeling;chylomicron assembly;very-low-density lipoprotein particle assembly;chylomicron remnant clearance;lipoprotein metabolic process;cholesterol homeostasis;reverse cholesterol transport;negative regulation of fatty acid biosynthetic process;negative regulation of lipid metabolic process;negative regulation of receptor-mediated endocytosis;negative regulation of lipid catabolic process;negative regulation of lipoprotein lipase activity;negative regulation of cholesterol import;triglyceride homeostasis
Cellular component: extracellular region;extracellular space;early endosome;very-low-density lipoprotein particle;intermediate-density lipoprotein particle;spherical high-density lipoprotein particle;chylomicron;collagen-containing extracellular matrix;extracellular exosome
Molecular function: phospholipid binding;cholesterol binding;enzyme regulator activity;lipase inhibitor activity;high-density lipoprotein particle receptor binding