APOC2

apolipoprotein C2, the group of Apolipoproteins

Basic information

Region (hg38): 19:44946035-44949565

Links

ENSG00000234906 ∙ NCBI:344 ∙ OMIM:608083 ∙ HGNC:609 ∙ Uniprot:P02655 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• familial apolipoprotein C-II deficiency (Strong), mode of inheritance: AR
• familial apolipoprotein C-II deficiency (Strong), mode of inheritance: Semidominant
• familial apolipoprotein C-II deficiency (Strong), mode of inheritance: AR
• familial apolipoprotein C-II deficiency (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Apolipoprotein C-II deficiency (Hyperlipoproteinemia, type Ib)	AR	Cardiovascular; Gastrointestinal	Depending on the severity of disease, individuals may present with manifestations ranging from neonatal encephalopathy to episodic acute pancreatitis, and dietary measures (eg, with low-fat diet, and medium-chain triglyceride supplementation in infancy) can be beneficial to help control lipid abnormalities, including decreasing the risk of episodes of acute pancreatitis; Treatment of acute pancreatitis involves fasting with low-calorie infusion, but serum triglycerides can also be rapidly decreased in emergent situations through normal plasma transfusion; Medical treatment (eg, with fibrates) may be beneficial in adults	Cardiovascular; Gastrointestinal; Neurologic	565877; 213719; 227429; 6101731; 6475985; 3944267; 3467353; 3171393; 3225819; 1479292; 2477392; 2501098; 7815420; 10225669; 12049186; 12783430; 16153625; 22129523

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the APOC2 gene.

• not provided (4 variants)
• Familial apolipoprotein C-II deficiency (1 variants)
• Cardiovascular phenotype (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the APOC2 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				20		20
missense			22	6		28
nonsense	2	2	1			5
start loss						0
frameshift	3					3
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			2	1	1	4
non coding			7	14	9	30
Total	5	2	30	40	9

Highest pathogenic variant AF is 0.0000328

Variants in APOC2

This is a list of pathogenic ClinVar variants found in the APOC2 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-44946044-C-T		Familial apolipoprotein C-II deficiency	Uncertain significance (Jan 13, 2018)
19-44946051-G-C		Familial apolipoprotein C-II deficiency	Uncertain significance (Jan 13, 2018)
19-44946071-G-A		Familial apolipoprotein C-II deficiency	Uncertain significance (Jan 13, 2018)
19-44946083-A-G		Familial apolipoprotein C-II deficiency	Uncertain significance (Jan 31, 2022)
19-44948185-A-G			Benign (Aug 30, 2018)
19-44948277-T-G			Likely benign (Jan 16, 2021)
19-44948363-T-A		not specified	Benign (Aug 30, 2018)
19-44948390-C-G			Benign (Oct 17, 2018)
19-44948391-C-G			Likely benign (Dec 20, 2018)
19-44948399-T-G			Benign (Aug 30, 2018)
19-44948477-C-T		Familial apolipoprotein C-II deficiency • Cardiovascular phenotype • APOC2-related disorder	Benign/Likely benign (Mar 12, 2024)
19-44948479-A-G		APOLIPOPROTEIN C-II (PARIS) • Familial apolipoprotein C-II deficiency	Pathogenic (Dec 15, 1989)
19-44948482-G-C		Cardiovascular phenotype	Uncertain significance (May 30, 2022)
19-44948486-C-T		Cardiovascular phenotype	Conflicting classifications of pathogenicity (Jan 19, 2024)
19-44948487-AC-A			Pathogenic (Aug 03, 2022)
19-44948488-C-G		Cardiovascular phenotype	Uncertain significance (Oct 07, 2022)
19-44948488-C-T		Familial apolipoprotein C-II deficiency	Conflicting classifications of pathogenicity (Jan 11, 2024)
19-44948489-G-A		Cardiovascular phenotype	Uncertain significance (Apr 11, 2024)
19-44948500-GCT-G			Pathogenic (May 26, 2023)
19-44948511-T-C			Likely benign (May 09, 2022)
19-44948512-G-A			Likely benign (Nov 13, 2023)
19-44948514-C-G		Cardiovascular phenotype	Likely benign (Nov 29, 2023)
19-44948517-C-T		Cardiovascular phenotype	Likely benign (Mar 17, 2020)
19-44948520-G-C			Likely benign (Aug 02, 2023)
19-44948530-T-G		Cardiovascular phenotype	Uncertain significance (Nov 28, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
APOC2	protein_coding	protein_coding	ENST00000590360	3	3580

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.402	0.563	125738	0	8	125746	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.329	44	50.6	0.870	0.00000263	642
Missense in Polyphen		12	15.355	0.7815		202
Synonymous	0.277	21	22.7	0.926	0.00000136	204
Loss of Function	1.67	1	5.06	0.198	3.19e-7	45

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000116	0.000116
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.000109	0.000109
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of chylomicrons, very low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL) in plasma. Plays an important role in lipoprotein metabolism as an activator of lipoprotein lipase. Both proapolipoprotein C-II and apolipoprotein C-II can activate lipoprotein lipase. In normolipidemic individuals, it is mainly distributed in the HDL, whereas in hypertriglyceridemic individuals, predominantly found in the VLDL and LDL. {ECO:0000269|PubMed:2209608, ECO:0000303|PubMed:22304839}.
• Disease: DISEASE: Hyperlipoproteinemia 1B (HLPP1B) [MIM:207750]: Autosomal recessive trait characterized by hypertriglyceridemia, xanthomas, and increased risk of pancreatitis and early atherosclerosis. {ECO:0000269|PubMed:8323539}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cholesterol metabolism - Homo sapiens (human);Statin Pathway, Pharmacodynamics;MECP2 and Associated Rett Syndrome;Plasma lipoprotein assembly, remodeling, and clearance;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: 0.103

Intolerance Scores

• loftool: 0.464
• rvis_EVS: 0.77
• rvis_percentile_EVS: 86.95

Haploinsufficiency Scores

• pHI: 0.0828
• hipred: N
• hipred_score: 0.146
• ghis: 0.564

Essentials

• essential_gene_CRISPR: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.372

Mouse Genome Informatics

• Gene name: Apoc2
• Phenotype: homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: apoc2
• Affected structure: macrophage
• Phenotype tag: abnormal
• Phenotype quality: increased amount

Gene ontology

• Biological process: retinoid metabolic process;positive regulation of phospholipase activity;positive regulation of triglyceride catabolic process;positive regulation of very-low-density lipoprotein particle remodeling;negative regulation of very-low-density lipoprotein particle clearance;lipid catabolic process;negative regulation of cholesterol transport;cholesterol efflux;phospholipid efflux;triglyceride-rich lipoprotein particle remodeling;chylomicron remodeling;very-low-density lipoprotein particle remodeling;high-density lipoprotein particle remodeling;chylomicron assembly;chylomicron remnant clearance;high-density lipoprotein particle clearance;response to drug;cholesterol homeostasis;lipoprotein transport;negative regulation of catalytic activity;reverse cholesterol transport;positive regulation of fatty acid biosynthetic process;negative regulation of lipid metabolic process;negative regulation of receptor-mediated endocytosis;positive regulation of lipoprotein lipase activity;positive regulation of phospholipid catabolic process;triglyceride homeostasis
• Cellular component: extracellular region;extracellular space;early endosome;very-low-density lipoprotein particle;low-density lipoprotein particle;intermediate-density lipoprotein particle;spherical high-density lipoprotein particle;chylomicron
• Molecular function: lipid binding;phospholipase activator activity;protein homodimerization activity;phospholipase binding;lipase inhibitor activity;lipoprotein lipase activator activity