APOC2

protein-coding

apolipoprotein C2, the group of Apolipoproteins

Gene summary

This gene encodes a lipid-binding protein belonging to the apolipoprotein gene family. The protein is secreted in plasma where it is a component of very low density lipoprotein. This protein activates the enzyme lipoprotein lipase, which hydrolyzes triglycerides and thus provides free fatty acids for cells. Mutations in this gene cause hyperlipoproteinemia type IB, characterized by hypertriglyceridemia, xanthomas, and increased risk of pancreatitis and early atherosclerosis. This gene is present in a cluster with other related apolipoprotein genes on chromosome 19. Naturally occurring read-through transcription exists between this gene and the neighboring upstream apolipoprotein C-IV (APOC4) gene. [provided by RefSeq, Mar 2011]

MANE transcript

NM_000483.5

Inheritance

AR, SD

ClinVar variants

P:18U:38B:41

Top phenotype

Apolipoprotein C-II deficiency (Hyperlipoproteinemia, type Ib)

gnomAD constraint

pLI —, LoF o/e 0.2

Max pathogenic AF

—

Genomic locus

chr19:44,946,035-44,949,565

External References & Databases

Ensembl (ENSG00000234906)

Transcript & Mutation Effects

hg38 • Region Span ~3.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

familial apolipoprotein C-II deficiencySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0008810

Submitter: Orphanet

familial apolipoprotein C-II deficiencyDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0008810

Submitter: G2P

familial apolipoprotein C-II deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0008810

Submitter: Genomics England PanelApp

familial apolipoprotein C-II deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0008810

Submitter: PanelApp Australia

familial apolipoprotein C-II deficiencySTRONG

Inheritance Pattern: SD

Disease ID:MONDO:0008810

Submitter: Ambry Genetics

familial apolipoprotein C-II deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0008810

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Apolipoprotein C-II deficiency (Hyperlipoproteinemia, type Ib)AR

Manifestation: Cardiovascular; Gastrointestinal; Neurologic

Intervention: Cardiovascular; Gastrointestinal

Rationale: 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

Refs: 565877; 213719; 227429; 6101731; 6475985; 3944267; 3467353; 3171393; 3225819; 1479292; 2477392; 2501098; 7815420; 10225669; 12049186; 12783430; 16153625; 22129523

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to APOC2 variants in ClinVar

16 Conditions Cataloged

Cardiovascular phenotypeTotal: 66

not providedTotal: 51

Familial apolipoprotein C-II deficiencyTotal: 38

APOC2-related disorderTotal: 7

not specifiedTotal: 7

APOLIPOPROTEIN C-II (PARIS)Total: 1

APOLIPOPROTEIN C-II (HAMBURG)Total: 1

APOLIPOPROTEIN C-II (BARI)Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000483.5. 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				33 clinvar		33
missense	1 clinvar		37 clinvar	8 clinvar		46
nonsense	2 clinvar	6 clinvar	1 clinvar			9
start loss		1 clinvar				1
frameshift	4 clinvar	2 clinvar				6
splice donor/acceptor (+/-2bp)	2 clinvar					2
Total	9	9	38	41	0	97

Highest pathogenic variant AF is 0.00003717675

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 50 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000483.5	RefSeq	NP_000474.2	3	MANE Select
ENST00000252490.7	Ensembl	ENSP00000252490.5	3	MANE Select
ENST00000585786.1	Ensembl	ENSP00000465001.1	2	Standard
ENST00000585786.2	Ensembl	ENSP00000465001.1	2	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
apoc2	Danio rerio	Structure: macrophage Quality: increased amount abnormal

Gene / Model

Organism

Observed Phenotype

apoc2

Danio rerio

Structure: macrophage

Quality: increased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cholesterol metabolism - Homo sapiens (human)
Statin Pathway, Pharmacodynamics
MECP2 and Associated Rett Syndrome
Plasma lipoprotein assembly, remodeling, and clearance
Statin Pathway

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

Molecular Function

lipid binding
phospholipase activator activity
protein homodimerization activity
phospholipase binding
lipase inhibitor activity

Cellular Component

extracellular region
extracellular space
early endosome
very-low-density lipoprotein particle
low-density lipoprotein particle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000590360
Coding exons: 3
Length: 3580
Individuals with no LoFs: 125738
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125746
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.329	44	50.6	0.870	0.00000263	642
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.103

Intolerance Scores

LoFtool: 0.464
RVIS EVS: 0.77
RVIS percentile EVS: 86.95

Essentials

Essential (CRISPR): N
Indispensability pred.: N
Indispensability score: 0.372