APOC3

Chr 11

apolipoprotein C3

Also known as: APOCIII, Apo-C3, ApoC-3

NCBI Gene: 345 ENSG00000110245 UniProt: P02656

This gene encodes a protein component of triglyceride (TG)-rich lipoproteins (TRLs) including very low density lipoproteins (VLDL), high density lipoproteins (HDL) and chylomicrons. The encoded protein plays a role in role in the metabolism of these TRLs through multiple modes. This protein has been shown to promote the secretion of VLDL1, inhibit lipoprotein lipase enzyme activity, and delay catabolism of TRL remnants. Mutations in this gene are associated with low plasma triglyceride levels and reduced risk of ischemic cardiovascular disease, and hyperalphalipoproteinemia, which is characterized by elevated levels of high density lipoprotein (HDL) and HDL cholesterol in human patients. This gene and other related genes comprise an apolipoprotein gene cluster on chromosome 11. [provided by RefSeq, Sep 2017]

Research

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtHyperalphalipoproteinemia 2

Active trials

187

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.76

LOEUF

GOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.76LOEUF

pLI 0.010

Z-score 0.36

OE 0.80 (0.36–1.76)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.06Z-score

OE missense 1.02 (0.83–1.27)

59 obs / 57.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.80 (0.36–1.76)

0≤0.351.4

Missense OE?1.02 (0.83–1.27)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 3 / 3.7Missense obs/exp: 59 / 57.8Syn Z: 0.31

Background carrier burden — how many people carry a rare variant somewhere in APOC3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 460

150 rare PASS variants

Rare truncating (LoF)

1 in 780

30 rare PASS variants

Rare synonymous (reference)

1 in 960

54 rare PASS variants

Rare missense and truncating variants are carried at similar rates in APOC3; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 690	1 in 1,100
South Asian	~43k	1 in 490	1 in 3,900
Remaining (unassigned)	~30k	1 in 890	1 in 600
European (Finnish)	~27k	1 in 1,600	1 in 1,900
Admixed American	~22k	1 in 320	1 in 620
African / African American	~21k	1 in 470	1 in 260
East Asian	~20k	1 in 270	≈ 1 in 5,000
Ashkenazi Jewish	~13k	≈ 1 in 3,300	none seen
Middle Eastern	~2,884	1 in 410	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓