APOA5

Chr 11ADAR

apolipoprotein A5

Also known as: APOAV, RAP3

NCBI Gene: 116519 ENSG00000110243 UniProt: Q6Q788 OMIM: 606368

The protein encoded by this gene is an apolipoprotein that plays an important role in regulating the plasma triglyceride levels, a major risk factor for coronary artery disease. It is a component of high density lipoprotein and is highly similar to a rat protein that is upregulated in response to liver injury. Mutations in this gene have been associated with hypertriglyceridemia and hyperlipoproteinemia type 5. This gene is located proximal to the apolipoprotein gene cluster on chromosome 11q23. Alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Oct 2009]

GeneReviews OMIM Research

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Hypertriglyceridemia, susceptibility to}MIM #145750

Hyperchylomicronemia, late-onsetMIM #144650

UniProtHyperlipoproteinemia 5

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Hyperchylomicronemia, late-onset; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.60

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — APOA5

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.60LOEUF

pLI 0.000

Z-score -0.10

OE 1.03 (0.68–1.60)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.86Z-score

OE missense 0.84 (0.75–0.95)

200 obs / 237.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.03 (0.68–1.60)

0≤0.351.4

Missense OE?0.84 (0.75–0.95)

0≤0.61.4

Synonymous OE?0.79

0≤1.21.6

LoF obs/exp: 14 / 13.6Missense obs/exp: 200 / 237.3Syn Z: 1.65

Background carrier burden — how many people carry a rare variant somewhere in APOA5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

519 rare PASS variants

Rare truncating (LoF)

1 in 1,100

70 rare PASS variants

Rare synonymous (reference)

1 in 150

203 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for APOA5. 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 150	1 in 1,000
South Asian	~43k	1 in 110	1 in 1,600
Remaining (unassigned)	~30k	1 in 120	1 in 1,100
European (Finnish)	~27k	1 in 460	1 in 1,700
Admixed American	~22k	1 in 130	1 in 1,200
African / African American	~21k	1 in 150	1 in 2,100
East Asian	~20k	1 in 120	1 in 1,400
Ashkenazi Jewish	~13k	1 in 440	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 82	none seen

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 ↓