APOA1

Chr 11ADAR

apolipoprotein A1

Also known as: AMYLD3, HPALP2, apo(a)

NCBI Gene: 335 ENSG00000118137 UniProt: P02647 OMIM: 107680

This gene encodes apolipoprotein A-I, which is the major protein component of high density lipoprotein (HDL) in plasma. The encoded preproprotein is proteolytically processed to generate the mature protein, which promotes cholesterol efflux from tissues to the liver for excretion, and is a cofactor for lecithin cholesterolacyltransferase (LCAT), an enzyme responsible for the formation of most plasma cholesteryl esters. This gene is closely linked with two other apolipoprotein genes on chromosome 11. Defects in this gene are associated with HDL deficiencies, including Tangier disease, and with systemic non-neuropathic amyloidosis. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein. [provided by RefSeq, Dec 2015]

GeneReviews OMIM Research

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Amyloidosis, hereditary systemic 3MIM #620657

Hypoalphalipoproteinemia, primary, 2MIM #618463

Hypoalphalipoproteinemia, primary, 2, intermediateMIM #619836

UniProtFamilial apolipoprotein gene cluster deletion syndrome

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Amyloidosis, hereditary systemic 3; Hypoalphalipoproteinemia, primary (+1); no ClinGen or GenCC tier

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

473

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

—

LOEUF

LOF

Mechanism· G2P

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GeneReview available — APOA1

Authoritative clinical overview · Recommended first read

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Some data sources returned errors (1)

gnomad: Error: gnomAD API error: 400

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in APOA1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

434 rare PASS variants

Rare truncating (LoF)

1 in 850

48 rare PASS variants

Rare synonymous (reference)

1 in 310

179 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for APOA1. 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 140	1 in 740
South Asian	~43k	1 in 170	1 in 1,600
Remaining (unassigned)	~30k	1 in 120	1 in 1,300
European (Finnish)	~27k	1 in 1,700	1 in 1,200
Admixed American	~22k	1 in 130	1 in 1,500
African / African American	~21k	1 in 180	≈ 1 in 9,300
East Asian	~20k	1 in 250	1 in 1,400
Ashkenazi Jewish	~13k	1 in 480	none seen
Middle Eastern	~2,884	1 in 140	≈ 1 in 2,900

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 ↓