APOA2

protein-coding

apolipoprotein A2, the group of Apolipoproteins

Gene summary

This gene encodes apolipoprotein (apo-) A-II, which is the second most abundant protein of the high density lipoprotein particles. The protein is found in plasma as a monomer, homodimer, or heterodimer with apolipoprotein D. Defects in this gene may result in apolipoprotein A-II deficiency or hypercholesterolemia. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001643.2

Inheritance

AD, AR

ClinVar variants

P:1U:11B:2

Top phenotype

Apolipoprotein A-II deficiency

gnomAD constraint

pLI —, LoF o/e 0.65

Max pathogenic AF

—

Genomic locus

chr1:161,222,290-161,223,631

External References & Databases

Ensembl (ENSG00000158874)

Transcript & Mutation Effects

hg38 • Region Span ~1.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

apolipoprotein A-II amyloidosisSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0016533

Submitter: Orphanet

hypercholesterolemia, familial, 1LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0007750

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Apolipoprotein A-II deficiencyAR

Manifestation: Cardiovascular

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 2107739; 12522687; 24387992

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to APOA2 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 19

not providedTotal: 6

APOLIPOPROTEIN A-II DEFICIENCYTotal: 4

APOA2-related disorderTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001643.2. 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			1 clinvar	1 clinvar	1 clinvar	3
missense			10 clinvar			10
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)	1 clinvar					1
Total	1	0	11	1	1	14

Highest pathogenic variant AF is 0.0000041042704

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 43 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001643.2	RefSeq	NP_001634.1	3	MANE Select
ENST00000367990.7	Ensembl	ENSP00000356969.3	3	MANE Select
ENST00000463273.5	Ensembl	ENSP00000476740.1	3	Standard
ENST00000463273.6	Ensembl	ENSP00000476740.2	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cholesterol metabolism - Homo sapiens (human)
PPAR signaling pathway - Homo sapiens (human)
Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)
PPAR Alpha Pathway
Nuclear Receptors Meta-Pathway

Biological Process

retinoid metabolic process
acute inflammatory response
negative regulation of cytokine secretion involved in immune response
triglyceride metabolic process
phosphatidylcholine biosynthetic process

Molecular Function

lipid transporter activity
protein binding
phospholipid binding
high-density lipoprotein particle binding
lipid binding

Cellular Component

extracellular region
early endosome
endoplasmic reticulum lumen
cytosol
very-low-density lipoprotein particle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000367990
Coding exons: 3
Length: 1340
Individuals with no LoFs: 125732
Homozygous LoFs: 0
Heterozygous LoFs: 9
Defined: 125741
p: 0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.313	46	52.4	0.878	0.00000286	637
Missense (PolyPhen)		11	15.138	0.72666		207
Synonymous	0.0674	22	22.4	0.982	0.00000138	200
Loss of Function	0.568	2	3.07	0.651	1.29e-7	40

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May stabilize HDL (high density lipoprotein) structure by its association with lipids, and affect the HDL metabolism.;

Recessive Scores

pRec: 0.431

Intolerance Scores

LoFtool: 0.359
RVIS EVS: -0.03
RVIS percentile EVS: 51.04

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.586

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Low	Low	Low
Primary Immunodeficiency	Low	Low	Low
Cancer	Low	Low	Low