APOA2

Summary

APOA2 (apolipoprotein A2, HGNC:601) is a protein-coding gene on chromosome 1q23.3, encoding Apolipoprotein A-II (P02652). May stabilize HDL (high density lipoprotein) structure by its association with lipids, and affect the HDL metabolism.

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.

Source: NCBI Gene 336 — RefSeq curated summary.

At a glance

• Gene–disease (curated): apolipoprotein A-II amyloidosis (Supportive, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 36 total — 1 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 12
• MANE Select transcript: NM_001643

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:601
Approved symbol	APOA2
Name	apolipoprotein A2
Location	1q23.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000158874
Ensembl biotype	protein_coding
OMIM	107670
Entrez	336

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 15 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000367990, ENST00000463273, ENST00000463812, ENST00000464492, ENST00000468465, ENST00000469730, ENST00000470459, ENST00000481413, ENST00000481511, ENST00000491350, ENST00000888433, ENST00000888434, ENST00000888435, ENST00000888436, ENST00000888437, ENST00000888438, ENST00000888439

RefSeq mRNA: 1 — MANE Select: NM_001643 NM_001643

CCDS: CCDS1226

Canonical transcript exons

ENST00000367990 — 4 exons

Exon	Start	End
ENSE00001041701	161223595	161223628
ENSE00003708696	161222292	161222522
ENSE00003710364	161222918	161223050
ENSE00003711228	161223350	161223425

Expression profiles

Bgee: expression breadth ubiquitous, 160 present calls, max score 99.96.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 38.5540 / max 7871.3413, expressed in 181 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15616	36.7467	177
201787	1.5868	58
201786	0.2205	38

Top tissues by expression

284 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.96	gold quality
liver	UBERON:0002107	99.96	gold quality
colonic epithelium	UBERON:0000397	87.69	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.07	gold quality
monocyte	CL:0000576	80.30	gold quality
mononuclear cell	CL:0000842	80.02	gold quality
leukocyte	CL:0000738	79.18	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.01	gold quality
adrenal tissue	UBERON:0018303	77.22	gold quality
bone marrow cell	CL:0002092	70.62	gold quality
granulocyte	CL:0000094	70.28	gold quality
left uterine tube	UBERON:0001303	70.04	gold quality
tendon of biceps brachii	UBERON:0008188	69.79	silver quality
blood	UBERON:0000178	65.74	gold quality
ectocervix	UBERON:0012249	65.60	gold quality
right coronary artery	UBERON:0001625	64.98	gold quality
metanephros cortex	UBERON:0010533	64.98	gold quality
right uterine tube	UBERON:0001302	64.30	gold quality
right lung	UBERON:0002167	63.92	gold quality
body of pancreas	UBERON:0001150	63.73	gold quality
vena cava	UBERON:0004087	63.68	gold quality
oocyte	CL:0000023	62.80	silver quality
stromal cell of endometrium	CL:0002255	61.76	gold quality
right atrium auricular region	UBERON:0006631	61.58	gold quality
endocervix	UBERON:0000458	61.30	gold quality
upper lobe of left lung	UBERON:0008952	60.95	gold quality
body of uterus	UBERON:0009853	60.92	gold quality
body of stomach	UBERON:0001161	60.85	gold quality
sural nerve	UBERON:0015488	60.84	gold quality
adenohypophysis	UBERON:0002196	60.83	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-CURD-98	yes	89572.27
E-MTAB-7407	yes	70861.07
E-MTAB-8221	yes	64506.13
E-GEOD-130473	yes	43867.00
E-MTAB-10553	yes	36820.61
E-HCAD-9	yes	30662.23
E-MTAB-9388	yes	14335.23
E-MTAB-10485	yes	3816.37
E-MTAB-8271	yes	2706.54
E-GEOD-89232	yes	1201.60
E-ANND-5	yes	966.07
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, CEBPG, FOXP3, HNF1A, HNF4A, LITAF, NR0B2, NR1H3, NR2F1, NR2F2, NR2F6, NR4A1, PITX2, PPARA, PPARD, PPARG, RARA, RXRA, SREBF1, SREBF2, THRB, USF1, USF2

miRNA regulators (miRDB)

11 targeting APOA2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-609	99.82	64.26	505
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-4435	95.90	65.47	1201

Literature-anchored findings (GeneRIF, showing 40)

• when expressed in transgenic mice, HDL shows antioxidant properties (PMID:11971944)
• Overexpression in transgenic mice does not increase their susceptibility to insulin resistance and obesity (PMID:12032642)
• Evaluated as a positional candidate gene for familial Type II diabetes, altered lipid concentrations, and insulin resistance (PMID:12136402)
• apolipoproteins appear to be a class of mediators that can participate in the regulation of the activity of neutrophils (PMID:12458630)
• Carriers of a novel splice-site mutation in the LDL-receptor gene were simultaneously homozygous for the -265C variant of apoA-II thus concluding that one variant of the apoA-II gene was associated with reduced plasma LDL cholesterol in FH patients (PMID:12522687)
• Results show that during the early stages, oxidation of HDL gives rise to specifically oxidized forms of apolipoproteins A-I and A-II. (PMID:12576517)
• This protein inhibits high density lipoprotein remodeling and lipid-poor apolipoprotein A-I formation (PMID:12690114)
• Genetic association of plasma apolipoprotein A-II levels with familial combined hyperlipidemia. (PMID:12738753)
• Analysis of trancription factors that bind response elements in the apoA-II promotor and modulate transcription. (PMID:12959642)
• apoA-II affects both the structure and the dynamic behavior of HDL particles and selectively modifies lipid metabolism (PMID:14967812)
• In transgenic mice overexpressing the human apoA-II gene, plasma human apoA-II concentration was positively correlated with blood glucose levels. (PMID:14988251)
• this protein-exonic splicing enhancer interaction is able to promote the incorporation of exon 3 in mRNA and suggest that they can rescue the splicing despite the noncanonical 3’ splice site. (PMID:15247216)
• Overexpressed human apoA-II in mice impairs HDL protection of apoB-lipoproteins from oxidation. Displacement of PON1 by apoA-II may explain why PON1 is found in HDL particles with apoA-I, not apoA-II, & apo-A-II-rich HDL’s poor antiatherogenic properties. (PMID:15388641)
• results indicate a significant association between the T265C APOA-II polymorphism and levels of visceral adipose tissue in premenopausal women present in white but not African-American women (PMID:15833935)
• NDRG1 interacts with APO A-I and A-II and may have a role in the general mechanisms of HDL-mediated cholesterol transport (PMID:15922294)
• Characterization of regulatory elements found in the apoA-II exon 3 and its flanking introns that are involved in the control of apoA-II exon 3 splicing. (PMID:16254078)
• Metabolic syndrome men exhibit hypercatabolism of the two major HDL lipoprotein particles, LpA-I and LpA-I:A-II. (PMID:16368749)
• findings show that serum opacity factor (SOF) interacts with HDL in human blood by binding to apoA-I and apoA-II and causing the release of HDL lipid cargo, which coalesces to form lipid droplets, resulting in opacification (PMID:16407233)
• the association of apoA-II with triglyceride-rich lipoproteins occurs in the circulation and induces postprandial hypertriglyceridemia (PMID:16990646)
• ApoA-II adopts a beltlike structure in which the protein helices wrap around the lipid- bilayer reconstituted high density lipoprotein (rHDL) disc. (PMID:17264082)
• ApoAII is efficiently reabsorbed in kidney proximal tubules in relation to its plasma concentration (PMID:17652309)
• carriers of the minor allele for Apo A-II -265T/C (CC/TC) have a lower postprandial response compared with TT homozygotes (PMID:17709437)
• ApoA-II is associated with a decreased risk of future coronary artery disease in apparently healthy people, implying that apoA-II itself exerts effects on specific antiatherogenic pathways. (PMID:17923573)
• APOAII rs5082 polymorphism may have a role in reducing risk of coronary artery disease in an Australian male population (PMID:18179799)
• results for dimeric apolipoprotein AII are similar to those we have reported for the monomeric apolipoprotein CI, which has a similar secondary structure but a different peptide sequence and net charge (PMID:18652418)
• procoagulant activities of plasma factor VIIc and factor Xc are positively and independently associated with concentrations of the high-density lipoprotein apolipoprotein, apo A-II (PMID:18766253)
• small sizes (i. e., number of kringle-4 repeats in the gene) of apolipoprotein (a) are risk factors for the development of atherothrombosis. (review) (PMID:19069164)
• Results indicate that CETP inhibition increases plasma concentrations of apoA-II by delaying HDL apoA-II catabolism and significantly alters the remodeling of apoA-II-containing HDL subpopulations. (PMID:19193611)
• The available data does not support a role for common variants in APOA2 on type 2 diabetes susceptibility or related quantitative traits in Northern Europeans (PMID:19216768)
• This study defines apo A-II stabilization of high-density lipoproteins to opacification by serum opacity factor (SOF) and provides a basis for evaluating the antiatherogenic potential of the opacification reaction that is catalyzed by SOF. (PMID:19618959)
• High density lipoproteins (HDL) apolipoproteins A-I, A-II and E have distinct intracellular and post-secretory pathways of hepatic lipidation and dimerization in the process of HDL formation. (PMID:19635584)
• In metabolic syndrome, fenofibrate, but not atorvastatin, influences high density lipoprotein metabolism by increasing the transport of APOA2 particles. (PMID:19651918)
• The expression of human apoAII in Tg rabbits resulted in increased levels of plasma triglycerides, total cholesterol, and phospholipids accompanied by a marked reduction in HDL-cholesterol levels compared with non-Tg littermates. (PMID:19778946)
• The serum apoA-II concentrations confer risk for MetS and diabetes and exhibit evidence of anti-inflammatory properties among Turks. (PMID:19817643)
• Prevalence of the CC genotype in study participants ranged from 10.5% to 16.2%. We identified statistically significant interactions between the APOA2 -265T>C and saturated fat regarding BMI in all 3 populations. (PMID:19901143)
• ApoA-II plays a crucial role in triglyceride catabolism by regulating lipoprotein lipase activity, at least in part, through HDL proteome modulation. (PMID:19910634)
• Low apolipoprotein-A2 is associated with metastatic renal cell cancer. (PMID:20022911)
• a gene-diet interaction involving the APOA2 -265T>C SNP and saturated fat intake determines body weight in a Mediterranean and an Asian populations (PMID:20975728)
• Human apolipoprotein A-II inhibits the production of interferon-gamma by concanavalin A-stimulated mouse and human CD4-positive T cells. (PMID:21300819)
• APOA2 m265 genotype may be associated with eating behaviours and dietary modulation of plasma ghrelin. (PMID:21386805)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Apoa2	ENSMUSG00000005681
rattus_norvegicus	Apoa2	ENSRNOG00000003500

Protein

Protein identifiers

Apolipoprotein A-II — P02652 (reviewed: P02652)

Alternative names: Apolipoprotein A2

All UniProt accessions (8): P02652, Q76EI7, V9GYC1, V9GYE3, V9GYG9, V9GYM3, V9GYS1, V9GYT0

UniProt curated annotations — full annotation on UniProt →

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

Subunit / interactions. Monomer. Homodimer; disulfide-linked. Also forms a disulfide-linked heterodimer with APOD. Interacts with NAXE and NDRG1. (Microbial infection) Interacts with HCV core protein.

Subcellular location. Secreted.

Tissue specificity. Plasma; synthesized in the liver and intestine.

Post-translational modifications. Phosphorylation sites are present in the extracellular medium. Apolipoprotein A-II is O-glycosylated.

Polymorphism. A homozygous transition at position 1 of intron 3 of APOA2 results in deficiency of apolipoprotein A-II, without significant influence either on lipid and lipoprotein profiles or on the occurrence of coronary artery disease [MIM:107670].

Similarity. Belongs to the apolipoprotein A2 family.

RefSeq proteins (1): NP_001634* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006801	ApoA-II	Family
IPR036172	ApoA-II_sf	Homologous_superfamily

Pfam: PF04711

UniProt features (11 total): modified residue 4, chain 3, signal peptide 1, sequence conflict 1, region of interest 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P02652-F1	75.92	0.03

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (4): 24, 49, 54, 68

Disulfide bonds (1): 29

Function

Pathways and Gene Ontology

Reactome pathways

19 pathways

ID	Pathway
R-HSA-1989781	PPARA activates gene expression
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-8957275	Post-translational protein phosphorylation
R-HSA-8963888	Chylomicron assembly
R-HSA-8963901	Chylomicron remodeling
R-HSA-975634	Retinoid metabolism and transport
R-HSA-1430728	Metabolism
R-HSA-174824	Plasma lipoprotein assembly, remodeling, and clearance
R-HSA-196854	Metabolism of vitamins and cofactors
R-HSA-2187338	Visual phototransduction
R-HSA-382551	Transport of small molecules
R-HSA-392499	Metabolism of proteins
R-HSA-400206	Regulation of lipid metabolism by PPARalpha
R-HSA-556833	Metabolism of lipids
R-HSA-597592	Post-translational protein modification
R-HSA-6806667	Metabolism of fat-soluble vitamins
R-HSA-8963898	Plasma lipoprotein assembly
R-HSA-8963899	Plasma lipoprotein remodeling
R-HSA-9709957	Sensory Perception

MSigDB gene sets: 300 (showing top): GOBP_CELLULAR_RESPONSE_TO_LIPOPROTEIN_PARTICLE_STIMULUS, GOBP_DIGESTION, MODULE_97, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLCHOLINE_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_POSITIVE_REGULATION_OF_INTERLEUKIN_8_PRODUCTION, GOBP_STEROL_HOMEOSTASIS, GOBP_LIPOPROTEIN_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLCHOLINE_BIOSYNTHETIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_LIPID_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_PRODUCTION_OF_MOLECULAR_MEDIATOR_OF_IMMUNE_RESPONSE, GNF2_HPN, GOBP_NEGATIVE_REGULATION_OF_CYTOKINE_PRODUCTION_INVOLVED_IN_IMMUNE_RESPONSE, MODULE_182

GO Biological Process (34): negative regulation of cytokine production involved in immune response (GO:0002719), triglyceride metabolic process (GO:0006641), phosphatidylcholine biosynthetic process (GO:0006656), cholesterol metabolic process (GO:0008203), phospholipid catabolic process (GO:0009395), response to glucose (GO:0009749), negative regulation of very-low-density lipoprotein particle remodeling (GO:0010903), protein oxidation (GO:0018158), peptidyl-methionine modification (GO:0018206), regulation of intestinal cholesterol absorption (GO:0030300), cholesterol transport (GO:0030301), regulation of protein stability (GO:0031647), negative regulation of cholesterol transport (GO:0032375), positive regulation of interleukin-8 production (GO:0032757), cholesterol efflux (GO:0033344), phospholipid efflux (GO:0033700), triglyceride-rich lipoprotein particle remodeling (GO:0034370), low-density lipoprotein particle remodeling (GO:0034374), high-density lipoprotein particle remodeling (GO:0034375), high-density lipoprotein particle assembly (GO:0034380), high-density lipoprotein particle clearance (GO:0034384), lipoprotein metabolic process (GO:0042157), cholesterol homeostasis (GO:0042632), reverse cholesterol transport (GO:0043691), diacylglycerol catabolic process (GO:0046340), positive regulation of phagocytosis (GO:0050766), protein stabilization (GO:0050821), negative regulation of lipid catabolic process (GO:0050995), positive regulation of lipid catabolic process (GO:0050996), negative regulation of cholesterol import (GO:0060621), cellular response to lipoprotein particle stimulus (GO:0071402), lipid transport (GO:0006869), signal transduction (GO:0007165), cellular response to amyloid-beta (GO:1904646)

GO Molecular Function (18): signaling receptor binding (GO:0005102), lipid carrier activity (GO:0005319), phospholipid binding (GO:0005543), high-density lipoprotein particle binding (GO:0008035), lipid binding (GO:0008289), cholesterol binding (GO:0015485), enzyme binding (GO:0019899), heat shock protein binding (GO:0031072), phosphatidylcholine binding (GO:0031210), apolipoprotein receptor binding (GO:0034190), protein homodimerization activity (GO:0042803), protein heterodimerization activity (GO:0046982), receptor ligand activity (GO:0048018), lipase inhibitor activity (GO:0055102), phosphatidylcholine-sterol O-acyltransferase activator activity (GO:0060228), high-density lipoprotein particle receptor binding (GO:0070653), protein binding (GO:0005515), cholesterol transfer activity (GO:0120020)

GO Cellular Component (11): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), early endosome (GO:0005769), endoplasmic reticulum lumen (GO:0005788), cytosol (GO:0005829), very-low-density lipoprotein particle (GO:0034361), high-density lipoprotein particle (GO:0034364), spherical high-density lipoprotein particle (GO:0034366), chylomicron (GO:0042627), extracellular exosome (GO:0070062), blood microparticle (GO:0072562)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Metabolism of proteins	2
Metabolism	2
Plasma lipoprotein assembly, remodeling, and clearance	2
Regulation of lipid metabolism by PPARalpha	1
Post-translational protein modification	1
Plasma lipoprotein assembly	1
Plasma lipoprotein remodeling	1
Visual phototransduction	1
Metabolism of fat-soluble vitamins	1
Transport of small molecules	1
Sensory Perception	1
Metabolism of lipids	1
Metabolism of vitamins and cofactors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
plasma lipoprotein particle remodeling	3
protein binding	3
cellular anatomical structure	3
cholesterol transport	2
binding	2
signaling receptor binding	2
protein dimerization activity	2
plasma lipoprotein particle	2
negative regulation of cytokine production	1
cytokine production involved in immune response	1
negative regulation of production of molecular mediator of immune response	1
regulation of cytokine production involved in immune response	1
acylglycerol metabolic process	1
phosphatidylcholine metabolic process	1
glycerophospholipid biosynthetic process	1
sterol metabolic process	1
secondary alcohol metabolic process	1
phospholipid metabolic process	1
lipid catabolic process	1
organophosphate catabolic process	1
response to hexose	1
regulation of very-low-density lipoprotein particle remodeling	1
very-low-density lipoprotein particle remodeling	1
negative regulation of cellular component organization	1
negative regulation of multicellular organismal process	1
protein modification process	1
peptidyl-amino acid modification	1
intestinal cholesterol absorption	1
regulation of intestinal lipid absorption	1
sterol transport	1
regulation of biological quality	1
negative regulation of sterol transport	1
regulation of cholesterol transport	1
positive regulation of cytokine production	1
interleukin-8 production	1
regulation of interleukin-8 production	1
phospholipid transport	1
plasma lipoprotein particle assembly	1
molecular carrier activity	1
lipid binding	1

Protein interactions and networks

STRING

1700 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
APOA2	APOA1	P02647	999
APOA2	APOE	P02649	998
APOA2	APOC3	P02656	996
APOA2	APOD	P05090	986
APOA2	APOB	P04114	985
APOA2	APOA4	P06727	967
APOA2	APOC1	P02654	960
APOA2	APOC2	P02655	930
APOA2	LCAT	P04180	912
APOA2	ALB	P02768	901
APOA2	CETP	P11597	898
APOA2	CLU	P10909	890
APOA2	LPA	P08519	883
APOA2	ABCA1	O95477	872
APOA2	APOM	O95445	856

IntAct

99 interactions, top by confidence:

A	B	Type	Score
MED21	MED19	psi-mi:“MI:0914”(association)	0.880
CATSPER1	APOA2	psi-mi:“MI:0915”(physical association)	0.780
APOA2	CATSPER1	psi-mi:“MI:0915”(physical association)	0.780
JUN	NFATC1	psi-mi:“MI:0914”(association)	0.610
APOA2		psi-mi:“MI:0915”(physical association)	0.560
APOA2	KIR2DL3	psi-mi:“MI:0915”(physical association)	0.560
APOA2	HSD17B13	psi-mi:“MI:0915”(physical association)	0.560
	APOA2	psi-mi:“MI:0915”(physical association)	0.560
APOA2	GJA8	psi-mi:“MI:0915”(physical association)	0.560
APOA2	AQP6	psi-mi:“MI:0915”(physical association)	0.560
APOA2	MUC1	psi-mi:“MI:0915”(physical association)	0.560
APOA2	SSMEM1	psi-mi:“MI:0915”(physical association)	0.560
APOA2	SLC7A1	psi-mi:“MI:0915”(physical association)	0.560
APOA2	STOM	psi-mi:“MI:0915”(physical association)	0.560
APOA2	PDZK1IP1	psi-mi:“MI:0915”(physical association)	0.560
APOA2	CIAO2A	psi-mi:“MI:0915”(physical association)	0.560
APOA2	PANX1	psi-mi:“MI:0915”(physical association)	0.560
APOA2	TMEM45A	psi-mi:“MI:0915”(physical association)	0.560
APOA2	CYBC1	psi-mi:“MI:0915”(physical association)	0.560
GET1	APOA2	psi-mi:“MI:0915”(physical association)	0.560
CREB3	APOA2	psi-mi:“MI:0915”(physical association)	0.550
APOA2	CREB3	psi-mi:“MI:0915”(physical association)	0.550
	CD5L	psi-mi:“MI:0915”(physical association)	0.400
APOA2	CREB3	psi-mi:“MI:0915”(physical association)	0.370
APOA2		psi-mi:“MI:0915”(physical association)	0.370

BioGRID (122): CATSPER1 (Two-hybrid), APOA2 (Affinity Capture-MS), APOA2 (Two-hybrid), APOA2 (Affinity Capture-MS), APOA2 (Affinity Capture-MS), APOA2 (Two-hybrid), APOA2 (FRET), APOA2 (Affinity Capture-MS), APOA2 (Reconstituted Complex), CATSPER1 (Two-hybrid), CREB3 (Two-hybrid), APOA2 (Affinity Capture-MS), APOA2 (Two-hybrid), APOA2 (Two-hybrid), APOA2 (Two-hybrid)

ESM2 similar proteins: A0A1B0GTC6, A0A2U3Y4D7, A0A2Y9HRM2, G5BQH4, G5BWH8, G8F204, P01257, P01261, P02652, P02656, P06759, P0CE37, P0CE39, P0CF78, P0DJD2, P0DJG2, P0DKV2, P0DKV3, P0DKV4, P0DM95, P0DM96, P0DMP9, P0DMR2, P0DMT9, P0DN36, P0DP50, P0DP84, P0DP85, P0DP86, P0DP87, P0DTQ3, P0DTQ5, P0DTR6, P0DTS5, P18656, P18659, P33622, P40148, P41547, P70160

Diamond homologs: A0A2Y9GES1, E2RAK7, G5BWH8, P02652, P02653, P04638, P09813, P0DJD2, P0DJG2, P0DM93, P0DM94, P0DM95, P0DM96, P0DN36, P0DP50, P0DP84, P0DP85, P0DP86, P0DP87, P0DTR1, P0DTR2, P18656, P81644, P83704, Q8MIQ5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 54 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Post-translational protein phosphorylation	5	14.7×	7e-04
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	5	12.7×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

36 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	2
Uncertain significance	15
Likely benign	3
Benign	11

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
17935	NM_001643.2(APOA2):c.185+1G>A	Pathogenic
2690543	NM_001643.2(APOA2):c.301T>A (p.Ter101Arg)	Likely pathogenic
4541826	NM_001643.2(APOA2):c.301T>G (p.Ter101Gly)	Likely pathogenic

SpliceAI

435 predictions. Top by Δscore:

Variant	Effect	Δscore
1:161222917:CTTGG:C	donor_gain	1.0000
1:161222914:TTAC:T	donor_loss	0.9900
1:161222915:TAC:T	donor_loss	0.9900
1:161222916:A:AC	donor_gain	0.9900
1:161222916:A:C	donor_loss	0.9900
1:161222917:C:CC	donor_gain	0.9900
1:161223056:C:T	acceptor_gain	0.9800
1:161222523:C:CC	acceptor_gain	0.9700
1:161222946:TG:T	donor_gain	0.9700
1:161223345:CCCA:C	donor_loss	0.9700
1:161223346:CCA:C	donor_loss	0.9700
1:161223347:CA:C	donor_loss	0.9700
1:161223348:A:AT	donor_loss	0.9700
1:161223349:CCT:C	donor_loss	0.9700
1:161222520:GAC:G	acceptor_gain	0.9600
1:161222917:CT:C	donor_gain	0.9600
1:161222917:CTT:C	donor_gain	0.9600
1:161222917:CTTG:C	donor_gain	0.9600
1:161223056:C:CT	acceptor_gain	0.9600
1:161222519:AGAC:A	acceptor_gain	0.9400
1:161222524:T:C	acceptor_loss	0.9400
1:161222527:A:C	acceptor_gain	0.9400
1:161223058:C:CT	acceptor_gain	0.9400
1:161222531:G:C	acceptor_gain	0.9300
1:161223048:CTC:C	acceptor_gain	0.9300
1:161222518:AAGAC:A	acceptor_gain	0.9200
1:161223060:C:CT	acceptor_gain	0.9100
1:161223064:C:CT	acceptor_gain	0.9100
1:161222521:AC:A	acceptor_gain	0.9000
1:161222522:CC:C	acceptor_gain	0.9000

AlphaMissense

637 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:161223376:A:C	L9R	0.936
1:161222960:A:G	L48P	0.925
1:161223350:C:G	G18R	0.909
1:161223350:C:T	G18R	0.909
1:161222493:A:G	L72P	0.900
1:161223379:A:T	V8E	0.891
1:161223373:A:C	L10R	0.887
1:161223376:A:T	L9Q	0.886
1:161223352:T:A	E17V	0.883
1:161222981:A:T	V41E	0.864
1:161223034:T:A	R23S	0.861
1:161223034:T:G	R23S	0.861
1:161222922:C:G	A61P	0.848
1:161223388:G:T	A5E	0.836
1:161223373:A:T	L10H	0.835
1:161223376:A:G	L9P	0.824
1:161222969:C:T	G45D	0.821
1:161222921:G:T	A61D	0.818
1:161222460:A:G	L83P	0.814
1:161223370:A:C	L11R	0.803
1:161223364:A:T	I13N	0.801
1:161222994:A:C	Y37D	0.800
1:161223035:C:G	R23T	0.782
1:161223041:A:T	V21D	0.770
1:161222472:G:T	A79D	0.762
1:161222481:A:T	I76N	0.762
1:161223370:A:T	L11H	0.760
1:161223002:A:T	V34D	0.750
1:161223355:A:T	L16H	0.742
1:161223362:A:G	C14R	0.741

dbSNP variants (sampled 300 via entrez): RS1002514058 (1:161225225 C>T), RS1003036836 (1:161224895 C>T), RS1003145358 (1:161223110 C>G,T), RS1004589432 (1:161223729 A>C), RS1004851301 (1:161225179 T>C), RS1005037531 (1:161221937 C>T), RS1006991518 (1:161222399 G>A), RS1008701521 (1:161222626 C>A), RS1008782647 (1:161224201 C>T), RS1009168604 (1:161222965 C>A), RS1010347429 (1:161225584 G>T), RS1011220295 (1:161224583 G>A), RS1012830265 (1:161223642 A>C,G), RS1013081167 (1:161223161 A>C,G), RS1013113091 (1:161223505 C>A)

Disease associations

OMIM: gene MIM:107670 | disease phenotypes: MIM:621417, MIM:143890

GenCC curated gene-disease

Disease	Classification	Inheritance
apolipoprotein A-II amyloidosis	Supportive	Autosomal dominant
hypercholesterolemia, familial, 1	Limited	Autosomal recessive

Mondo (3): apolipoprotein A-II deficiency (MONDO:0980749), hypercholesterolemia, familial, 1 (MONDO:0007750), apolipoprotein A-II amyloidosis (MONDO:0016533)

Orphanet (2): AApoAII amyloidosis (Orphanet:238269), Homozygous familial hypercholesterolemia (Orphanet:391665)

HPO phenotypes

12 total (12 of 12 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0001084	Corneal arcus
HP:0001114	Xanthelasma
HP:0001677	Coronary artery atherosclerosis
HP:0002155	Hypertriglyceridemia
HP:0003107	Abnormal circulating cholesterol concentration
HP:0003141	Increased LDL cholesterol concentration
HP:0010874	Tendon xanthomatosis
HP:0031799	Decreased circulating apolipoprotein A-I concentration
HP:0034075	Decreased circulating apolipoprotein B concentration
HP:0034602	Decreased circulating apolipoprotein A-II concentration

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3813627	APOA2, TOMM40L		0.00	0

CTD chemical–gene interactions

56 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases expression	5
perfluorooctanoic acid	decreases expression, increases expression	3
methylmercuric chloride	decreases expression	2
sodium arsenite	decreases expression, increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
perfluorooctane sulfonic acid	decreases expression, increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Bezafibrate	increases expression	2
Cadmium	affects binding, decreases expression, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tretinoin	increases secretion, increases expression, increases reaction, affects expression	2
Aflatoxin B1	affects expression, decreases methylation	2
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	affects expression	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
tris(2-butoxyethyl) phosphate	affects expression	1
2-amino-9H-pyrido(2,3-b)indole	decreases expression	1
perfluorodecanoic acid	affects expression	1
2,2’-azobis(2-amidinopropane)	increases oxidation, affects cotreatment, decreases reaction	1
LG 100268	increases expression, increases reaction	1
perfluoro-n-heptanoic acid	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
perfluorobutane	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
obeticholic acid	increases expression	1
perfluorohexanesulfonic acid	affects expression	1
perfluorohexanoic acid	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
perfluorododecanoic acid	affects expression	1
perfluoroundecanoic acid	affects expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E0TP	Ubigene Hep G2 APOA2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

28 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT06231459	PHASE4	COMPLETED	Expression of Pro- and Anti-inflammatory Cytokines During Anti-PCSK9 in Familial Hypercholesterolemia
NCT00000594	PHASE3	COMPLETED	NHLBI Type II Coronary Intervention Study
NCT00092833	PHASE3	TERMINATED	Investigational Drug in Patients With Hypercholesterolemia or in Patients With Sitosterolemia (0653-026)(COMPLETED)
NCT00134485	PHASE3	COMPLETED	Study To Evaluate The Safety And Efficacy Of Torcetrapib/Atorvastatin In Subjects With Familial Hypercholerolemia
NCT00134511	PHASE3	COMPLETED	Study To Evaluate The Effect Of Torcetrapib/Atorvastatin In Patients With Genetic High Cholesterol Disorder
NCT00136981	PHASE3	COMPLETED	Carotid B-Mode Ultrasound Study to Compare Anti-Atherosclerotic Effect of Torcetrpib/Atorvastatin to Atorvastatin Alone.
NCT00384293	PHASE3	TERMINATED	Carotid IMT (Intima Media Thickening) Study (0524A-041)(TERMINATED)
NCT01524289	PHASE3	COMPLETED	Study to Assess the Tolerability and Efficacy of Anacetrapib (MK-0859) Co-Administered With Statin in Participants With Heterozygous Familial Hypercholesterolemia (MK-0859-020)
NCT00280995	PHASE2	COMPLETED	Dose-escalating Safety Study of ISIS 301012 in Homozygous Familial Hypercholesterolemia Subjects on Lipid Lowering Therapy
NCT00281008	PHASE2	COMPLETED	Study of ISIS 301012 (Mipomersen) in Heterozygous Familial Hypercholesterolemia Subjects on Lipid Lowering Therapy
NCT01375751	PHASE2	COMPLETED	Reduction of Low-Density Lipoprotein Cholesterol (LDL-C) With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study
NCT00515307	PHASE1	COMPLETED	Bone Marrow Stem Cells as a Source of Allogenic Hepatocyte Transplantation in Homozygous Familial Hypercholesterolemia
NCT01583647	PHASE1	TERMINATED	A Study of Extended-release (ER) Niacin/Laropiprant in Adolescents With Heterozygous Familial Hypercholesterolemia (MK-0524A-158)
NCT00005168	Not specified	COMPLETED	Hyperapo B and Coronary Heart Disease
NCT01753232	Not specified	COMPLETED	Safety and Efficacy of the DALI LDL-adsorber and MONET Lipoprotein Filter
NCT03018678	Not specified	COMPLETED	Screening Protocol for a Gene Therapy Trial in Subjects With Homozygous Familial Hypercholesterolemia
NCT03110432	Not specified	COMPLETED	Prospective German Very High Cardiovascular Risk Patients Dyslipidemia Treatment Indication Registry
NCT03795038	Not specified	COMPLETED	Comparison of the Plasma Lipoprotein Apheresis Systems DIAMED and MONET vs. the Whole Blood Apheresis System DALI
NCT03989167	Not specified	RECRUITING	Clinical Decision Support for Familial Hypercholesterolemia
NCT04073797	Not specified	RECRUITING	PET Imaging of Inflammation and Lipid Lowering Study
NCT04118348	Not specified	COMPLETED	Evaluating the Efficacy of Pediatric Lipid Screening Alerts
NCT04313270	Not specified	UNKNOWN	Subclinical Atherosclerosis in Patients With Familial Hypercholesterolemia Treated With Evolocumab®
NCT04526457	Not specified	COMPLETED	Is Family Screening Improved by Genetic Testing of Familial Hypercholesterolemia
NCT04656028	Not specified	ACTIVE_NOT_RECRUITING	Genetic Testing and Motivational Counseling for FH
NCT04722068	Not specified	COMPLETED	Regeneron 1331 Kinetics Sub-Study HoFH
NCT04837638	Not specified	UNKNOWN	Diet Quality and Coronary Artery Calcification in Adults With Heterozygous Familial Hypercholesterolemia
NCT06555120	Not specified	RECRUITING	Screening for Familial Hypercholesterolemia in Children
NCT07543731	Not specified	NOT_YET_RECRUITING	A Real-World Study of Long-Term Adherence and Persistence to Inclisiran, Evolocumab, and Alirocumab