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GeneE
50 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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APOA1
apolipoprotein A1
Chromosome 11 Β· 11q23.3
NCBI Gene: 335Ensembl: ENSG00000118137.11HGNC: HGNC:600UniProt: A0A024R3E3
1,127PubMed Papers
24Diseases
0Drugs
33Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneTransporter
RESEARCH IMPACT
Highly StudiedTrending
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
positive regulation of substrate adhesion-dependent cell spreadingERK1 and ERK2 cascadecholesterol transportcholesterol transfer activityhypoalphalipoproteinemia, primary, 2familial visceral amyloidosisFamilial renal amyloidosishypoalphalipoproteinemia, primary, 2, intermediate
✦AI Summary

APOA1 (apolipoprotein A1) is the primary protein component of high-density lipoprotein (HDL) particles and functions as a master regulator of lipid and vascular homeostasis. Its primary role involves reverse cholesterol transport, whereby APOA1 promotes cholesterol efflux from peripheral tissues and acts as a cofactor for lecithin cholesterol acyltransferase (LCAT), facilitating cholesterol esterification and subsequent hepatic excretion 1. Beyond lipid metabolism, APOA1 exerts potent anti-inflammatory, anti-atherogenic, anti-apoptotic, and anti-thrombotic effects 1. Recent evidence reveals APOA1 modulates platelet function 2 and regulates matrix metalloproteinase-2 bioavailability through direct binding interactions 3. In pathological contexts, APOA1 dysfunction contributes to cardiovascular disease through multiple mechanisms. Proteolytic cleavage of APOA1 by asparagine endopeptidase at the N208 residue impairs HDL formation and cholesterol efflux, accelerating atherosclerosis development 4. Post-translational modifications of APOA1 by neutrophil myeloperoxidase generate immunogenic neo-epitopes that trigger proatherogenic IgG antibodies, predicting myocardial infarction and acute coronary syndrome risk 5. The APOA1 rs5069 polymorphism associates with early myocardial infarction susceptibility 6. Additionally, APOA1 depletion during sepsis severely compromises endothelial barrier integrity and microvascular perfusion 7, highlighting its critical protective role in vascular homeostasis. Therapeutic interventions including APOA1-mimetic peptides and synthetic reconstituted HDL are under clinical development 8.

Sources cited
1
APOA1 is the vital protein in HDL particles essential for reverse cholesterol transport and possesses anti-inflammatory, anti-atherogenic, anti-apoptotic, and anti-thrombotic properties
PMID: 36063649
2
Asparagine endopeptidase cleaves APOA1 at N208 residue, impairing cholesterol efflux and HDL formation, thereby accelerating atherosclerosis development
PMID: 40371638
3
Post-translational modifications of APOA1 by myeloperoxidase generate immunogenic neo-epitopes that induce proatherogenic APOA1-specific IgG antibodies associated with myocardial infarction and acute coronary syndrome
PMID: 27183204
4
APOA1 rs5069 polymorphism is significantly associated with early myocardial infarction in patients under 45 years of age
PMID: 39295604
5
APOA1/HDL depletion during sepsis impairs endothelial barrier integrity and microvascular flow through loss of protective mechanisms
PMID: 41063278
6
APOA1 and HDL modulate platelet function, which may influence atherothrombotic responses and cardiovascular disease risk
PMID: 40207365
7
APOA1 binds and regulates matrix metalloproteinase-2 bioavailability in blood through direct protein-protein interactions
PMID: 40263360
8
APOA1-mimetic peptides and synthetic reconstituted HDL preparations are under clinical development for multiple disease states
PMID: 33591433
Disease Associationsβ“˜24
hypoalphalipoproteinemia, primary, 2Open Targets
0.77Strong
familial visceral amyloidosisOpen Targets
0.73Strong
Familial renal amyloidosisOpen Targets
0.73Strong
hypoalphalipoproteinemia, primary, 2, intermediateOpen Targets
0.62Moderate
apolipoprotein A-I deficiencyOpen Targets
0.60Moderate
dengue diseaseOpen Targets
0.58Moderate
AL amyloidosisOpen Targets
0.46Moderate
Abnormality of the cardiovascular systemOpen Targets
0.39Weak
amyloidosisOpen Targets
0.39Weak
Tangier diseaseOpen Targets
0.38Weak
AApoAI amyloidosisOpen Targets
0.37Weak
Familial renal amyloidosis due to Apolipoprotein AI variantOpen Targets
0.37Weak
Severe intellectual disability and progressive spastic paraplegiaOpen Targets
0.33Weak
Spastic paraplegiaOpen Targets
0.33Weak
HypercholesterolemiaOpen Targets
0.31Weak
hypertensionOpen Targets
0.26Weak
response to xenobiotic stimulusOpen Targets
0.23Weak
hypoalphalipoproteinemia, primary, 1Open Targets
0.20Weak
chronic kidney diseaseOpen Targets
0.16Weak
familial hyperlipidemiaOpen Targets
0.16Weak
Amyloidosis, hereditary systemic 3UniProt
Familial apolipoprotein gene cluster deletion syndromeUniProt
Hypoalphalipoproteinemia, primary, 2UniProt
Hypoalphalipoproteinemia, primary, 2, intermediateUniProt
Pathogenic Variants33
NM_000039.3(APOA1):c.148G>C (p.Gly50Arg)Pathogenic
Familial amyloid polyneuropathy, Iowa type|Hypoalphalipoproteinemia, primary, 2;Hypoalphalipoproteinemia, primary, 2, intermediate;Familial amyloid polyneuropathy, Iowa type|not provided|Familial visceral amyloidosis, Ostertag type
β˜…β˜…β˜†β˜†2025β†’ Residue 50
NM_000039.3(APOA1):c.532_533dup (p.His179fs)Pathogenic
not provided|Familial visceral amyloidosis, Ostertag type;Hypoalphalipoproteinemia, primary, 2;Hypoalphalipoproteinemia, primary, 2, intermediate|Cardiovascular phenotype
β˜…β˜…β˜†β˜†2025β†’ Residue 179
NM_000039.3(APOA1):c.296T>C (p.Leu99Pro)Pathogenic
not provided|Cardiovascular phenotype|Hypoalphalipoproteinemia, primary, 2;Hypoalphalipoproteinemia, primary, 2, intermediate;Familial amyloid polyneuropathy, Iowa type
β˜…β˜…β˜†β˜†2025β†’ Residue 99
NM_000039.3(APOA1):c.590G>C (p.Arg197Pro)Pathogenic
not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 197
NM_000039.3(APOA1):c.67C>T (p.Gln23Ter)Pathogenic
not provided|Hypoalphalipoproteinemia, primary, 2
β˜…β˜…β˜†β˜†2024β†’ Residue 23
NM_000039.3(APOA1):c.200+1G>TPathogenic
not provided
β˜…β˜†β˜†β˜†2026
NM_000039.3(APOA1):c.220T>C (p.Trp74Arg)Pathogenic
Familial amyloid polyneuropathy, Iowa type|not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 74
NM_000039.3(APOA1):c.100C>T (p.Arg34Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 34
NM_000039.3(APOA1):c.66G>A (p.Trp22Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 22
NM_000039.3(APOA1):c.494T>G (p.Leu165Arg)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 165
NM_000039.3(APOA1):c.532_533del (p.Ala178fs)Likely pathogenic
Cardiovascular phenotype
β˜…β˜†β˜†β˜†2023β†’ Residue 178
NM_000039.3(APOA1):c.126C>G (p.Tyr42Ter)Likely pathogenic
Familial visceral amyloidosis, Ostertag type
β˜…β˜†β˜†β˜†2023β†’ Residue 42
NM_000039.3(APOA1):c.364C>T (p.Gln122Ter)Likely pathogenic
Hypoalphalipoproteinemia, primary, 2
β˜…β˜†β˜†β˜†2022β†’ Residue 122
NM_000039.3(APOA1):c.542A>G (p.Asp181Gly)Likely pathogenic
Hypoalphalipoproteinemia, primary, 2
β˜…β˜†β˜†β˜†2022β†’ Residue 181
NM_000039.3(APOA1):c.478G>T (p.Glu160Ter)Pathogenic
Hypoalphalipoproteinemia, primary, 2, intermediate
β˜†β˜†β˜†β˜†2024β†’ Residue 160
NM_000039.3(APOA1):c.250_284delinsGTCAC (p.Leu84_Phe95delinsValThr)Pathogenic
Familial amyloid polyneuropathy, Iowa type
β˜†β˜†β˜†β˜†2024β†’ Residue 84
NM_000039.3(APOA1):c.589C>T (p.Arg197Cys)Pathogenic
APOLIPOPROTEIN A-I (MILANO)
β˜†β˜†β˜†β˜†2003β†’ Residue 197
NM_000039.3(APOA1):c.595G>C (p.Ala199Pro)Pathogenic
Familial amyloid polyneuropathy, Iowa type
β˜†β˜†β˜†β˜†2002β†’ Residue 199
NM_000039.3(APOA1):c.593T>C (p.Leu198Ser)Pathogenic
Familial amyloid polyneuropathy, Iowa type
β˜†β˜†β˜†β˜†1999β†’ Residue 198
NM_000039.3(APOA1):c.518G>C (p.Arg173Pro)Pathogenic
Familial amyloid polyneuropathy, Iowa type
β˜†β˜†β˜†β˜†1999β†’ Residue 173
View on ClinVar β†—
Related Genes
HBBProtein interaction100%SAR1BProtein interaction100%ABCG5Protein interaction100%SELENOSProtein interaction100%APOFProtein interaction99%APOBProtein interaction99%
Tissue Expression6 tissues
Liver
100%
Heart
0%
Ovary
0%
Lung
0%
Bone Marrow
0%
Brain
0%
Gene Interaction Network
Click a node to explore
APOA1HBBSAR1BABCG5SELENOSAPOFAPOB
PROTEIN STRUCTURE
Preparing viewer…
PDB7KJR Β· 2.08 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.17LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.82 [0.58–1.17]
RankingsWhere APOA1 stands among ~20K protein-coding genes
  • #131of 20,598
    Most Researched1,127 Β· top 1%
  • #1,713of 5,498
    Most Pathogenic Variants33
  • #12,214of 17,882
    Most Constrained (LOEUF)1.17
Genes detectedAPOA1
Sources retrieved50 papers
Response timeβ€”
πŸ“„ Sources
50β–Ό
1
ApoA1 and ApoA1-specific self-antibodies in cardiovascular disease.
PMID: 27183204
Lab Invest Β· 2016
1.00
2
Asparagine endopeptidase cleaves apolipoprotein A1 and accelerates pathogenesis of atherosclerosis.
PMID: 40371638
J Clin Invest Β· 2025
0.90
3
Imbalance of APOB Lipoproteins and Large HDL in Type 1 Diabetes Drives Atherosclerosis.
PMID: 38828596
Circ Res Β· 2024
0.88
4
Interaction between APOE, APOA1, and LPL Gene Polymorphisms and Variability in Changes in Lipid and Blood Pressure following Orange Juice Intake: A Pilot Study.
PMID: 37128695
Mol Nutr Food Res Β· 2023
0.86
5
Low Serum Apolipoprotein A1 Levels Impair Antitumor Immunity of CD8+ T Cells via the HIF-1Ξ±-Glycolysis Pathway.
PMID: 38752667
Cancer Immunol Res Β· 2024
0.84