Gene Report

Basic Information

Approved Symbol	APOE
Approved Name	apolipoprotein E
Previous Symbol	AD2
Previous Name	"Alzheimer disease 2 (APOE*E4-associated, late onset)"
Location	19q13.31
Position	chr19:45412508-45412650 (+)
External Links	Entrez Gene: 348 Ensembl: ENSG00000130203 UCSC: uc002pab.3 HGNC ID: 613
No. of Studies (Positive/Negative)	2(0/2)
Type	Literature-origin; Protein mapped

Positive relationships between APOE and MDD (count: 0)

Positive relationships between APOE and other components at different levels (count: 0)

Positive relationship network of APOE in MK4MDD

Network loading ...

Note:
1. The different color of the nodes denotes the level of the nodes.

Genetic/Epigenetic Locus	Protein and Other Molecule	Cell and Molecular Pathway	Neural System	Cognition and Behavior	Symptoms and Signs	Environment	MDD

2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network. If the mapped gene or protein is not from literature, square node would be used instead of Circle node. Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node. Right-click will show also the menus to link to the report page of the node and remove the node and related edges. Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web

Negative relationships between APOE and MDD (count: 2)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
APOE	Steffens DC, 2003	nomal people		There was no overall association between APOE and depression...... There was no overall association between APOE and depression. More...
APOE	Surtees PG, 2009	nomal people		No associations were found between APOE genotypes and measu...... No associations were found between APOE genotypes and measures either of past-year or lifetime MDD More...

Negative relationships between APOE and other components at different levels (count: 0)

APOE related SNPs in MK4MDD (count: 0)

APOE related proteins in MK4MDD (count: 1)

Approved Name	UniportKB	No. of Studies (Positive/Negative)	Source
Apolipoprotein E	P02649	2(2/0)	Literature-origin

APOE related GO terms (count: 126)

ID	Name	Type	Evidence
Literature-origin GO terms
GO:0016209	antioxidant activity	molecular function	IDA[9685360]

ID	Name	Type	Evidence
Gene mapped GO terms
GO:1901216	positive regulation of neuron death	biological process	IDA[24259049]
GO:0034374	low-density lipoprotein particle remodeling	biological process	IEA
GO:0005543	phospholipid binding	molecular function	IDA[4066713]
GO:0031102	neuron projection regeneration	biological process	IBA
GO:0033344	cholesterol efflux	biological process	IDA[11162594\|16443932]
GO:0006775	fat-soluble vitamin metabolic process	biological process	TAS
GO:0006695	cholesterol biosynthetic process	biological process	IBA
GO:0005319	lipid transporter activity	molecular function	IDA[17305370]
GO:0046889	positive regulation of lipid biosynthetic process	biological process	IDA[12042316]
GO:0019934	cGMP-mediated signaling	biological process	IDA[8995232]
GO:0042158	lipoprotein biosynthetic process	biological process	IEA
GO:1903002	positive regulation of lipid transport across blood brain barrier	biological process	IDA[24345162]
GO:0005634	nucleus	cellular component	IDA[21630459]
GO:0061000	negative regulation of dendritic spine development	biological process	IDA[24328732]
GO:0019068	virion assembly	biological process	IMP[25122793]
GO:0034361	very-low-density lipoprotein particle	cellular component	IDA[8245722\|17154273]
GO:0006898	receptor-mediated endocytosis	biological process	IDA[1917954]; TAS
GO:0010875	positive regulation of cholesterol efflux	biological process	IDA[12042316\|14754908]; IGI[12401887]
GO:1903001	negative regulation of lipid transport across blood brain barrier	biological process	IDA[24345162]
GO:0007010	cytoskeleton organization	biological process	TAS[9622609]
GO:1902430	negative regulation of beta-amyloid formation	biological process	IDA[24154541\|24259049]
GO:0070062	extracellular exosome	cellular component	IDA[19056867\|20458337\|23376485\|23533145]
GO:0051044	positive regulation of membrane protein ectodomain proteolysis	biological process	IDA[15950758]
GO:0010873	positive regulation of cholesterol esterification	biological process	IDA[15654758]
GO:0005886	plasma membrane	cellular component	TAS
GO:0010468	regulation of gene expression	biological process	IEA
GO:0006707	cholesterol catabolic process	biological process	IBA
GO:0007263	nitric oxide mediated signal transduction	biological process	IDA[8995232]
GO:1903561	extracellular vesicle	cellular component	IDA[24769233]
GO:1902947	regulation of tau-protein kinase activity	biological process	IDA[24154541]
GO:0032805	positive regulation of low-density lipoprotein particle receptor catabolic process	biological process	IDA[15950758]
GO:0042311	vasodilation	biological process	IEA
GO:0007186	G-protein coupled receptor signaling pathway	biological process	IDA[16443932]
GO:0060999	positive regulation of dendritic spine development	biological process	IDA[24328732]
GO:1901630	negative regulation of presynaptic membrane organization	biological process	IDA[24259049]
GO:0051000	positive regulation of nitric-oxide synthase activity	biological process	IDA[8995232]
GO:0043407	negative regulation of MAP kinase activity	biological process	IDA[9685360]
GO:0072562	blood microparticle	cellular component	IDA[22516433]
GO:0005515	protein binding	molecular function	IPI[7566652\|7972031\|8245722\|12950167\|19758344\|21163940\|21593558\|24447298\|25122793]
GO:0097114	NMDA glutamate receptor clustering	biological process	IDA[24328732]
GO:0090370	negative regulation of cholesterol efflux	biological process	IDA[12042316]
GO:0042802	identical protein binding	molecular function	IDA[4066713]
GO:0043025	neuronal cell body	cellular component	NAS[8083695]
GO:0031012	extracellular matrix	cellular component	IDA[23658023]
GO:0030828	positive regulation of cGMP biosynthetic process	biological process	IDA[8995232]
GO:1902004	positive regulation of beta-amyloid formation	biological process	IDA[24154541\|24259049]
GO:0071682	endocytic vesicle lumen	cellular component	TAS
GO:1902952	positive regulation of dendritic spine maintenance	biological process	IDA[24328732]
GO:1901215	negative regulation of neuron death	biological process	IDA[24259049]
GO:0034375	high-density lipoprotein particle remodeling	biological process	IGI[12401887]
GO:0034363	intermediate-density lipoprotein particle	cellular component	IDA[17336988]
GO:0017127	cholesterol transporter activity	molecular function	IBA
GO:0010544	negative regulation of platelet activation	biological process	IDA[8995232]
GO:0005576	extracellular region	cellular component	TAS
GO:0001523	retinoid metabolic process	biological process	TAS
GO:0033700	phospholipid efflux	biological process	IDA[11162594]
GO:0008203	cholesterol metabolic process	biological process	IDA[9649566]; IMP[3771793]
GO:0043524	negative regulation of neuron apoptotic process	biological process	IBA
GO:1902995	positive regulation of phospholipid efflux	biological process	IDA[12042316]
GO:0017038	protein import	biological process	IDA[24446231]
GO:1901628	positive regulation of postsynaptic membrane organization	biological process	IDA[24259049]
GO:0034382	chylomicron remnant clearance	biological process	IMP[7175379]
GO:1902999	negative regulation of phospholipid efflux	biological process	IDA[12042316]
GO:1900221	regulation of beta-amyloid clearance	biological process	IDA[24446231]
GO:0090090	negative regulation of canonical Wnt signaling pathway	biological process	TAS[22988876]
GO:0034362	low-density lipoprotein particle	cellular component	IDA[8245722]
GO:0070326	very-low-density lipoprotein particle receptor binding	molecular function	IDA[1384047]; IPI[12950167]
GO:0000302	response to reactive oxygen species	biological process	NAS[11743999]
GO:0048156	tau protein binding	molecular function	IPI[7566652]
GO:0005794	Golgi apparatus	cellular component	IDA[25122793]
GO:0005783	endoplasmic reticulum	cellular component	IDA[25122793]
GO:1902951	negative regulation of dendritic spine maintenance	biological process	IDA[24328732]
GO:0032489	regulation of Cdc42 protein signal transduction	biological process	IDA[16443932]
GO:0042632	cholesterol homeostasis	biological process	IDA[9649566]
GO:0097113	AMPA glutamate receptor clustering	biological process	IDA[24328732]
GO:0006641	triglyceride metabolic process	biological process	IDA[9649566]; IMP[3771793]
GO:0048168	regulation of neuronal synaptic plasticity	biological process	TAS[9622609]
GO:0043537	negative regulation of blood vessel endothelial cell migration	biological process	IDA[9685360]
GO:0046907	intracellular transport	biological process	TAS[9622609]
GO:0048844	artery morphogenesis	biological process	IEA
GO:0034364	high-density lipoprotein particle	cellular component	IDA[210174]
GO:0030195	negative regulation of blood coagulation	biological process	IDA[8995232]
GO:0019433	triglyceride catabolic process	biological process	IBA
GO:0051055	negative regulation of lipid biosynthetic process	biological process	IDA[12042316]
GO:0001937	negative regulation of endothelial cell proliferation	biological process	IDA[9685360]
GO:0007271	synaptic transmission, cholinergic	biological process	TAS[9622609]
GO:1901214	regulation of neuron death	biological process	IDA[24154541]
GO:0034447	very-low-density lipoprotein particle clearance	biological process	IDA[1917954]; IMP[9649566]
GO:0015485	cholesterol binding	molecular function	IBA
GO:0002021	response to dietary excess	biological process	IEA
GO:0050750	low-density lipoprotein particle receptor binding	molecular function	IDA[210175]; IPI[17326667]
GO:0043691	reverse cholesterol transport	biological process	IDA[8127890]
GO:0015909	long-chain fatty acid transport	biological process	IDA[24345162]
GO:0030425	dendrite	cellular component	NAS[8083695]
GO:0005737	cytoplasm	cellular component	NAS[8083695]; TAS[9622609]
GO:0050728	negative regulation of inflammatory response	biological process	IC[8995232]
GO:0006766	vitamin metabolic process	biological process	TAS
GO:0008289	lipid binding	molecular function	IDA[4066713]
GO:0044281	small molecule metabolic process	biological process	TAS
GO:0034380	high-density lipoprotein particle assembly	biological process	IDA[17305370]
GO:1901627	negative regulation of postsynaptic membrane organization	biological process	IDA[24259049]
GO:0055089	fatty acid homeostasis	biological process	IDA[24345162]
GO:0042159	lipoprotein catabolic process	biological process	IBA
GO:0042627	chylomicron	cellular component	IDA[8245722\|16935699]
GO:0051651	maintenance of location in cell	biological process	IEA
GO:0006874	cellular calcium ion homeostasis	biological process	IEA
GO:0005769	early endosome	cellular component	TAS
GO:0046911	metal chelating activity	molecular function	IDA[9685360]
GO:0016020	membrane	cellular component	IDA[19946888]
GO:0098869	cellular oxidant detoxification	biological process	IDA[9685360]
GO:0042157	lipoprotein metabolic process	biological process	TAS
GO:0030516	regulation of axon extension	biological process	TAS[9622609]
GO:0044794	positive regulation by host of viral process	biological process	IMP[25122793]
GO:1902998	positive regulation of neurofibrillary tangle assembly	biological process	IDA[24154541]
GO:1901631	positive regulation of presynaptic membrane organization	biological process	IDA[24259049]
GO:0071813	lipoprotein particle binding	molecular function	IEA
GO:0045541	negative regulation of cholesterol biosynthetic process	biological process	IDA[1917954]
GO:0005615	extracellular space	cellular component	IDA[16502470\|20551380]
GO:0008201	heparin binding	molecular function	IDA[2745454]
GO:0042803	protein homodimerization activity	molecular function	IPI[8245722]
GO:0007603	phototransduction, visible light	biological process	TAS
GO:0060228	phosphatidylcholine-sterol O-acyltransferase activator activity	molecular function	IDA[15654758]
GO:0034372	very-low-density lipoprotein particle remodeling	biological process	IDA[15654758]; IGI[12401887]
GO:0001540	beta-amyloid binding	molecular function	IDA[11305869]
GO:0034384	high-density lipoprotein particle clearance	biological process	IDA[210175]

APOE related KEGG pathways (count: 1)

ID	Name	Brief Description	Full Description
Gene mapped KEGG pathways
hsa05010	alzheimers disease	Alzheimer's disease	Alzheimer's disease (AD) is a chronic disorder that slowly d...... Alzheimer's disease (AD) is a chronic disorder that slowly destroys neurons and causes serious cognitive disability. AD is associated with senile plaques and neurofibrillary tangles (NFTs). Amyloid-beta (Abeta), a major component of senile plaques, has various pathological effects on cell and organelle function. The extracellular Abeta oligomers may activate caspases through activation of cell surface death receptors. Alternatively, intracellular Abeta may contribute to pathology by facilitating tau hyper-phosphorylation, disrupting mitochondria function, and triggering calcium dysfunction. To date genetic studies have revealed four genes that may be linked to autosomal dominant or familial early onset AD (FAD). These four genes include: amyloid precursor protein (APP), presenilin 1 (PS1), presenilin 2 (PS2) and apolipoprotein E (ApoE). All mutations associated with APP and PS proteins can lead to an increase in the production of Abeta peptides, specifically the more amyloidogenic form, Abeta42. FAD-linked PS1 mutation downregulates the unfolded protein response and leads to vulnerability to ER stress. More...

APOE related BioCarta pathways (count: 0)

APOE related Reactome pathways (count: 3)

ID	Name	Description
Gene mapped Reactome pathways
REACT_602	metabolism of_lipids_and_lipoproteins	Lipids are hydrophobic but otherwise chemically diverse mole...... Lipids are hydrophobic but otherwise chemically diverse molecules that play a wide variety of roles in human biology. They include ketone bodies, fatty acids, triacylglycerols, phospholipids and sphingolipids, eicosanoids, cholesterol, bile salts, steroid hormones, and fat-soluble vitamins, and function as a major source of energy (fatty acids, triacylglycerols, and ketone bodies), are major constituents of cell membranes (cholesterol and phospholipids), play a major role in their own digestion and uptake (bile salts), and participate in numerous signaling and regulatory processes (steroid hormones, eicosanoids, and sphingolipids). Because of their poor solubility in water, most lipids in extracellular spaces in the human body are found as complexes with specific carrier proteins. Regulation of the formation and movement of these lipoprotein complexes is a critical aspect of human lipid metabolism, and lipoprotein abnormalities are associated with major human disease processes including atherosclerosis and diabetes. Aspects of lipid metabolism currently annotated in Reactome include lipid digestion, trafficking of dietary sterols, triacylglycerol synthesis (fatty acid synthesis and triacylglycerol assembly), hormone-sensitive lipase-mediated triacylglycerol breakdown, and beta-oxidation of fatty acids, ketone body metabolism (synthesis and utilization), the synthesis of cholesterol, bile salts, and steroid hormones, and sphingolipid metabolism. Three aspects of lipoprotein function are currently annotated: chylomicron-mediated lipid transport, HDL (high density lipoprotein)-mediated lipid transport, and LDL (low density lipoprotein) endocytosis and degradation. More...
REACT_6823	lipoprotein metabolism	Because of their hydrophobicity, lipids are found in the ext...... Because of their hydrophobicity, lipids are found in the extracellular spaces of the human body primarily in the form of lipoprotein complexes. Chylomicrons form in the small intestine and transport dietary lipids to other tissues in the body. Very low density lipoproteins (VLDL) form in the liver and transport triacylglycerol synthesized there to other tissues of the body. As they circulate, VLDL are acted on by lipoprotein lipases on the endothelial surfaces of blood vessels, liberating fatty acids and glycerol to be taken up by tissues and converting the VLDL first to intermediate density lipoproteins (IDL) and then to low density lipoproteins (LDL). IDL and LDL are cleared from the circulation via a specific cell surface receptor, found in the body primarily on the surfaces of liver cells. High density lipoprotein (HDL) particles, initially formed primarily by the liver, shuttle several kinds of lipids between tissues and other lipoproteins. Notably, they are responsible for the so-called reverse transport of cholesterol from peripheral tissues to LDL for return to the liver. Three aspects of lipoprotein function are currently annotated in Reactome: chylomicron-mediated lipid transport, LDL endocytosis and degradation, and HDL-mediated lipid transport. More...
REACT_6841	chylomicron mediated_lipid_transport	Chylomicrons transport triacylglycerol, phospholipid, and ch...... Chylomicrons transport triacylglycerol, phospholipid, and cholesterol derived from dietary lipid from the small intestine to other tissues of the body. Each chylomicron assembles around a single molecule of apolipoprotein B-48 which at the time the particle leaves the intestine and enters the lymphatic circulation is complexed with >200,000 molecules of triacylglycerol. As chylomicrons circulate in the body, they acquire molecules of apolipoproteins C and E, and through interaction with endothelial lipases can lose a large fraction of their triacylglycerol. These changes convert them to chylomicron remnants which bind to LDL receptors, primarily on the surfaces of liver cells, clearing them from the circulation. This whole sequence of events is rapid: the normal lifespan of a chylomicron is 30 - 60 minutes. More...

APOE related interactors from protein-protein interaction data in HPRD (count: 17)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
APOE	VLDLR	No	in vivo	12167620
APOE	CNTF	No	in vitro	9236223
APOE	APOE	Yes	in vitro	9147408 , 7566652
APOE	PRNP	No	in vivo	15146195
APOE	LRP2	No	in vivo	11421580
APOE	PLTP	No	in vitro;in vivo	12810820
APOE	NEFM	No	in vitro	8620924
APOE	ALB	No	in vitro	8063017
APOE	SCARB1	No	in vitro;in vivo	12138091
APOE	MAPT	No	in vitro;in vivo	9147408 , 7566652 , 9512010
APOE	A2M	No	in vitro;in vivo	9831625
APOE	MAP2	No	in vitro	8624078
APOE	CTSB	Yes	in vivo	12057992
APOE	LRP8	Yes	in vivo	12167620 , 12950167
APOE	APP	No	in vitro	10559559
APOE	LRP1	No	in vivo	11421580
APOE	LDLR	No	in vitro;in vivo	12036962

Gene Report

Literature-origin GO terms

Gene mapped GO terms

Gene mapped KEGG pathways

Gene mapped Reactome pathways