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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

APOE Gene

protein-coding GIFtS: 69
GCID: GC19P045408

apolipoprotein E

(Previous names: Alzheimer disease 2 (APOE*E4-associated, late onset) )
(Previous symbol: AD2)

Explore 288 diseases affiliated with
APOE via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Apolipoprotein E¹ ²		Alzheimer Disease 2 (APOE*E4-Associated, Late Onset)¹
AD2¹ ² ⁵		Apo-E³
LDLCQ5² ⁵		Apolipoprotein E3²
LPG² ⁵		Apo-E³

External Ids:	HGNC: 613¹	Entrez Gene: 348²	Ensembl: ENSG00000130203⁷	OMIM: 107741⁵	UniProtKB: P02649³

Export aliases for APOE gene to outside databases

Previous GC identifers: GC19P046053 GC19P045799 GC19P050085 GC19P050100 GC19P041839

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for APOE:

Chylomicron remnants and very low density lipoprotein (VLDL) remnants are rapidly removed from the circulation by

receptor-mediated endocytosis in the liver. Apolipoprotein E, a main apoprotein of the chylomicron, binds to a

specific receptor on liver cells and peripheral cells. ApoE is essential for the normal catabolism of

triglyceride-rich lipoprotein constituents. The APOE gene is mapped to chromosome 19 in a cluster with APOC1 and

APOC2. Defects in apolipoprotein E result in familial dysbetalipoproteinemia, or type III hyperlipoproteinemia (HLP

III), in which increased plasma cholesterol and triglycerides are the consequence of impaired clearance of chylomicron

and VLDL remnants. (provided by RefSeq, Jul 2008)

UniProtKB/Swiss-Prot: APOE_HUMAN, P02649

Function: Mediates the binding, internalization, and catabolism of lipoprotein particles. It can serve as a ligand for

the LDL (apo B/E) receptor and for the specific apo-E receptor (chylomicron remnant) of hepatic tissues

Gene Wiki entry for APOE (Apolipoprotein E)

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000019.9 NC_018930.1 NT_011109.16

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the APOE gene promoter:
c-Fos Sp1 AP-1 ATF-2 c-Jun
Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 4): APOE promoter sequence

Search SABiosciences Chromatin IP Primers for APOE

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat APOE

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 19q13.2 Ensembl cytogenetic band: 19q13.32 HGNC cytogenetic band: 19q13.31

APOE Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
APOE gene location

GeneLoc information about chromosome 19 GeneLoc Exon Structure

GeneLoc location for GC19P045408: view genomic region (about GC identifiers)

Start:	45,409,011 bp from pter	End:	45,412,650 bp from pter
Size:	3,640 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: APOE_HUMAN, P02649 (See protein sequence)

Recommended Name: Apolipoprotein E precursor

Size: 317 amino acids; 36154 Da

Subcellular location: Secreted

6/17 PDB 3D structures from and Proteopedia for APOE (see all 17):

1B68 (3D)

1BZ4 (3D)

1EA8 (3D)

1GS9 (3D)

1H7I (3D)

1LE2 (3D)

Secondary accessions: B2RC15 C0JYY5 Q9P2S4

Explore the universe of human proteins at neXtProt for APOE: NX_P02649

Post-translational modifications:

Synthesized with the sialic acid attached by O-glycosidic linkage and is subsequently desialylated in plasma.

O-glycosylated with core 1 or possibly core 8 glycans. Thr-307 and Thr-314 are minor glycosylation siteS compared to

Ser-308¹

Glycated in plasma VLDL of normal subjects, and of hyperglycemic diabetic patients at a higher level (2-3 fold)¹

Phosphorylation sites are present in the extracellular medium¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P02649

APOE Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins: NP_000032.1

ENSEMBL proteins:

ENSP00000252486 ENSP00000413135 ENSP00000413653 ENSP00000410423

Reactome Protein details: P02649
Human Recombinant Protein Products for APOE:

	EMD Millipore Purified and/or Recombinant APOE Protein
	R&D Systems Recombinant & Natural Proteins for APOE (Apolipoprotein E3/ApoE3)
	Browse recombinant and purified proteins available from Enzo Life Sciences
	OriGene Purified Protein: APOE OriGene Protein Over-expression Lysate: APOE OriGene Custom Protein Services for APOE
	GenScript Custom Purified and Recombinant Proteins Services for APOE
	Novus Biologicals APOE Proteins Novus Biologicals APOE Lysate
	Browse Sino Biological Recombinant Proteins
	Browse ProSpec Recombinant Proteins
	Uscn Proteins for APOE

Gene Ontology (GO): 5/16 cellular component terms (GO ID links to tree view) (see all 16): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005576	extracellular region	TAS	--
GO:0005615	extracellular space	IDA	--
GO:0005737	cytoplasm	TAS	9622609
GO:0005769	early endosome	--	--
GO:0005770	late endosome	IEA	--

APOE for ontologies About GeneDecksing

APOE Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of APOE
	R&D Systems Antibodies for APOE (Apolipoprotein E/ApoE, Apolipoprotein E3/ApoE3)
	Cell Signaling Technology (CST) Antibodies for APOE (ApoE iso4)
	OriGene Antibodies (see all 6): APOE OriGene Custom Antibody Services for APOE
	GenScript Superior Antibodies for APOE
	Novus Biologicals APOE Antibodies
	Abcam antibodies for APOE
	Uscn Antibodies for APOE
	ThermoFisher Antibody for APOE

Assay Products for APOE:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	Browse R&D Systems for biochemical assays
	GenScript Custom Assay Services for APOE
	Browse Enzo Life Sciences for kits & assays
	Uscn ELISAs and CLIAs for APOE

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

APOE for domains About GeneDecksing

2 InterPro domains/families:

IPR000074 ApoA1_A4_E

IPR013326 ApoA

Graphical View of Domain Structure for InterPro Entry P02649

ProtoNet protein and cluster: P02649

1 Blocks protein family: IPB000074 Apolipoprotein A1/A4/E

UniProtKB/Swiss-Prot: APOE_HUMAN, P02649

Similarity: Belongs to the apolipoprotein A1/A4/E family

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, Sirion Biotech, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, Sirion Biotech, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Molecular Function:

UniProtKB/Swiss-Prot Summary: APOE_HUMAN, P02649

Function: Mediates the binding, internalization, and catabolism of lipoprotein particles. It can serve as a ligand for

the LDL (apo B/E) receptor and for the specific apo-E receptor (chylomicron remnant) of hepatic tissues

Genatlas biochemistry entry for APOE:

apolipoprotein E,component of VLDL and ApoE receptors,putative susceptibility factor (epsilon 4 allele) for agressive

multiple sclerosis and for early-onset coronary heart disease

Gene Ontology (GO): 5/18 molecular function terms (GO ID links to tree view) (see all 18): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0001540	beta-amyloid binding	IDA	11305869
GO:0005319	lipid transporter activity	IDA	17305370
GO:0005515	protein binding	IPI	--
GO:0005543	phospholipid binding	IDA	4066713
GO:0008201	heparin binding	IDA	2745454

APOE for ontologies About GeneDecksing

Phenotypes:
1 GenomeRNAi human phenotype for APOE:

Decreased G3BP1 protein expres

15/26 MGI mutant phenotypes (inferred from 16 alleles) (MGI details for Apoe) (see all 26):

adipose tissue	behavior/neurological	cardiovascular system	cellular	digestive/alimentary
endocrine/exocrine gland	growth/size	hearing/vestibular/ear	hematopoietic system	homeostasis/metabolism
immune system	integument	limbs/digits/tail	liver/biliary system	mortality/aging

APOE for phenotypes About GeneDecksing

Animal Models:
Mouse knock-outs for APOE: Apoe^tm4Mae Apoe^tm1Lmh Apoe^tm1Bres Apoe^tm1Unc

inGenious Targeting Laboratory - Customizable classic, inducible, and humanized mouse model solutions for APOE

miRNA Products:		OriGene 3'-UTR Clone: APOE Browse MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat APOE
		Search QIAGEN for miScript miRNA Assays for microRNAs that regulate APOE
		Browse SwitchGear 3'UTR luciferase reporter plasmids

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for APOE (see all 7) OriGene shRNA RFP: APOE OriGene siRNA: APOE
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat APOE
		Sirion Biotech Custom design and validation of potent shRNA sequences against APOE

Gene Editing Products:			DNA2.0 Custom Protein Engineering Service for APOE
			Sirion Biotech Customized adenovirus for overexpression of APOE Sirion Biotech Customized adenovirus for potent knockdown of APOE

Clone Products:		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for APOE (see all 3) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for APOE OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector: APOE (NM_000041)
		Sino Biological Human cDNA Clone for APOE
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for APOE
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat APOE

Cell Line Products:		GenScript Custom overexpressing Cell Line Services for APOE
		LifeMap BioReagents: cell line associated with APOE: PureStem ES-210, Ecto-ntu Progenitor
		Sirion Biotech Customized stable knockdown cell line services for APOE Sirion Biotech Customized inducible knockdown cell line services for APOE Sirion Biotech Customized stable overexpressing cell line services for APOE Sirion Biotech Customized inducible overexpressing cell line services for APOE

In Situ Assay
Products:

Search Advanced Cell Diagnostics for RNAscope RNA in situ hybridization assays for APOE

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways - 5/13 super-pathways (see all 13) About this table

See pathways by source

Super-pathway

contained gene-specific pathways

Lipoprotein metabolism

	Lipoprotein metabolism	1.00			Chylomicron-mediated lipid transport	0.57
	HDL-mediated lipid transport	0.57			Lipid digestion, mobilization, and transport	0.56

Retinoid metabolism and transport

	Retinoid metabolism and transport	1.00			Diseases associated with visual transduction	0.73
	Visual phototransduction	0.74

Transcription_Role of VDR in regulation of genes involved in osteoporosis

Transcription_Role of VDR in regulation of genes involved in osteoporosis

1.00

Transcription Role of VDR in regulation of genes involved in osteoporosis

0.80

Metabolism

Metabolism

1.00

Metabolism of lipids and lipoproteins

0.34

Statin Pathway, Pharmacodynamics

Statin Pathway, Pharmacodynamics

1.00

Statin Pathway

0.80

Pathway sources
See GeneCards unified pathways
Show all pathways

1 EMD Millipore Pathway for APOE

Transcription Role of VDR in regulation of genes involved in osteoporosis

1 R&D Systems Pathway for APOE

A-beta Uptake & Degradation

2 Downloadable PowerPoint Slides of QIAGEN Pathway Central Maps for APOE

	Reelin Pathway (Cajal-Retzius cells)
	Alzheimers Disease Pathway

2 Cell Signaling Technology (CST) Pathways for APOE

	Neuroscience
	Glucose / Energy Metabolism

1 GeneGo (Thomson Reuters) Pathway for APOE

Transcription Role of VDR in regulation of genes involved in osteoporosis

2 BioSystems Pathways for APOE

	Statin Pathway
	Alzheimers Disease

5/11 Reactome Pathways for APOE (see all 11)

	Diseases associated with visual transduction
	Metabolism
	Chylomicron-mediated lipid transport
	Visual phototransduction
	Disease

1 PharmGKB Pathway for APOE

Statin Pathway, Pharmacodynamics

1 Kegg Pathway (Kegg details for APOE):

Alzheimer's disease

APOE for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for APOE

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

5/51 Interacting proteins for APOE (P02649^{1, 2, 3} ENSP00000252486⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 51)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
CDC37	Q16543¹^,³	EBI-1222467,EBI-295634 I2D: score=1
ECSIT	Q9BQ95¹^,³	EBI-1222467,EBI-712452 I2D: score=1
ST13	P50502¹^,³	EBI-1222467,EBI-357285 I2D: score=1
HP	P00738²^,³, ENSP00000348170⁴	MINT-7258801 MINT-7258760 MINT-7258778 MINT-7258819 MINT-7258848 MINT-7258877 MINT-7258791 I2D: score=2 STRING: ENSP00000348170
PDCD4	Q53EL6¹^,³, ENSP00000280154⁴	EBI-1222467,EBI-935824 I2D: score=1 STRING: ENSP00000280154

About this table

Gene Ontology (GO): 5/68 biological process terms (GO ID links to tree view) (see all 68): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000302	response to reactive oxygen species	NAS	11743999
GO:0001937	negative regulation of endothelial cell proliferation	IDA	9685360
GO:0002021	response to dietary excess	IEA	--
GO:0006629	lipid metabolic process	TAS	--
GO:0006641	triglyceride metabolic process	IMP	3771793

APOE for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

APOE for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse Tocris compounds for APOE

1 HMDB Compound for APOE About this table

Compound	Synonyms	CAS #	PubMed Ids
Heparin	Arteven (see all 17)	9005-49-6	--

2 DrugBank Compounds for APOE About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
Human Serum Albumin	--	9048-49-1	target	--	12887764 12860569 17553935 17141733 16554356
Serum albumin iodonated	--	9048-49-1	target	--	17016423 17378158 17139284 16441928

10/119 Novoseek chemical compound relationships for APOE gene (see all 119) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
cholesterol	88.7	2199	9541497 (7), 11369802 (7), 16185081 (7), 10484608 (7) (see all 99)
lipid	82.2	1527	15264189 (6), 16295048 (5), 10693931 (5), 15487712 (5) (see all 99)
24s-hydroxy-cholesterol	67.6	24	15975088 (4), 17822846 (4), 16524875 (3), 12707064 (2) (see all 10)
xbai	59.1	34	9298741 (2), 16699281 (2), 15543563 (2), 8013886 (2) (see all 23)
cholesterol ester	58.9	32	8420942 (3), 10870678 (3), 15955471 (2), 12919138 (2) (see all 16)
lathosterol	53.7	5	8548414 (1), 11726725 (1), 15331430 (1), 1865824 (1)
phospholipid	52.9	140	1730636 (4), 8908157 (4), 19159618 (3), 1540589 (3) (see all 73)
homocysteine	52.4	98	17764386 (6), 17243563 (3), 18023533 (2), 17420762 (2) (see all 43)
dimyristoylphosphatidylcholine	50.5	33	12633731 (3), 10751422 (2), 12364553 (2), 2026270 (1) (see all 11)
sterol	49	77	10760464 (5), 16254198 (5), 11893773 (5), 11742879 (5) (see all 27)

3 PharmGKB related drug/compound annotations for APOE gene About this table

Drug/compound	PharmGKB Annotation
"Antivirals for treatment of HIV infections, combinations"	CA
pravastatin	DL
ritonavir	CA

Search CenterWatch for drugs/clinical trials and news about APOE

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, Sirion Biotech, microRNA from QIAGEN,
Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for APOE gene:

NM_000041.2

Unigene Cluster for APOE:

Apolipoprotein E

Hs.654439 [show with all ESTs]

Unigene Representative Sequence: BQ683419

5 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000252486(uc002pab.3) ENST00000446996 ENST00000485628 ENST00000434152

ENST00000425718

miRNA Products:		OriGene 3'-UTR Clone: APOE Browse OriGene MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat APOE
		Search QIAGEN for miScript miRNA Assays for microRNAs that regulate APOE
		Browse SwitchGear 3'UTR luciferase reporter plasmids

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for APOE (see all 7) OriGene shRNA RFP: APOE OriGene siRNA: APOE
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat APOE
		Sirion Biotech Custom design and validation of potent shRNA sequences against APOE

Clone Products:		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for APOE (see all 3) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for APOE OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector: APOE (NM_000041)
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for APOE
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat APOE

Primer Products:		OriGene genome-wide validated SYBR primer pairs in human, mouse, rat for APOE Browse OriGene validated miRNA SYBR primer pairs
		SABiosciences RT² qPCR Primer Assay in human, mouse, rat APOE
		QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat APOE
		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat APOE

Additional cDNA sequence:

AK308546.1 AK314898.1 BC003557.1 K00396.1 M12529.1 X00199.1 Z70760.1

23 DOTS entries:

DT.100888329 DT.451248 DT.40133697 DT.97779727 DT.100888334 DT.100888336 DT.97792321 DT.91981242

DT.92463553 DT.100888335 DT.92463568 DT.92463567 DT.100045379 DT.100888330 DT.100888341 DT.121427095

DT.92015941 DT.92463546 DT.95136088 DT.95136093 DT.95136111 DT.100879799 DT.121121638

24/1484 AceView cDNA sequences (see all 1484):

AV709078 BU849868 AV690116 CB163752 AI360846 AI244051 BF221800 AV653141

N59187 AI359206 AI076868 AI983585 BF061098 BU628900 T67899 AI479896

AI694053 CA307890 BF061118 AI151046 AI589679 CA437408 AI497936 AI417309

GeneLoc Exon Structure

4 Alternative Splicing Database (ASD) splice patterns (SP) for APOE About this scheme

ExUns:	1a	·	1b	·	1c	·	1d	^	2a	·	2b	·	2c	^	3	^	4a	·	4b	·	4c	·	4d
SP1:							-		-		-
SP2:							-		-
SP3:									-		-
SP4:

ECgene alternative splicing isoforms for APOE

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

APOE expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: CGACCCCACG

About this image

APOE expression in embryonic tissues and stem cells
Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

3 LifeMap In Vivo Development Anatomical Compartments/Cells

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Eye

Inner Nuclear Layer

Mature Muller Glia Cells

Muller Glia, Retina

Brain

Liver

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

Stem Cell Differentiation: 10/12 LifeMap Cells (see all 12)

Name

Category

PureStem™ myogenic progenitor Z11 (Embryonic Progenitor Cell)

Heart, Myocardium, Smooth Muscle

PureStem™ mesenchymal Progenitor SK11 (Embryonic Progenitor Cell)

Adipose, Bone, Cartilage

PureStem™ mesenchymal progenitor SM30 (Embryonic Progenitor Cell)

Adipose, Bone, Cartilage

PureStem™ mesenchymal progenitor 7PEND24 (Embryonic Progenitor Cell)

Cartilage, Neural Crest

PureStem™ progenitor EN13 (Embryonic Progenitor Cell)

PureStem™ progenitor EN7 (Embryonic Progenitor Cell)

PureStem™ progenitor RASMO12 (Embryonic Progenitor Cell)

PureStem™ progenitor SK17 (Embryonic Progenitor Cell)

PureStem™ progenitor W10 (Embryonic Progenitor Cell)

PureStem™ progenitor W8 (Embryonic Progenitor Cell)

See APOE Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for APOE

SOURCE GeneReport for Unigene cluster: Hs.654439

UniProtKB/Swiss-Prot: APOE_HUMAN, P02649

Tissue specificity: Occurs in all lipoprotein fractions in plasma. It constitutes 10-20% of very low density

lipoproteins (VLDL) and 1-2% of high density lipoproteins (HDL). APOE is produced in most organs. Significant

quantities are produced in liver, brain, spleen, lung, adrenal, ovary, kidney and muscle

SABiosciences Expression via Pathway-Focused PCR Arrays including APOE (see all 14):

Neurogenesis in human mouse rat

Oxidative Stress in human mouse rat

Nitric Oxide Signaling Pathway in human mouse rat

Alzheimer's Disease in human mouse rat

Drug Metabolism in human mouse rat

Primer Products:		OriGene genome-wide validated SYBR primer pairs in human, mouse, rat for APOE Browse OriGene validated miRNA SYBR primer pairs
		SABiosciences RT² qPCR Primer Assay in human, mouse, rat APOE
		QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat APOE
		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat APOE

In Situ
Assay Products:

Search Advanced Cell Diagnostics for RNAscope RNA in situ hybridization assays for APOE

(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the common ancestor of chordates.

Orthologs for APOE gene from 2/8 species (see all 8) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Apoe^{1 , 5}	apolipoprotein E^{1, 5}	78.57(n)¹ 73.38(a)¹		7 (9.94 cM)⁵ 11816¹ NM_009696.3¹ NP_033826.2¹ 19696109⁵
zebrafish (Danio rerio)	Actinopterygii	apoeb¹	apolipoprotein Eb	47.36(n) 30.22(a)		30314 NM_131098.1 NP_571173.1

ENSEMBL Gene Tree for APOE (if available)
TreeFam Gene Tree for APOE (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

Paralogs for APOE gene

APOA1² APOA4² APOA5²

APOE for paralogs About GeneDecksing

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

UniProtKB/Swiss-Prot: APOE_HUMAN, P02649

Polymorphism: Three common APOE alleles have been identified: APOE*2, APOE*3, and APOE*4. The corresponding three major

isoforms, E2, E3, and E4, are recognized according to their relative position after isoelectric focusing. Different

mutations causing the same migration pattern after isoelectric focusing define different isoform subtypes. The most

common isoform is E3 and is present in 40-90% of the population. Common APOE variants influence lipoprotein metabolism

in healthy individuals

SNP ID	Valid	Clinical significance	Chr 19 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs11083750^1,2	C	non-pathogenic	41842644(+)	`GACCCA/C/GGGTGG`	3	Q P R	mis¹ ese³		0	--	--	--	--
rs121918392^1,2	C	pathogenic	41841820(+)	`AGGTGA/GAGCAA`	2	K E	mis¹		0	--	--	--	--
rs201672011^1,2	C	pathogenic	41841850(+)	`AGCCCA/GAGCTG`	2	K E	mis¹		0	--	--	--	--
rs769455^1,2	C,F,H	pathogenic	41842826(+)	`AGCTGC/TGTAAG`	2	R C	mis¹ ese³		11		NA EU CSAM MN NS WA	1524
rs121918397^1,2	C	pathogenic	41842827(+)	`GCTGCA/C/GTAAGC`	3	H P R	mis¹		0	--	--	--	--
rs121918394^1,2	C	pathogenic	41842829(+)	`TGCGTA/C/GAGCGG`	3	K Q E	mis¹		0	--	--	--	--
rs7412^1,2	C,F,A,H	pathogenic	41842865(+)	`AGAAGC/TGCCTG`	2	R C	mis¹		24		NA EU CSAM MN EA NS WA	6867
rs140808909^1,2	C	pathogenic	41843123(+)	`AGCTGA/GAGGAG`	2	K E	mis¹		0	--	--	--	--
rs190853081^1,2	C	pathogenic	41843126(+)	`TGGAGA/GAGCAG`	2	K E	mis¹		0	--	--	--	--
rs769452^1,2	C,F	untested	41841896(+)	`GGAACT/CGGCAC`	2	/P /L	mis¹		8		NA EU CSAM MN	5353

HapMap Linkage Disequilibrium report for APOE (45409011 - 45412650 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV) variations for APOE: --
Human Gene Mutation Database (HGMD): APOE

SABiosciences Cancer Mutation PCR Assays

QIAGEN SeqTarget long-range PCR primers in human, mouse, rat for resequencing APOE

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

APOE for disorders           About GeneDecksing

OMIM gene information: 107741
OMIM disorders: 269600  104310  603075  611771
UniProtKB/Swiss-Prot: APOE_HUMAN, P02649

Defects in APOE are a cause of hyperlipoproteinemia type 3 (HLPP3) [MIM:107741]; also known as familial

dysbetalipoproteinemia. Individuals with HLPP3 are clinically characterized by xanthomas, yellowish lipid deposits in

the palmar crease, or less specific on tendons and on elbows. The disorder rarely manifests before the third decade in

men. In women, it is usually expressed only after the menopause. The vast majority of the patients are homozygous for

APOE*2 alleles. More severe cases of HLPP3 have also been observed in individuals heterozygous for rare APOE variants.

The influence of APOE on lipid levels is often suggested to have major implications for the risk of coronary artery

disease (CAD). Individuals carrying the common APOE*4 variant are at higher risk of CAD

Genetic variations in APOE are associated with Alzheimer disease type 2 (AD2) [MIM:104310]. It is a late-onset

neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of

fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular

amyloid deposits. The major constituent of these plaques is the neurotoxic amyloid-beta-APP 40-42 peptide (s), derived

proteolytically from the transmembrane precursor protein APP by sequential secretase processing. The cytotoxic

C-terminal fragments (CTFs) and the caspase-cleaved products such as C31 derived from APP, are also implicated in

neuronal death. Note=The APOE*4 allele is genetically associated with the common late onset familial and sporadic

forms of Alzheimer disease. Risk for AD increased from 20% to 90% and mean age at onset decreased from 84 to 68 years

with increasing number of APOE*4 alleles in 42 families with late onset AD. Thus APOE*4 gene dose is a major risk

factor for late onset AD and, in these families, homozygosity for APOE*4 was virtually sufficient to cause AD by age

80. The mechanism by which APOE*4 participates in pathogenesis is not known

Defects in APOE are a cause of sea-blue histiocyte disease (SBHD) [MIM:269600]; also known as sea-blue

histiocytosis. This disorder is characterized by splenomegaly, mild thrombocytopenia and, in the bone marrow, numerous

histiocytes containing cytoplasmic granules which stain bright blue with the usual hematologic stains. The syndrome is

the consequence of an inherited metabolic defect analogous to Gaucher disease and other sphingolipidoses

Defects in APOE are a cause of lipoprotein glomerulopathy (LPG) [MIM:611771]. LPG is an uncommon kidney

disease characterized by proteinuria, progressive kidney failure, and distinctive lipoprotein thrombi in glomerular

capillaries. It mainly affects people of Japanese and Chinese origin. The disorder has rarely been described in

Caucasians

Defects in APOE are a cause of familial hypercholesterolemia (FH) [MIM:143890]. FH is a condition

characterized by elevated circulating cholesterol contained in either low-density lipoproteins alone or also in

very-low-density lipoproteins

20/288 diseases for APOE (see all 288): About MalaCards

hyperlipoproteinemia proximal spinal muscular atrophy smith-lemli-opitz syndrome defective apolipoprotein b-100

alzheimer's disease familial creutzfeldt-jakob disease angle-closure glaucoma cerebral amyloid angiopathy

spinal cord injury hyperlipoproteinemia type iii spinal muscular atrophy open-angle glaucoma

variant creutzfeldt-jakob disease persistent vegetative state primary angle-closure glaucoma hyperlipoproteinemia type v

inclusion body myositis finnish type amyloidosis wernicke-korsakoff syndrome normal pressure hydrocephalus

19 diseases from the University of Copenhagen DISEASES database for APOE:

Alzheimer's disease Atherosclerosis Vascular dementia Coronary heart disease

Amyloidosis Cerebrovascular accident Diabetes mellitus Familial hyperlipidemia

Aortic disease Lewy body dementia Hypertension Myocardial infarction

Down syndrome Frontotemporal dementia Abdominal aortic aneurysm Parkinson's disease

Kidney disease Progressive supranuclear palsy Age related macular degeneration

10/94 Novoseek disease relationships for APOE gene (see all 94) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
alzheimers disease	95	2575	14757857 (6), 9831633 (5), 11071064 (5), 9468467 (5) (see all 99)
hyperlipoproteinemia type iii	89.8	89	8175773 (4), 1730728 (3), 8185134 (3), 7772063 (3) (see all 55)
late onset alzheimer disease	88.1	55	8971103 (4), 7970184 (2), 8840393 (1), 11283204 (1) (see all 35)
dementia	86.6	681	9678314 (6), 12634288 (5), 9074395 (5), 19720080 (4) (see all 99)
senile plaques	85.4	257	9100668 (4), 11325345 (4), 7615568 (3), 10487843 (3) (see all 99)
cerebral amyloid angiopathy	82.6	68	8571412 (2), 15654038 (2), 18755411 (2), 17322072 (2) (see all 43)
neurofibrillary tangles	82.4	131	10487843 (3), 9018389 (3), 9258912 (2), 2029618 (2) (see all 86)
atherosclerosis	80.6	547	11369802 (5), 11007687 (5), 7593602 (5), 10933930 (5) (see all 99)
dementia vascular	77.9	92	8848934 (3), 8786847 (3), 9147873 (3), 15084782 (2) (see all 54)
hypertriglyceridemia	70.7	101	11337906 (4), 17919884 (3), 11163021 (3), 15576362 (3) (see all 53)

Genetic Association Database (GAD): APOE
Human Genome Epidemiology (HuGE) Navigator: APOE (2777 documents)

Export disorders for APOE gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
About This Section

PubMed articles for APOE gene, integrated from 9 sources (see all 5404):
(articles sorted by number of sources associating them with APOE)

Utopia: connect your pdf to the dynamic
world of online information

Familial splenomegaly: macrophage hypercatabolism of lipoproteins associated with apolipoprotein E mutation [apolipoprotein E (delta149 Leu)]. (PubMed id 11095479)^{1, 2, 4, 9} Nguyen T.T.... O'Brien T. (2000)
Analysis of association at single nucleotide polymorphisms in the APOE region. (PubMed id 10662539)^{1, 3, 4} Martin E.R....Vance J.M. (2000)
Variation at the APOE -491 promoter locus is associated with altered brain levels of apolipoprotein E. (PubMed id 12232782)^{1, 4, 9} Laws S.M....Martins R.N. (2002)
APOE and APOC1 promoter polymorphisms and the risk of Alzheimer disease in African American and Caribbean Hispanic individuals. (PubMed id 15364690)^{1, 4, 9} Tycko B....Mayeux R. (2004)
Modeling the influence of APOC3, APOE, and TNF polymorphisms on the risk of antiretroviral therapy-associated lipid disorders. (PubMed id 15809899)^{1, 4, 9} Tarr P.E....Telenti A. (2005)
Intronic CYP46 polymorphism along with ApoE genotype in sporadic Alzheimer Disease: from risk factors to disease modulators. (PubMed id 15165699)^{1, 4, 9} Borroni B....Padovani A. (2004)
Lp(a) and apoE polymorphisms in young South African Indians with myocardial infarction. (PubMed id 15258620)^{1, 4, 9} Ranjith N....Naidoo D.P. (2004)
The effects of gender and CYP46 and apo E polymorphism on 24S-hydroxycholesterol levels in Alzheimer's patients treated with statins. (PubMed id 15975088)^{1, 4, 9} Vega G.L....Moore C. (2004)
[Apolipoprotein E polymorphism in a Moroccan population: allele frequency and relation to plasma lipid concentrations] (PubMed id 11830396)^{1, 4, 9} Lahlali-Kacemi N....Lahrichi M. (2002)
Lack of association between apolipoprotein E genoype and ischaemic stroke in a Scottish population. (PubMed id 11454010)^{1, 4, 9} MacLeod M.J....Clair D.S. (2001)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
About This Section

Entrez Gene: 348	HGNC: 613	AceView: APOEandAPOC1	Ensembl:ENSG00000130203	euGenes: HUgn348
ECgene: APOE	Kegg: 348	H-InvDB: APOE

(According to HUGE)
About This Section

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Name	Description
PharmGKB entry for APOE	Pharmacogenomics, SNPs, Pathways
ATLAS Chromosomes in Cancer entry for APOE	Genetics and Cytogenetics in Oncology and Haematology
GeneReviews	http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/APOE
SHMPD	http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=APOE
Wikipedia	http://en.wikipedia.org/wiki/Apolipoprotein_E
Protein Spotlight	http://web.expasy.org/spotlight/back_issues/sptlt083.shtml

Intellectual Property for APOE gene
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Patent Information for APOE gene:
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GeneCards and IP:
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Supranuclear Palsy Progressive
Dementia
Down Syndrome
Genetic Susceptibility
cognitive disorder
Hyperlipoproteinemia Type V
cognitive dysfunction
Hyperlipidemia
Hypertriglyceridemias Familial
Atherosclerosis
ENDOGENOUS HYPERTRIGLYCERIDEMIA
Dementia Presenile
Memory impairment
Hypercholesterolemia
Nephrotic Syndrome
TUBEROUS XANTHOMA
alcoholic dementia
Amyloidosis
CETP DEFICIENCY
FRONTOTEMPORAL DEMENTIA
CREUTZFELDT-JAKOB DISEASE
Coronary Atherosclerosis
Familial Creutzfeldt-Jakob Disease
Xanthomatosis
Hyperlipidemia Familial Combined
Lipid Disorders
Sporadic Inclusion Body Myositis
Dyslipidemia
RENAL DISEASE
Maculopathy Age-Related
Early Onset Alzheimer Disease
Multiple Sclerosis
Inflammation
Xanthoma
Late Onset Alzheimer Disease
Diabetic Nephropathies
Drusen
Hyperhomocysteinemia
Hyperlipoproteinemia Type III
LACUNE
LCAT deficiency
Intracerebral Hemorrhage
Cardiovascular Diseases
Tangier Disease
Sporadic Cerebral Amyloid Angiopathy
Carotid Atherosclerosis
HEMORRHAGIC STROKE
Coronary Heart Disease
Neurofibrillary Tangles
Senile Plaques
APOLIPOPROTEIN B-100, FAMILIAL DEFECTIVE
Cerebral Amyloid Angiopathy
lipoprotein disorder
Neurodegenerative Diseases
Communication Disorders
Neurological Disorders
Memory Disorders
Parkinson Disease
Amyloid deposition
Abetalipoproteinemia
atherosclerotic plaque
paired helical filament
Infarction Lacunar
Neuropil Threads
Alzheimers Disease
Hyperlipoproteinemia
neurodegeneration
SENILE PLAQUE FORMATION
Combined hyperlipidemia
cognitive deficit
Carotid Artery Plaque
Myocardial Infarction
dyslipoproteinemia
Coronary Artery Disease
FINNISH TYPE AMYLOIDOSIS
Hypobetalipoproteinemia
Dementia Vascular
Hypertriglyceridemia
Picks Disease
OBESITY
Amyloidosis Systemic
Mixed hyperlipidemia
Atrophy
HYPOCHOLESTEROLEMIA
STROKE
Lewy Body Disease
Vascular Diseases
Brain Diseases
brain atrophy
CEREBROVASCULAR DISEASE
NIDDM
Hypercholesterolemia Familial
Dementia Multi-Infarct
Neuropathology

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