AiPD: Autoinhibited Protein Database

P02649

Gene name	APOE
Protein name	Apolipoprotein E
Names	Apo-E
Species	Homo sapiens (Human)
KEGG Pathway	hsa:348
EC number
Protein Class

Descriptions

The autoinhibited protein was predicted that may have potential autoinhibitory elements via cis-regPred.

Autoinhibitory domains (AIDs)

1-142 (Predicted disordered autoinhibitory region) PR

Target domain
Relief mechanism
Assay	cis-regPred

AID

1-142 (Predicted disordered autoinhibitory region)

Target domain

Relief mechanism

Assay

cis-regPred

Accessory elements

No accessory elements

References

Yeon JH et al. (2016) "Systems-wide Identification of cis-Regulatory Elements in Proteins", Cell Systems, 2, 89-100

Autoinhibited structure

Activated structure

29 structures for P02649

Entry ID	Method	Resolution	Chain	Position	Source
1B68	X-ray	200 A	A	19-209	PDB
1BZ4	X-ray	185 A	A	40-183	PDB
1EA8	X-ray	195 A	A	19-209	PDB
1GS9	X-ray	170 A	A	19-183	PDB
1H7I	X-ray	190 A	A	19-209	PDB
1LE2	X-ray	300 A	A	41-184	PDB
1LE4	X-ray	250 A	A	41-184	PDB
1LPE	X-ray	225 A	A	41-184	PDB
1NFN	X-ray	180 A	A	19-209	PDB
1NFO	X-ray	200 A	A	19-209	PDB
1OEF	NMR	-	A	281-304	PDB
1OEG	NMR	-	A	285-307	PDB
1OR2	X-ray	250 A	A	19-183	PDB
1OR3	X-ray	173 A	A	19-183	PDB
2KC3	NMR	-	A	19-201	PDB
2KNY	NMR	-	A	147-167	PDB
2L7B	NMR	-	A	19-317	PDB
6IWB	X-ray	250 A	A/C	41-186	PDB
6NCN	X-ray	182 A	A	19-180	PDB
6NCO	X-ray	171 A	A	19-180	PDB
7FCR	X-ray	140 A	A	19-209	PDB
7FCS	X-ray	160 A	A	19-209	PDB
7UVJ	X-ray	199 A	A/B	40-183	PDB
8AX8	X-ray	155 A	A	19-317	PDB
8AX9	X-ray	155 A	A	19-317	PDB
8CDY	X-ray	190 A	A	19-317	PDB
8CE0	X-ray	175 A	A	19-317	PDB
8GRX	EM	300 A	A/C	41-180	PDB
AF-P02649-F1	Predicted				AlphaFoldDB

398 variants for P02649

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
rs121918392 RCV000019429 VAR_000645 CA127499	21	E>K	HYPERLIPOPROTEINEMIA, TYPE III, AND ATHEROSCLEROSIS ASSOCIATED WITH APOE5 ApoE5; associated with hyperlipoproteinemia and atherosclerosis; increased binding to LDL receptor [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt 1000Genomes ExAC TOPMed dbSNP gnomAD
RCV002225641 RCV000019443 rs201672011 VAR_000646 RCV000019453 CA041327	31	E>K	Familial type 3 hyperlipoproteinemia HLPP3; ApoE4 Philadelphia, ApoE5 French-Canadian and ApoE5-type; only ApoE4 Philadelphia is associated with HLPP3 [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt 1000Genomes ExAC TOPMed dbSNP gnomAD
rs121918399 CA127525 VAR_042734 RCV000019468 RCV002496418	43	R>C	Alzheimer disease 3 Lipoprotein glomerulopathy (lpg) Lipoprotein glomerulopathy LPG; ApoE2 Kyoto [ClinVar, Ensembl, UniProt]	Yes	ClinGen ClinVar UniProt ExAC dbSNP gnomAD
RCV001195944 rs769452 RCV000429606 RCV002379036 CA041808 RCV000019456 VAR_000647 RCV001175124	46	L>P	Alzheimer disease 4 APOE4(-)-FREIBURG Familial hypercholesterolemia found in a patient with hypercholesterolemia; unknown pathological significance; ApoE4 Freiburg [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
CA127515 VAR_000648 rs28931576 RCV000019457	60	T>A	APOE3(-)-FREIBURG ApoE3 Freiburg [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt ExAC TOPMed dbSNP gnomAD
RCV000019459 CA042275 VAR_000651 rs28931577	117	A>T	APOE3 VARIANT ApoE3* [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV000074336 rs587778876 CA345321	122	L>M	Major depressive disorder [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
rs429358 RCV000856604 RCV000019447	130	C>=	Alzheimer disease 3, protection against, due to APOE3-Christchurch APOE3 ISOFORM [ClinVar]	Yes	ClinVar dbSNP
rs429358 CA127512 RCV000019455 RCV000019448 RCV000019458 RCV001262791 RCV000826089 RCV000019438 RCV000991302 VAR_000652 RCV000845581 RCV001195807 RCV000292119 RCV000019456 RCV001175124	130	C>R	Alzheimer disease 4 Primary degenerative dementia of the Alzheimer type, presenile onset Lipoprotein glomerulopathy APOE4(-)-FREIBURG Familial type 3 hyperlipoproteinemia Alzheimer disease Alzheimer disease 2 Familial hypercholesterolemia HLPP3 and AD2; ApoE4, ApoE3 Leiden, ApoE3, ApoE5-Frankfurt and ApoE5-type; ApoE3 Leiden and ApoE3 are associated with HLPP3; ApoE4 is associated with AD2; changed protein structure; no effect on binding to LDL receptor; decreased association with HDL and enrichment in VLDL and IDL; may prevent the interaction with MAP2 and MAPT; changed interaction with APP/A4 amyloid-beta peptide; increased ability to induce APP transcription; increased C-terminal proteolytic processing in neurons; decreased function in neurite outgrowth; ApoE4 is associated with higher susceptibility to SARS-CoV-2 infection in neurons and astrocytes [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
RCV000019434 rs397514254	139	E>missing	Familial type 3 hyperlipoproteinemia [ClinVar]	Yes	ClinVar dbSNP
rs1969863273 RCV001175125	141	Q>R	Familial type 3 hyperlipoproteinemia [ClinVar]	Yes	ClinVar dbSNP
rs267606664 RCV001262660 RCV001579351 RCV000019439 VAR_000653 CA041273 RCV002476210	145	G>D	Alzheimer disease 3 Hyperlipoproteinemia due to APOE1 found in a patient with hypercholesterolemia; unknown pathological significance; ApoE1 Weisgraber [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt ESP ExAC TOPMed dbSNP gnomAD
VAR_000654	145	G>GEVQAMLG	HLPP3; ApoE3 Leiden; no effect on glycosylation [UniProt]	Yes	UniProt
rs587778877 CA345323 RCV000074337	151	L>M	Major depressive disorder [ClinVar]	Yes	ClinGen ClinVar ExAC dbSNP gnomAD
rs28931578 VAR_000655 CA127517 RCV000019460	152	R>Q	APOE2 VARIANT ApoE2-type; no hyperlipidemia [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt TOPMed dbSNP gnomAD
CA9506071 rs121918393 VAR_000657	154	R>C	HLPP3; ApoE2-type [UniProt]	Yes	ClinGen UniProt ExAC TOPMed dbSNP gnomAD
RCV000019430 RCV000856604 rs121918393 CA127501 VAR_000656	154	R>S	Alzheimer disease 3, protection against, due to APOE3-Christchurch Familial type 3 hyperlipoproteinemia HLPP3; ApoE2 Christchurch; decreased binding to LDL receptor [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt ExAC TOPMed dbSNP gnomAD
rs387906567 CA041132 RCV000019438 VAR_000658	160	R>C	Familial type 3 hyperlipoproteinemia HLPP3; ApoE3** [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt dbSNP gnomAD
RCV000019443 CA127502 VAR_000659 rs769455 RCV000019432 RCV002326680 RCV001777143 RCV000884152	163	R>C	Familial type 3 hyperlipoproteinemia HLPP3; also found in a patient with hypercholesterolemia; ApoE4 Philadelphia and ApoE2-type [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
RCV000019449 CA127513 VAR_000660 RCV002250463 rs121918397	163	R>H	Lipoprotein glomerulopathy (lpg) Familial type 3 hyperlipoproteinemia Lipoprotein glomerulopathy HLPP3; unknown pathological significance; ApoE Kochi [Ensembl, ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt dbSNP gnomAD
VAR_042735 rs121918397 CA127524 RCV000019466	163	R>P	Lipoprotein glomerulopathy (lpg) Lipoprotein glomerulopathy LPG; ApoE2 Sendai; decreased binding to LDL receptor; induces intraglomerular deposition of ApoE-containing lipoproteins [Ensembl, ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt dbSNP gnomAD
rs121918394 VAR_000662 RCV000019440 CA127506	164	K>E	Familial type 3 hyperlipoproteinemia HLPP3; ApoE1 Harrisburg; decreased binding to LDL receptor; probable dominant negative effect; decreased in vitro binding to heparin [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt dbSNP gnomAD
rs121918394 VAR_000661 RCV001804151 CA127507	164	K>Q	Hyperlipoproteinemia, type III, due to APOE2 HLPP3; ApoE2** [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt dbSNP gnomAD
RCV003221804 rs515726148 RCV000202536 RCV002336246	167	L>missing	Sea-blue histiocyte syndrome [ClinVar]	Yes	ClinVar dbSNP
VAR_035015	167	L>del	SBHD; also found in patients with a diagnosis of familial combined hyperlipidemia [UniProt]	Yes	UniProt
RCV000019459 CA042396 VAR_000663 rs267606662	170	A>P	APOE3 VARIANT ApoE3*; decreased binding to LDL receptor [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV000019428 RCV000346955 RCV000845582 RCV001529800 RCV000019452 rs7412 VAR_000664 RCV001262472 RCV000019454 RCV000019439 CA127498 RCV000211178	176	R>C	Familial type 3 hyperlipoproteinemia Hyperlipoproteinemia due to APOE1 HLPP3; ApoE2, ApoE2 Fukuoka, ApoE1 Weisgraber and ApoE3; ApoE3 is associated with HLPP3; changed protein structure; decreased binding to LDLR and other lipoprotein receptors; decreased in vitro binding to heparin; no effect on distribution among plasma lipoproteins [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
RCV000856605 RCV000019445 CA127510 rs121918396	228	W>*	Familial type 3 hyperlipoproteinemia HYPERLIPOPROTEINEMIA, TYPE III, ASSOCIATED WITH APOE3(WASHINGTON) [ClinVar]	Yes	ClinGen ClinVar TOPMed dbSNP gnomAD
VAR_081136	228	W>del	HLPP3; ApoE3 Washington [UniProt]	Yes	UniProt
RCV000019452 rs267606663 CA041342 VAR_000665	242	R>Q	Familial type 3 hyperlipoproteinemia ApoE2 Fukuoka [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt ExAC dbSNP gnomAD
rs121918395 CA127508 VAR_000666 RCV000019442	246	R>C	Variant assessed as Somatic; 0.0 impact. APOE2-DUNEDIN ApoE2 Dunedin [NCI-TCGA, ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt ESP ExAC NCI-TCGA TOPMed dbSNP gnomAD
RCV001579858 VAR_000667 rs199768005 CA041472 RCV000019454 RCV001701092	254	V>E	Familial type 3 hyperlipoproteinemia ApoE2 WG [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt ESP ExAC TOPMed dbSNP gnomAD
rs140808909 RCV000019435 CA040712	262	E>K	HYPERLIPOPROTEINEMIA, TYPE III, AND ATHEROSCLEROSIS ASSOCIATED WITH APOE7 [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ExAC TOPMed dbSNP gnomAD
VAR_000668	262	E>KK	HLPP3; ApoE7 Suita [UniProt]	Yes	UniProt
rs190853081 RCV000019435 CA041004	263	E>K	HYPERLIPOPROTEINEMIA, TYPE III, AND ATHEROSCLEROSIS ASSOCIATED WITH APOE7 [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ExAC TOPMed dbSNP gnomAD
RCV000019455 RCV002483522 CA041514 VAR_000669 rs267606661 RCV001565388	269	R>G	Alzheimer disease 3 Familial type 3 hyperlipoproteinemia ApoE3 HB [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt ExAC TOPMed dbSNP gnomAD
rs121918398 VAR_000671 CA127519 RCV000019461	292	R>H	APOE4 VARIANT ApoE4 PD [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt dbSNP gnomAD
rs28931579 CA127521 VAR_000672 RCV000019462	314	S>R	APOE4(+) ApoE4 HG [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt ExAC TOPMed dbSNP gnomAD
CA9505925 rs777551553	5	W>*		No	ClinGen ExAC gnomAD
CA406301950 rs1568615382	6	A>T		No	ClinGen Ensembl
CA9505926 rs754318486	7	A>V		No	ClinGen ExAC gnomAD
rs923895447 CA308883668	8	L>*		No	ClinGen Ensembl
rs779278130 CA9505928	9	L>P		No	ClinGen ExAC gnomAD
rs1599950832 CA406302083	10	V>G		No	ClinGen Ensembl
CA406302071 rs1461741495	10	V>I		No	ClinGen gnomAD
CA9505931 rs144354013	11	T>A		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA9505930 rs144354013	11	T>S		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA406302118 rs1381224336	12	F>L		No	ClinGen gnomAD
CA9505932 rs747078681	12	F>Y		No	ClinGen ExAC TOPMed gnomAD
CA406302138 rs1568615443	13	L>R		No	ClinGen Ensembl
CA308883691 rs559532612	14	A>T		No	ClinGen 1000Genomes
rs752693941 CA308883724	15	G>*		No	ClinGen Ensembl
rs533904656 CA9505967	18	A>P		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs533904656 CA9505966	18	A>T		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
TCGA novel	19	K>R	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1456562720 CA406302412	22	Q>H		No	ClinGen TOPMed
CA9505969 rs776242156	23	A>V		No	ClinGen ExAC TOPMed gnomAD
CA406302420 rs1394832846	24	V>L		No	ClinGen TOPMed gnomAD
CA406302419 rs1394832846	24	V>M		No	ClinGen TOPMed gnomAD
CA406302425 rs1440976751	25	E>K		No	ClinGen Ensembl
rs764929617 CA9505972	28	P>L		No	ClinGen ExAC TOPMed gnomAD
CA9505975 rs752079771	33	R>C		No	ClinGen ExAC gnomAD
rs1212454788 CA406302480	33	R>H		No	ClinGen TOPMed gnomAD
TCGA novel	33	R>L	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1249808975 CA406302495	35	Q>R		No	ClinGen gnomAD
TCGA novel	36	T>S	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA9505978 rs142480126	37	E>K	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ESP ExAC NCI-TCGA gnomAD
CA406303216 rs1301411037	38	W>L		No	ClinGen TOPMed
rs756353413 COSM3960197 CA9505979	39	Q>R	lung [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs1599951908 CA406303267	41	G>D		No	ClinGen Ensembl
rs749406635 CA9505981	41	G>S		No	ClinGen ExAC TOPMed gnomAD
CA9505983 rs371694216	43	R>H		No	ClinGen ESP ExAC gnomAD
rs371694216 CA406303313	43	R>P		No	ClinGen ESP ExAC gnomAD
CA9505985 rs768684471	44	W>*		No	ClinGen ExAC gnomAD
rs1599951966 CA406303348	45	E>G		No	ClinGen Ensembl
rs769452 CA406303362	46	L>Q		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA406303377 rs1439276876	48	L>V		No	ClinGen gnomAD
rs1599952025 CA406303392	49	G>D		No	ClinGen Ensembl
rs1599952017 CA406303387	49	G>S		No	ClinGen Ensembl
CA9505987 rs11542029	50	R>C		No	ClinGen ExAC gnomAD
rs11542029 CA9505988	50	R>G		No	ClinGen ExAC gnomAD
CA9505991 rs762461580	50	R>H	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA TOPMed gnomAD
rs762461580 CA9505989	50	R>L		No	ClinGen ExAC TOPMed gnomAD
rs762461580 CA9505990	50	R>P		No	ClinGen ExAC TOPMed gnomAD
rs11542029 RCV000520712 CA406303398	50	R>S		No	ClinGen ClinVar ExAC dbSNP gnomAD
rs752790054 CA9505994	56	R>H	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA TOPMed gnomAD
rs28931576 CA406303469	60	T>S		No	ClinGen ExAC TOPMed gnomAD
rs1599952129 CA406303491	63	E>D		No	ClinGen Ensembl
CA406303486 rs1265280650	63	E>Q		No	ClinGen TOPMed
VAR_014114 rs370594287 CA9505996	64	Q>H	confirmed at protein level [UniProt]	No	ClinGen UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs780035531 CA9505998	67	E>K		No	ClinGen ExAC gnomAD
rs1052163943 CA406303522	68	E>*		No	ClinGen gnomAD
rs1418355128 CA406303526	68	E>D		No	ClinGen gnomAD
CA308884581 rs1052163943	68	E>K		No	ClinGen gnomAD
rs1184253344 CA406303525	68	E>V		No	ClinGen gnomAD
CA9506000 rs768780599	69	L>P		No	ClinGen ExAC TOPMed gnomAD
CA406303530 rs768780599	69	L>Q		No	ClinGen ExAC TOPMed gnomAD
rs1426176730 CA406303534	70	L>F		No	ClinGen gnomAD
CA406303535 rs1599952206	70	L>H		No	ClinGen Ensembl
CA308884592 rs757100480	72	S>P		No	ClinGen Ensembl
rs757100480 CA406303546	72	S>T		No	ClinGen Ensembl
CA406303551 rs1599952234	73	Q>K		No	ClinGen Ensembl
CA406303556 rs1164895411	73	Q>R		No	ClinGen gnomAD
rs769366285 CA9506003	74	V>A		No	ClinGen ExAC gnomAD
rs747975000 CA9506002	74	V>F		No	ClinGen ExAC TOPMed
rs747975000 CA308884594	74	V>I		No	ClinGen ExAC TOPMed
CA9506005 rs762703669	76	Q>R		No	ClinGen ExAC gnomAD
CA9506006 rs770545391	77	E>K		No	ClinGen ExAC TOPMed gnomAD
CA9506025 rs774000134	80	A>E		No	ClinGen ExAC gnomAD
rs557845700 CA308885232	82	M>I		No	ClinGen 1000Genomes
rs1407867184 CA406303629	82	M>R		No	ClinGen gnomAD
rs767980905 CA406303638	83	D>E		No	ClinGen ExAC TOPMed gnomAD
CA308885238 rs1023086190	84	E>K		No	ClinGen gnomAD
CA406303654 rs1434287349	86	M>V		No	ClinGen gnomAD
rs1334600571 CA406303671	88	E>Q		No	ClinGen gnomAD
CA406303675 rs1183932967	88	E>V		No	ClinGen TOPMed
rs368210726 CA9506028	89	L>S		No	ClinGen ESP ExAC TOPMed gnomAD
CA406303685 rs1278944082	90	K>E		No	ClinGen gnomAD
CA406303691 rs1377553244	90	K>N	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen NCI-TCGA gnomAD
rs1241692890 CA406303692	91	A>T		No	ClinGen gnomAD
rs1300558735 CA406303702	92	Y>C		No	ClinGen gnomAD
CA406303712 rs371331933	93	K>N		No	ClinGen ESP ExAC TOPMed gnomAD
rs761285934 CA406303709	93	K>R		No	ClinGen ExAC TOPMed gnomAD
CA9506029 rs761285934	93	K>T		No	ClinGen ExAC TOPMed gnomAD
CA9506031 rs776830091	94	S>*		No	ClinGen ExAC gnomAD
rs1238105907 CA406303729	96	L>P		No	ClinGen gnomAD
rs527236160 RCV000132772	98	E>missing		No	ClinVar dbSNP
CA406303740 rs1440786605	98	E>*		No	ClinGen TOPMed gnomAD
CA406303739 rs1440786605	98	E>K		No	ClinGen TOPMed gnomAD
rs1180612218 CA406303747 VAR_000649	99	Q>K	ApoE5 Frankfurt [UniProt]	No	ClinGen UniProt dbSNP gnomAD
rs577618688 CA9506033	99	Q>R		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1599952958 CA406303764	101	T>I		No	ClinGen Ensembl
rs11083750 CA308885271	102	P>L	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ESP ExAC NCI-TCGA TOPMed gnomAD
rs11083750 CA308885274	102	P>Q		No	ClinGen ESP ExAC TOPMed gnomAD
VAR_000650 rs11083750 RCV000019458 CA042073	102	P>R	ApoE5-type; no hyperlipidemia [UniProt]	No	ClinGen ClinVar UniProt ESP ExAC TOPMed dbSNP gnomAD
rs11542040 CA308885268	102	P>T		No	ClinGen Ensembl
CA406303768 rs1327865483 CA406303769	103	V>L		No	ClinGen TOPMed gnomAD
rs767382895 CA9506035	104	A>T		No	ClinGen ExAC TOPMed gnomAD
rs1448845160 CA406303777	104	A>V		No	ClinGen gnomAD
rs1369662219 CA406303787	106	E>Q		No	ClinGen gnomAD
rs749160976 CA9506039	108	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA308885296 rs1050106163	108	R>W	Variant assessed as Somatic; impact. [NCI-TCGA]	No	ClinGen Ensembl NCI-TCGA
CA406303804 rs1599953056	109	A>T		No	ClinGen Ensembl
CA406303808 rs1330045687	109	A>V		No	ClinGen TOPMed
CA9506042 rs778348297	110	R>Q		No	ClinGen ExAC TOPMed gnomAD
TCGA novel	111	L>M	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs745552623 CA9506043	112	S>Y		No	ClinGen ExAC TOPMed gnomAD
CA9506044 rs771594795	113	K>E		No	ClinGen ExAC gnomAD
CA406303825 rs1167428194	113	K>T		No	ClinGen TOPMed
CA406303830 rs1169728519	114	E>K		No	ClinGen gnomAD
CA406303838 rs1424027593	115	L>M		No	ClinGen gnomAD
rs1466963971 CA406303841	115	L>R		No	ClinGen gnomAD
rs1413443775 CA406303845	116	Q>*		No	ClinGen TOPMed
rs372938213 CA406303853	117	A>E		No	ClinGen ESP ExAC gnomAD
CA9506046 rs372938213	117	A>V	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ESP ExAC NCI-TCGA gnomAD
CA308885365 rs947015878	118	A>V	Variant assessed as Somatic; impact. [NCI-TCGA]	No	ClinGen NCI-TCGA TOPMed
CA9506048 rs777291619	119	Q>P		No	ClinGen ExAC TOPMed gnomAD
rs1429543001 CA406303870	120	A>D		No	ClinGen gnomAD
rs1324343215 CA406303868	120	A>S		No	ClinGen gnomAD
CA9506049 rs11542037	121	R>W		No	ClinGen ExAC TOPMed gnomAD
rs587778876 CA406303877	122	L>V		No	ClinGen Ensembl
TCGA novel	123	G>A	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA406303884 rs1356186009	123	G>D		No	ClinGen gnomAD
CA406303882 rs1271901056	123	G>R		No	ClinGen gnomAD
CA308885402 rs937063425 VAR_016789	124	A>V	Variant assessed as Somatic; impact. ApoE3 Basel [NCI-TCGA, UniProt]	No	ClinGen UniProt NCI-TCGA TOPMed dbSNP
CA406303892 rs993409614	125	D>H		No	ClinGen TOPMed
CA308885407 rs993409614	125	D>N		No	ClinGen TOPMed
CA9506052 rs763313394	128	D>N		No	ClinGen ExAC gnomAD
CA308885445 rs752600356	129	V>L		No	ClinGen ExAC gnomAD
CA9506054 rs752600356	129	V>M		No	ClinGen ExAC gnomAD
rs1367830766 CA406303929	130	C>Y		No	ClinGen gnomAD
rs1458301734 CA406303934	131	G>C		No	ClinGen gnomAD
CA406303937 rs1599953294	131	G>D		No	ClinGen Ensembl
rs1458301734 CA406303936	131	G>S		No	ClinGen gnomAD
rs11542041 CA9506055	132	R>C		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1263042140 CA406303941	132	R>H		No	ClinGen TOPMed gnomAD
CA406303943 rs1263042140	132	R>L		No	ClinGen TOPMed gnomAD
rs11542041 CA308885481	132	R>S		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA406303959 rs753798476	135	Q>L		No	ClinGen ExAC TOPMed gnomAD
CA9506056 rs753798476	135	Q>R		No	ClinGen ExAC TOPMed gnomAD
rs1341982092 CA406303966	136	Y>C		No	ClinGen gnomAD
rs573658040 CA9506058	137	R>C		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs573658040 CA406303971	137	R>G		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA308885519 rs11542035	137	R>H		No	ClinGen TOPMed gnomAD
rs543363163 CA406303975	138	G>C		No	ClinGen 1000Genomes ExAC gnomAD
CA406303976 rs1246120787	138	G>D		No	ClinGen gnomAD
rs543363163 CA9506059	138	G>S		No	ClinGen 1000Genomes ExAC gnomAD
CA308885532 rs41382345	139	E>V		No	ClinGen Ensembl
CA406303986 CA9506061 rs779569800	140	V>L		No	ClinGen ExAC TOPMed gnomAD
CA9506062 rs779569800	140	V>M		No	ClinGen ExAC TOPMed gnomAD
rs1162012100 CA406304000	142	A>T		No	ClinGen TOPMed
CA9506064 CA9506063 rs768925016	143	M>L		No	ClinGen ExAC gnomAD
CA406304013 rs1287096724	144	L>I		No	ClinGen gnomAD
CA406304018 rs267606664	145	G>A		No	ClinGen ESP ExAC TOPMed gnomAD
rs748703149 CA308885595	145	G>C		No	ClinGen ExAC TOPMed gnomAD
CA406304017 rs748703149	145	G>R		No	ClinGen ExAC TOPMed gnomAD
rs748703149 CA9506065	145	G>S		No	ClinGen ExAC TOPMed gnomAD
CA406304022 rs1189593420	146	Q>*		No	ClinGen gnomAD
rs1032082950 CA308885618	148	T>I		No	ClinGen Ensembl
rs762933906 CA9506068	149	E>D		No	ClinGen ExAC gnomAD
rs1438607869 CA406304041	149	E>K		No	ClinGen gnomAD
CA308885645 rs11542034	150	E>G		No	ClinGen Ensembl
rs1289377244 CA406304058	151	L>R		No	ClinGen TOPMed
rs28931578 CA406304060	152	R>L		No	ClinGen TOPMed gnomAD
rs28931578 CA308885664	152	R>P		No	ClinGen TOPMed gnomAD
rs531939919 CA9506070	152	R>W		No	ClinGen 1000Genomes ExAC gnomAD
rs1599953509 CA406304064	153	V>A		No	ClinGen Ensembl
rs990344075 CA308885673	153	V>M		No	ClinGen TOPMed gnomAD
RCV000417087 rs200703101 CA16044403	154	R>L		No	ClinGen ClinVar Ensembl dbSNP
rs200703101 CA308885705	154	R>P		No	ClinGen Ensembl
CA406304068 rs1018669382	155	L>F		No	ClinGen TOPMed gnomAD
rs1018669382 CA308885718	155	L>V		No	ClinGen TOPMed gnomAD
CA308885722 rs954186991	156	A>S		No	ClinGen TOPMed gnomAD
rs954186991 CA308885721	156	A>T	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen NCI-TCGA TOPMed gnomAD
CA406304081 rs1483485796	157	S>F		No	ClinGen gnomAD
rs998239069 CA308885728	157	S>T		No	ClinGen TOPMed
CA308885733 rs868094551	158	H>N		No	ClinGen gnomAD
CA406304083 rs868094551	158	H>Y		No	ClinGen gnomAD
CA308885734 rs867004984	159	L>M		No	ClinGen gnomAD
CA406304092 rs1457217956	159	L>P		No	ClinGen gnomAD
CA406304095 rs387906567	160	R>G		No	ClinGen gnomAD
CA406304096 rs1452005331	160	R>H		No	ClinGen gnomAD
rs867215645 CA308885740	161	K>N		No	ClinGen Ensembl
CA406304106 rs1377830202	162	L>M		No	ClinGen TOPMed gnomAD
CA406304124 rs1332591068	165	R>L		No	ClinGen gnomAD
CA406304121 rs1402219759	165	R>W		No	ClinGen TOPMed
CA406304137 rs867594573	168	R>C		No	ClinGen gnomAD
CA9506074 rs376170967	168	R>H		No	ClinGen ESP ExAC TOPMed gnomAD
rs867594573 CA308885772	168	R>S		No	ClinGen gnomAD
rs1300930146 CA406304143	169	D>Y		No	ClinGen gnomAD
rs1599953786 CA406304161	171	D>E		No	ClinGen Ensembl
CA406304154 rs1249355043	171	D>N	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen NCI-TCGA gnomAD
rs757859088 CA9506075	172	D>E		No	ClinGen ExAC TOPMed gnomAD
CA308885778 rs988698841	172	D>N		No	ClinGen TOPMed gnomAD
rs1190120890 CA406304173	174	Q>K		No	ClinGen gnomAD
CA406304209 rs1421977676	179	V>A		No	ClinGen gnomAD
rs1403079937 CA406304216	180	Y>*		No	ClinGen gnomAD
CA9506076 rs751200677	180	Y>H		No	ClinGen ExAC gnomAD
rs1434405741 CA406304219	181	Q>E		No	ClinGen TOPMed gnomAD
CA9506077 CA406304224 rs754627330	181	Q>H		No	ClinGen ExAC TOPMed gnomAD
rs1434405741 CA406304218	181	Q>K		No	ClinGen TOPMed gnomAD
CA308885811 rs796443813	182	A>P		No	ClinGen TOPMed
rs796443813 CA308885815	182	A>S		No	ClinGen TOPMed
rs1388704077 CA406304230 CA406304229	183	G>R		No	ClinGen gnomAD
CA308885824 rs981058595	184	A>D		No	ClinGen TOPMed
CA406304236 rs1276509170	184	A>S		No	ClinGen gnomAD
CA406304235 rs1276509170 COSM3787717	184	A>T	pancreas [Cosmic]	No	ClinGen cosmic curated gnomAD
CA406304243 rs1339651557	185	R>H		No	ClinGen gnomAD
rs1339651557 CA406304244	185	R>P		No	ClinGen gnomAD
rs1332509626 CA406304258	187	G>A		No	ClinGen TOPMed gnomAD
rs1332509626 CA406304259	187	G>V		No	ClinGen TOPMed gnomAD
CA308885826 rs11542032	189	E>K		No	ClinGen TOPMed gnomAD
CA406304266 rs11542032	189	E>Q		No	ClinGen TOPMed gnomAD
CA406304270 rs1402325936	189	E>V		No	ClinGen TOPMed
CA308885840 rs937011116	190	R>C		No	ClinGen TOPMed gnomAD
rs1265472491 CA406304278	191	G>S		No	ClinGen TOPMed gnomAD
rs1599953984 CA406304285	192	L>V		No	ClinGen Ensembl
CA9506079 rs748506927	193	S>R		No	ClinGen ExAC gnomAD
rs1599954003 CA406304298	194	A>T		No	ClinGen Ensembl
rs1380773651 CA406304307	195	I>F		No	ClinGen TOPMed
CA406304312 rs1184454715	195	I>M		No	ClinGen gnomAD
CA9506080 rs770485817	196	R>C		No	ClinGen ExAC gnomAD
CA9506081 rs778425259	196	R>H	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA gnomAD
CA406304324 rs1303558981	197	E>G		No	ClinGen TOPMed
CA406304331 rs1426426514	198	R>C		No	ClinGen TOPMed gnomAD
rs1048982607 CA308885889	198	R>L		No	ClinGen Ensembl
rs916989869 CA308885893	199	L>R		No	ClinGen TOPMed
rs1164213063 CA406304341	200	G>R		No	ClinGen gnomAD
rs11542030 CA308885900	205	Q>R		No	ClinGen Ensembl
CA406304402 rs1385100920	206	G>D		No	ClinGen Ensembl
rs749750245 CA9506082	207	R>C		No	ClinGen ExAC TOPMed gnomAD
CA406304410 rs1459489355	207	R>H		No	ClinGen gnomAD
CA406304411 rs1459489355	207	R>P		No	ClinGen gnomAD
rs749750245 CA406304406	207	R>S		No	ClinGen ExAC TOPMed gnomAD
rs770942678 CA9506083	208	V>L		No	ClinGen ExAC TOPMed gnomAD
rs770942678 CA308885904	208	V>M		No	ClinGen ExAC TOPMed gnomAD
CA308885916 rs1047319304	209	R>Q		No	ClinGen TOPMed
CA406304422 rs1459595735	209	R>W		No	ClinGen TOPMed
CA406304440 rs1376916580	211	A>T		No	ClinGen gnomAD
rs1227709957 CA406304462	213	V>G		No	ClinGen TOPMed gnomAD
CA9506085 rs759721023	214	G>S		No	ClinGen ExAC TOPMed gnomAD
CA308885927 rs11542027	215	S>F		No	ClinGen TOPMed
CA406304507 rs1466115957	218	G>D		No	ClinGen TOPMed
rs1488379910 CA406304503	218	G>R		No	ClinGen TOPMed gnomAD
CA406304502 rs1488379910	218	G>S		No	ClinGen TOPMed gnomAD
rs941248161 CA406304513	219	Q>*		No	ClinGen TOPMed gnomAD
rs941248161 CA308885934	219	Q>E		No	ClinGen TOPMed gnomAD
rs1265743589 CA406304532	220	P>L		No	ClinGen TOPMed gnomAD
rs1471997722 CA406304541	221	L>P		No	ClinGen gnomAD
rs1181840153 CA406304550	222	Q>*		No	ClinGen TOPMed gnomAD
rs1181840153 CA406304547	222	Q>K		No	ClinGen TOPMed gnomAD
CA308885935 rs1039633588	222	Q>L		No	ClinGen TOPMed gnomAD
CA406304555 rs1039633588	222	Q>R		No	ClinGen TOPMed gnomAD
rs1425703838 CA406304592	224	R>L		No	ClinGen TOPMed gnomAD
CA406304589 rs1425703838	224	R>P		No	ClinGen TOPMed gnomAD
rs547472686 CA308885936	225	A>T		No	ClinGen 1000Genomes TOPMed gnomAD
rs1360151558 CA406304634	227	A>S		No	ClinGen gnomAD
CA406304670 rs1299844242	229	G>R	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen NCI-TCGA gnomAD
rs1357260388 CA406304682	229	G>V		No	ClinGen gnomAD
rs567353589 CA308885947	230	E>K		No	ClinGen 1000Genomes TOPMed gnomAD
rs1237339516 CA406304711	231	R>Q		No	ClinGen gnomAD
rs1381171305 CA406304708	231	R>W		No	ClinGen gnomAD
rs554251788 CA406304732	233	R>C		No	ClinGen TOPMed
rs554251788 CA308885948	233	R>G		No	ClinGen TOPMed
CA406304738 rs1307832357	233	R>H		No	ClinGen gnomAD
rs1241924076 CA406304743	234	A>T		No	ClinGen gnomAD
rs1276043726 CA406304752	234	A>V		No	ClinGen gnomAD
rs1238565583 CA406304762	235	R>Q		No	ClinGen gnomAD
CA9506087 rs530010303	235	R>W		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA406304783 rs1555790637	236	M>I		No	ClinGen Ensembl
rs1335550286 CA406304791	237	E>K		No	ClinGen TOPMed gnomAD
rs892532644 CA308885963	238	E>D		No	ClinGen TOPMed gnomAD
rs761592007 CA9506088	239	M>I		No	ClinGen ExAC gnomAD
rs1391215146 CA406304841	240	G>D		No	ClinGen TOPMed
rs1440369210 CA406304839	240	G>R		No	ClinGen TOPMed gnomAD
CA308885968 rs1009671345	241	S>N		No	ClinGen TOPMed
CA406304856 rs1237443001	241	S>R		No	ClinGen TOPMed gnomAD
rs387906568 CA308885969	242	R>G		No	ClinGen gnomAD
rs267606663 CA9506089	242	R>P		No	ClinGen ExAC gnomAD
CA406304858 rs387906568	242	R>W		No	ClinGen gnomAD
CA406304869 rs1413700881	243	T>N		No	ClinGen gnomAD
CA406304889 rs1334498236	245	D>N		No	ClinGen gnomAD
rs1330553726 CA406304912	246	R>P		No	ClinGen gnomAD
rs121918395 CA406304904	246	R>S		No	ClinGen ESP ExAC TOPMed gnomAD
CA406304959 rs1221046029	248	D>E		No	ClinGen gnomAD
rs762906934 CA406304961	249	E>*		No	ClinGen ExAC TOPMed gnomAD
rs765845034 CA9506091	249	E>G		No	ClinGen ExAC TOPMed gnomAD
CA406304965 rs762906934	249	E>K		No	ClinGen ExAC TOPMed gnomAD
CA9506090 rs762906934	249	E>Q		No	ClinGen ExAC TOPMed gnomAD
rs1453797593 CA406305024	252	E>D		No	ClinGen TOPMed
CA9506093 rs780984110	255	A>V		No	ClinGen ExAC gnomAD
CA406305114 rs1197351070	256	E>V		No	ClinGen TOPMed gnomAD
CA406305153 rs1599954391	257	V>G		No	ClinGen Ensembl
rs1003367097 CA308886000	258	R>C		No	ClinGen Ensembl
COSM1183264 CA9506095 rs756564996	258	R>H	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs778237451 CA9506096	259	A>P		No	ClinGen ExAC gnomAD
CA406305164 rs778237451	259	A>T	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA gnomAD
rs1245215443 CA406305223	262	E>G		No	ClinGen gnomAD
rs1463848099 CA406305269	265	A>T		No	ClinGen gnomAD
CA406305283 rs1350058178	266	Q>E		No	ClinGen TOPMed
rs1466737235 CA406305305	267	Q>*		No	ClinGen gnomAD
rs745950059 CA9506098	267	Q>R		No	ClinGen ExAC gnomAD
CA9506100 rs267606661	269	R>C		No	ClinGen ExAC TOPMed gnomAD
VAR_000670	270	L>E	ApoE1 HE; requires 2 nucleotide substitutions [UniProt]	No	UniProt
TCGA novel	272	A>D	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1217176327 CA406305380	272	A>T		No	ClinGen gnomAD
rs951182634 CA308886041	273	E>G		No	ClinGen TOPMed gnomAD
CA9506102 rs551256627	274	A>G		No	ClinGen ExAC TOPMed gnomAD
rs1599954500 CA406305426	274	A>T		No	ClinGen Ensembl
CA406305437 rs551256627	274	A>V		No	ClinGen ExAC TOPMed gnomAD
CA9506103 rs371110159	276	Q>*		No	ClinGen ESP ExAC TOPMed gnomAD
CA406305500 rs1199910165	277	A>V		No	ClinGen gnomAD
CA9506104 rs762845923	278	R>C		No	ClinGen ExAC TOPMed gnomAD
CA9506106 rs767339630	278	R>H		No	ClinGen ExAC TOPMed
CA406305515 COSM1525698 rs767339630	278	R>L	lung Variant assessed as Somatic; 0.0 impact. [Cosmic, NCI-TCGA]	No	ClinGen cosmic curated ExAC NCI-TCGA TOPMed
CA406305528 rs1476757984	279	L>F		No	ClinGen gnomAD
rs1599954557 CA406305562	281	S>G		No	ClinGen Ensembl
CA406305567 rs1479320041	281	S>N		No	ClinGen TOPMed
CA406305575 rs1463421531	281	S>R		No	ClinGen gnomAD
CA308886085 rs778901516	282	W>C		No	ClinGen TOPMed gnomAD
CA308886090 rs954301448	283	F>L		No	ClinGen TOPMed gnomAD
CA9506108 rs759118026	284	E>D		No	ClinGen ExAC
CA9506107 rs773797268	284	E>G		No	ClinGen ExAC gnomAD
CA406305632 rs1396111554	284	E>K	Variant assessed as Somatic; impact. [NCI-TCGA]	No	ClinGen NCI-TCGA gnomAD
rs1358158446 CA406305652	285	P>H		No	ClinGen TOPMed gnomAD
CA406305644 rs1325189389	285	P>T		No	ClinGen gnomAD
CA9506110 rs750138933	286	L>M		No	ClinGen ExAC TOPMed gnomAD
rs755792921 CA9506111	287	V>M		No	ClinGen ExAC gnomAD
rs1568618190 CA406305685	289	D>A		No	ClinGen Ensembl
CA406305691 rs77903069	289	D>E		No	ClinGen 1000Genomes TOPMed
CA406305706 rs1282920511	290	M>I		No	ClinGen gnomAD
CA406305704 rs1282294107	290	M>K		No	ClinGen TOPMed
rs1599954673 CA406305720	291	Q>H		No	ClinGen Ensembl
rs1599954663 CA406305717	291	Q>R		No	ClinGen Ensembl
rs1355806321 CA406305723	292	R>C		No	ClinGen gnomAD
CA406305756 rs557715042	294	W>*		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs557715042 CA9506112	294	W>C		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA9506113 rs754211171	295	A>T		No	ClinGen ExAC gnomAD
CA9506115 rs757764781	296	G>R		No	ClinGen ExAC TOPMed gnomAD
CA9506114 rs757764781	296	G>W		No	ClinGen ExAC TOPMed gnomAD
CA308886167 rs1039600156	297	L>P		No	ClinGen TOPMed gnomAD
CA406305798 rs1367811482	299	E>Q		No	ClinGen TOPMed gnomAD
rs780067631 CA9506118	300	K>N		No	ClinGen ExAC gnomAD
CA9506117 rs758487955	300	K>R		No	ClinGen ExAC gnomAD
CA406305847 rs1418673754	301	V>G		No	ClinGen gnomAD
rs1378119160 CA406305837	301	V>L		No	ClinGen TOPMed gnomAD
CA406305832 rs1378119160	301	V>M		No	ClinGen TOPMed gnomAD
CA406305874 rs1298395482	303	A>S		No	ClinGen gnomAD
rs539470710 CA9506120	304	A>G		No	ClinGen ExAC
rs1340326154 CA406305916	305	V>G		No	ClinGen gnomAD
CA9506122 rs749102800	305	V>M	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA TOPMed gnomAD
CA406305927 rs1245628517	306	G>D		No	ClinGen gnomAD
rs770562611 CA9506123	307	T>I		No	ClinGen ExAC gnomAD
CA406305949 rs1599954804	308	S>R		No	ClinGen Ensembl
rs1351828960 CA406305965	309	A>T		No	ClinGen gnomAD
CA9506125 rs759501381	311	P>A		No	ClinGen ExAC TOPMed gnomAD
rs1486760107 CA406305996	312	V>L		No	ClinGen gnomAD
rs775113061 CA406306076	318	H>S		No	ClinGen ExAC

4 associated diseases with P02649

[MIM: 617347]: Hyperlipoproteinemia 3 (HLPP3)

A disorder characterized by the accumulation of intermediate-density lipoprotein particles (IDL or broad-beta-lipoprotein) rich in cholesterol. Clinical features include 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. {ECO:0000269|PubMed:1361196, ECO:0000269|PubMed:1674745, ECO:0000269|PubMed:2101409, ECO:0000269|PubMed:22481068, ECO:0000269|PubMed:2556398, ECO:0000269|PubMed:26802169, ECO:0000269|PubMed:2738044, ECO:0000269|PubMed:7635945, ECO:0000269|PubMed:8287539}. Note=The disease is caused by variants affecting the gene represented in this entry. 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.

[MIM: 104310]: Alzheimer disease 2 (AD2)

A late-onset form of Alzheimer disease. Alzheimer disease is a 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 constituents of these plaques are neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, that are produced by the proteolysis of the transmembrane APP protein. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products, such as C31, are also implicated in neuronal death. {ECO:0000269|PubMed:10903326, ECO:0000269|PubMed:11258893, ECO:0000269|PubMed:11447277, ECO:0000269|PubMed:28111074, ECO:0000269|PubMed:2987927, ECO:0000269|PubMed:7891887, ECO:0000269|PubMed:7972031, ECO:0000269|PubMed:8071364, ECO:0000269|PubMed:8346443, ECO:0000269|PubMed:8367470, ECO:0000269|PubMed:8939961}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry. The APOE*4 allele (APOE form E4) 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. {ECO:0000269|PubMed:8346443}.

[MIM: 269600]: Sea-blue histiocyte disease (SBHD)

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. {ECO:0000269|PubMed:11095479, ECO:0000269|PubMed:16094309, ECO:0000269|PubMed:22481068, ECO:0000269|PubMed:22949395, ECO:0000269|PubMed:24267230, ECO:0000269|PubMed:26802169}. Note=The disease is caused by variants affecting the gene represented in this entry.

[MIM: 611771]: Lipoprotein glomerulopathy (LPG)

Uncommon kidney disease characterized by proteinuria, progressive kidney failure, and distinctive lipoprotein thrombi in glomerular capillaries. {ECO:0000269|PubMed:10432380, ECO:0000269|PubMed:10903326, ECO:0000269|PubMed:18077821, ECO:0000269|PubMed:9176854}. Note=The disease is caused by variants affecting the gene represented in this entry.

Without disease ID

A disorder characterized by the accumulation of intermediate-density lipoprotein particles (IDL or broad-beta-lipoprotein) rich in cholesterol. Clinical features include 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. {ECO:0000269|PubMed:1361196, ECO:0000269|PubMed:1674745, ECO:0000269|PubMed:2101409, ECO:0000269|PubMed:22481068, ECO:0000269|PubMed:2556398, ECO:0000269|PubMed:26802169, ECO:0000269|PubMed:2738044, ECO:0000269|PubMed:7635945, ECO:0000269|PubMed:8287539}. Note=The disease is caused by variants affecting the gene represented in this entry. 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.
A late-onset form of Alzheimer disease. Alzheimer disease is a 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 constituents of these plaques are neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, that are produced by the proteolysis of the transmembrane APP protein. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products, such as C31, are also implicated in neuronal death. {ECO:0000269|PubMed:10903326, ECO:0000269|PubMed:11258893, ECO:0000269|PubMed:11447277, ECO:0000269|PubMed:28111074, ECO:0000269|PubMed:2987927, ECO:0000269|PubMed:7891887, ECO:0000269|PubMed:7972031, ECO:0000269|PubMed:8071364, ECO:0000269|PubMed:8346443, ECO:0000269|PubMed:8367470, ECO:0000269|PubMed:8939961}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry. The APOE*4 allele (APOE form E4) 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. {ECO:0000269|PubMed:8346443}.
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. {ECO:0000269|PubMed:11095479, ECO:0000269|PubMed:16094309, ECO:0000269|PubMed:22481068, ECO:0000269|PubMed:22949395, ECO:0000269|PubMed:24267230, ECO:0000269|PubMed:26802169}. Note=The disease is caused by variants affecting the gene represented in this entry.
Uncommon kidney disease characterized by proteinuria, progressive kidney failure, and distinctive lipoprotein thrombi in glomerular capillaries. {ECO:0000269|PubMed:10432380, ECO:0000269|PubMed:10903326, ECO:0000269|PubMed:18077821, ECO:0000269|PubMed:9176854}. Note=The disease is caused by variants affecting the gene represented in this entry.

No regional properties for P02649

Type	Name	Position	InterPro Accession
No domain, repeats, and functional sites for P02649

Functions

		Description
EC Number
Subcellular Localization	Secreted Secreted, extracellular space Secreted, extracellular space, extracellular matrix Extracellular vesicle Endosome, multivesicular body	In the plasma, APOE is associated with chylomicrons, chylomicrons remnants, VLDL, LDL and HDL lipoproteins (PubMed:1911868, PubMed:8340399) Lipid poor oligomeric APOE is associated with the extracellular matrix in a calcium- and heparan-sulfate proteoglycans-dependent manner (PubMed:9488694) Lipidation induces the release from the extracellular matrix (PubMed:9488694) Colocalizes with CD63 and PMEL at exosomes and in intraluminal vesicles within multivesicular endosomes
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category	No pathway information available

30 GO annotations of cellular component

Name	Definition
blood microparticle	A phospholipid microvesicle that is derived from any of several cell types, such as platelets, blood cells, endothelial cells, or others, and contains membrane receptors as well as other proteins characteristic of the parental cell. Microparticles are heterogeneous in size, and are characterized as microvesicles free of nucleic acids.
chylomicron	A large lipoprotein particle (diameter 75-1200 nm) composed of a central core of triglycerides and cholesterol surrounded by a protein-phospholipid coating. The proteins include one molecule of apolipoprotein B-48 and may include a variety of apolipoproteins, including APOAs, APOCs and APOE. Chylomicrons are found in blood or lymph and carry lipids from the intestines into other body tissues.
clathrin-coated endocytic vesicle membrane	The lipid bilayer surrounding a clathrin-coated endocytic vesicle.
collagen-containing extracellular matrix	An extracellular matrix consisting mainly of proteins (especially collagen) and glycosaminoglycans (mostly as proteoglycans) that provides not only essential physical scaffolding for the cellular constituents but can also initiate crucial biochemical and biomechanical cues required for tissue morphogenesis, differentiation and homeostasis. The components are secreted by cells in the vicinity and form a sheet underlying or overlying cells such as endothelial and epithelial cells.
cytoplasm	The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
dendrite	A neuron projection that has a short, tapering, morphology. Dendrites receive and integrate signals from other neurons or from sensory stimuli, and conduct nerve impulses towards the axon or the cell body. In most neurons, the impulse is conveyed from dendrites to axon via the cell body, but in some types of unipolar neuron, the impulse does not travel via the cell body.
discoidal high-density lipoprotein particle	A newly formed high-density lipoprotein particle; consists of a phospholipid bilayer surrounded by two or more APOA1 molecules. The discoidal HDL particle is formed when lipid-free or lipid-poor APOA1 acquires phospholipids and unesterified cholesterol from either cell membranes or triglyceride-rich lipoproteins (undergoing lipolysis by lipoprotein lipase).
early endosome	A membrane-bounded organelle that receives incoming material from primary endocytic vesicles that have been generated by clathrin-dependent and clathrin-independent endocytosis; vesicles fuse with the early endosome to deliver cargo for sorting into recycling or degradation pathways.
endocytic vesicle lumen	The volume enclosed by the membrane of an endocytic vesicle.
endoplasmic reticulum	The irregular network of unit membranes, visible only by electron microscopy, that occurs in the cytoplasm of many eukaryotic cells. The membranes form a complex meshwork of tubular channels, which are often expanded into slitlike cavities called cisternae. The ER takes two forms, rough (or granular), with ribosomes adhering to the outer surface, and smooth (with no ribosomes attached).
endoplasmic reticulum lumen	The volume enclosed by the membranes of the endoplasmic reticulum.
extracellular exosome	A vesicle that is released into the extracellular region by fusion of the limiting endosomal membrane of a multivesicular body with the plasma membrane. Extracellular exosomes, also simply called exosomes, have a diameter of about 40-100 nm.
extracellular matrix	A structure lying external to one or more cells, which provides structural support, biochemical or biomechanical cues for cells or tissues.
extracellular region	The space external to the outermost structure of a cell. For cells without external protective or external encapsulating structures this refers to space outside of the plasma membrane. This term covers the host cell environment outside an intracellular parasite.
extracellular space	That part of a multicellular organism outside the cells proper, usually taken to be outside the plasma membranes, and occupied by fluid.
extracellular vesicle	Any vesicle that is part of the extracellular region.
glutamatergic synapse	A synapse that uses glutamate as a neurotransmitter.
Golgi apparatus	A membrane-bound cytoplasmic organelle of the endomembrane system that further processes the core oligosaccharides (e.g. N-glycans) added to proteins in the endoplasmic reticulum and packages them into membrane-bound vesicles. The Golgi apparatus operates at the intersection of the secretory, lysosomal, and endocytic pathways.
high-density lipoprotein particle	A lipoprotein particle with a high density (typically 1.063-1.21 g/ml) and a diameter of 5-10 nm that contains APOAs and may contain APOCs and APOE; found in blood and carries lipids from body tissues to the liver as part of the reverse cholesterol transport process.
intermediate-density lipoprotein particle	A triglyceride-rich lipoprotein particle that typically contains APOB100, APOE and APOCs and has a density of 1.006-1.019 g/ml and a diameter of between 25-30 nm. IDL particles are found in blood and are formed by the delipidation of very-low-density lipoprotein particles (VLDL). IDL particles are removed from blood by the liver, following binding to the APOE receptor, or are converted to low-density lipoprotein (LDL).
lipoprotein particle	A spherical particle containing non-covalently associated proteins and lipids. Examples are plasma lipoprotein particles which transport lipids in the blood or lymph.
low-density lipoprotein particle	A lipoprotein particle, rich in cholesterol esters and low in triglycerides that is typically composed of APOB100 and APOE and has a density of 1.02-1.06 g/ml and a diameter of between 20-25 nm. LDL particles are formed from VLDL particles (via IDL) by the loss of triglyceride and gain of cholesterol ester. They transport endogenous cholesterol (and to some extent triglycerides) from peripheral tissues back to the liver.
melanosome	A tissue-specific, membrane-bounded cytoplasmic organelle within which melanin pigments are synthesized and stored. Melanosomes are synthesized in melanocyte cells.
membrane	A lipid bilayer along with all the proteins and protein complexes embedded in it an attached to it.
multivesicular body	A type of endosome in which regions of the limiting endosomal membrane invaginate to form internal vesicles; membrane proteins that enter the internal vesicles are sequestered from the cytoplasm.
neuronal cell body	The portion of a neuron that includes the nucleus, but excludes cell projections such as axons and dendrites.
nucleus	A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
plasma membrane	The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
synaptic cleft	The narrow gap that separates the presynaptic and postsynaptic membranes, into which neurotransmitter is released.
very-low-density lipoprotein particle	A triglyceride-rich lipoprotein particle that is typically composed of APOB100, APOE and APOCs and has a density of about 1.006 g/ml and a diameter of between 20-80 nm. It is found in blood and transports endogenous products (newly synthesized cholesterol and triglycerides) from the liver.

21 GO annotations of molecular function

Name	Definition
amyloid-beta binding	Binding to an amyloid-beta peptide/protein.
antioxidant activity	Inhibition of the reactions brought about by dioxygen (O2) or peroxides. Usually the antioxidant is effective because it can itself be more easily oxidized than the substance protected. The term is often applied to components that can trap free radicals, thereby breaking the chain reaction that normally leads to extensive biological damage.
cholesterol transfer activity	Removes cholesterol from a membrane or a monolayer lipid particle, transports it through the aqueous phase while protected in a hydrophobic pocket, and brings it to an acceptor membrane or lipid particle.
enzyme binding	Binding to an enzyme, a protein with catalytic activity.
heparan sulfate proteoglycan binding	Binding to a heparan sulfate proteoglycan, any proteoglycan containing heparan sulfate as the glycosaminoglycan carbohydrate unit.
heparin binding	Binding to heparin, a member of a group of glycosaminoglycans found mainly as an intracellular component of mast cells and which consist predominantly of alternating alpha-(1->4)-linked D-galactose and N-acetyl-D-glucosamine-6-sulfate residues.
identical protein binding	Binding to an identical protein or proteins.
lipid binding	Binding to a lipid.
lipid transporter activity	Enables the directed movement of lipids into, out of or within a cell, or between cells.
lipoprotein particle binding	Binding to a lipoprotein particle. A lipoprotein particle, also known as a lipoprotein, is a clathrate complex consisting of a lipid enwrapped in a protein host without covalent binding in such a way that the complex has a hydrophilic outer surface consisting of all the protein and the polar ends of any phospholipids.
low-density lipoprotein particle receptor binding	Binding to a low-density lipoprotein receptor.
metal chelating activity	The formation of bonds from two or more atoms within the same ligand to a metal atom in complexes in which the metal is part of a ring.
phosphatidylcholine-sterol O-acyltransferase activator activity	Increases the activity of phosphatidylcholine-sterol O-acyltransferase, an enzyme that converts cholesterol and phosphatidylcholine (lecithins) to cholesteryl esters and lyso-phosphatidylcholines.
phospholipid binding	Binding to a phospholipid, a class of lipids containing phosphoric acid as a mono- or diester.
protein dimerization activity	The formation of a protein dimer, a macromolecular structure consists of two noncovalently associated identical or nonidentical subunits.
protein homodimerization activity	Binding to an identical protein to form a homodimer.
protein-containing complex binding	Binding to a macromolecular complex.
signaling receptor binding	Binding to one or more specific sites on a receptor molecule, a macromolecule that undergoes combination with a hormone, neurotransmitter, drug or intracellular messenger to initiate a change in cell function.
structural molecule activity	The action of a molecule that contributes to the structural integrity of a complex or its assembly within or outside a cell.
tau protein binding	Binding to tau protein. tau is a microtubule-associated protein, implicated in Alzheimer's disease, Down Syndrome and ALS.
very-low-density lipoprotein particle receptor binding	Binding to a very-low-density lipoprotein receptor.

112 GO annotations of biological process

Name	Definition
AMPA glutamate receptor clustering	The glutamate receptor clustering process in which alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors are localized to distinct domains in the cell membrane.
amyloid precursor protein metabolic process	The chemical reactions and pathways involving amyloid precursor protein (APP), the precursor of amyloid-beta, a glycoprotein associated with Alzheimer's disease.
artery morphogenesis	The process in which the anatomical structures of arterial blood vessels are generated and organized. Arteries are blood vessels that transport blood from the heart to the body and its organs.
cellular calcium ion homeostasis	Any process involved in the maintenance of an internal steady state of calcium ions at the level of a cell.
cGMP-mediated signaling	Any intracellular signal transduction in which the signal is passed on within the cell via cyclic GMP (cGMP). Includes production of cGMP, and downstream effectors that further transmit the signal within the cell.
cholesterol catabolic process	The chemical reactions and pathways resulting in the breakdown of cholesterol, cholest-5-en-3 beta-ol, the principal sterol of vertebrates and the precursor of many steroids, including bile acids and steroid hormones.
cholesterol efflux	The directed movement of cholesterol, cholest-5-en-3-beta-ol, out of a cell or organelle.
cholesterol homeostasis	Any process involved in the maintenance of an internal steady state of cholesterol within an organism or cell.
cholesterol metabolic process	The chemical reactions and pathways involving cholesterol, cholest-5-en-3 beta-ol, the principal sterol of vertebrates and the precursor of many steroids, including bile acids and steroid hormones. It is a component of the plasma membrane lipid bilayer and of plasma lipoproteins and can be found in all animal tissues.
chylomicron remnant clearance	The process in which a chylomicron remnant is removed from the blood via receptor-mediated endocytosis into liver cells and its constituent parts degraded.
cytoskeleton organization	A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of cytoskeletal structures.
fatty acid homeostasis	Any process involved in the maintenance of an internal steady state of fatty acid within an organism or cell.
G protein-coupled receptor signaling pathway	The series of molecular signals initiated by a ligand binding to its receptor, in which the activated receptor promotes the exchange of GDP for GTP on the alpha-subunit of an associated heterotrimeric G-protein complex. The GTP-bound activated alpha-G-protein then dissociates from the beta- and gamma-subunits to further transmit the signal within the cell. The pathway begins with receptor-ligand interaction, and ends with regulation of a downstream cellular process. The pathway can start from the plasma membrane, Golgi or nuclear membrane.
gene expression	The process in which a gene's sequence is converted into a mature gene product (protein or RNA). This includes the production of an RNA transcript and its processing, translation and maturation for protein-coding genes.
high-density lipoprotein particle assembly	The non-covalent aggregation and arrangement of proteins and lipids to form a high-density lipoprotein particle.
high-density lipoprotein particle clearance	The process in which a high-density lipoprotein particle is removed from the blood via receptor-mediated endocytosis and its constituent parts degraded.
high-density lipoprotein particle remodeling	The acquisition, loss or modification of a protein or lipid within a high-density lipoprotein particle, including the hydrolysis of triglyceride by hepatic lipase, with the subsequent loss of free fatty acid, and the transfer of cholesterol esters from LDL to a triglyceride-rich lipoprotein particle by cholesteryl ester transfer protein (CETP), with the simultaneous transfer of triglyceride to LDL.
intermediate-density lipoprotein particle clearance	The process in which a intermediate-density lipoprotein particle is removed from the blood via receptor-mediated endocytosis and its constituent parts degraded.
intracellular transport	The directed movement of substances within a cell.
lipid transport involved in lipid storage	The directed movement of lipids into cells that is part of their accumulation and maintenance.
lipoprotein biosynthetic process	The chemical reactions and pathways resulting in the formation of any conjugated, water-soluble protein in which the covalently attached nonprotein group consists of a lipid or lipids.
lipoprotein catabolic process	The chemical reactions and pathways resulting in the breakdown of any conjugated, water-soluble protein in which the covalently attached nonprotein group consists of a lipid or lipids.
locomotory exploration behavior	The specific movement from place to place of an organism in response to a novel environment.
long-chain fatty acid transport	The directed movement of long-chain fatty acids into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. A long-chain fatty acid is a fatty acid with a chain length between C13 and C22.
long-term memory	The memory process that deals with the storage, retrieval and modification of information a long time (typically weeks, months or years) after receiving that information. This type of memory is typically dependent on gene transcription regulated by second messenger activation.
low-density lipoprotein particle remodeling	The acquisition, loss or modification of a protein or lipid within a low-density lipoprotein particle, including the hydrolysis of triglyceride by hepatic lipase, with the subsequent loss of free fatty acid, and the transfer of cholesterol esters from LDL to a triglyceride-rich lipoprotein particle by cholesteryl ester transfer protein (CETP), with the simultaneous transfer of triglyceride to LDL.
maintenance of location in cell	Any process in which a substance or cellular entity, such as a protein complex or organelle, is maintained in a specific location within, or in the membrane of, a cell, and is prevented from moving elsewhere.
melanosome organization	A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of a melanosome. A melanosome is a tissue-specific, membrane-bounded cytoplasmic organelle within which melanin pigments are synthesized and stored.
negative regulation of amyloid fibril formation	Any process that stops, prevents or reduces the frequency, rate or extent of amyloid fibril formation.
negative regulation of amyloid-beta formation	Any process that stops, prevents or reduces the frequency, rate or extent of amyloid-beta formation.
negative regulation of blood coagulation	Any process that stops, prevents, or reduces the frequency, rate or extent of blood coagulation.
negative regulation of blood vessel endothelial cell migration	Any process that stops, prevents, or reduces the frequency, rate or extent of the migration of the endothelial cells of blood vessels.
negative regulation of canonical Wnt signaling pathway	Any process that decreases the rate, frequency, or extent of the Wnt signaling pathway through beta-catenin, the series of molecular signals initiated by binding of a Wnt protein to a frizzled family receptor on the surface of the target cell, followed by propagation of the signal via beta-catenin, and ending with a change in transcription of target genes.
negative regulation of cholesterol biosynthetic process	Any process that stops, prevents, or reduces the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of cholesterol.
negative regulation of cholesterol efflux	Any process that decreases the frequency, rate or extent of cholesterol efflux. Cholesterol efflux is the directed movement of cholesterol, cholest-5-en-3-beta-ol, out of a cell or organelle.
negative regulation of dendritic spine development	Any process that decreases the rate, frequency, or extent of dendritic spine development, the process whose specific outcome is the progression of the dendritic spine over time, from its formation to the mature structure.
negative regulation of dendritic spine maintenance	Any process that stops, prevents or reduces the frequency, rate or extent of dendritic spine maintenance.
negative regulation of endothelial cell migration	Any process that decreases the rate, frequency, or extent of the orderly movement of an endothelial cell into the extracellular matrix to form an endothelium.
negative regulation of endothelial cell proliferation	Any process that stops, prevents, or reduces the rate or extent of endothelial cell proliferation.
negative regulation of gene expression	Any process that decreases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA).
negative regulation of inflammatory response	Any process that stops, prevents, or reduces the frequency, rate or extent of the inflammatory response.
negative regulation of lipid biosynthetic process	Any process that stops, prevents, or reduces the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of lipids.
negative regulation of lipid transport across blood-brain barrier	Any process that stops, prevents or reduces the frequency, rate or extent of lipid transport across blood-brain barrier.
negative regulation of long-term synaptic potentiation	Any process that stops, prevents or reduces the frequency, rate or extent of long-term synaptic potentiation.
negative regulation of MAP kinase activity	Any process that stops, prevents, or reduces the frequency, rate or extent of MAP kinase activity.
negative regulation of neuron apoptotic process	Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process in neurons.
negative regulation of neuron death	Any process that stops, prevents or reduces the frequency, rate or extent of neuron death.
negative regulation of neuron projection development	Any process that decreases the rate, frequency or extent of neuron projection development. Neuron projection development is the process whose specific outcome is the progression of a neuron projection over time, from its formation to the mature structure. A neuron projection is any process extending from a neural cell, such as axons or dendrites (collectively called neurites).
negative regulation of phospholipid efflux	Any process that stops, prevents or reduces the frequency, rate or extent of phospholipid efflux.
negative regulation of platelet activation	Any process that decreases the rate or frequency of platelet activation. Platelet activation is a series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue.
negative regulation of postsynaptic membrane organization	Any process that stops, prevents or reduces the frequency, rate or extent of postsynaptic membrane organization.
negative regulation of protein metabolic process	Any process that stops, prevents, or reduces the frequency, rate or extent of chemical reactions and pathways involving a protein.
negative regulation of protein secretion	Any process that stops, prevents, or reduces the frequency, rate or extent of the controlled release of a protein from a cell.
negative regulation of smooth muscle cell proliferation	Any process that stops, prevents or reduces the rate or extent of smooth muscle cell proliferation.
negative regulation of triglyceride metabolic process	Any process that decreases the frequency, rate or extent of the chemical reactions and pathways involving triglyceride, any triester of glycerol.
neuron projection development	The process whose specific outcome is the progression of a neuron projection over time, from its formation to the mature structure. A neuron projection is any process extending from a neural cell, such as axons or dendrites (collectively called neurites).
nitric oxide mediated signal transduction	Any intracellular signal transduction in which the signal is passed on within the cell via nitric oxide (NO). Includes synthesis of nitric oxide, receptors/sensors for nitric oxide (such as soluble guanylyl cyclase/sGC) and downstream effectors that further transmit the signal within the cell. Nitric oxide transmits its downstream effects through either cyclic GMP (cGMP)-dependent or independent mechanisms.
NMDA glutamate receptor clustering	The receptor clustering process in which N-methyl-D-aspartate (NMDA) receptors are localized to distinct domains in the cell membrane.
phospholipid efflux	The directed movement of a phospholipid out of a cell or organelle.
positive regulation by host of viral process	A process in which a host organism activates or increases the frequency, rate or extent of the release of a process being mediated by a virus with which it is infected.
positive regulation of amyloid fibril formation	Any process that activates or increases the frequency, rate or extent of amyloid fibril formation.
positive regulation of amyloid-beta clearance	Any process that activates or increases the frequency, rate or extent of amyloid-beta clearance.
positive regulation of amyloid-beta formation	Any process that activates or increases the frequency, rate or extent of amyloid-beta formation.
positive regulation of cholesterol efflux	Any process that increases the frequency, rate or extent of cholesterol efflux. Cholesterol efflux is the directed movement of cholesterol, cholest-5-en-3-beta-ol, out of a cell or organelle.
positive regulation of cholesterol metabolic process	Any process that increases the rate, frequency, or extent of cholesterol metabolism, the chemical reactions and pathways involving cholesterol, cholest-5-en-3 beta-ol, the principal sterol of vertebrates and the precursor of many steroids, including bile acids and steroid hormones.
positive regulation of CoA-transferase activity	Any process that activates or increases the frequency, rate or extent of CoA-transferase activity.
positive regulation of dendritic spine development	Any process that increases the rate, frequency, or extent of dendritic spine development, the process whose specific outcome is the progression of the dendritic spine over time, from its formation to the mature structure.
positive regulation of dendritic spine maintenance	Any process that activates or increases the frequency, rate or extent of dendritic spine maintenance.
positive regulation of DNA-templated transcription	Any process that activates or increases the frequency, rate or extent of cellular DNA-templated transcription.
positive regulation of endocytosis	Any process that activates or increases the frequency, rate or extent of endocytosis.
positive regulation of ERK1 and ERK2 cascade	Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the ERK1 and ERK2 cascade.
positive regulation of heparan sulfate binding	Any process that activates or increases the frequency, rate or extent of heparan sulfate binding.
positive regulation of heparan sulfate proteoglycan binding	Any process that activates or increases the frequency, rate or extent of heparan sulfate proteoglycan binding.
positive regulation of lipid biosynthetic process	Any process that activates or increases the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of lipids.
positive regulation of lipid transport across blood-brain barrier	Any process that activates or increases the frequency, rate or extent of lipid transport across blood-brain barrier.
positive regulation of low-density lipoprotein particle receptor catabolic process	Any process that activates or increases the frequency, rate or extent of the chemical reactions and pathways resulting in the breakdown of low-density lipoprotein particle receptors.
positive regulation of membrane protein ectodomain proteolysis	Any process that activates or increases the frequency, rate or extent of membrane protein ectodomain peptidolysis.
positive regulation of neurofibrillary tangle assembly	Any process that activates or increases the frequency, rate or extent of neurofibrillary tangle assembly.
positive regulation of neuron death	Any process that activates or increases the frequency, rate or extent of neuron death.
positive regulation of neuron projection development	Any process that increases the rate, frequency or extent of neuron projection development. Neuron projection development is the process whose specific outcome is the progression of a neuron projection over time, from its formation to the mature structure. A neuron projection is any process extending from a neural cell, such as axons or dendrites (collectively called neurites).
positive regulation of nitric-oxide synthase activity	Any process that activates or increases the activity of the enzyme nitric-oxide synthase.
positive regulation of phospholipid efflux	Any process that activates or increases the frequency, rate or extent of phospholipid efflux.
positive regulation of presynaptic membrane organization	Any process that activates or increases the frequency, rate or extent of presynaptic membrane organization.
protein import	The targeting and directed movement of proteins into a cell or organelle. Not all import involves an initial targeting event.
receptor-mediated endocytosis	An endocytosis process in which cell surface receptors ensure specificity of transport. A specific receptor on the cell surface binds tightly to the extracellular macromolecule (the ligand) that it recognizes; the plasma-membrane region containing the receptor-ligand complex then undergoes endocytosis, forming a transport vesicle containing the receptor-ligand complex and excluding most other plasma-membrane proteins. Receptor-mediated endocytosis generally occurs via clathrin-coated pits and vesicles.
regulation of amyloid fibril formation	Any process that modulates the frequency, rate or extent of amyloid fibril formation.
regulation of amyloid precursor protein catabolic process	Any process that modulates the frequency, rate or extent of amyloid precursor protein catabolic process.
regulation of amyloid-beta clearance	Any process that modulates the frequency, rate or extent of amyloid-beta clearance.
regulation of axon extension	Any process that modulates the rate, direction or extent of axon extension.
regulation of behavioral fear response	Any process that modulates the frequency, rate or extent of behavioral fear response.
regulation of Cdc42 protein signal transduction	Any process that modulates the frequency, rate or extent of Cdc42 protein signal transduction.
regulation of cellular response to very-low-density lipoprotein particle stimulus	Any process that modulates the frequency, rate or extent of cellular response to very-low-density lipoprotein particle stimulus.
regulation of cholesterol metabolic process	Any process that modulates the rate, frequency, or extent of cholesterol metabolism, the chemical reactions and pathways involving cholesterol, cholest-5-en-3 beta-ol, the principal sterol of vertebrates and the precursor of many steroids, including bile acids and steroid hormones.
regulation of innate immune response	Any process that modulates the frequency, rate or extent of the innate immune response, the organism's first line of defense against infection.
regulation of neuron death	Any process that modulates the frequency, rate or extent of neuron death.
regulation of neuronal synaptic plasticity	A process that modulates neuronal synaptic plasticity, the ability of neuronal synapses to change as circumstances require. They may alter function, such as increasing or decreasing their sensitivity, or they may increase or decrease in actual numbers.
regulation of proteasomal protein catabolic process	Any process that modulates the rate, frequency, or extent of the chemical reactions and pathways resulting in the breakdown of a protein or peptide by hydrolysis of its peptide bonds that is mediated by the proteasome.
regulation of protein metabolic process	Any process that modulates the frequency, rate or extent of the chemical reactions and pathways involving a protein.
regulation of protein-containing complex assembly	Any process that modulates the frequency, rate or extent of protein complex assembly.
regulation of tau-protein kinase activity	Any process that modulates the frequency, rate or extent of tau-protein kinase activity.
response to caloric restriction	A change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a caloric restriction, insufficient food energy intake.
response to dietary excess	The physiological process in which dietary excess is sensed by the central nervous system, resulting in a reduction in food intake and increased energy expenditure.
response to reactive oxygen species	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a reactive oxygen species stimulus. Reactive oxygen species include singlet oxygen, superoxide, and oxygen free radicals.
reverse cholesterol transport	The directed movement of peripheral cell cholesterol, cholest-5-en-3-beta-ol, towards the liver for catabolism.
synaptic transmission, cholinergic	The vesicular release of acetylcholine from a presynapse, across a chemical synapse, the subsequent activation of dopamine receptors at the postsynapse of a target cell (neuron, muscle, or secretory cell) and the effects of this activation on the postsynaptic membrane potential and ionic composition of the postsynaptic cytosol. This process encompasses both spontaneous and evoked release of neurotransmitter and all parts of synaptic vesicle exocytosis. Evoked transmission starts with the arrival of an action potential at the presynapse.
triglyceride homeostasis	Any process involved in the maintenance of an internal steady state of triglyceride within an organism or cell.
triglyceride metabolic process	The chemical reactions and pathways involving triglyceride, any triester of glycerol. The three fatty acid residues may all be the same or differ in any permutation. Triglycerides are important components of plant oils, animal fats and animal plasma lipoproteins.
triglyceride-rich lipoprotein particle clearance	The process in which a triglyceride-rich lipoprotein particle is removed from the blood via receptor-mediated endocytosis and its constituent parts degraded.
vasodilation	An increase in the internal diameter of blood vessels, especially arterioles or capillaries, due to relaxation of smooth muscle cells that line the vessels, and usually resulting in a decrease in blood pressure.
very-low-density lipoprotein particle clearance	The process in which a very-low-density lipoprotein particle is removed from the blood via receptor-mediated endocytosis and its constituent parts degraded.
very-low-density lipoprotein particle remodeling	The acquisition, loss or modification of a protein or lipid within a very-low-density lipoprotein particle, including the hydrolysis of triglyceride by hepatic lipase or lipoprotein lipase and the subsequent loss of free fatty acid.
virion assembly	A late phase of the viral life cycle during which all the components necessary for the formation of a mature virion collect at a particular site in the cell and the basic structure of the virus particle is formed.

6 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
Q03247	APOE	Apolipoprotein E	Bos taurus (Bovine)	PR
P18649	APOE	Apolipoprotein E	Canis lupus familiaris (Dog) (Canis familiaris)	PR
Q6Q788	APOA5	Apolipoprotein A-V	Homo sapiens (Human)	PR
P08226	Apoe	Apolipoprotein E	Mus musculus (Mouse)	PR
Q8C7G5	Apoa5	Apolipoprotein A-V	Mus musculus (Mouse)	PR
P02650	Apoe	Apolipoprotein E	Rattus norvegicus (Rat)	PR

10	20	30	40	50	60
MKVLWAALLV	TFLAGCQAKV	EQAVETEPEP	ELRQQTEWQS	GQRWELALGR	FWDYLRWVQT
70	80	90	100	110	120
LSEQVQEELL	SSQVTQELRA	LMDETMKELK	AYKSELEEQL	TPVAEETRAR	LSKELQAAQA
130	140	150	160	170	180
RLGADMEDVC	GRLVQYRGEV	QAMLGQSTEE	LRVRLASHLR	KLRKRLLRDA	DDLQKRLAVY
190	200	210	220	230	240
QAGAREGAER	GLSAIRERLG	PLVEQGRVRA	ATVGSLAGQP	LQERAQAWGE	RLRARMEEMG
250	260	270	280	290	300
SRTRDRLDEV	KEQVAEVRAK	LEEQAQQIRL	QAEAFQARLK	SWFEPLVEDM	QRQWAGLVEK
310
VQAAVGTSAA	PVPSDNH