AiPD: Autoinhibited Protein Database

P49768

Gene name	PSEN1 (AD3, PS1, PSNL1)
Protein name	Presenilin-1
Names	PS-1, Protein S182
Species	Homo sapiens (Human)
KEGG Pathway	hsa:5663
EC number
Protein Class

Descriptions

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

Autoinhibitory domains (AIDs)

6-86 (Predicted disordered autoinhibitory region) PR

Target domain
Relief mechanism
Assay	cis-regPred

AID

6-86 (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

17 structures for P49768

Entry ID	Method	Resolution	Chain	Position	Source
2KR6	NMR	-	A	292-467	PDB
4UIS	EM	440 A	B	81-463	PDB
5A63	EM	340 A	B	1-467	PDB
5FN2	EM	420 A	B	1-467	PDB
5FN3	EM	410 A	B	1-467	PDB
5FN4	EM	400 A	B	1-467	PDB
5FN5	EM	430 A	B	1-467	PDB
6IDF	EM	270 A	B	1-467	PDB
6IYC	EM	260 A	B	1-467	PDB
6LQG	EM	310 A	B	1-467	PDB
6LR4	EM	300 A	B	1-467	PDB
7C9I	EM	310 A	B	1-467	PDB
7D8X	EM	260 A	B	1-467	PDB
7Y5T	EM	290 A	B	1-467	PDB
8IM7	EM	340 A	B	1-467	PDB
8K8E	EM	260 A	B	1-467	PDB
AF-P49768-F1	Predicted				AlphaFoldDB

499 variants for P49768

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
RCV000274293 CA10635145 rs886050663 RCV000357249 RCV001313651	27	R>C	Alzheimer disease 3 Dilated cardiomyopathy 1U [ClinVar]	Yes	ClinGen ClinVar dbSNP gnomAD
rs149562759 RCV001120055 RCV001120056 CA7256652	27	R>H	Alzheimer disease 3 Variant assessed as Somatic; 0.0 impact. Dilated cardiomyopathy 1U [ClinVar, NCI-TCGA]	Yes	ClinGen ClinVar ESP ExAC NCI-TCGA TOPMed dbSNP gnomAD
RCV000172094 RCV001120057 VAR_075260 RCV001120058 CA224981 RCV000084280 RCV000640608 rs63750592	35	R>Q	Alzheimer disease 3 Alzheimer disease Dilated cardiomyopathy 1U AD3; unknown pathological significance; decreased protease activity with APP [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt ESP ExAC TOPMed dbSNP gnomAD
rs746691776 RCV001090096 CA7256673	35	R>W	Frontotemporal dementia [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
RCV001120059 RCV001120060 CA7256686 rs367775281 RCV001856575	42	R>Q	Alzheimer disease 3 Dilated cardiomyopathy 1U [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
RCV001296368 rs777427451 CA7256694	60	R>W	Alzheimer disease 3 [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
RCV000019787 RCV000084281 rs63749824 VAR_006413 RCV000529477 CA224983	79	A>V	Alzheimer disease 3 AD3; also found in late-onset Alzheimer disease; impaired protease activity with APP; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio; no effect on interaction with GFAP [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt ExAC dbSNP gnomAD
CA224984 rs63749967 RCV000084282 VAR_006414	82	V>L	AD3; decreased protease activity with APP; no effect on interaction with GFAP [UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
VAR_075261	83	I>T	AD3 [UniProt]	Yes	UniProt
RCV000084284 VAR_081228 rs63750599 CA127841 RCV000019783	85	L>P	Alzheimer disease, familial, 3, with spastic paraparesis and apraxia AD3; the patient also manifest spastic paraparesis and apraxia; loss of protease activity with APP in vitro; altered amyloid-beta production in cells transfected with the mutant and increased amyloid-beta 42/amyloid-beta 40 ratio [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
CA390303263 rs1594998354 RCV000853575	86	F>C	Alzheimer disease 3 [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
rs1897874329 RCV001261949	88	P>R	Frontotemporal dementia [ClinVar]	Yes	ClinVar dbSNP
rs1897874234 RCV001208063	88	P>T	Alzheimer disease 3 [ClinVar]	Yes	ClinVar dbSNP
RCV000084285 CA224987 RCV000020083 VAR_081229 rs63750815	89	V>L	Alzheimer disease 3 AD3; decreased protease activity with APP; increased amyloid-beta 42/amyloid-beta 40 ratio [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV001043730 rs1007193620 CA262614455	90	T>S	Alzheimer disease 3 [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
rs63751141 RCV000084286 CA224989 VAR_016214 RCV000019772	92	C>S	Alzheimer disease 3 AD3; loss of protease activity with APP [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
rs63750831 RCV000084287 CA224990 VAR_081230 RCV001854471	94	V>M	Alzheimer disease 3 AD3; unknown pathological significance; reduced protease activity with APP; no relevant change in amyloid-beta 42/amyloid-beta 40 ratio [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt ExAC dbSNP gnomAD
CA224992 VAR_006415 rs63750601 RCV000084288	96	V>F	AD3; loss of protease activity with APP [UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
rs63750852 VAR_081231 RCV000084289 CA224993	97	V>L	AD3; unknown pathological significance; slightly reduced protease activity with APP [UniProt]	Yes	ClinGen ClinVar UniProt TOPMed dbSNP gnomAD
RCV001230382 rs1897876766	103	V>G	Alzheimer disease 3 [ClinVar]	Yes	ClinVar dbSNP
RCV000084291 VAR_009208 CA224997 rs63750321	105	F>L	AD3 [UniProt]	Yes	ClinGen ClinVar UniProt dbSNP gnomAD
rs63751399 RCV000019775 RCV001228362 RCV000084292 CA224998 VAR_016215 RCV000020084	113	L>P	Alzheimer disease 3 Frontotemporal dementia Frontotemporal dementia (ftd) frontotemporal dementia [ClinVar, Ensembl, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
CA225002 VAR_006416 rs63750450 RCV000640610 RCV001199924 RCV000084295	115	Y>C	Alzheimer disease 3 AD3 [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
VAR_006417	115	Y>H	AD3; impaired protease activity with APP and increased amyloid-beta 42/amyloid-beta 40 ratio [UniProt]	Yes	UniProt
RCV002514493 VAR_081232 RCV000084296 rs63750730 CA225003	116	T>I	Alzheimer disease 3 AD3 [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
VAR_010120 CA390304675 rs63750730 RCV000816670	116	T>N	Alzheimer disease 3 AD3; unusual amyloid cotton wool plaques detected in one patient's brain; severe decrease of protease activity with APP; results in increased amyloid-beta 42/amyloid-beta 40 ratio [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV002272062 VAR_009209 CA225007 RCV000084298 rs63749805	117	P>L	Alzheimer disease 3 AD3; impaired ability to cleave Ephb2/CTF1; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio; impaired regulation of neurite outgrowth [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
rs63750550 RCV002514494 RCV000084297 CA225005 VAR_081233	117	P>S	Alzheimer disease 3 AD3; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio; impaired regulation of neurite outgrowth [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV000782176 RCV001196175 rs1566630791 CA390304710	119	T>I	Alzheimer disease 3 Frontotemporal dementia [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
CA225009 rs63751272 VAR_006418 RCV000019765 RCV000084300 CA390304722	120	E>D	Alzheimer disease 3 AD3; impaired protease activity with APP and increased amyloid-beta 42/amyloid-beta 40 ratio [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV000084299 VAR_006419 rs63750800 CA225008	120	E>K	AD3; impaired protease activity with APP and increased amyloid-beta 42/amyloid-beta 40 ratio [UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
rs1566630811 RCV000736265 CA390304742	122	T>A	Frontotemporal dementia [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
rs1595002439 VAR_070023 RCV000823608 CA390304887	134	L>R	Alzheimer disease 3 AD3; uncertain pathological significance; loss of protease activity with APP [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
rs63750353 CA225012 VAR_010121 RCV001854472 RCV000084302	135	N>D	Alzheimer disease 3 AD3; impaired protease activity with APP and increased amyloid-beta 42/amyloid-beta 40 ratio [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV000824341 rs63751278 CA225013 RCV000084303	135	N>S	Alzheimer disease 3 [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
RCV000736260 CA390304909 rs1566630884	137	A>T	Frontotemporal dementia [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
rs63750522 CA225017 VAR_006420 CA390304940 RCV000084306	139	M>I	AD3 [UniProt]	Yes	ClinGen Ensembl ClinVar UniProt dbSNP
CA390304935 rs63751106 VAR_010122	139	M>K	AD3 [UniProt]	Yes	ClinGen UniProt Ensembl dbSNP
VAR_006421 rs63751106 CA225016 RCV000084305 RCV001290408	139	M>T	Alzheimer disease 3 AD3 [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
rs63751037 CA225015 RCV000019756 RCV000084304 VAR_006422	139	M>V	Alzheimer disease 3 AD3; increased amyloid-beta 42/amyloid-beta 40 ratio [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
VAR_081234	142	V>F	AD3; unknown pathological significance [UniProt]	Yes	UniProt
CA390304971 RCV000736266 rs1566630910	142	V>I	Alzheimer disease [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
CA225018 rs63750322 VAR_006423 RCV000084307	143	I>F	AD3 [UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
CA225019 VAR_006424 RCV001071503 rs63750004 RCV000084308	143	I>T	Alzheimer disease 3 AD3; impaired protease activity with APP; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
CA258121 RCV001854473 CA390305025 VAR_006425 rs63750391 RCV000084311 CA225023 RCV000019767	146	M>I	Alzheimer disease 3 AD3 [ClinVar, UniProt]	Yes	ClinGen Ensembl ClinVar UniProt dbSNP
RCV000019751 RCV003105774 RCV000084310 RCV002247483 VAR_006426 CA225022 rs63750306 CA341490 RCV001248367	146	M>L	Alzheimer disease 3 Pick disease AD3; disease phenotype shows high clinical variability; founder mutation originating from Southern Italy and distributed worldwide; alters the conformation of the active site; slightly increased protease activity with APP; decreased activity for Notch1 cleavage; no loss of its ability to cleave Ephb2/CTF1 [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
CA258120 RCV000019757 VAR_006427 rs63750306	146	M>V	Alzheimer disease 3 AD3; loss of function as calcium-leak channel; results in calcium overload in the endoplasmic reticulum [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV000084312 rs63750907 CA225024 VAR_010123	147	T>I	AD3; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio [UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
VAR_081235 rs63751441 RCV000084313 CA225025	153	L>V	AD3; abolishes protease activity with APP resulting in decreased amyloid-beta 42 and amyloid-beta 40 production [UniProt]	Yes	ClinGen ClinVar UniProt ExAC TOPMed dbSNP gnomAD
RCV000084315 rs63751292 VAR_081236 CA225029	154	Y>C	AD3; unknown pathological significance [UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
CA225027 rs63750588 RCV000084314 VAR_081237	154	Y>N	AD3; disease phenotype includes spastic paraparesis; abolishes protease activity with APP resulting in decreased amyloid-beta 42 and amyloid-beta 40 production [UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV002271336 RCV000084316 rs63750631	155	K>FI	Alzheimer disease, familial, 3, with spastic paraparesis and unusual plaques [ClinVar]	Yes	ClinVar dbSNP
VAR_075262	156	Y>FTY	AD3; unknown pathological significance [UniProt]	Yes	UniProt
VAR_081238 rs778630379 CA390305138	159	Y>F	AD3; unknown pathological significance [UniProt]	Yes	ClinGen UniProt ExAC dbSNP gnomAD
RCV003222216 rs1897961716 RCV001067591	159	Y>H	Alzheimer disease 3 [ClinVar]	Yes	ClinVar dbSNP
rs1898533490 RCV001315317	161	V>I	Alzheimer disease 3 [ClinVar]	Yes	ClinVar dbSNP
rs1898533739 RCV001070299	162	I>S	Alzheimer disease 3 [ClinVar]	Yes	ClinVar dbSNP
RCV002490394 CA225034 VAR_006428 RCV000019752 RCV000084318 RCV000534810 rs63750590	163	H>R	Alzheimer disease 3 AD3; abolishes protease activity with APP; decreased activity for Notch cleavage [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
CA225033 rs63749885 RCV000019758 VAR_006429 RCV000084317	163	H>Y	Alzheimer disease 3 AD3; slightly increased protease activity with APP and slightly increased amyloid-beta 42 production [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
CA225037 VAR_010124 rs63751484 RCV000084320	165	W>C	AD3 [UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
VAR_016216 CA258123 rs63750265 RCV000019776	166	L>P	Alzheimer disease 3 AD3; onset in adolescence; severe decrease of protease activity with APP; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio; results in reduced Notch proteolysis [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
VAR_081239	168	I>del	AD3; unknown pathological significance; abolishes protease activity with APP resulting in decreased amyloid-beta 42 and amyloid-beta 40 production [UniProt]	Yes	UniProt
RCV002513897 VAR_006430 CA225045 RCV000084325 rs63751210	169	S>L	Alzheimer disease 3 AD3 [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
rs63750418 RCV000084324 VAR_006431 CA225044	169	S>P	AD3; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio [UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
VAR_081240 RCV000084326 CA225046 rs63750577 RCV000019788	170	S>F	Alzheimer disease 3 AD3; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV001047251 rs63750577	170	S>Y	Alzheimer disease 3 [ClinVar]	Yes	ClinVar dbSNP
rs1566638673 RCV000736263	170	S>Y	Alzheimer disease [ClinVar]	Yes	ClinVar dbSNP
VAR_006432 rs63750963 RCV000084327 CA225048 RCV002514495	171	L>P	Alzheimer disease 3 AD3; abolishes protease activity with APP [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
CA225049 RCV000084328 rs63750299 VAR_010125	173	L>W	AD3; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio [UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
rs63751144 VAR_016217 CA225050 RCV000084329 RCV000019777	174	L>M	Alzheimer disease 3 AD3; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV000850226 rs1595026031	174	L>missing	Alzheimer disease 3 [ClinVar]	Yes	ClinVar dbSNP
RCV000084332 rs63749911 VAR_075263 CA225055	177	F>L	AD3; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio [UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV002513898 VAR_075264 rs63749806 CA225057 RCV000084333	177	F>S	Alzheimer disease 3 AD3; unknown pathological significance [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV000640607 rs63750155 CA225059 VAR_075265 RCV000084334	178	S>P	Alzheimer disease 3 AD3; unknown pathological significance; abolishes protease activity with APP [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV000019779 VAR_081241 RCV000020085 RCV000084335 rs63751068 CA225061	183	G>V	Alzheimer disease 3 Pick disease PIDB and AD3; neuropathologic examination of brain sections from the patient shows the presence of Pick bodies and absence of beta-amyloid plaques; unknown pathological significance; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio in vitro [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt TOPMed dbSNP
RCV000084336 VAR_081242 rs63750311 RCV001857411 CA225063	184	E>D	Alzheimer disease 3 AD3; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV000785875 CA390298871 rs1566641934	184	E>G	Alzheimer disease 3 [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
rs556147068 CA7256783 RCV001325814	189	Y>C	Alzheimer disease 3 [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ExAC TOPMed dbSNP gnomAD
RCV000640609 RCV002482890 rs63750082 CA258122 VAR_016218 RCV000518563 RCV000019773	206	G>A	Alzheimer disease 3 AD3; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt 1000Genomes ExAC TOPMed dbSNP gnomAD
RCV000995615 CA390299366 VAR_081243 rs63750082	206	G>D	Alzheimer disease 3 AD3; affects APP processing resulting in increased amyloid-beta 42/amyloid-beta 40 ratio; does not affect NOTCH processing; does not affect endoproteolysis; reduced interaction with PEN2; results in decreased protein levels in the endoplasmic reticulum but increased levels in early endosome; reduced ability to maintain ER calcium homeostasis [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt 1000Genomes ExAC TOPMed dbSNP gnomAD
VAR_075266 RCV000084337 CA225065 rs63750569	206	G>S	AD3; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio [UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV000813898 CA7256794 rs543391977	208	V>L	Alzheimer disease 3 [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ExAC dbSNP gnomAD
rs63750053 CA390299412 VAR_075267 RCV000821428	209	G>E	Alzheimer disease 3 AD3; unknown pathological significance [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
rs63749880 RCV000084339 VAR_009210 CA225069	209	G>R	AD3; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio [UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
VAR_006433 rs63750053 RCV000640604 RCV000084340 CA225070	209	G>V	Alzheimer disease 3 AD3; abolishes protease activity with APP [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
rs1555355250 CA390299466 RCV000712873 RCV001055042	212	S>Y	Alzheimer disease 3 [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
CA262609413 rs63750861 VAR_075268	213	I>L	AD3; increases protease activity with APP resulting in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio [UniProt]	Yes	ClinGen UniProt Ensembl dbSNP
CA225073 VAR_006434 RCV000084342 rs63751309	213	I>T	AD3; decreased protease activity with APP resulting in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio [UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV001377214 CA127843 VAR_081244 rs267606983 RCV000019789	217	G>R	Alzheimer disease 3 Alzheimer disease, familial, 3, with unusual plaques AD3; with unusual amyloid cotton wool plaques; decreased protease activity with APP resulting in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
rs63750761 VAR_010126 CA225079 RCV000084346 RCV002272063	219	L>P	Familial Alzheimer disease AD3 [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV000803782 CA7256798 rs763831389	220	R>Q	Alzheimer disease 3 [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
RCV000736262 rs63750009 CA390299622	222	Q>P	Alzheimer disease [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
CA225080 VAR_075269 RCV000084347 rs63750009	222	Q>R	AD3; unknown pathological significance; slightly increased protease activity with APP and slightly increased amyloid-beta 42/amyloid-beta 40 ratio [UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV001350081 rs1898776259	223	Q>K	Alzheimer disease 3 [ClinVar]	Yes	ClinVar dbSNP
rs63749970 RCV000084351 CA225088 VAR_081245	229	I>F	AD3; decreased protease activity with APP resulting in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio [UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
VAR_006435 RCV000084352 rs63749836 RCV000763347 CA225090	231	A>T	Alzheimer disease 3 AD3; decreased protease activity with APP resulting in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
VAR_006436 CA225091 rs63750799 RCV000084353	231	A>V	AD3; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio [UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
CA225092 VAR_009211 rs63751287 RCV000084354	233	M>L	AD3; slightly decreased protease activity with APP resulting in altered amyloid-beta production and mildly increased amyloid-beta 42/amyloid-beta 40 ratio [UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV000084355 CA225093 VAR_006437 rs63751024 RCV001808318	233	M>T	Alzheimer disease 3 AD3; decreased protease activity with APP resulting in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
CA341527 RCV000020086 RCV000712874 COSM957594 RCV000818883 rs63751287	233	M>V	Alzheimer disease 3 Variant assessed as Somatic; impact. endometrium [ClinVar, NCI-TCGA, Cosmic]	Yes	ClinGen cosmic curated ClinVar Ensembl NCI-TCGA dbSNP
VAR_006438 CA225098 rs63749835 RCV000084358	235	L>P	AD3; abolishes protease activity with APP [UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
VAR_081246	235	L>R	AD3; abolishes protease activity with APP [UniProt]	Yes	UniProt
VAR_081247 CA225096 rs63751130 RCV000084357	235	L>V	AD3; reduced APP cleavage resulting in decreased amyloid-beta 42 and amyloid-beta 40 production; no relevant change in amyloid-beta 42/amyloid-beta 40 ratio [UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
CA390299710 rs63750858 VAR_081248	237	F>I	AD3; disease phenotype includes spastic paraparesis; unknown pathological significance; severe decrease of protease activity with APP; results in decreased amyloid-beta 42 and amyloid-beta 40 production [UniProt]	Yes	ClinGen UniProt Ensembl dbSNP
CA225100 RCV002243711 rs63750858 RCV000084359 VAR_081249	237	F>L	AD3; unknown pathological significance [UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
rs1595035030 RCV000022446	242	P>missing	Acne inversa, familial, 3 [ClinVar]	Yes	ClinVar dbSNP
CA225104 rs63750526 RCV000019753 RCV000084361 VAR_006439 RCV000542870	246	A>E	Alzheimer disease 3 AD3; nearly abolishes protease activity with APP; increased amyloid-beta 42/amyloid-beta 40 ratio; no loss of its ability to cleave Ephb2/CTF1 [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
rs1362575880 CA390299857 RCV001378264 RCV001289155	249	I>L	Alzheimer disease 3 [ClinVar]	Yes	ClinGen ClinVar dbSNP gnomAD
CA225107 RCV000019768 VAR_006440 RCV000084363 rs63751163	250	L>S	Alzheimer disease 3 AD3; nearly abolishes protease activity with APP; increased amyloid-beta 42/amyloid-beta 40 ratio [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
rs63751320 RCV000020087 RCV000084364 CA225108	256	Y>S	Alzheimer disease 3 [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
rs63751420 VAR_006441 CA225110 RCV000084365	260	A>V	AD3; nearly abolishes protease activity with APP; increased amyloid-beta 42/amyloid-beta 40 ratio; impaired ability to cleave Ephb2/CTF1 [UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
CA225111 RCV000084366 VAR_075270 rs63750964	261	V>F	AD3; nearly abolishes protease activity with APP; increased amyloid-beta 42/amyloid-beta 40 ratio [UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV000984884 CA390301925 rs63750964	261	V>I	Early onset Alzheimer disease with behavioral disturbance [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
VAR_006442 CA225113 RCV000084367 CA7256822 rs63750248	262	L>F	AD3; decreased protease activity with APP resulting in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio [UniProt]	Yes	ClinGen ExAC gnomAD ClinVar UniProt dbSNP
VAR_070025	262	L>V	AD3 [UniProt]	Yes	UniProt
rs63751102 VAR_081250 CA225115 RCV000084369	263	C>F	AD3; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio [UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
CA225114 RCV000084368 rs63750543 VAR_006443	263	C>R	AD3; decreased protease activity with APP; increased amyloid-beta 42/amyloid-beta 40 ratio [UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV000084370 rs63750301 RCV000415376 CA225117 RCV001387954 VAR_006444	264	P>L	Alzheimer disease 3 AD3; decreased protease activity with APP; increased amyloid-beta 42/amyloid-beta 40 ratio; impaired ability to cleave Ephb2/CTF1 [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt dbSNP gnomAD
VAR_016219 rs121917807 RCV000019774 CA127839	266	G>S	Alzheimer disease, familial, 3, with spastic paraparesis and apraxia AD3; nearly abolishes protease activity with APP; increased amyloid-beta 42/amyloid-beta 40 ratio [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
rs63750779 RCV002514496 RCV001261442 CA225119 RCV000084372	267	P>L	Alzheimer disease 3 [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
CA225118 VAR_006445 RCV000019762 RCV000084371 rs63751229	267	P>S	Alzheimer disease 3 AD3; decreased protease activity with APP; increased amyloid-beta 42/amyloid-beta 40 ratio [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
rs63751229 RCV001281064	267	P>T	Alzheimer disease 3 [ClinVar]	Yes	ClinVar dbSNP
VAR_006447 CA225121 rs63751019 RCV000084373	269	R>G	AD3; decreased protease activity with APP; increased amyloid-beta 42/amyloid-beta 40 ratio [UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV000084374 VAR_006448 CA225122 RCV000689465 rs63750900 RCV000031858	269	R>H	Alzheimer disease 3 Alzheimer disease 4 AD3 [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt ExAC TOPMed dbSNP gnomAD
RCV001325624 rs1899028511	270	M>T	Alzheimer disease 3 [ClinVar]	Yes	ClinVar dbSNP
RCV000019778 RCV001204170 RCV000984888 RCV000084375 RCV002051789 CA127840 VAR_016220 rs63750886	271	L>V	Alzheimer disease 3 Alzheimer disease, familial, 3, with unusual plaques AD3; abolishes protease activity with APP [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
VAR_075271 RCV000084378 rs63750284 CA225127 RCV001857412	274	T>R	Alzheimer disease 3 AD3; unknown pathological significance; abolishes protease activity with APP [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
CA390302088 rs1555355869 VAR_081251	275	A>V	AD3; unknown pathological significance; reduced protease activity with APP resulting in reduced amyloid-beta 40 levels but no relevant changes in amyloid-beta 42/amyloid-beta 40 ratio [UniProt]	Yes	ClinGen UniProt Ensembl dbSNP
RCV000019782 RCV000084379 RCV002513126 CA225129 rs63749891 VAR_081252	278	R>I	Alzheimer disease 3 AD3; atypical phenotype presenting as language impairment, impaired frontal executive function and relative preservation of memory; severe decrease of APP and Notch proteolysis [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
CA127838 RCV001814004 rs63749891 VAR_006449 RCV000019769	278	R>T	Alzheimer disease, familial, with spastic paraparesis and unusual plaques AD3 [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
rs63750231 RCV000701892 CA341491 VAR_006450 RCV000019759	280	E>A	Alzheimer disease 3 AD3; strong deposition of amyloid-beta 42 is observed in brain regions of AD3 patients; decreased protease activity with APP resulting in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio; decreased activity for Notch1 cleavage [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
CA127837 VAR_006451 rs63750231 RCV000019760 RCV000084381 RCV000019761 RCV002513125	280	E>G	Alzheimer disease 3 Alzheimer disease, familial, with spastic paraparesis and unusual plaques AD3; some AD3 patients manifest spastic paraparesis and unusual amyloid plaques with prominent amyloid angiopathy on brain biopsy; decreased protease activity with APP; increased amyloid-beta 42/amyloid-beta 40 ratio; impaired ability to cleave Ephb2/CTF1 [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV000084383 rs63750050 VAR_009212 CA225135	282	L>R	AD3; abolishes protease activity with APP [UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
CA225133 VAR_081253 RCV000084382 rs63749937	282	L>V	AD3; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio [UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV001808319 rs63751139 VAR_006452 RCV000084386 CA225140	285	A>V	Early-onset autosomal dominant Alzheimer disease AD3; slightly decreased protease activity with APP and slightly decreased amyloid-beta 42/amyloid-beta 40 ratio [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV000084387 rs63751235 CA225141 VAR_006453 RCV000019754	286	L>V	Alzheimer disease 3 AD3; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
VAR_010127	289	S>C	AD3 [UniProt]	Yes	UniProt
RCV000799361 CA390304864 rs1594750510	303	P>A	Alzheimer disease 3 [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
RCV000172776 RCV000242303 VAR_006454 RCV000290884 rs17125721 RCV000382419 CA225145 RCV000084390 RCV000559984	318	E>G	Alzheimer disease 3 Alzheimer disease Dilated cardiomyopathy 1U [ClinVar]	Yes	ClinGen ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
RCV000877625 RCV000019786 VAR_064902 RCV000171844 CA258124 rs121917809	333	D>G	Alzheimer disease 3 Primary dilated cardiomyopathy Dilated cardiomyopathy 1U CMD1U; results in slightly decreased protease activity with APP and slightly decreased amyloid-beta 42/amyloid-beta 40 ratio [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
RCV001240561 rs1018763711 CA262618707	345	D>G	Alzheimer disease 3 [ClinVar]	Yes	ClinGen ClinVar TOPMed dbSNP gnomAD
VAR_075272	352	R>RR	AD3; unknown pathological significance [UniProt]	Yes	UniProt
CA225149 VAR_075273 RCV000084392 rs63751164	354	T>I	AD3; unknown pathological significance; results in decreased protease activity with APP and decreased amyloid-beta 42/amyloid-beta 40 ratio [UniProt]	Yes	ClinGen ClinVar UniProt TOPMed dbSNP gnomAD
RCV001314550 CA262618753 RCV000518371 rs63751174	358	R>P	Alzheimer disease 3 [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
CA225151 VAR_075274 RCV000084393 rs63751174	358	R>Q	AD3; unknown pathological significance; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio [UniProt]	Yes	ClinGen ClinVar UniProt ExAC TOPMed dbSNP gnomAD
RCV001116885 RCV000797696 rs199715992 CA7256917 RCV001116884	360	A>T	Alzheimer disease 3 Dilated cardiomyopathy 1U [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
RCV000084394 CA225153 rs63750941 VAR_075275	365	S>Y	AD3; unknown pathological significance [UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV000084395 rs63751051 CA225155 VAR_081255	377	R>M	AD3; unknown pathological significance [UniProt]	Yes	ClinGen ClinVar Ensembl dbSNP UniProt
rs63750323 RCV001092312 RCV002249680 VAR_006455	378	G>E	Pick disease AD3; decreased protease activity with APP; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio [ClinVar, UniProt]	Yes	ClinVar dbSNP UniProt
VAR_081256 RCV000084396 rs63750323 CA225157	378	G>V	AD3; abolishes protease activity with APP [UniProt]	Yes	ClinGen ClinVar UniProt ExAC dbSNP gnomAD
VAR_081257 RCV000106293 CA150766 RCV000625969 rs63750687	381	L>F	Alzheimer disease 3 Alzheimer disease familial 3, with spastic paraparesis AD3 [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV000198517 VAR_081258 RCV000084397 CA225159 rs63750687	381	L>V	Alzheimer disease 3 AD3; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
rs1566656647 RCV000697016 CA390305731	383	L>W	Alzheimer disease 3 [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
VAR_006456 CA225161 RCV000084398 rs63750646	384	G>A	AD3; results in reduced APP and Notch proteolysis; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio [UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
VAR_010128 CA225164 rs63750883 RCV000084400	390	S>I	AD3; abolishes protease activity with APP [UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
rs63750218 CA225168 RCV002514122 RCV000084403 RCV000020082	392	L>P	Alzheimer disease 3 [ClinVar]	Yes	ClinGen ClinVar TOPMed dbSNP
VAR_006457 RCV000084402 rs63751416 CA225167 RCV002513899	392	L>V	Alzheimer disease 3 AD3; results in reduced APP and Notch proteolysis; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
CA390305793 RCV000736267 rs1566656702	393	V>F	Alzheimer disease [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
RCV000084404 RCV002513900 VAR_075276 CA225170 rs63750929	394	G>V	Alzheimer disease 3 AD3; unknown pathological significance; abolishes protease activity with APP [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
VAR_070026	396	A>T	AD3; unknown pathological significance; decreased protease activity with APP; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio [UniProt]	Yes	UniProt
CA225172 RCV000084405 VAR_010129 rs63751254	405	N>S	AD3; unknown pathological significance; decreased protease activity with APP [UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
VAR_075277 CA262620274 rs906454643	408	I>T	AD3 [UniProt]	Yes	ClinGen UniProt TOPMed dbSNP gnomAD
rs63750227 VAR_009213 CA225173 RCV000084406 RCV000811198	409	A>T	Alzheimer disease 3 AD3; unknown pathological significance; decreased protease activity with APP [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt TOPMed dbSNP
VAR_006458 RCV000019755 RCV000084407 rs661 RCV000640605 CA225174	410	C>Y	Alzheimer disease 3 AD3; results in reduced APP and Notch proteolysis [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt ExAC dbSNP
rs777734426 RCV001324627	414	I>V	Alzheimer disease 3 [ClinVar]	Yes	ClinVar dbSNP
VAR_081259	417	G>A	AD3; unknown pathological significance [UniProt]	Yes	UniProt
RCV000084408 CA225175 VAR_075278 RCV002282436 rs63751316 RCV001049005	418	L>F	Alzheimer disease 3 AD3; unknown pathological significance; nearly abolishes protease activity with APP [ClinVar, UniProt]	Yes	ClinGen ClinVar Ensembl dbSNP UniProt
RCV000790841 rs1555358260 RCV000995205 CA390305997	424	L>V	Alzheimer disease 3 [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
VAR_006459 RCV000084411 RCV000763348 CA225181 rs63751223 RCV000019766	426	A>P	Alzheimer disease 3 AD3; unknown pathological significance; slightly decreased protease activity with APP [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
rs63750083 VAR_025605 RCV000019785 CA341492 RCV000517533 RCV000640606	431	A>E	Alzheimer disease 3 AD3; decreased protease activity with APP; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV002288582 RCV000084412 CA225182 rs63750083	431	A>V	Frontotemporal dementia [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
RCV000736264 CA390306056 rs1566657804	433	P>S	Alzheimer disease [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
CA225525 rs281875357 RCV000019771 RCV000084588	434	A>C	Alzheimer disease 3 [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
CA225184 RCV000084413 rs63750001 VAR_075280	435	L>F	AD3; with unusual amyloid cotton wool plaques; almost abolishes gamma-secretase activity; no endoproteolytic cleavage; no APP nor NOTCH1 processing; no detectable amyloid-beta [UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
CA225518 RCV000084580 RCV000019780 rs121917808 VAR_006460	436	P>Q	Alzheimer disease 3 AD3; severe decrease of protease activity with APP [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV000084414 VAR_008141 rs63749925 CA225186	436	P>S	AD3; partially abolishes gamma-secretase activity; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio [UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV001871727 rs764971634 RCV001289154 CA7256970	437	I>V	Alzheimer disease 3 [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
RCV000084415 rs63750249 VAR_075282 RCV002470762 CA225187	439	I>V	Alzheimer disease 3 AD3; unknown pathological significance; no significant change of protease activity with APP [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt TOPMed dbSNP gnomAD
RCV002271337 rs63750470 RCV000084416	440	T>missing	Alzheimer disease, familial, 3, with spastic paraparesis and unusual plaques [ClinVar]	Yes	ClinVar dbSNP
rs1900050658 RCV001058511	440	T>N	Alzheimer disease 3 [ClinVar]	Yes	ClinVar dbSNP
rs1430581353 RCV000805834 CA390306206	457	M>V	Alzheimer disease 3 Variant assessed as Somatic; impact. [ClinVar, NCI-TCGA]	Yes	ClinGen ClinVar NCI-TCGA TOPMed dbSNP
rs1171880969 CA390295546	5	P>L		No	ClinGen gnomAD
TCGA novel	5	P>S	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1313248233 CA390295580	7	P>L		No	ClinGen gnomAD
CA390295751 rs1330528266	15	Q>H		No	ClinGen gnomAD
rs199759305 CA7256646	16	M>R		No	ClinGen ESP ExAC TOPMed gnomAD
CA7256647 rs199759305	16	M>T		No	ClinGen ESP ExAC TOPMed gnomAD
CA390295809 rs1555350551	19	D>N	Variant assessed as Somatic; impact. [NCI-TCGA]	No	ClinGen Ensembl NCI-TCGA
CA390295864 rs1231923457	20	N>S		No	ClinGen gnomAD
CA262604155 rs780917786	22	L>P		No	ClinGen Ensembl
rs568497767 CA7256649	23	S>N		No	ClinGen 1000Genomes ExAC gnomAD
rs1203994295 CA390295990	24	N>D		No	ClinGen TOPMed
TCGA novel	24	N>K	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA7256650 rs200598249	24	N>S		No	ClinGen ExAC TOPMed gnomAD
rs200598249 CA262604159	24	N>T		No	ClinGen ExAC TOPMed gnomAD
CA262604160 rs201945418	25	T>I		No	ClinGen gnomAD
CA390296043 rs201945418	25	T>S		No	ClinGen gnomAD
CA262604162 rs918641083	26	V>A		No	ClinGen Ensembl
rs747750345 CA7256653	29	Q>H		No	ClinGen ExAC gnomAD
CA7256670 rs200824179	32	N>S		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA7256672 rs777371921	33	R>T	Variant assessed as Somatic; impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA gnomAD
CA390302510 rs776584385	36	Q>*		No	ClinGen ExAC TOPMed gnomAD
rs776584385 CA7256674	36	Q>E		No	ClinGen ExAC TOPMed gnomAD
rs200958188 CA7256676	37	E>G		No	ClinGen ExAC gnomAD
rs1413353989 CA390302524	38	H>D		No	ClinGen gnomAD
rs938687393 CA262614355	38	H>Q		No	ClinGen gnomAD
CA390302539 rs775543665	40	D>H		No	ClinGen ExAC TOPMed gnomAD
CA7256680 rs775543665	40	D>N		No	ClinGen ExAC TOPMed gnomAD
rs1258736994 CA390302545	41	R>G		No	ClinGen gnomAD
rs997923176 CA262614373	41	R>S		No	ClinGen TOPMed
rs961074832 CA262614369	41	R>T		No	ClinGen TOPMed
CA7256685 rs140189461	42	R>G		No	ClinGen ESP ExAC TOPMed gnomAD
rs367775281 CA7256687	42	R>L		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs367775281 CA390302550	42	R>P		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
COSM1222302 rs140189461 CA7256684	42	R>W	Variant assessed as Somatic; 0.0 impact. large_intestine [NCI-TCGA, Cosmic]	No	ClinGen cosmic curated ESP ExAC NCI-TCGA TOPMed gnomAD
CA390302558 rs1594997980	43	S>R		No	ClinGen Ensembl
rs1198845230 CA390302551	43	S>R		No	ClinGen gnomAD
rs1312532981 CA390302575	46	H>R		No	ClinGen TOPMed
CA262614394 rs947643420	47	P>L		No	ClinGen Ensembl
rs1377702483 CA390302584	48	E>K		No	ClinGen TOPMed
CA7256689 rs200373970	49	P>A		No	ClinGen ESP ExAC TOPMed gnomAD
CA390302618 rs1475323603	51	S>C		No	ClinGen TOPMed gnomAD
CA390302623 rs1181060667	52	N>D		No	ClinGen gnomAD
rs201216284 CA7256690	54	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs766630576 CA7256691	55	P>S		No	ClinGen ExAC TOPMed gnomAD
CA390302701 rs755402092	56	Q>H		No	ClinGen ExAC gnomAD
CA7256692 rs754392688	56	Q>R		No	ClinGen ExAC TOPMed gnomAD
CA262614408 rs986331634	59	S>C		No	ClinGen TOPMed
rs1315157428 CA390302764	60	R>Q		No	ClinGen TOPMed gnomAD
rs1594998137 CA390302800	62	V>G		No	ClinGen Ensembl
rs116314689 CA390302795	62	V>L		No	ClinGen 1000Genomes ExAC gnomAD
CA7256695 rs116314689	62	V>M		No	ClinGen 1000Genomes ExAC gnomAD
CA390302819 rs1594998144	63	V>G		No	ClinGen Ensembl
rs1349963459 CA390302837	64	E>D		No	ClinGen Ensembl
CA390302871 rs1594998176	66	D>G		No	ClinGen Ensembl
TCGA novel	68	E>D	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs756816679 CA7256696	68	E>G		No	ClinGen ExAC gnomAD
rs1195019145 CA390302944	69	E>D		No	ClinGen TOPMed
TCGA novel	69	E>K	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs762907738 CA262614421	71	E>D		No	ClinGen Ensembl
CA390303129 rs63749824	79	A>G		No	ClinGen ExAC gnomAD
rs769650189 CA7256699	79	A>T		No	ClinGen ExAC TOPMed gnomAD
rs1203318928 CA390303144	80	K>R		No	ClinGen gnomAD
rs63750307 RCV000084283	83	I>missing		No	ClinVar dbSNP
CA7256700 rs749249788	84	M>L		No	ClinGen ExAC gnomAD
CA390303223 rs1266124242	84	M>R		No	ClinGen gnomAD
rs1897874329 RCV001092310	88	P>L		No	ClinVar dbSNP
CA7256704 rs146855665	93	M>V		No	ClinGen ESP ExAC gnomAD
rs1356498068 CA390303449	97	V>A		No	ClinGen gnomAD
rs63750852 COSM1562548 CA262614468	97	V>M	large_intestine Variant assessed as Somatic; impact. [Cosmic, NCI-TCGA]	No	ClinGen cosmic curated NCI-TCGA TOPMed gnomAD
rs1335033402 CA390303486	100	I>L		No	ClinGen TOPMed
rs760760368 CA7256705	100	I>T		No	ClinGen ExAC TOPMed gnomAD
rs766798700 CA7256706	101	K>E		No	ClinGen ExAC TOPMed gnomAD
rs1057518919 CA16043483 RCV000415024	105	F>C		No	ClinGen ClinVar Ensembl dbSNP
CA224995 RCV000084290 rs63750325	105	F>I		No	ClinGen ClinVar Ensembl dbSNP
rs200646139 CA7256709	108	R>Q		No	ClinGen ExAC TOPMed gnomAD
RCV000172095 rs200576075 CA237495	108	R>W	Variant assessed as Somatic; impact. [NCI-TCGA]	No	ClinGen ClinVar Ensembl NCI-TCGA dbSNP
rs1382127121	113	L>=	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs63751399 CA390303716	113	L>Q	Frontotemporal dementia (ftd) [Ensembl]	No	ClinGen Ensembl
RCV000084294 CA225000 rs63749962	115	Y>D		No	ClinGen ClinVar Ensembl dbSNP
rs63750550 CA390304680	117	P>A		No	ClinGen Ensembl
CA390304684 rs63749805	117	P>R		No	ClinGen Ensembl
CA390304698 rs1377123050	118	F>L		No	ClinGen TOPMed
rs1555353066 CA390304718	120	E>G		No	ClinGen Ensembl
CA225010 RCV000084301 rs63750378	123	E>K		No	ClinGen ClinVar dbSNP gnomAD
CA390304753 rs63750378	123	E>Q		No	ClinGen gnomAD
rs771002035 CA7256725	124	T>A		No	ClinGen ExAC TOPMed gnomAD
CA262615181 rs199951212	129	A>T		No	ClinGen TOPMed
RCV000712871 CA390304839 rs1566630838	130	L>P		No	ClinGen ClinVar Ensembl dbSNP
CA390304853 rs1555353072	131	H>R	Variant assessed as Somatic; impact. [NCI-TCGA]	No	ClinGen Ensembl NCI-TCGA
CA7256727 rs200937800	132	S>A		No	ClinGen ESP ExAC gnomAD
CA390304870 rs1287002178	133	I>V		No	ClinGen TOPMed
TCGA novel	135	N>K	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs63750353 CA390304891 RCV000518263	135	N>Y		No	ClinGen ClinVar Ensembl dbSNP
CA262615195 rs41345849	136	A>G		No	ClinGen Ensembl
rs1206214428 CA390304924	138	I>V		No	ClinGen TOPMed
CA7256728 rs765670175	140	I>N		No	ClinGen ExAC gnomAD
rs63751071 CA225020 RCV000084309	143	I>M		No	ClinGen ClinVar Ensembl dbSNP
rs63750004 CA390304987	143	I>N		No	ClinGen Ensembl
rs63750322 CA390304983	143	I>V		No	ClinGen Ensembl
CA390305028 rs1555353092	147	T>P		No	ClinGen Ensembl
CA390305039 rs747363386	148	I>L		No	ClinGen ExAC TOPMed gnomAD
CA7256731 rs747363386	148	I>V		No	ClinGen ExAC TOPMed gnomAD
CA390305055 rs1388079504	149	L>F		No	ClinGen gnomAD
CA390305078 rs1345768014	151	V>A		No	ClinGen TOPMed
CA262615244 rs142093869	152	V>L		No	ClinGen ESP TOPMed
CA262615250 rs866914724	153	L>P		No	ClinGen Ensembl
CA7256737 rs201617677	157	R>S		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA390305131 rs1234812912	158	C>F		No	ClinGen gnomAD
CA7256738 rs778630379	159	Y>C		No	ClinGen ExAC gnomAD
RCV000595802 CA390295943 rs1555354560	164	A>V		No	ClinGen ClinVar Ensembl dbSNP
CA225035 RCV000084319 rs63751010	165	W>G		No	ClinGen ClinVar Ensembl dbSNP
rs1898534725 RCV001092311	165	W>L		No	ClinVar dbSNP
rs63750265 CA390296001	166	L>H		No	ClinGen Ensembl
rs63750265 RCV000084322 CA225040	166	L>R		No	ClinGen ClinVar Ensembl dbSNP
rs1555354564 CA390295988	166	L>V		No	ClinGen Ensembl
rs63751458 RCV000084321	166	L>missing		No	ClinVar dbSNP
rs201641438 CA262604773	167	I>T		No	ClinGen Ensembl
TCGA novel	168	I>L	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA390296034 rs1395342213	168	I>V		No	ClinGen gnomAD
RCV000084323 rs63750879	168	I>missing		No	ClinVar dbSNP
TCGA novel	170	S>missing	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA390296202 rs1555354581	173	L>F		No	ClinGen Ensembl
rs63751025 CA225051 RCV000084330	174	L>R		No	ClinGen ClinVar Ensembl dbSNP
CA390296275 COSM957592 rs1566638724 RCV000712872	175	F>L	endometrium [Cosmic]	No	ClinGen cosmic curated ClinVar Ensembl dbSNP
RCV000084331 CA225053 rs63750771	175	F>S		No	ClinGen ClinVar Ensembl dbSNP
rs1335871359 CA390296311	176	F>C		No	ClinGen gnomAD
rs944088683 CA262604819	180	I>V	Variant assessed as Somatic; impact. [NCI-TCGA]	No	ClinGen Ensembl NCI-TCGA
rs63751068 CA262604836	183	G>A		No	ClinGen TOPMed
rs781376659 CA7256765	183	G>W		No	ClinGen ExAC gnomAD
CA7256780 CA390298895 rs762700122	185	V>L		No	ClinGen ExAC TOPMed gnomAD
rs781431904 CA7256785	190	N>D		No	ClinGen ExAC gnomAD
rs112451138 CA262609308	191	V>A		No	ClinGen TOPMed
CA7256786 rs750585566	191	V>I		No	ClinGen ExAC gnomAD
rs756256461 CA7256787	192	A>T		No	ClinGen ExAC gnomAD
CA7256788 rs780461228	193	V>G		No	ClinGen ExAC TOPMed gnomAD
rs200065583 CA262609315	195	Y>C		No	ClinGen TOPMed gnomAD
CA390299173 rs1162159737	196	I>V		No	ClinGen TOPMed gnomAD
CA7256790 rs768923334	198	V>D		No	ClinGen ExAC gnomAD
CA262609317 rs201375628	198	V>L		No	ClinGen TOPMed gnomAD
rs779296437 CA7256791	202	I>F		No	ClinGen ExAC gnomAD
rs748608184 CA7256792	202	I>M		No	ClinGen ExAC
rs1384308168 CA390299309	203	W>C		No	ClinGen gnomAD
rs1042864 VAR_011876 CA262609352	205	F>L		No	ClinGen UniProt Ensembl dbSNP
CA7256793 rs772573771	205	F>S		No	ClinGen ExAC gnomAD
RCV000084338 rs63750082 CA225067	206	G>V		No	ClinGen ClinVar 1000Genomes ExAC TOPMed dbSNP gnomAD
rs1231165169 CA390299369	207	V>M		No	ClinGen TOPMed
TCGA novel	210	M>*	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs769265539 CA7256795	210	M>I		No	ClinGen ExAC gnomAD
RCV000084341 rs63750861 CA225071	213	I>F		No	ClinGen ClinVar Ensembl dbSNP
CA390299494 rs63751003	214	H>D		No	ClinGen gnomAD
CA225074 VAR_070024 rs63751003 RCV000084343	214	H>Y	probable disease-associated variant found in a patient with dementia [UniProt]	No	ClinGen ClinVar UniProt dbSNP gnomAD
CA16621660 rs1064797189 RCV000487858	215	W>R		No	ClinGen ClinVar Ensembl dbSNP
CA225075 RCV000084344 rs63750444	217	G>D		No	ClinGen ClinVar Ensembl dbSNP
rs140064975 CA7256796	218	P>L		No	ClinGen ESP ExAC TOPMed gnomAD
CA225077 rs63749987 RCV000084345	219	L>F		No	ClinGen ClinVar dbSNP gnomAD
rs63750761 CA390299607	219	L>R		No	ClinGen Ensembl
rs1258906393 CA390299609	220	R>G		No	ClinGen TOPMed
RCV000084348 rs63751072 CA225082	222	Q>H		No	ClinGen ClinVar Ensembl dbSNP
rs1555355278 CA390299629	223	Q>R		No	ClinGen Ensembl
RCV000084349 rs63750487 CA225084	226	L>F		No	ClinGen ClinVar Ensembl dbSNP
rs63749961 RCV000084350 CA225086	226	L>R		No	ClinGen ClinVar Ensembl dbSNP
rs199842082 CA7256799	227	I>V		No	ClinGen 1000Genomes ExAC gnomAD
CA390299671 rs1595034903	229	I>M		No	ClinGen Ensembl
CA390299675 rs1555355284 RCV000516980	230	S>N		No	ClinGen ClinVar Ensembl dbSNP
CA390299679 rs1485140378	230	S>R		No	ClinGen gnomAD
RCV000084356 CA225094 rs63751479	233	M>I		No	ClinGen ClinVar Ensembl dbSNP
rs767625974 CA7256801	237	F>S		No	ClinGen ExAC
CA390299722 rs1555355289 RCV000518834	238	I>M		No	ClinGen ClinVar Ensembl dbSNP
rs1314899260 CA390299717	238	I>V		No	ClinGen TOPMed
rs1595035012 CA390299724 RCV000992720	239	K>E		No	ClinGen ClinVar Ensembl dbSNP
rs1555355290 CA390299729	239	K>N		No	ClinGen Ensembl
TCGA novel	241	L>P	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA225102 RCV000084360 rs63750888	245	T>P		No	ClinGen ClinVar Ensembl dbSNP
rs1373228424 CA390299842	248	L>F		No	ClinGen TOPMed
CA390299846 rs1555355302	248	L>R		No	ClinGen Ensembl
RCV000084362 rs63750634 CA225105	250	L>V		No	ClinGen ClinVar Ensembl dbSNP
rs755161885 CA7256806	252	V>A		No	ClinGen ExAC gnomAD
CA390299908 rs1391776671	252	V>M		No	ClinGen TOPMed gnomAD
rs568741200 CA7256820	259	V>L		No	ClinGen 1000Genomes ExAC gnomAD
RCV000172775 rs199723282 CA200044	261	V>G		No	ClinGen ClinVar ExAC dbSNP gnomAD
rs63750964 CA390301926	261	V>L		No	ClinGen Ensembl
CA390301955 rs1203424298	266	G>V		No	ClinGen gnomAD
CA390301959 rs63751229 RCV000516919	267	P>A		No	ClinGen ClinVar Ensembl dbSNP
rs1179768627 CA390301967	268	L>R		No	ClinGen gnomAD
TCGA novel	269	R>V	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA262613168 rs114317083	270	M>L		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs114317083 CA7256828	270	M>V		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs63750680 RCV000084376 CA225123	272	V>A		No	ClinGen ClinVar Ensembl dbSNP
CA7256830 rs200915258	272	V>I		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs63750772 RCV000084377 CA225125	273	E>A		No	ClinGen ClinVar Ensembl dbSNP
RCV000518734 rs1555355866 CA390302078	275	A>P		No	ClinGen ClinVar Ensembl dbSNP
rs748891711 CA7256831	276	Q>L		No	ClinGen ExAC gnomAD
rs63750524 RCV000084380 CA225131	278	R>S		No	ClinGen ClinVar Ensembl dbSNP
CA7256832 rs114378630	281	T>M		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs63749937 CA390302255	282	L>F		No	ClinGen Ensembl
RCV000084385 CA225138 rs63750863	284	P>L		No	ClinGen ClinVar Ensembl dbSNP
CA225136 RCV000084384 rs63750324	284	P>S		No	ClinGen ClinVar Ensembl dbSNP
rs1555355888 CA390302320	286	L>P		No	ClinGen Ensembl
CA390304682 rs63750298	291	T>A		No	ClinGen Ensembl
rs63750298 CA225143 RCV000084389	291	T>P		No	ClinGen ClinVar Ensembl dbSNP
TCGA novel rs1332096103 CA390304703	292	M>I	Variant assessed as Somatic; impact. [NCI-TCGA]	No	ClinGen gnomAD NCI-TCGA
rs1230478062 CA390304715	293	V>M		No	ClinGen gnomAD
rs1594750482 CA390304775	297	N>T		No	ClinGen Ensembl
rs1428166701 CA390304797	298	M>I		No	ClinGen TOPMed
rs1566650613 CA390304793	298	M>T		No	ClinGen Ensembl
CA7256852 rs778244504	299	A>S		No	ClinGen ExAC gnomAD
rs1594750501 CA390304824	300	E>G		No	ClinGen Ensembl
CA390304837 rs1417396990	301	G>R		No	ClinGen TOPMed
rs1195945223 CA390304858	302	D>E		No	ClinGen TOPMed
rs147638016 CA262616821	303	P>L		No	ClinGen ESP TOPMed gnomAD
CA7256855 rs777545298	305	A>S		No	ClinGen ExAC TOPMed gnomAD
COSM957597 CA390304892 rs777545298	305	A>T	Variant assessed as Somatic; 0.0 impact. endometrium [NCI-TCGA, Cosmic]	No	ClinGen cosmic curated ExAC NCI-TCGA TOPMed gnomAD
CA7256857 rs770625924	307	R>K		No	ClinGen ExAC gnomAD
CA7256860 CA7256858 rs554783173	307	R>S		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA390304939 rs1305412719	308	R>T		No	ClinGen TOPMed
rs1594750572 CA390304954	309	V>G		No	ClinGen Ensembl
rs754432497 CA262616860	309	V>I		No	ClinGen Ensembl
CA7256861 rs115865530 VAR_081254	311	K>R	probable disease-associated variant found in patients with late-onset Alzheimer disease; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio [UniProt]	No	ClinGen UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
CA390304988 rs1218781036	312	N>T		No	ClinGen TOPMed
TCGA novel	313	S>F	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA390304999 rs1400103909	313	S>P		No	ClinGen gnomAD
VAR_064747	315	Y>C	found in a renal cell carcinoma sample; somatic mutation [UniProt]	No	UniProt
CA390305324 rs1594754406 COSM459114	321	E>K	cervix [Cosmic]	No	ClinGen cosmic curated Ensembl
CA7256894 rs745694325	324	S>L		No	ClinGen ExAC gnomAD
CA7256896 rs774033846	327	T>I		No	ClinGen ExAC gnomAD
CA7256897 rs774033846	327	T>N		No	ClinGen ExAC gnomAD
CA7256895 rs755937539	327	T>P		No	ClinGen ExAC gnomAD
rs768730001 CA7256898	328	V>A		No	ClinGen ExAC TOPMed gnomAD
CA390305379 rs1334330042	329	A>V		No	ClinGen gnomAD
rs121917809 CA390305410	333	D>V		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA390305420 CA7256900 rs138871096	335	G>R	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ESP ExAC TOPMed gnomAD NCI-TCGA
rs200753166 CA7256901	336	F>V		No	ClinGen ExAC gnomAD
CA390305438 rs761010563	337	S>R		No	ClinGen ExAC gnomAD
rs766834989 CA7256903	338	E>G		No	ClinGen ExAC gnomAD
CA390305454 rs1594754470	340	W>R		No	ClinGen Ensembl
rs760051592 CA7256906	342	A>G		No	ClinGen ExAC gnomAD
rs760051592 CA7256905	342	A>V		No	ClinGen ExAC gnomAD
CA7256908 rs756764981	346	S>N	Variant assessed as Somatic; impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA
rs767146336 CA7256909	347	H>Q		No	ClinGen ExAC gnomAD
CA262618717 rs199740663	350	P>S		No	ClinGen TOPMed
rs755878292 CA7256912	351	H>P		No	ClinGen ExAC
CA7256910 rs750080931	351	H>Y		No	ClinGen ExAC
RCV000084391 rs63750762	352	R>missing		No	ClinVar dbSNP
CA7256913 rs571825723	352	R>C		No	ClinGen 1000Genomes ExAC gnomAD
CA7256914 rs149299753	352	R>H	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ESP ExAC NCI-TCGA TOPMed gnomAD
CA390305549 rs376433615	355	P>A		No	ClinGen ESP ExAC TOPMed gnomAD
CA7256915 rs376433615	355	P>S		No	ClinGen ESP ExAC TOPMed gnomAD
rs143683769 CA262618737	356	E>A		No	ClinGen ESP
rs111759355 CA262618740	357	S>L		No	ClinGen Ensembl
CA262618748 rs1033217198	358	R>*		No	ClinGen TOPMed
rs199715992 CA390305574	360	A>S		No	ClinGen ExAC TOPMed gnomAD
rs1019919048 CA262618760	361	V>I		No	ClinGen TOPMed gnomAD
rs1019919048 CA390305578	361	V>L		No	ClinGen TOPMed gnomAD
CA390305586 rs1302810284	362	Q>P		No	ClinGen TOPMed
rs996227958 CA262618763	363	E>K		No	ClinGen gnomAD
CA390305592 rs996227958	363	E>Q	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen NCI-TCGA gnomAD
rs966909396 CA262618766	364	L>P		No	ClinGen TOPMed gnomAD
rs200888596 CA7256919	365	S>A		No	ClinGen ExAC TOPMed gnomAD
CA390305616 rs1485025978	367	S>G		No	ClinGen TOPMed gnomAD
CA7256921 rs777093611	367	S>R		No	ClinGen ExAC gnomAD
CA262618783 rs141822345	370	A>G		No	ClinGen ESP
CA390305635 rs760139599	370	A>S		No	ClinGen ExAC gnomAD
CA7256922 rs760139599	370	A>T		No	ClinGen ExAC gnomAD
rs1169974839 CA390305644	371	G>V		No	ClinGen TOPMed
rs765890474 CA7256923	373	D>H		No	ClinGen ExAC gnomAD
rs63751051 CA262620232	377	R>K		No	ClinGen Ensembl
rs1555357544 CA390305683	377	R>W		No	ClinGen Ensembl
rs63750323 CA7256941	378	G>A		No	ClinGen ExAC gnomAD
CA390305705 rs1171109621	379	V>I		No	ClinGen TOPMed
RCV000712869 CA390305717 rs63750687	381	L>I		No	ClinGen ClinVar Ensembl dbSNP
rs1555358095 CA390305752 COSM3793832 RCV000992719	386	F>L	Variant assessed as Somatic; impact. urinary_tract [NCI-TCGA, Cosmic]	No	ClinGen cosmic curated ClinVar Ensembl NCI-TCGA dbSNP
rs63749860 CA225162 RCV000084399	386	F>S		No	ClinGen ClinVar Ensembl dbSNP
rs1435320764 CA615002741	389	Y>*		No	ClinGen gnomAD
rs63751066 CA225165 RCV000084401	391	V>F		No	ClinGen ClinVar Ensembl dbSNP
rs63750218 CA262620263	392	L>R		No	ClinGen TOPMed
CA7256944 rs771515240	399	T>P		No	ClinGen ExAC gnomAD
rs772731175 CA7256945	400	A>S		No	ClinGen ExAC TOPMed gnomAD
TCGA novel	402	G>E	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1046703781 CA262620270	406	T>P		No	ClinGen TOPMed gnomAD
CA7256947 rs766060557	407	T>S		No	ClinGen ExAC gnomAD
CA7256949 rs759384156	408	I>V		No	ClinGen ExAC gnomAD
CA7256950 rs661	410	C>F		No	ClinGen ExAC
CA262620284 rs200525059	412	V>I		No	ClinGen ExAC TOPMed gnomAD
rs200525059 CA7256953	412	V>L		No	ClinGen ExAC TOPMed gnomAD
rs1168620389 CA390305922	414	I>K		No	ClinGen gnomAD
rs777734426 CA7256954	414	I>L		No	ClinGen ExAC gnomAD
CA7256968 rs776278107	420	L>F		No	ClinGen ExAC gnomAD
CA225177 RCV000084409 rs63750802	420	L>R		No	ClinGen ClinVar Ensembl dbSNP
rs1555358260 CA390305998	424	L>F		No	ClinGen Ensembl
rs63751032 CA390306000	424	L>H		No	ClinGen Ensembl
rs63751032 RCV000084410 CA225179	424	L>R		No	ClinGen ClinVar Ensembl dbSNP
rs1555358265 CA390306011	426	A>V		No	ClinGen Ensembl
CA390306012 rs1398951357	427	I>V		No	ClinGen TOPMed gnomAD
rs1221139878 CA390306024	428	F>C		No	ClinGen TOPMed gnomAD
TCGA novel	428	F>S	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1295994514 CA390306031	429	K>R		No	ClinGen gnomAD
CA390306062 rs1555358268	434	A>S		No	ClinGen Ensembl
CA390306067 rs63750001 RCV000995206	435	L>V		No	ClinGen ClinVar Ensembl dbSNP
CA262620910 rs764971634	437	I>F		No	ClinGen ExAC TOPMed gnomAD
rs1555358271 CA390306090	439	I>S		No	ClinGen Ensembl
rs1377617803 CA390306094	440	T>A		No	ClinGen gnomAD
CA390306118 rs764128019	444	V>I		No	ClinGen ExAC gnomAD
rs764128019 CA7256973	444	V>L		No	ClinGen ExAC gnomAD
CA262620926 rs1054251214	446	Y>C		No	ClinGen TOPMed gnomAD
rs1353469692 CA390306151	448	A>V		No	ClinGen gnomAD
rs200644664 CA262620928	450	D>G		No	ClinGen Ensembl
TCGA novel	450	D>Y	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1372132329 CA390306174	452	L>V		No	ClinGen TOPMed
rs1064797190 RCV000488276 CA16621661	453	V>I		No	ClinGen ClinVar Ensembl dbSNP
CA7256975 rs140169796	455	P>S		No	ClinGen ESP ExAC TOPMed gnomAD
TCGA novel	456	F>L	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA390306217 rs1488771168	458	D>G		No	ClinGen gnomAD
rs1186921147 CA390306239	461	A>S		No	ClinGen gnomAD
CA390306242 rs1235843749	461	A>V		No	ClinGen gnomAD
rs780119074 CA7256979	463	H>R		No	ClinGen ExAC TOPMed gnomAD
rs779764234 CA262620944	464	Q>*		No	ClinGen Ensembl
CA390306260 rs1257458181	464	Q>P		No	ClinGen TOPMed
CA390306278 rs1566657960	466	Y>C		No	ClinGen Ensembl

5 associated diseases with P49768

[MIM: 607822]: Alzheimer disease 3 (AD3)

A familial early-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:10025789, ECO:0000269|PubMed:10090481, ECO:0000269|PubMed:10200054, ECO:0000269|PubMed:10208579, ECO:0000269|PubMed:10439444, ECO:0000269|PubMed:10441572, ECO:0000269|PubMed:10447269, ECO:0000269|PubMed:10533070, ECO:0000269|PubMed:10631141, ECO:0000269|PubMed:10644793, ECO:0000269|PubMed:11027672, ECO:0000269|PubMed:11524469, ECO:0000269|PubMed:11561050, ECO:0000269|PubMed:11568920, ECO:0000269|PubMed:11701593, ECO:0000269|PubMed:11710891, ECO:0000269|PubMed:11796781, ECO:0000269|PubMed:11920851, ECO:0000269|PubMed:12048239, ECO:0000269|PubMed:12058025, ECO:0000269|PubMed:12370477, ECO:0000269|PubMed:12484344, ECO:0000269|PubMed:12493737, ECO:0000269|PubMed:12552037, ECO:0000269|PubMed:15004326, ECO:0000269|PubMed:15122701, ECO:0000269|PubMed:15364419, ECO:0000269|PubMed:15534188, ECO:0000269|PubMed:15534260, ECO:0000269|PubMed:15851849, ECO:0000269|PubMed:16305624, ECO:0000269|PubMed:16344340, ECO:0000269|PubMed:16628450, ECO:0000269|PubMed:16752394, ECO:0000269|PubMed:16897084, ECO:0000269|PubMed:16959576, ECO:0000269|PubMed:17366635, ECO:0000269|PubMed:17428795, ECO:0000269|PubMed:17502474, ECO:0000269|PubMed:18430735, ECO:0000269|PubMed:19667325, ECO:0000269|PubMed:19797784, ECO:0000269|PubMed:20164095, ECO:0000269|PubMed:20460383, ECO:0000269|PubMed:21335660, ECO:0000269|PubMed:21501661, ECO:0000269|PubMed:22461631, ECO:0000269|PubMed:22503161, ECO:0000269|PubMed:22529981, ECO:0000269|PubMed:23123781, ECO:0000269|PubMed:23843529, ECO:0000269|PubMed:24121961, ECO:0000269|PubMed:24495933, ECO:0000269|PubMed:24582897, ECO:0000269|PubMed:25394380, ECO:0000269|PubMed:26145164, ECO:0000269|PubMed:26280335, ECO:0000269|PubMed:26549787, ECO:0000269|PubMed:27073747, ECO:0000269|PubMed:27930341, ECO:0000269|PubMed:29175279, ECO:0000269|PubMed:29404783, ECO:0000269|PubMed:29466804, ECO:0000269|PubMed:30180983, ECO:0000269|PubMed:30200536, ECO:0000269|PubMed:7550356, ECO:0000269|PubMed:7596406, ECO:0000269|PubMed:7651536, ECO:0000269|PubMed:8634711, ECO:0000269|PubMed:8634712, ECO:0000269|PubMed:8733303, ECO:0000269|PubMed:8837617, ECO:0000269|PubMed:9172170, ECO:0000269|PubMed:9225696, ECO:0000269|PubMed:9298817, ECO:0000269|PubMed:9384602, ECO:0000269|PubMed:9507958, ECO:0000269|PubMed:9521423, ECO:0000269|PubMed:9719376, ECO:0000269|PubMed:9831473, ECO:0000269|PubMed:9833068, ECO:0000269|Ref.93}. Note=The disease is caused by variants affecting the gene represented in this entry.

[MIM: 600274]: Frontotemporal dementia (FTD)

A form of dementia characterized by pathologic finding of frontotemporal lobar degeneration, presenile dementia with behavioral changes, deterioration of cognitive capacities and loss of memory. In some cases, parkinsonian symptoms are prominent. Neuropathological changes include frontotemporal atrophy often associated with atrophy of the basal ganglia, substantia nigra, amygdala. In most cases, protein tau deposits are found in glial cells and/or neurons. {ECO:0000269|PubMed:11094121}. Note=The disease is caused by variants affecting the gene represented in this entry.

[MIM: 613694]: Cardiomyopathy, dilated 1U (CMD1U)

A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269|PubMed:17186461, ECO:0000269|PubMed:27930341}. Note=The disease is caused by variants affecting the gene represented in this entry.

[MIM: 613737]: Acne inversa, familial, 3 (ACNINV3)

A chronic relapsing inflammatory disease of the hair follicles characterized by recurrent draining sinuses, painful skin abscesses, and disfiguring scars. Manifestations typically appear after puberty. {ECO:0000269|PubMed:20929727}. Note=The disease is caused by variants affecting the gene represented in this entry.

[MIM: 172700]: Pick disease of the brain (PIDB)

A rare form of dementia pathologically defined by severe atrophy, neuronal loss and gliosis. It is characterized by the occurrence of tau-positive inclusions, swollen neurons (Pick cells) and argentophilic neuronal inclusions known as Pick bodies that disproportionally affect the frontal and temporal cortical regions. Clinical features include aphasia, apraxia, confusion, anomia, memory loss and personality deterioration. {ECO:0000269|PubMed:15122701}. Note=The gene represented in this entry may be involved in disease pathogenesis.

Without disease ID

A familial early-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:10025789, ECO:0000269|PubMed:10090481, ECO:0000269|PubMed:10200054, ECO:0000269|PubMed:10208579, ECO:0000269|PubMed:10439444, ECO:0000269|PubMed:10441572, ECO:0000269|PubMed:10447269, ECO:0000269|PubMed:10533070, ECO:0000269|PubMed:10631141, ECO:0000269|PubMed:10644793, ECO:0000269|PubMed:11027672, ECO:0000269|PubMed:11524469, ECO:0000269|PubMed:11561050, ECO:0000269|PubMed:11568920, ECO:0000269|PubMed:11701593, ECO:0000269|PubMed:11710891, ECO:0000269|PubMed:11796781, ECO:0000269|PubMed:11920851, ECO:0000269|PubMed:12048239, ECO:0000269|PubMed:12058025, ECO:0000269|PubMed:12370477, ECO:0000269|PubMed:12484344, ECO:0000269|PubMed:12493737, ECO:0000269|PubMed:12552037, ECO:0000269|PubMed:15004326, ECO:0000269|PubMed:15122701, ECO:0000269|PubMed:15364419, ECO:0000269|PubMed:15534188, ECO:0000269|PubMed:15534260, ECO:0000269|PubMed:15851849, ECO:0000269|PubMed:16305624, ECO:0000269|PubMed:16344340, ECO:0000269|PubMed:16628450, ECO:0000269|PubMed:16752394, ECO:0000269|PubMed:16897084, ECO:0000269|PubMed:16959576, ECO:0000269|PubMed:17366635, ECO:0000269|PubMed:17428795, ECO:0000269|PubMed:17502474, ECO:0000269|PubMed:18430735, ECO:0000269|PubMed:19667325, ECO:0000269|PubMed:19797784, ECO:0000269|PubMed:20164095, ECO:0000269|PubMed:20460383, ECO:0000269|PubMed:21335660, ECO:0000269|PubMed:21501661, ECO:0000269|PubMed:22461631, ECO:0000269|PubMed:22503161, ECO:0000269|PubMed:22529981, ECO:0000269|PubMed:23123781, ECO:0000269|PubMed:23843529, ECO:0000269|PubMed:24121961, ECO:0000269|PubMed:24495933, ECO:0000269|PubMed:24582897, ECO:0000269|PubMed:25394380, ECO:0000269|PubMed:26145164, ECO:0000269|PubMed:26280335, ECO:0000269|PubMed:26549787, ECO:0000269|PubMed:27073747, ECO:0000269|PubMed:27930341, ECO:0000269|PubMed:29175279, ECO:0000269|PubMed:29404783, ECO:0000269|PubMed:29466804, ECO:0000269|PubMed:30180983, ECO:0000269|PubMed:30200536, ECO:0000269|PubMed:7550356, ECO:0000269|PubMed:7596406, ECO:0000269|PubMed:7651536, ECO:0000269|PubMed:8634711, ECO:0000269|PubMed:8634712, ECO:0000269|PubMed:8733303, ECO:0000269|PubMed:8837617, ECO:0000269|PubMed:9172170, ECO:0000269|PubMed:9225696, ECO:0000269|PubMed:9298817, ECO:0000269|PubMed:9384602, ECO:0000269|PubMed:9507958, ECO:0000269|PubMed:9521423, ECO:0000269|PubMed:9719376, ECO:0000269|PubMed:9831473, ECO:0000269|PubMed:9833068, ECO:0000269|Ref.93}. Note=The disease is caused by variants affecting the gene represented in this entry.
A form of dementia characterized by pathologic finding of frontotemporal lobar degeneration, presenile dementia with behavioral changes, deterioration of cognitive capacities and loss of memory. In some cases, parkinsonian symptoms are prominent. Neuropathological changes include frontotemporal atrophy often associated with atrophy of the basal ganglia, substantia nigra, amygdala. In most cases, protein tau deposits are found in glial cells and/or neurons. {ECO:0000269|PubMed:11094121}. Note=The disease is caused by variants affecting the gene represented in this entry.
A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269|PubMed:17186461, ECO:0000269|PubMed:27930341}. Note=The disease is caused by variants affecting the gene represented in this entry.
A chronic relapsing inflammatory disease of the hair follicles characterized by recurrent draining sinuses, painful skin abscesses, and disfiguring scars. Manifestations typically appear after puberty. {ECO:0000269|PubMed:20929727}. Note=The disease is caused by variants affecting the gene represented in this entry.
A rare form of dementia pathologically defined by severe atrophy, neuronal loss and gliosis. It is characterized by the occurrence of tau-positive inclusions, swollen neurons (Pick cells) and argentophilic neuronal inclusions known as Pick bodies that disproportionally affect the frontal and temporal cortical regions. Clinical features include aphasia, apraxia, confusion, anomia, memory loss and personality deterioration. {ECO:0000269|PubMed:15122701}. Note=The gene represented in this entry may be involved in disease pathogenesis.

No regional properties for P49768

Type	Name	Position	InterPro Accession
No domain, repeats, and functional sites for P49768

Functions

		Description
EC Number
Subcellular Localization	Endoplasmic reticulum Endoplasmic reticulum membrane ; Multi-pass membrane protein Golgi apparatus membrane ; Multi-pass membrane protein Cytoplasmic granule Cell membrane ; Multi-pass membrane protein Cell projection, growth cone Early endosome Early endosome membrane ; Multi-pass membrane protein Cell projection, neuron projection Cell projection, axon Synapse	Translocates with bound NOTCH1 from the endoplasmic reticulum and/or Golgi to the cell surface (PubMed:10593990) Colocalizes with CDH1/2 at sites of cell-cell contact Colocalizes with CTNNB1 in the endoplasmic reticulum and the proximity of the plasma membrane (PubMed:9738936) Also present in azurophil granules of neutrophils (PubMed:11987239) Colocalizes with UBQLN1 in the cell membrane and in cytoplasmic juxtanuclear structures called aggresomes (PubMed:21143716)
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category	No pathway information available

41 GO annotations of cellular component

Name	Definition
aggresome	An inclusion body formed by dynein-dependent retrograde transport of an aggregated protein on microtubules.
anchoring junction	A cell junction that mechanically attaches a cell (and its cytoskeleton) to neighboring cells or to the extracellular matrix.
apical plasma membrane	The region of the plasma membrane located at the apical end of the cell.
azurophil granule membrane	The lipid bilayer surrounding an azurophil granule, a primary lysosomal granule found in neutrophil granulocytes that contains a wide range of hydrolytic enzymes and is released into the extracellular fluid.
cell cortex	The region of a cell that lies just beneath the plasma membrane and often, but not always, contains a network of actin filaments and associated proteins.
cell junction	A cellular component that forms a specialized region of connection between two or more cells, or between a cell and the extracellular matrix, or between two membrane-bound components of a cell, such as flagella.
cell surface	The external part of the cell wall and/or plasma membrane.
centrosome	A structure comprised of a core structure (in most organisms, a pair of centrioles) and peripheral material from which a microtubule-based structure, such as a spindle apparatus, is organized. Centrosomes occur close to the nucleus during interphase in many eukaryotic cells, though in animal cells it changes continually during the cell-division cycle.
ciliary rootlet	A cytoskeleton-like structure, originating from the basal body at the proximal end of a cilium, and extending proximally toward the cell nucleus. Rootlets are typically 80-100 nm in diameter and contain cross striae distributed at regular intervals of approximately 55-70 nm.
dendritic shaft	Cylindric portion of the dendrite, directly stemming from the perikaryon, and carrying the dendritic spines.
early endosome membrane	The lipid bilayer surrounding an early endosome.
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 membrane	The lipid bilayer surrounding the endoplasmic reticulum.
gamma-secretase complex	A protein complex that has aspartic-type endopeptidase activity and contains a presenilin catalytic subunit (either PSEN1 or PSEN2), an APH1 subunit (multiple genes and splice variants exist), nicastrin (NCT), and presenilin enhancer (aka PEN-2 or Psenen), as the core complex. Variants of the complex with different subunit compositions differ in localization and specific substrates. Additionally, variants of the complex exist that contain a additional regulatory subunit as well as the four core subunits; known regulatory subunits include gamma-secretase-activating protein (aka gSAP), TMP1 (aka TMED10), and CD147 antigen (aka basigin). Gamma-secretase cleaves type I transmembrane protein substrates, including the cell surface receptor Notch and the amyloid-beta precursor protein.
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.
Golgi membrane	The lipid bilayer surrounding any of the compartments of the Golgi apparatus.
growth cone	The migrating motile tip of a growing neuron projection, where actin accumulates, and the actin cytoskeleton is the most dynamic.
integral component of membrane	The component of a membrane consisting of the gene products and protein complexes having at least some part of their peptide sequence embedded in the hydrophobic region of the membrane.
integral component of plasma membrane	The component of the plasma membrane consisting of the gene products and protein complexes having at least some part of their peptide sequence embedded in the hydrophobic region of the membrane.
integral component of presynaptic membrane	The component of the presynaptic membrane consisting of the gene products and protein complexes having at least some part of their peptide sequence embedded in the hydrophobic region of the membrane.
kinetochore	A multisubunit complex that is located at the centromeric region of DNA and provides an attachment point for the spindle microtubules.
lysosomal membrane	The lipid bilayer surrounding the lysosome and separating its contents from the cell cytoplasm.
membrane	A lipid bilayer along with all the proteins and protein complexes embedded in it an attached to it.
membrane raft	Any of the small (10-200 nm), heterogeneous, highly dynamic, sterol- and sphingolipid-enriched membrane domains that compartmentalize cellular processes. Small rafts can sometimes be stabilized to form larger platforms through protein-protein and protein-lipid interactions.
mitochondrial inner membrane	The inner, i.e. lumen-facing, lipid bilayer of the mitochondrial envelope. It is highly folded to form cristae.
mitochondrion	A semiautonomous, self replicating organelle that occurs in varying numbers, shapes, and sizes in the cytoplasm of virtually all eukaryotic cells. It is notably the site of tissue respiration.
neuromuscular junction	The junction between the axon of a motor neuron and a muscle fiber. In response to the arrival of action potentials, the presynaptic button releases molecules of neurotransmitters into the synaptic cleft. These diffuse across the cleft and transmit the signal to the postsynaptic membrane of the muscle fiber, leading to a change in post-synaptic potential.
neuron projection	A prolongation or process extending from a nerve cell, e.g. an axon or dendrite.
neuronal cell body	The portion of a neuron that includes the nucleus, but excludes cell projections such as axons and dendrites.
nuclear membrane	Either of the lipid bilayers that surround the nucleus and form the nuclear envelope; excludes the intermembrane space.
nuclear outer membrane	The outer, i.e. cytoplasm-facing, lipid bilayer of the nuclear envelope; continuous with the endoplasmic reticulum of the cell and sometimes studded with ribosomes.
nucleoplasm	That part of the nuclear content other than the chromosomes or the nucleolus.
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.
perinuclear region of cytoplasm	Cytoplasm situated near, or occurring around, the nucleus.
plasma membrane	The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
protein-containing complex	A stable assembly of two or more macromolecules, i.e. proteins, nucleic acids, carbohydrates or lipids, in which at least one component is a protein and the constituent parts function together.
rough endoplasmic reticulum	The rough (or granular) endoplasmic reticulum (ER) has ribosomes adhering to the outer surface; the ribosomes are the site of translation of the mRNA for those proteins which are either to be retained within the cisternae (ER-resident proteins), the proteins of the lysosomes, or the proteins destined for export from the cell. Glycoproteins undergo their initial glycosylation within the cisternae.
sarcolemma	The outer membrane of a muscle cell, consisting of the plasma membrane, a covering basement membrane (about 100 nm thick and sometimes common to more than one fiber), and the associated loose network of collagen fibers.
smooth endoplasmic reticulum	The smooth endoplasmic reticulum (smooth ER or SER) has no ribosomes attached to it. The smooth ER is the recipient of the proteins synthesized in the rough ER. Those proteins to be exported are passed to the Golgi complex, the resident proteins are returned to the rough ER and the lysosomal proteins after phosphorylation of their mannose residues are passed to the lysosomes. Glycosylation of the glycoproteins also continues. The smooth ER is the site of synthesis of lipids, including the phospholipids. The membranes of the smooth ER also contain enzymes that catalyze a series of reactions to detoxify both lipid-soluble drugs and harmful products of metabolism. Large quantities of certain compounds such as phenobarbital cause an increase in the amount of the smooth ER.
synaptic vesicle	A secretory organelle, typically 50 nm in diameter, of presynaptic nerve terminals; accumulates in high concentrations of neurotransmitters and secretes these into the synaptic cleft by fusion with the 'active zone' of the presynaptic plasma membrane.
Z disc	Platelike region of a muscle sarcomere to which the plus ends of actin filaments are attached.

9 GO annotations of molecular function

Name	Definition
aspartic endopeptidase activity, intramembrane cleaving	Catalysis of the hydrolysis of nonterminal peptide bonds in a polypeptide chain, occurring within a membrane.
aspartic-type endopeptidase activity	Catalysis of the hydrolysis of internal, alpha-peptide bonds in a polypeptide chain by a mechanism in which a water molecule bound by the side chains of aspartic residues at the active center acts as a nucleophile.
ATPase binding	Binding to an ATPase, any enzyme that catalyzes the hydrolysis of ATP.
beta-catenin binding	Binding to a catenin beta subunit.
cadherin binding	Binding to cadherin, a type I membrane protein involved in cell adhesion.
calcium channel activity	Enables the facilitated diffusion of a calcium ion (by an energy-independent process) involving passage through a transmembrane aqueous pore or channel without evidence for a carrier-mediated mechanism.
endopeptidase activity	Catalysis of the hydrolysis of internal, alpha-peptide bonds in a polypeptide chain.
growth factor receptor binding	Binding to a growth factor receptor.
PDZ domain binding	Binding to a PDZ domain of a protein, a domain found in diverse signaling proteins.

90 GO annotations of biological process

Name	Definition
amyloid precursor protein catabolic process	The chemical reactions and pathways resulting in the breakdown of amyloid precursor protein (APP), the precursor of amyloid-beta, a glycoprotein associated with Alzheimer's disease.
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.
amyloid-beta formation	The generation of amyloid-beta by cleavage of the amyloid precursor protein (APP).
amyloid-beta metabolic process	The chemical reactions and pathways involving amyloid-beta, a glycoprotein associated with Alzheimer's disease, and its precursor, amyloid precursor protein (APP).
apoptotic signaling pathway	The series of molecular signals which triggers the apoptotic death of a cell. The pathway starts with reception of a signal, and ends when the execution phase of apoptosis is triggered.
astrocyte activation	A change in morphology and behavior of an astrocyte resulting from exposure to a cytokine, chemokine, cellular ligand, or soluble factor.
astrocyte activation involved in immune response	A change in the morphology or behavior of an astrocyte resulting from exposure to an activating factor such as a cellular or soluble ligand, leading to the initiation or perpetuation of an immune response.
autophagosome assembly	The formation of a double membrane-bounded structure, the autophagosome, that occurs when a specialized membrane sac, called the isolation membrane, starts to enclose a portion of the cytoplasm.
blood vessel development	The process whose specific outcome is the progression of a blood vessel over time, from its formation to the mature structure. The blood vessel is the vasculature carrying blood.
brain morphogenesis	The process in which the anatomical structures of the brain are generated and organized. The brain is one of the two components of the central nervous system and is the center of thought and emotion. It is responsible for the coordination and control of bodily activities and the interpretation of information from the senses (sight, hearing, smell, etc.).
Cajal-Retzius cell differentiation	The process in which a neuroblast acquires specialized structural and/or functional features of a Cajal-Retzius cell, one of a transient population of pioneering neurons in the cerebral cortex. These cells are slender bipolar cells of the developing marginal zone. One feature of these cells in mammals is that they express the Reelin gene.
calcium ion transport	The directed movement of calcium (Ca) ions into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.
cell fate specification	The process involved in the specification of cell identity. Once specification has taken place, a cell will be committed to differentiate down a specific pathway if left in its normal environment.
cell-cell adhesion	The attachment of one cell to another cell via adhesion molecules.
cellular response to amyloid-beta	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a amyloid-beta stimulus.
cellular response to DNA damage stimulus	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus indicating damage to its DNA from environmental insults or errors during metabolism.
cerebellum development	The process whose specific outcome is the progression of the cerebellum over time, from its formation to the mature structure. The cerebellum is the portion of the brain in the back of the head between the cerebrum and the pons. In mice, the cerebellum controls balance for walking and standing, modulates the force and range of movement and is involved in the learning of motor skills.
cerebral cortex cell migration	The orderly movement of cells from one site to another in the cerebral cortex.
choline transport	The directed movement of choline into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. Choline (2-hydroxyethyltrimethylammonium) is an amino alcohol that occurs widely in living organisms as a constituent of certain types of phospholipids and in the neurotransmitter acetylcholine.
dorsal/ventral neural tube patterning	The process in which the neural tube is regionalized in the dorsoventral axis.
embryonic limb morphogenesis	The process, occurring in the embryo, by which the anatomical structures of the limb are generated and organized. A limb is an appendage of an animal used for locomotion or grasping.
endoplasmic reticulum calcium ion homeostasis	Any process involved in the maintenance of an internal steady state of calcium ions within the endoplasmic reticulum of a cell or between the endoplasmic reticulum and its surroundings.
epithelial cell proliferation	The multiplication or reproduction of epithelial cells, resulting in the expansion of a cell population. Epithelial cells make up the epithelium, the covering of internal and external surfaces of the body, including the lining of vessels and other small cavities. It consists of cells joined by small amounts of cementing substances.
heart looping	The tube morphogenesis process in which the primitive heart tube loops asymmetrically. This looping brings the primitive heart chambers into alignment preceding their future integration. Heart looping begins with dextral-looping and ends when the main regional divisions of the mature heart and primordium of the great arterial trunks become established preceeding septation.
hematopoietic progenitor cell differentiation	The process in which precursor cell type acquires the specialized features of a hematopoietic progenitor cell, a class of cell types including myeloid progenitor cells and lymphoid progenitor cells.
intracellular signal transduction	The process in which a signal is passed on to downstream components within the cell, which become activated themselves to further propagate the signal and finally trigger a change in the function or state of the cell.
L-glutamate import across plasma membrane	The directed movement of L-glutamate from outside of a cell, across the plasma membrane and into the cytosol.
learning or memory	The acquisition and processing of information and/or the storage and retrieval of this information over time.
locomotion	Self-propelled movement of a cell or organism from one location to another.
membrane protein ectodomain proteolysis	The proteolytic cleavage of transmembrane proteins and release of their ectodomain (extracellular domain).
membrane protein intracellular domain proteolysis	The proteolytic cleavage of a transmembrane protein leading to the release of an intracellular domain.
memory	The activities involved in the mental information processing system that receives (registers), modifies, stores, and retrieves informational stimuli. The main stages involved in the formation and retrieval of memory are encoding (processing of received information by acquisition), storage (building a permanent record of received information as a result of consolidation) and retrieval (calling back the stored information and use it in a suitable way to execute a given task).
mitochondrial transport	Transport of substances into, out of or within a mitochondrion.
myeloid dendritic cell differentiation	The process in which a monocyte acquires the specialized features of a dendritic cell, an immunocompetent cell of the lymphoid and hemopoietic systems and skin.
negative regulation of apoptotic process	Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process.
negative regulation of apoptotic signaling pathway	Any process that stops, prevents or reduces the frequency, rate or extent of apoptotic signaling pathway.
negative regulation of axonogenesis	Any process that stops, prevents, or reduces the frequency, rate or extent of axonogenesis.
negative regulation of core promoter binding	Any process that stops, prevents or reduces the frequency, rate or extent of core promoter binding.
negative regulation of epidermal growth factor-activated receptor activity	Any process that stops, prevents, or reduces the frequency, rate or extent of EGF-activated receptor activity.
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 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 transcription by RNA polymerase II	Any process that stops, prevents, or reduces the frequency, rate or extent of transcription mediated by RNA polymerase II.
negative regulation of ubiquitin-dependent protein catabolic process	Any process that stops, prevents, or reduces the frequency, rate or extent of ubiquitin-dependent protein catabolic process.
negative regulation of ubiquitin-protein transferase activity	Any process that stops, prevents, or reduces the frequency, rate or extent of ubiquitin transferase activity.
neural retina development	The progression of the neural retina over time from its initial formation to the mature structure. The neural retina is the part of the retina that contains neurons and photoreceptor cells.
neuron apoptotic process	Any apoptotic process in a neuron, the basic cellular unit of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system.
neuron cellular homeostasis	The cellular homeostatic process that preserves a neuron in a stable, differentiated functional and structural state.
neuron development	The process whose specific outcome is the progression of a neuron over time, from initial commitment of the cell to a specific fate, to the fully functional differentiated cell.
neuron migration	The characteristic movement of an immature neuron from germinal zones to specific positions where they will reside as they mature.
neuron projection maintenance	The organization process that preserves a neuron projection in a stable functional or structural state. A neuron projection is a prolongation or process extending from a nerve cell, e.g. an axon or dendrite.
Notch receptor processing	The series of successive proteolytic cleavages of the Notch protein, which result in an active form of the receptor.
Notch signaling pathway	The series of molecular signals initiated by an extracellular ligand binding to the receptor Notch on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription.
positive regulation of amyloid fibril formation	Any process that activates or increases the frequency, rate or extent of amyloid fibril formation.
positive regulation of apoptotic process	Any process that activates or increases the frequency, rate or extent of cell death by apoptotic process.
positive regulation of catalytic activity	Any process that activates or increases the activity of an enzyme.
positive regulation of coagulation	Any process that activates or increases the frequency, rate or extent of coagulation.
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 DNA-templated transcription	Any process that activates or increases the frequency, rate or extent of cellular DNA-templated transcription.
positive regulation of gene expression	Any process that increases 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).
positive regulation of glycolytic process	Any process that activates or increases the frequency, rate or extent of glycolysis.
positive regulation of L-glutamate import across plasma membrane	Any process that activates or increases the frequency, rate or extent of L-glutamate import into a cell.
positive regulation of MAP kinase activity	Any process that activates or increases the frequency, rate or extent of MAP kinase activity.
positive regulation of phosphorylation	Any process that activates or increases the frequency, rate or extent of addition of phosphate groups to a molecule.
positive regulation of proteasomal ubiquitin-dependent protein catabolic process	Any process that activates or increases the frequency, rate or extent of the breakdown of a protein or peptide by hydrolysis of its peptide bonds, initiated by the covalent attachment of ubiquitin, and mediated by the proteasome.
positive regulation of protein binding	Any process that activates or increases the frequency, rate or extent of protein binding.
positive regulation of protein import into nucleus	Any process that activates or increases the frequency, rate or extent of movement of proteins from the cytoplasm into the nucleus.
positive regulation of receptor recycling	Any process that activates or increases the frequency, rate or extent of receptor recycling.
positive regulation of tumor necrosis factor production	Any process that activates or increases the frequency, rate or extent of tumor necrosis factor production.
post-embryonic development	The process whose specific outcome is the progression of the organism over time, from the completion of embryonic development to the mature structure. See embryonic development.
protein glycosylation	A protein modification process that results in the addition of a carbohydrate or carbohydrate derivative unit to a protein amino acid, e.g. the addition of glycan chains to proteins.
protein processing	Any protein maturation process achieved by the cleavage of a peptide bond or bonds within a protein. Protein maturation is the process leading to the attainment of the full functional capacity of a protein.
protein transport	The directed movement of proteins into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.
regulation of canonical Wnt signaling pathway	Any process that modulates 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.
regulation of gene expression	Any process that modulates 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).
regulation of neuron projection development	Any process that modulates 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).
regulation of phosphorylation	Any process that modulates the frequency, rate or extent of addition of phosphate groups into a molecule.
regulation of resting membrane potential	Any process that modulates the establishment or extent of a resting potential, the electrical charge across the plasma membrane, with the interior of the cell negative with respect to the exterior. The resting potential is the membrane potential of a cell that is not stimulated to be depolarized or hyperpolarized.
regulation of synaptic plasticity	A process that modulates synaptic plasticity, the ability of 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 synaptic transmission, glutamatergic	Any process that modulates the frequency, rate or extent of glutamatergic synaptic transmission, the process of communication from a neuron to another neuron across a synapse using the neurotransmitter glutamate.
response to oxidative stress	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 oxidative stress, a state often resulting from exposure to high levels of reactive oxygen species, e.g. superoxide anions, hydrogen peroxide (H2O2), and hydroxyl radicals.
sequestering of calcium ion	The process of binding or confining calcium ions such that they are separated from other components of a biological system.
skeletal system morphogenesis	The process in which the anatomical structures of the skeleton are generated and organized.
skin morphogenesis	The process in which the anatomical structures of the skin are generated and organized. The skin is the external membranous integument of an animal. In vertebrates the skin generally consists of two layers, an outer nonsensitive and nonvascular epidermis (cuticle or skarfskin) composed of cells which are constantly growing and multiplying in the deeper, and being thrown off in the superficial layers, as well as an inner, sensitive and vascular dermis (cutis, corium or true skin) composed mostly of connective tissue.
smooth endoplasmic reticulum calcium ion homeostasis	Any process involved in the maintenance of an internal steady state of calcium ions within the smooth endoplasmic reticulum of a cell or between the smooth endoplasmic reticulum and its surroundings.
somitogenesis	The formation of mesodermal clusters that are arranged segmentally along the anterior posterior axis of an embryo.
synapse organization	A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of a synapse, the junction between a neuron and a target (neuron, muscle, or secretory cell).
synaptic vesicle targeting	The process in which synaptic vesicles are directed to specific destination membranes, mediated by molecules at the vesicle membrane and target membrane surfaces.
T cell activation involved in immune response	The change in morphology and behavior of a mature or immature T cell resulting from exposure to a mitogen, cytokine, chemokine, cellular ligand, or an antigen for which it is specific, leading to the initiation or perpetuation of an immune response.
T cell receptor signaling pathway	The series of molecular signals initiated by the cross-linking of an antigen receptor on a T cell.
thymus development	The process whose specific outcome is the progression of the thymus over time, from its formation to the mature structure. The thymus is a symmetric bi-lobed organ involved primarily in the differentiation of immature to mature T cells, with unique vascular, nervous, epithelial, and lymphoid cell components.

3 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
P49810	PSEN2	Presenilin-2	Homo sapiens (Human)	PR
Q61144	Psen2	Presenilin-2	Mus musculus (Mouse)	PR
P49769	Psen1	Presenilin-1	Mus musculus (Mouse)	PR

10	20	30	40	50	60
MTELPAPLSY	FQNAQMSEDN	HLSNTVRSQN	DNRERQEHND	RRSLGHPEPL	SNGRPQGNSR
70	80	90	100	110	120
QVVEQDEEED	EELTLKYGAK	HVIMLFVPVT	LCMVVVVATI	KSVSFYTRKD	GQLIYTPFTE
130	140	150	160	170	180
DTETVGQRAL	HSILNAAIMI	SVIVVMTILL	VVLYKYRCYK	VIHAWLIISS	LLLLFFFSFI
190	200	210	220	230	240
YLGEVFKTYN	VAVDYITVAL	LIWNFGVVGM	ISIHWKGPLR	LQQAYLIMIS	ALMALVFIKY
250	260	270	280	290	300
LPEWTAWLIL	AVISVYDLVA	VLCPKGPLRM	LVETAQERNE	TLFPALIYSS	TMVWLVNMAE
310	320	330	340	350	360
GDPEAQRRVS	KNSKYNAEST	ERESQDTVAE	NDDGGFSEEW	EAQRDSHLGP	HRSTPESRAA
370	380	390	400	410	420
VQELSSSILA	GEDPEERGVK	LGLGDFIFYS	VLVGKASATA	SGDWNTTIAC	FVAILIGLCL
430	440	450	460
TLLLLAIFKK	ALPALPISIT	FGLVFYFATD	YLVQPFMDQL	AFHQFYI