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PSEN2 Gene

protein-coding GIFtS: 74

GC01P225124

presenilin 2 (Alzheimer disease 4)
Symbol approved by the HUGO Gene Nomenclature Committee (HGNC) database
(Previous symbol: AD4)

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

Aliases
AD3L ^¹, ²
AD3LP ^³
AD4 ^², ³, ⁵
AD5 ^³
E5-1 ^³
EC 3.4.23.- ^³
OTTHUMP00000035671 ^²
PS-2 ^³
PS2 ^¹, ², ³
PSNL2 ^³
STM-2 ^³
STM2 ^¹, ², ³, ⁵

Descriptions
Alzheimer's disease 3-like ^²
presenilin 2 ^²
presenilin 2 (Alzheimer disease 4) ^²

External Ids
HGNC: 9509¹
Entrez Gene: 5664²
UniProtKB: P49810³
Ensembl: ENSG00000143801⁷

Search outside databases for aliases for PSEN2 gene

Previous GC identifers: GC01P225587 GC01P222803 GC01P223443 GC01P224033 GC01P224032 GC01P223365

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

EntrezGene summary for PSEN2:

Alzheimer's disease (AD) patients with an inherited form of the disease carry mutations in the

presenilin proteins (PSEN1 or PSEN2) or the amyloid precursor protein (APP). These disease-linked

mutations result in increased production of the longer form of amyloid-beta (main component of

amyloid deposits found in AD brains). Presenilins are postulated to regulate APP processing

through their effects on gamma-secretase, an enzyme that cleaves APP. Also, it is thought that the

presenilins are involved in the cleavage of the Notch receptor such that, they either directly

regulate gamma-secretase activity, or themselves act are protease enzymes. Two alternatively

spliced transcript variants encoding different isoforms of PSEN2 have been identified. [provided

by RefSeq]

UniProtKB/Swiss-Prot: PSN2_HUMAN, P49810

Function: Probable catalytic subunit of the gamma-secretase complex, an endoprotease complex that

catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP

(beta-amyloid precursor protein). Requires the other members of the gamma-secretase complex to

have a protease activity. May play a role in intracellular signaling and gene expression or in

linking chromatin to the nuclear membrane. May function in the cytoplasmic partitioning of

proteins

Gene Wiki entry for PSEN2

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 36),
and/or miRBase,
Genomic Views according to UCSC and Ensembl, Transcription factor binding sites according to SABiosciences)
About This Section

Genomic View:

UCSC Golden Path with GeneCards custom track

Transcription factor binding sites upstream to the PSEN2 gene

Entrez Gene cytogenetic band: 1q31-q42 Ensembl cytogenetic band: 1q42.13 HGNC cytogenetic band: 1q31-q42

PSEN2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)

GeneLoc gene densities for chromosome 1 GeneLoc Exon Structure

GeneLoc location for GC01P225124: (about GC identifiers)

Start:	225,124,896 bp from pter
End:	225,150,429 bp from pter
Size:	25,534 bases
Orientation:	plus strand

RefSeq DNA sequence:

NC_000001.9 NT_004559.13

(According to ¹UniProtKB, and/or Ensembl, Phosphorylation sites according to ²Phosphosite, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from Invitrogen, Millipore, Sigma-Aldrich, R&D Systems, Enzo Life Sciences, Abnova, OriGene and/or, Abcam,
Biochemical Assays by Invitrogen, Millipore, R&D Systems, Cell Signaling Technology, and/or Enzo Life Sciences, Ontologies according to Gene Ontology Consortium 01 Apr 2009 and Entrez Gene, Antibodies by Invitrogen, Millipore, Sigma-Aldrich, R&D Systems, Cell Signaling Technology, Abcam, Abnova, and/or Novus Biologicals)
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UniProtKB/Swiss-Prot: PSN2_HUMAN, P49810 (See protein sequence)

Recommended Name: Presenilin-2

Size: 448 amino acids; 50140 Da

Subunit: Interacts with DOCK3 (By similarity). Homodimer. Component of the gamma-secretase complex,

a complex composed of a presenilin homodimer (PSEN1 or PSEN2), nicastrin (NCSTN), APH1 (APH1A or

APH1B) and PEN2. Such minimal complex is sufficient for secretase activity, although other

components may exist. Interacts with HERPUD1, FLNA, FLNB and PARL

Subcellular location: Endoplasmic reticulum membrane; Multi-pass membrane protein. Golgi apparatus

membrane; Multi-pass membrane protein

Secondary accessions: Q96P32

Alternative splicing: 2 isoforms: P49810-1 P49810-2

Post-translational modifications:

Heterogeneous proteolytic processing generates N-terminal and C-terminal fragments¹

Phosphorylated on serine residues¹

View phosphorylation sites using PhosphoSite²

REFSEQ proteins (2 alternative transcripts):

NP_000438.2 NP_036618.2

ENSEMBL proteins:

ENSP00000375745 ENSP00000355746 ENSP00000355747 ENSP00000339860

Human Recombinant Proteins

	Browse Drug Discovery Central at Invitrogen for human recombinant proteins
	Millipore Purified and/or Recombinant PSEN2 Protein
	Sigma-Aldrich Proteins for PSEN2
	Browse R&D Systems for human recombinant proteins
	Browse recombinant and purified proteins available from Enzo Life Sciences
	Recombinant Proteins from Abcam (Presenilin 1 + 2, Presenilin 2)
	Human Recombinant Proteins from Abnova (PSEN2)

Browse Origene for full length recombinant human proteins expressed in human HEK293 cells

5/8 Gene Ontology (GO) cellular component terms (links to tree view) (see all 8 ):

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000139	Golgi membrane	IEA	--
GO:0000776	kinetochore	TAS	9298903
GO:0005639	integral to nuclear inner membrane	TAS	9298903
GO:0005783	endoplasmic reticulum	IDA	15274632
GO:0005789	endoplasmic reticulum membrane	IEA	--

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Antibodies for PSEN2:

	Invitrogen Antibodies for PSEN2
	Millipore Mono- and Polyclonal Antibodies for the study of PSEN2
	Sigma-Aldrich Antibodies for PSEN2
	R&D Systems Antibodies for PSEN2 (Presenilin-2)
	Antibodies from Abcam (Presenilin 1 + 2, Presenilin 2), each with their Abpromise^SM
	Monoclonal and Polyclonal Antibodies from Abnova (PSEN2)
	Novus Biologicals Antibody for PSEN2

Assays for PSEN2:

	Browse Invitrogen for biochemical assays
	Browse Kits and Assays available from Millipore
	Browse R&D Systems for biochemical assays
	Browse biochemical assays available from Enzo Life Sciences

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

Graphical View of Domain Structure for InterPro Entry P49810

ProtoNet protein and cluster: P49810

2 Blocks protein families:

IPB001493 Presenilin 2 signature

IPB006639 Presenilin signal peptide peptidase

UniProtKB/Swiss-Prot: PSN2_HUMAN, P49810

Domain: The PAL motif is required for normal active site conformation (By similarity)

Similarity: Belongs to the peptidase A22A family

(According to MGI Jun 06 2009, UniProtKB, IUBMB,and/or Genatlas,
shRNA from OriGene, Sigma-Aldrich, RNAi from Sigma-Aldrich,
RNAi Products, Clones, and Q-PCR Products from Invitrogen, Millipore, OriGene, and/or Abnova, siRNAs from Applied Biosystems, SYBR primers from OriGene, Cell-based Assays from Millipore, Ontologies according to Gene Ontology Consortium 01 Apr 2009 via Entrez Gene.)
About This Section

Inhib. RNA:		Invitrogen RNAi Products for gene knock-down (PSEN2)
		Browse for Gene Knock-down Tools from Millipore
		Abnova Chimera RNAi Products for Gene knock-down (PSEN2)

OriGene 29mer shRNA kit in GFP-retroviral vectors (see all 2): NM_000447

Applied Biosystems Silencer® siRNAs for PSEN2

Sigma-Aldrich siRNA and siRNA Panels for PSEN2

Sigma-Aldrich shRNA for PSEN2

Explore Sigma-Aldrich super-pooled esiRNAs

Clones:		Invitrogen Clones for PSEN2
		Browse Clones for the Expression of Recombinant Proteins Available from Millipore

OriGene GFP tagged cDNA clones in CMV expression vector (see all 2): NM_000447
Myc/DDK tagged cDNA clones in CMV expression vector (see all 2): NM_000447
untagged cDNA clones in CMV expression vector (see all 3): NM_000447

Primers:

Browse Quantitative PCR Central at Invitrogen for Q-PCR LUX™ Primers

OriGene genome-wide validated SYBR primer pairs: NM_000447

UniProtKB/Swiss-Prot: PSN2_HUMAN, P49810

Function: Probable catalytic subunit of the gamma-secretase complex, an endoprotease complex that

catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP

(beta-amyloid precursor protein). Requires the other members of the gamma-secretase complex to

have a protease activity. May play a role in intracellular signaling and gene expression or in

linking chromatin to the nuclear membrane. May function in the cytoplasmic partitioning of

proteins

Enzyme Number (IUBMB): EC 3.4.23.-

Genatlas biochemistry entry for PSEN2:

presenilin 2,forming a multimeric complex with catenin beta (CTNNB1),expressed in several parts of

the brain in cardiac and skeletal muscle,in pancreas,predominantly located in intracellular

membranous organelles such as nuclear envelope,endoplasmic reticulum and Golgi apparatus with 80%

homology to S182 (C. elegans Sel-12 gene),interacting with Rab11 and may be involved in APP

vesicular trafficking to the right compartment for activity,homologous to C elegans

SPE-4,controlling the alpha secretase derived product APP alpha

15/20 MGI mutant phenotypes (inferred from 3 alleles) (MGI details for Psen2) (see all 20 ):

	behavior/neurological	cellular	craniofacial	digestive/alimentary
embryogenesis	endocrine/exocrine gland	growth/size	hematopoietic system	homeostasis/metabolism
immune system	lethality-prenatal/perinatal	life span-post-weaning/aging	limbs/digits/tail	nervous system

2 Gene Ontology (GO) molecular function terms (links to tree view):

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005515	protein binding	IPI	12297508
GO:0008233	peptidase activity	IEA	--

About this table

(Pathways according to Invitrogen (maps by GeneGo), Millipore, Cell Signaling Technology, Sigma-Aldrich, KEGG and/or UniProtKB,
Sets of similar genes according to GeneDecks, Proteins Network according to SABiosciences, Interactions according to ¹UniProtKB, ²MINT, and/or ³STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2009 via Entrez Gene.)
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4 Sigma-Aldrich "Your Favorite Gene" Pathways for PSEN2 (Your Favorite Gene powered by Ingenuity)

Amyloid Processing
Notch Signaling
Molecular Mechanisms of Cancer
Mitochondrial Dysfunction

GeneDecks PSEN2 for the pathways selected above

About GeneDecksing

Gene Network Central^TM Interacting Genes and Proteins Network for PSEN2

5/77 Interacting proteins for PSEN2 (ENSP00000355746³ P49810^{1, 2}) via UniProtKB, MINT, and/or STRING (see all 77 )

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
APP	P05067¹	STRING (score=.976) EBI-2010251, EBI-77613
CIB1	Q99828²	STRING (score=.97) MINT-15561 MINT-15560 MINT-15562
FHL2	Q14192²	STRING (score=.983) MINT-16272 MINT-16270 MINT-16271
UBQLN1	Q9UMX0²	STRING (score=.98) MINT-17616 MINT-17615 MINT-17617
FLNA	P21333²	STRING (score=.746) MINT-13994 MINT-13995

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5/7 Gene Ontology (GO) biological process terms (links to tree view) (see all 7 ):

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0006509	membrane protein ectodomain proteolysis	IDA	15274632
GO:0007059	chromosome segregation	TAS	9298903
GO:0007220	Notch receptor processing	TAS	15274632
GO:0008219	cell death	IEA	--
GO:0016485	protein processing	IDA	15274632

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(Chemical Compounds according to UniProtKB, Enzo Life Sciences, Sigma-Aldrich, Tocris Bioscience, and/or Novoseek and Drugs according to Enzo Life Sciences and/or PharmGKB)
About This Section

Browse drugs & compounds from Enzo Life Sciences

Sigma-Aldrich Small Molecules for PSEN2:

Inhibitor

Compounds for PSEN2 available from Tocris Bioscience

Compound	Action	CAS number
JLK 6	Inhibitor of gamma-secretase-mediated betaAPP processing	[62252-26-0]
Compound W	gamma-secretase inhibitor	[173550-33-9]
DAPT	gamma-secretase inhibitor	[208255-80-5]

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10/19 Novoseek chemical compound relationships for PSEN2 gene (see all 19 )

Compound	Score	Articles	PubMed IDs for Articles with Shared Sentences (# sentences)
s-182	84.53	2	9118312 (1), 9067452 (1)
progesterone	61.14	57	10517346 (2), 10917137 (2), 7927897 (2), 10967555 (2) (see all 44)
estradiol	36.47	16	17068199 (2), 18644870 (2), 1485091 (1), 19041697 (1) (see all 11)
steroid	24.72	7	10522772 (2), 16840538 (1), 9496537 (1), 11435612 (1) (see all 5)
fatty acid	4.51	2	7926273 (1), 8083200 (1)
glucose	3.61	1	16292511 (1)
cholesterol	2.68	3	17401156 (3)
nitric oxide	1.12	2	11436125 (1)
oxygen	0.34	2	12232783 (1)
lysine	0.00	5	17614368 (2), 9923762 (1)

About this table

(GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 219 Homo sapiens; Jun 2 2009) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView,
non coding RNAs according to RNAdb,
ESTs according to GeneTide,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from Invitrogen, Millipore, and/or Abnova,
siRNAs from Applied Biosystems, Sigma-Aldrich,
shRNA from Sigma-Aldrich, OriGene,
Tagged/untagged cDNA clones from OriGene,
Expression Assays from Applied Biosystems)
About This Section

Inhib. RNA:		Invitrogen RNAi Products for gene knock-down (PSEN2)
		Browse for Gene Knock-down Tools from Millipore
		Abnova Chimera RNAi Products for Gene knock-down (PSEN2)

OriGene 29mer shRNA kit in GFP-retroviral vectors (see all 2): NM_000447

Sigma-Aldrich siRNA and siRNA Panels for PSEN2

Sigma-Aldrich shRNA for PSEN2

Explore Sigma-Aldrich super-pooled esiRNAs

Applied Biosystems Silencer® siRNAs:

NM_000447 NM_012486

REFSEQ mRNAs for PSEN2 gene (2 alternative transcripts):

NM_000447.2 NM_012486.2

Applied Biosystems TaqMan ® Gene Expression Assays:

NM_000447 NM_012486

               OriGene GFP tagged cDNA clones in CMV expression vector (see all 2): NM_000447
                                 Myc/DDK tagged cDNA clones in CMV expression vector (see all 2): NM_000447
                                 untagged cDNA clones in CMV expression vector (see all 3): NM_000447

Additional cDNA sequence:

AF416718.1 AK292299.1 AK301143.1 BC006365.2 BT006984.1 CR594395.1 L43964.1 L44577.1

U34349.1

11 DOTS entries:

DT.451603 DT.100791211 DT.101980870 DT.100791210 DT.97802189 DT.97771435 DT.121427797 DT.95375318

DT.100693380 DT.40110274 DT.97780884

24/173 AceView cDNA sequences (see all 173 ):

AI924549 CA310542 AI093291 AI675803 CD513489 CD358381 AL047795 CK823284

BI761633 BX093003 CD512951 AI474673 AI340021 AI142959 AI927349 CD672922

AA993681 CD673541 CR594395 L43964 R46426 BM763155 BG761270 CF780920

highest scoring ESTs for PSEN2:

L43964 AA152294 AA235060 AA450249 AA578749 AI091221 AI129231 AI168440 AI263363 AI340021

Unigene Cluster for PSEN2:

Presenilin 2 (Alzheimer disease 4)

Hs.25363 [show with all ESTs]

Unigene Representative Sequence: BC006365

GeneLoc Exon Structure

5/8 Alternative Splicing Database (ASD) splice patterns (SP) for PSEN2 (see all 8 )

ExUns:	1	^	2a	·	2b	^	3	^	4a	·	4b	^	5	^	6a	·	6b	^	7a	·	7b	^	8	^	9a	·	9b	^	10	^	11	^	12	^	13a	·	13b	^	14	^	15	^	16a	·	16b
SP1:													-										-
SP2:													-										-
SP3:
SP4:													-		-		-		-		-		-		-		-
SP5:													-

About this scheme

ECgene alternative splicing isoforms for PSEN2

4 Ensembl transcripts including schematic representations:

ENST00000391872 ENST00000366782 ENST00000366783 ENST00000340188

(Experimental results according to ¹GeneNote and GNF BioGPS,
probe sets-to-genes annotations according to ²GeneAnnot , ³GeneTide , Sets of similar genes according to GeneDecks, Electronic Northern calculations according to data from UniGene (Build 219 Homo sapiens), SAGE tags according to CGAP, plus additional links to SOURCE, and/or GNF BioGPS, and/or EXPOLDB, and/or UniProtKB,
Expression Assays from Applied Biosystems )
About This Section

PSEN2 expression in normal and diseased human tissues

Applied Biosystems TaqMan ® Gene Expression Assays for PSEN2

¹ / ² / ³

7 probe-sets matching PSEN2 gene

Affymetrix probe-set	Array	# genes	Sensitivity	Specificity	Correlation	Length	Gb_Accession	Consensus	Uniqueness	Score	Rank
Affymetrix probe-set	Array	GeneAnnot data			GeneNote data		GeneTide data
41349_at²^{, 3}	U95-A	1	1.00	1.00	1.00	1.00	L43964	1.00	1.00	1.00	1
204262_s_at²^{, 3}	U133-A	1	1.00	1.00	--	--	NM_000447	0.60	1.00	0.82	1
204261_s_at²^{, 3}	U133-A	1	1.00	1.00	--	--	AA716657	0.60	1.00	0.82	1
211373_s_at²^{, 3}	U133-A	1	1.00	1.00	--	--	U34349	0.60	1.00	0.82	1
204262_s_at²	U133Plus2	1	1.00	1.00	--	--	--	--	--	--	--
204261_s_at²	U133Plus2	1	1.00	1.00	--	--	--	--	--	--	--
211373_s_at²	U133Plus2	1	1.00	1.00	--	--	--	--	--	--	--

GeneDecks PSEN2 for binary patterns associated with the probe-sets selected above

About GeneDecksing

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Data from

(Publications) and GNF BioGPS
About these images
About these images

CGAP SAGE TAG: ATGTCCTTGT

SOURCE GeneReport for Unigene cluster: Hs.25363
Expression variation in blood from EXPOLDB for PSEN2
UniProtKB/Swiss-Prot: PSN2_HUMAN, P49810
Tissue specificity: Isoform 1 is seen in the placenta, skeletal muscle and heart while isoform 2 is
seen in the heart, brain, placenta, liver, skeletal muscle and kidney

(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD and/or ⁵MGI Jun 06 2009, with possible further links to Flybase and/or WormBase, Gene Trees according to Ensembl)
About This Section

Orthologs for PSEN2 gene from 5/15 species (see all 15 )

Organism	Gene	Locus	Description	Human Similarity	NCBI accessions
dog (Canis familiaris)	PSEN2¹	--	presenilin 2 (Alzheimer disease 4)	90.7(n) 95.98(a)	490382 XM_547503.2 XP_547503.2
chimpanzee (Pan troglodytes)	PSEN2¹	--	presenilin 2 (Alzheimer disease 4)	99.33(n) 99.78(a)	457790 XM_514247.2 XP_514247.2
cow (Bos taurus)	PSEN2¹	--	presenilin 2 (Alzheimer disease 4)	92.34(n) 97.54(a)	282010 NM_174440.3 NP_776865.2
rat (Rattus norvegicus)	Psen2¹	--	presenilin 2	89.43(n) 95.09(a)	81751 NM_031087.1 NP_112349.1
mouse (Mus musculus)	Psen2^{1, 5}	1 (101.00 cM)⁵	presenilin 2^{1, 5}	89.29(n)¹ 95.54(a)¹	19165¹ NM_011183.1¹ NP_035313.1¹ AF038935⁵ AI118332⁵ (see all 17)

About this table Species with no ortholog for PSEN2

ENSEMBL Gene Tree for PSEN2

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

Paralogs for PSEN2 gene

PSEN1²

(According to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, and UniProtKB, Linkage Disequilibrium by HapMap, Genotyping Reagents from Applied Biosystems)
About This Section

10/169 NCBI SNPs in PSEN2 are shown (see all 169 )
(Click for Applied Biosystems TaqMan ® Genotyping Assay) (see all 81)

AB	SNP ID	Valid	Chr 1 pos	Sequence	Recs	AA Chg	Type	More	Recs	Allele freq	Pop	Total sample	More
AB	Genomic Data				Transcription Data				Allele Frequencies
				--	--	--		--	--				--
	rs3177404^1,2	A,C,F,H,O	225129852(+)	`GACCTC/TTCTGC`	2	--	ut5¹ ese³		12		NS EU EA WA NA	650
	rs1295645^1,2	A,C,F,H	225125660(+)	`GTCCCC/TCCTCT`	2	--	ut5¹ ese³ trp³		5		MN EU EA WA	602
	rs8383^1,2	A,C,F	225150173(+)	`TAGGGT/CGGGGA`	2	--	ut3¹ ese³		3		MN	556
	rs6665033^1,2	F,H	225125597(+)	`CCAGCA/GGTGAG`	2	--	ut5¹ ese³		4		EU EA WA	416
	rs16846619^1,2	F,H	225150439(+)	`GGTCCG/ATTGTA`	2	--	ng3¹		7		NA EU EA WA	546
--	rs12758915^1,2	A	225124967(+)	`GCGGCA/GGAGCA`	2	--	ut5¹ ese³		0	--	--	--	--
	rs1046240^1,2	C,F,H,O	225138148(+)	`AAGCAT/CGTGAT`	2	H/H	syn¹		6		MN EU EA WA	652
	rs11405^1,2	A,C,F,H	225136300(+)	`TCGGCC/TGAGAG`	2	A/A	syn¹		16		MN EA NA EU WA	2660
	rs6759^1,2	C,F,H	225136360(+)	`GAGAAC/TACTGC`	2	N/N	syn¹		12		EA MN NS EU WA NA	2130
--	rs6426553^1,2	A,C	225145618(+)	`TGGACG/TGTTGG`	2	T/T	syn¹ ese³		0	--	--	--	--

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HapMap Linkage Disequilibrium images for PSEN2 (up to first 250kb)

(in which this Gene is Involved, According to OMIM, UniProtKB, Novoseek, PharmGKB, Genatlas, GeneTests, Blood group antigen gene mutations by BGMUT, HGMD, GAD, HuGE Navigator, BCGD, and/or TGDB.)
About This Section

OMIM: 600759

UniProtKB/Swiss-Prot: PSN2_HUMAN, P49810

Defects in PSEN2 are the cause of Alzheimer disease type 4 (AD4) [MIM:606889]. AD is an

autosomal dominant 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 constituent of these plaques is the neurotoxic

amyloid-beta-APP 40-42 peptide (s), derived proteolytically from the transmembrane precursor

protein APP by sequential secretase processing. The cytotoxic C-terminal fragments (CTFs) and the

caspase-cleaved products such as C31 derived from APP, are also implicated in neuronal death

Three causative genes have been identified that when mutated lead to presenile Alzheimer

disease: APP (amyloid precursor protein gene), PSEN1 and PSEN2. These three genes account for half

of the families with autosomal dominant presenile AD, which represent approximately 10% of the

whole AD population. In addition, apolipoprotein E has been identified as a risk-modifying locus

10/34 Novoseek disease relationships for PSEN2 gene (see all 34 )

Disease	Score	Articles	PubMed IDs for Articles with Shared Sentences (# sentences)
alzheimers disease	89.05	322	12925374 (4), 9694871 (3), 16233903 (3), 8952521 (2) (see all 99)
early onset alzheimer disease	84.60	8	9602061 (1), 10069575 (1), 12354302 (1), 12629906 (1) (see all 6)
senile plaques	74.86	11	9050898 (1), 10069575 (1), 9450781 (1), 11816789 (1) (see all 11)
neurofibrillary tangles	68.07	9	8952521 (1), 9450781 (1), 12581338 (1), 9683997 (1) (see all 6)
breast cancer	62.61	60	16503540 (5), 9472649 (5), 8318427 (4), 14659340 (3) (see all 31)
dementia	62.12	13	11810290 (1), 14503010 (1), 18300294 (1), 18587238 (1) (see all 12)
amyloid deposition	56.56	2	10468510 (1)
late onset alzheimer disease	52.33	2	10430506 (1)
neuropil threads	52.09	1	12581338 (1)
frontotemporal dementia	51.84	1	19012865 (1)

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GeneTests: PSEN2

Early-Onset Familial Alzheimer Disease

Human Gene Mutation Database: PSEN2
Genetic Association Database: PSEN2
Human Genome Epidemiology Navigator: PSEN2 (18 documents)

(Possibly Related Articles in Doctor's Guide)
About This Section

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

10/496 PubMed articles for PSEN2 gene (see all 496 ):

A novel mutation in the PSEN2 gene (T430M) associated with variable expression in a family with early-onset Alzheimer disease. (PubMed id 12925374)^{1, 3, 6} Ezquerra M....Oliva R. (2003)
Regulatory region variability in the human presenilin-2 (PSEN2) gene: potential contribution to the gene activity and risk for AD. (PubMed id 12232783)^{1, 3, 6} Riazanskaia N....Rogaev E. (2002)
A novel mutation in the predicted TM2 domain of the presenilin 2 gene in Spanish patient with late-onset Alzheimer's disease. (PubMed id 10732806)^{1, 3, 4} Lao J.I.... Cacabelos R. (1998)
Alzheimer-associated presenilins 1 and 2: neuronal expression in brain and localization to intracellular membranes in mammalian cells. (PubMed id 8574969)^{1, 3, 4} Kovacs D.M.... Wasco W. (1996)
The transmembrane aspartates in presenilin 1 and 2 are obligatory for gamma-secretase activity and amyloid beta-protein generation. (PubMed id 10652302)^{1, 3, 4} Kimberly W.T.... Selkoe D.J. (2000)
Polymorphism of the regulatory region of the presenilin-2 gene in sporadic Alzheimer's disease: a case-control study. (PubMed id 16233903)^{1, 3, 6} Quan W....Maeda K. (2006)
Mutations in presenilin 1, presenilin 2 and amyloid precursor protein genes in patients with early-onset Alzheimer's disease in Poland. (PubMed id 14769392)^{1, 3, 6} Zekanowski C....Barcikowska M. (2003)
Presenilin mutations in Alzheimer's disease. (PubMed id 9521418)^{1, 3, 4} Cruts M. and van Broeckhoven C. (1998)
Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene. (PubMed id 7651536)^{1, 3, 4} Rogaev E.I.... St George-Hyslop P.H. (1995)
Prevalence of pathogenic mutations in an Italian clinical series of patients with familial dementia. (PubMed id 15975068)^{1, 3, 6} Signorini S....Binetti G. (2004)

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Aliases
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(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, and/or H-InvDB)
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Entrez Gene: 5664	HGNC: 9509	AceView: PSEN2	Ensembl:ENSG00000143801	euGenes: HUgn5664
ECgene: PSEN2	H-InvDB: PSEN2

(According to HUGE)
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(According to ATLAS, HORDE, IMGT, MTDB, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
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Name	Description
ATLAS Chromosomes in Cancer entry for PSEN2	Genetics and Cytogenetics in Oncology and Haematology
Alzheimer Research Forum	http://www.alzforum.org/res/com/mut/pre/default.asp
GeneReviews	http://www.genetests.org/query?gene=PSEN2

Licensable Technologies for PSEN2
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(Reagents available from Applied Biosystems, Antibodies and assays by Cell Signaling Technology, Abcam, Novus Biologicals,
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Enzo Life Sciences, and/or Tocris Bioscience)
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Products for PSEN2:

TaqMan ® Gene Expression Assays

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Invitrogen Clones	Invitrogen Q-PCR Products
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PSEN2 Gene

protein-coding GIFtS: 74

Aliases &
Descriptions
for PSEN2

Summaries
for PSEN2

Genomic Location
for PSEN2

Proteins
for PSEN2

Protein Domains/
Families
for PSEN2

Gene Function
for PSEN2

Pathways & Interactions
for PSEN2

Drugs & Compounds
for PSEN2

Transcripts
for PSEN2

Expression
for PSEN2

Orthologs
for PSEN2

Paralogs
for PSEN2

SNPs/Variants
for PSEN2

Disorders & Mutations
for PSEN2

Medical News
for PSEN2

Publications
for PSEN2

Search for PSEN2

Genome Databases showing PSEN2

Other Databases showing PSEN2

Specialized Databases showing PSEN2

Licensable Technologies
for PSEN2

Services
for PSEN2

Gene Index: 3 5 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

PSEN2 Gene

protein-coding GIFtS: 74

Aliases & Descriptionsfor PSEN2

Summariesfor PSEN2

Genomic Locationfor PSEN2

Proteinsfor PSEN2

Protein Domains/Familiesfor PSEN2

Gene Functionfor PSEN2

Pathways & Interactionsfor PSEN2

Drugs & Compoundsfor PSEN2

Transcriptsfor PSEN2

Expression for PSEN2

Orthologsfor PSEN2

Paralogsfor PSEN2

SNPs/Variantsfor PSEN2

Disorders & Mutationsfor PSEN2

Medical Newsfor PSEN2

Publicationsfor PSEN2

Search for PSEN2

Genome Databases showing PSEN2

Other Databases showing PSEN2

Specialized Databases showing PSEN2

Licensable Technologiesfor PSEN2

Servicesfor PSEN2

Gene Index: 3 5 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

Aliases &
Descriptions
for PSEN2

Summaries
for PSEN2

Genomic Location
for PSEN2

Proteins
for PSEN2

Protein Domains/
Families
for PSEN2

Gene Function
for PSEN2

Pathways & Interactions
for PSEN2

Drugs & Compounds
for PSEN2

Transcripts
for PSEN2

Expression
for PSEN2

Orthologs
for PSEN2

Paralogs
for PSEN2

SNPs/Variants
for PSEN2

Disorders & Mutations
for PSEN2

Medical News
for PSEN2

Publications
for PSEN2

Licensable Technologies
for PSEN2

Services
for PSEN2