PSEN2 presenilin 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PSEN2provided by HGNC
Official Full Name: presenilin 2provided by HGNC
Primary source: HGNC:HGNC:9509
See related: Ensembl:ENSG00000143801 MIM:600759; AllianceGenome:HGNC:9509
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: AD4; PS2; AD3L; STM2; CMD1V
Summary: 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, Jul 2008]
Expression: Ubiquitous expression in testis (RPKM 4.6), prostate (RPKM 4.4) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1q42.13

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (226870616..226903668)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (226058503..226091743)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (227058317..227083799)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Cerebral organoids derived from patients with Alzheimer's disease with PSEN1/2 mutations have defective tissue patterning and altered development.
Title: Cerebral organoids derived from patients with Alzheimer's disease with PSEN1/2 mutations have defective tissue patterning and altered development.
Quantitative comparison of presenilin protein expression reveals greater activity of PS2-gamma-secretase.
Title: Quantitative comparison of presenilin protein expression reveals greater activity of PS2-γ-secretase.
Different transmembrane domains determine the specificity and efficiency of the cleavage activity of the gamma-secretase subunit presenilin.
Title: Different transmembrane domains determine the specificity and efficiency of the cleavage activity of the γ-secretase subunit presenilin.
Aberrant splicing of PSEN2, but not PSEN1, in individuals with sporadic Alzheimer's disease.
Title: Aberrant splicing of PSEN2, but not PSEN1, in individuals with sporadic Alzheimer's disease.
The associations of APP, PSEN1, and PSEN2 genes with Alzheimer's disease: A large case-control study in Chinese population.
Title: The associations of APP, PSEN1, and PSEN2 genes with Alzheimer's disease: A large case-control study in Chinese population.
PSEN2 Mutation Spectrum and Novel Functionally Validated Mutations in Alzheimer's Disease: Data from PUMCH Dementia Cohort.
Title: PSEN2 Mutation Spectrum and Novel Functionally Validated Mutations in Alzheimer's Disease: Data from PUMCH Dementia Cohort.
Presenilin Is Essential for ApoE Secretion, a Novel Role of Presenilin Involved in Alzheimer's Disease Pathogenesis.
Title: Presenilin Is Essential for ApoE Secretion, a Novel Role of Presenilin Involved in Alzheimer's Disease Pathogenesis.
A Rare Variation in the 3' Untranslated Region of the Presenilin 2 Gene Is Linked to Alzheimer's Disease.
Title: A Rare Variation in the 3' Untranslated Region of the Presenilin 2 Gene Is Linked to Alzheimer's Disease.
Conformational Models of APP Processing by Gamma Secretase Based on Analysis of Pathogenic Mutations.
Title: Conformational Models of APP Processing by Gamma Secretase Based on Analysis of Pathogenic Mutations.
Plasma amyloid beta levels are driven by genetic variants near APOE, BACE1, APP, PSEN2: A genome-wide association study in over 12,000 non-demented participants.
Title: Plasma amyloid β levels are driven by genetic variants near APOE, BACE1, APP, PSEN2: A genome-wide association study in over 12,000 non-demented participants.

Submit: New GeneRIF Correction See all GeneRIFs (158)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Alzheimer disease 4 MedGen: C1847200 OMIM: 606889 GeneReviews: Alzheimer Disease Overview	Compare labs
Dilated cardiomyopathy 1V MedGen: C3150958 OMIM: 613697 GeneReviews: Dilated Cardiomyopathy Overview	Compare labs
Primary dilated cardiomyopathy MedGen: C0007193 GeneReviews: Dilated Cardiomyopathy Overview	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of presenilin 2 (Alzheimer disease 4, PSEN2) by siRNA inhibits the early stages of HIV-1 replication in 293T cells infected with VSV-G pseudotyped HIV-1	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D1S479 (e-PCR)
- UniSTS:9041

D1S3685E (e-PCR)
- UniSTS:474204

D1S3686E (e-PCR)
- UniSTS:474205

PSEN2_2369 (e-PCR)
- UniSTS:280931

SHGC-35541 (e-PCR)
- UniSTS:38313

RH80332 (e-PCR)
- UniSTS:85946

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables aspartic endopeptidase activity, intramembrane cleaving	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in Notch receptor processing	TAS Traceable Author Statement more info	PubMed
involved_in Notch signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in amyloid precursor protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in amyloid precursor protein catabolic process	TAS Traceable Author Statement more info	PubMed
involved_in amyloid-beta formation	IBA Inferred from Biological aspect of Ancestor more info
involved_in amyloid-beta formation	IDA Inferred from Direct Assay more info	PubMed
involved_in calcium ion homeostasis	IBA Inferred from Biological aspect of Ancestor more info
involved_in intracellular signal transduction	IEA Inferred from Electronic Annotation more info
involved_in membrane protein ectodomain proteolysis	IBA Inferred from Biological aspect of Ancestor more info
involved_in membrane protein ectodomain proteolysis	IDA Inferred from Direct Assay more info	PubMed
involved_in mitochondrion-endoplasmic reticulum membrane tethering	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of catalytic activity	IDA Inferred from Direct Assay more info	PubMed
involved_in protein processing	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein processing	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of calcium import into the mitochondrion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to hypoxia	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
located_in Golgi membrane	IEA Inferred from Electronic Annotation more info
located_in centrosome	IDA Inferred from Direct Assay more info	PubMed
located_in early endosome	IEA Inferred from Electronic Annotation more info
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum membrane	IEA Inferred from Electronic Annotation more info
part_of gamma-secretase complex	IBA Inferred from Biological aspect of Ancestor more info
part_of gamma-secretase complex	IDA Inferred from Direct Assay more info	PubMed
located_in kinetochore	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	HDA more info	PubMed
located_in nuclear inner membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
located_in presynaptic membrane	IEA Inferred from Electronic Annotation more info
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed
located_in synaptic vesicle	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: presenilin-2

Names: AD3LP; AD5; Alzheimer disease 3-like; Alzheimer disease 4; E5-1; PS-2; STM-2

NP_000438.2

EC 3.4.23.-

NP_036618.2

EC 3.4.23.-

XP_005273256.1

EC 3.4.23.-

XP_016857324.1

EC 3.4.23.-

XP_016857325.1

EC 3.4.23.-

XP_047281552.1

EC 3.4.23.-

XP_047281553.1

EC 3.4.23.-

XP_047281557.1

EC 3.4.23.-

XP_054193713.1

EC 3.4.23.-

XP_054193714.1

EC 3.4.23.-

XP_054193715.1

EC 3.4.23.-

XP_054193716.1

EC 3.4.23.-

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_007381.2 RefSeqGene

Range

5433..30915

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_225

mRNA and Protein(s)

NM_000447.3 → NP_000438.2 presenilin-2 isoform 1

See identical proteins and their annotated locations for NP_000438.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

BT006984, DA198818, DA915823, L43964

Consensus CDS

CCDS1556.1

UniProtKB/Swiss-Prot

A8K8D4, B1AP21, P49810, Q96P32

UniProtKB/TrEMBL

A0A218KGQ4

Related

ENSP00000355747.3, ENST00000366783.8

Conserved Domains (1) summary

pfam01080
Location:82 → 438

Presenilin
NM_012486.3 → NP_036618.2 presenilin-2 isoform 2

See identical proteins and their annotated locations for NP_036618.2

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate splice acceptor site at exon 10 compared to transcript variant 1, resulting in an isoform (2) that is 1 aa shorter than isoform 1.

Source sequence(s)

DA198818, DA915823, L43964, U34349

Consensus CDS

CCDS44324.1

UniProtKB/TrEMBL

A0A218KGQ4

Related

ENSP00000403737.2, ENST00000422240.6

Conserved Domains (1) summary

pfam01080
Location:82 → 437

Presenilin