gene

PSEN2

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about PSEN2: its mechanistic relationships (Knowledge Graph edges), hypotheses targeting it, analyses mentioning it, and supporting scientific papers. The interactive graph below shows its immediate neighbors. All content is AI-synthesized from peer-reviewed literature.

869Connections

0Hypotheses

1Analyses

50Outgoing

50Incoming

0Experiments

1Debates

Summary

Presenilin 2 (PSEN2) is a catalytic subunit of the gamma-secretase complex that cleaves APP to produce amyloid-beta peptides. Mutations in PSEN2 cause familial Alzheimer's disease with later onset (50-70 years) compared to PSEN1 mutations. PSEN2 mutations shift the Abeta42/Abeta40 ratio toward longer, more aggregation-prone peptides. Beyond APP cleavage, PSEN2 processes Notch, ErbB4, and other type I transmembrane proteins. PSEN2 also regulates calcium homeostasis in the endoplasmic reticulum and mitochondria-associated ER membranes (MAMs). PSEN2 is highly expressed in peripheral tissues as well as brain, suggesting systemic roles. The Volga German kindred carrying PSEN2 N141I provided early evidence linking presenilin mutations to familial AD.

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🧬 Gene Info

Gene Symbol	PSEN2
Full Name	Presenilin 2
Chromosome	1q42.13
Protein Type	Aspartyl protease (catalytic subunit)
Function	Initial cleavage: APP pre-processed by BACE1 to generate C99
Molecular Weight	50 kDa
Amino Acids	448 aa
Exons	13
Pathways	Blood-Brain Barrier, Cholesterol, Dysbiosis, Epigenetic, Gut Microbiome
UniProt ID	O00287
NCBI Gene ID	5664
GeneCards	PSEN2
Human Protein Atlas	PSEN2
Associated Diseases	AD, Aging, Als, Alzheimer, Alzheimer Disease
Known Drugs/Compounds	rapamycin, RAPAMYCIN
Interactions	A2M, ABCA1, ABCA7, AD, AKT, AKT1
KG Connections	869 knowledge graph edges
Databases	GeneCards HPA STRING

🔮 Predicted Structure: PSEN2 — AlphaFold O00287 Click to expand

AI-predicted structure from AlphaFold | Powered by Mol*

Wiki Pages (7)

Knowledge base pages for this entity

Canonical Page

Pathway Diagram

flowchart TD
    PSEN2["PSEN2
(Presenilin 2)"]
    
    PSEN1["PSEN1
(Presenilin 1)"]
    PEN2["PEN2
(Gamma-secretase
component)"]
    MAPT["MAPT
(Tau protein)"]
    
    AmyloidBeta["Amyloid-beta
(Abeta peptide)"]
    GammaSecretase["gamma-Secretase
Complex"]
    
    EOAD["Early-onset
Alzheimer's Disease"]
    AD["Alzheimer's
Disease"]
    Neurodegeneration["Neurodegeneration"]
    
    AmyloidPlaques["Amyloid
Plaques"]
    TauTangles["Tau
Tangles"]
    
    A2M["A2M
(Alpha-2-Macroglobulin)"]
    DHCR24["DHCR24
(Cholesterol
synthesis)"]
    PARP1["PARP1
(DNA repair)"]
    
    CognitiveDecline["Cognitive
Decline"]
    Apoptosis["Neuronal
Death"]
    
    PSEN2 -->|"forms"| GammaSecretase
    PSEN1 -->|"forms"| GammaSecretase
    PEN2 -->|"forms"| GammaSecretase
    
    PSEN2 -->|"regulates"| AmyloidBeta
    GammaSecretase -->|"cleaves APP to produce"| AmyloidBeta
    
    PSEN2 -->|"activates"| MAPT
    MAPT -->|"forms"| TauTangles
    
    PSEN2 -->|"causes"| EOAD
    PSEN2 -->|"causes"| AD
    AmyloidBeta -->|"aggregates into"| AmyloidPlaques
    
    AmyloidPlaques -->|"leads to"| Neurodegeneration
    TauTangles -->|"leads to"| Neurodegeneration
    Neurodegeneration -->|"results in"| CognitiveDecline
    Neurodegeneration -->|"results in"| Apoptosis
    
    A2M -->|"interacts with"| PSEN2
    DHCR24 -->|"interacts with"| PSEN2
    PARP1 -->|"interacts with"| PSEN2
    
    style PSEN2 fill:#006494
    style AmyloidBeta fill:#ef5350
    style EOAD fill:#5d4400
    style AD fill:#5d4400
    style Neurodegeneration fill:#ef5350
    style AmyloidPlaques fill:#ef5350
    style TauTangles fill:#ef5350
    style CognitiveDecline fill:#5d4400
    style Apoptosis fill:#ef5350
    style PSEN1 fill:#4a1a6b
    style PEN2 fill:#4a1a6b
    style MAPT fill:#4a1a6b
    style A2M fill:#1b5e20
    style DHCR24 fill:#4a1a6b
    style PARP1 fill:#1b5e20

Outgoing (467)

Target	Relation	Type	Str
ad_genetic_risk_loci:PSEN2	data_in	dataset_row	0.00
benchmark_ot_ad_answer_key:PSEN2	data_in	dataset_row	0.00
ds-f50762b67605	provides_data_for	dataset	1.00
ds-83b31ef18d49	provides_data_for	dataset	1.00
Autosomal Dominant Alzheimer's Disease	causes	disease	0.95
Familial Alzheimer's Disease	causes	disease	0.95
Alzheimer'S Disease	causes	disease	0.95
Alzheimer's Disease	risk_factor_for	disease	0.90
Early-Onset Alzheimer's Disease	causes	disease	0.90
Γ-SECRETASE COMPLEX	component_of	enzyme	0.90
Amyloid-β	upregulates	protein	0.85
APP processing	involved_in	process	0.80
amyloid production	no change	process	0.80
APP	associated_with	entity	0.80
Alzheimer's Disease	causes	disease	0.80
neural stem cells	regulates	cell_type	0.80
PSEN1	associated_with	gene	0.80
Alzheimer	associated_with	disease	0.75
EOAD	causes	disease	0.72
TAU	targets	gene	0.70
STING	activates	gene	0.70
SQSTM1	interacts_with	gene	0.70
GENES	associated_with	gene	0.70
ALZHEIMER	associated_with	gene	0.70
neurodegeneration	expressed_in	disease	0.70
Alzheimer's disease	causes	disease	0.70
amyloid-β	regulates	protein	0.70
AMYLOID	associated_with	gene	0.70
PRESENILIN	associated_with	gene	0.70
ALZHEIMER'S DISEASE	associated_with	gene	0.70
Alzheimer's disease	associated_with	disease	0.70
Dementia	inhibits	disease	0.65
Alzheimer	causes	disease	0.65
Aging	causes	disease	0.65
ALS	interacts_with	disease	0.65
RAPAMYCIN	targets	drug	0.65
Alzheimer	degrades	disease	0.65
Atherosclerosis	degrades	disease	0.65
Als	degrades	disease	0.65
Inflammation	associated_with	disease	0.65
Inflammation	regulates	disease	0.65
ALS	transports	disease	0.65
ALS	causes	disease	0.65
Als	inhibits	disease	0.65
Neuroinflammation	regulates	disease	0.65
Aging	regulates	disease	0.65
Alzheimer	therapeutic_target	disease	0.65
Alzheimer	regulates	disease	0.65
Dementia	regulates	disease	0.65
Neuroinflammation	activates	disease	0.65

Incoming (402)

Source	Relation	Type	Str
benchmark_ot_ad_answer_key:PSEN2	data_in	dataset_row	0.00
ad_genetic_risk_loci:PSEN2	data_in	dataset_row	0.00
ds-f50762b67605	data_in	dataset	1.00
ds-83b31ef18d49	data_in	dataset	1.00
ALZHEIMER'S DISEASE	associated_with	gene	1.00
AMYLOID	associated_with	gene	1.00
APOE	associated_with	gene	0.90
CRISPR/CAS9	enables_genetic_modification_of	technology	0.80
APP	associated_with	gene	0.74
CDK5	associated_with	gene	0.70
APP	transports	gene	0.70
NOTCH	interacts_with	gene	0.70
LAMP1	interacts_with	gene	0.70
INSULIN SIGNALING	regulates	pathway	0.70
LRRK2	interacts_with	gene	0.70
PSEN1	biomarker_for	gene	0.70
PSEN1	targets	gene	0.70
MAPT	targets	gene	0.70
MAPT	interacts_with	gene	0.70
APP	targets	gene	0.70
LAMP1	activates	gene	0.70
NEURONS	activates	cell_type	0.70
INSULIN SIGNALING	activates	pathway	0.70
PLP1	regulates	gene	0.70
GRIN2B	regulates	gene	0.70
GRIN1	regulates	gene	0.70
GSK3B	interacts_with	gene	0.70
IDE	regulates	gene	0.70
CR1	regulates	gene	0.70
CD33	regulates	gene	0.70
PSEN1	associated_with	gene	0.70
APOE	phosphorylates	entity	0.70
APOPTOSIS	associated_with	gene	0.66
NEURODEGENERATION	associated_with	gene	0.66
APP	activates	gene	0.66
APP	causes	gene	0.66
MAPT	activates	gene	0.66
PSEN1	degrades	gene	0.65
PSEN1	causes	gene	0.65
HIPPOCAMPUS	regulates	brain_region	0.65
HIPPOCAMPUS	activates	brain_region	0.65
PSEN1	stabilizes	gene	0.65
MITOPHAGY	treats	phenotype	0.65
ABCA7	co_discussed	gene	0.65
TAU	associated_with	protein	0.64
LMNA	interacts_with	gene	0.60
FAS	interacts_with	gene	0.60
APH1B	interacts_with	gene	0.60
BECN1	associated_with	gene	0.60
AD	interacts_with	gene	0.60

Targeting Hypotheses (0)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
No targeting hypotheses

Mentioning Analyses (1)

Scientific analyses that reference this entity

How does PSEN2 mechanistically regulate α-synuclein expression and pathology in

neurodegeneration | 2026-04-13 | 0 hypotheses

Experiments (0)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
No experiments found

Related Papers (0)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
No papers found

Debates (1)

Multi-agent debates referencing this entity

The study shows PSEN2 is essential in cortical and dopaminergic neurons and regu

closed · Rounds: 4 · Score: 0.68 · 2026-04-16

Related Research

Hypotheses and analyses mentioning PSEN2 in their description or question text

No additional research found

PSEN2

Understanding Entity Pages

Summary

Wiki Pages (7)

PSEN2 — Presenilin 2

PSEN2 Presenilin 2 AD Causal Chain

PSEN2 Protein (Presenilin-2)

PSEN2 Mutations in Alzheimer's Disease

Presenilin-2 (PSEN2)

PSEN2 (Redirect)

PSEN2-Mutant Neurons