protein

CALCINEURIN

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about CALCINEURIN: 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.

338Connections

7Hypotheses

9Analyses

50Outgoing

50Incoming

1Experiments

11Debates

Summary

CALCINEURIN is a protein involved in neurodegeneration research. Key relationships include: activates, regulates, treats. Associated with ALS, Als, Alzheimer. Connected to 138 entities in the SciDEX knowledge graph.

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🔬 Protein Info

Gene Symbol	PPP3CA
Full Name	Protein Phosphatase 3 Catalytic Subunit Alpha (Calcineurin)
Aliases	Calcineurin
Chromosome	4p16.3
Protein Type	Phosphatase
Function	is a unique calcium/calmodulin-dependent phosphatase that plays critical roles in neuronal signal transduction, synaptic plasticity, gene transcription, and immune cell activation[@klee1979].
Primary Expression	a tissue-specific manner:
Molecular Weight	59 kDa
Amino Acids	521 aa
Exons	14
GeneCards	PPP3CA
Human Protein Atlas	PPP3CA
Associated Diseases	Axon Repulsion, neurodegeneration
Interactions	NLRP3
KG Connections	4 knowledge graph edges
Databases	GeneCards UniProt NCBI Gene HPA STRING

Wiki Pages (1)

Knowledge base pages for this entity

Canonical Page

PPP3CA — Protein Phosphatase 3 Catalytic Subunit Alpha

gene · 1663 words

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Pathway Diagram

graph TD
    CALCINEURIN["CALCINEURIN"]
    CALCINEURIN -->|"activates"| TFEB["TFEB"]
    CALCINEURIN -->|"activates"| Amyotrophic_Lateral_Sclerosis["Amyotrophic Lateral Sclerosis"]
    CALCINEURIN -->|"activates"| Neurodegeneration["Neurodegeneration"]
    CALCINEURIN -->|"activates"| Ataxia["Ataxia"]
    CALCINEURIN -->|"activates"| Als["Als"]
    CALCINEURIN -->|"activates"| Parkinson["Parkinson"]
    CALCINEURIN -->|"activates"| Huntington["Huntington"]
    CALCINEURIN -->|"regulates"| Ms["Ms"]
    RCAN1["RCAN1"] -->|"inhibits"| CALCINEURIN
    STIP1["STIP1"] -->|"activates"| CALCINEURIN
    LGALS3["LGALS3"] -->|"activates"| CALCINEURIN
    HSPA8["HSPA8"] -->|"activates"| CALCINEURIN
    MCOLN1["MCOLN1"] -->|"activates"| CALCINEURIN
    SQSTM1["SQSTM1"] -->|"activates"| CALCINEURIN
    SOD1["SOD1"] -->|"activates"| CALCINEURIN
    BCL2["BCL2"] -->|"activates"| CALCINEURIN
    CTSB["CTSB"] -->|"activates"| CALCINEURIN
    TPP1["TPP1"] -->|"activates"| CALCINEURIN

Outgoing (219)

Target	Relation	Type	Str
TFEB dephosphorylation	regulates	phenotype	0.90
Als	regulates	disease	0.75
Parkinson's disease models	associated_with	phenotype	0.70
FUNDC1	activates	gene	0.70
TFEB	activates	protein	0.70
NFAT	regulates	protein	0.70
TFEB nuclear translocation	activates	process	0.70
HDAC9 nuclear import	activates	process	0.70
neurodegeneration	decreases_risk	disease	0.70
Alzheimer's disease models	associated_with	phenotype	0.70
TFEB	activates	protein	0.70
NFAT	activates	protein	0.70
REST degradation	activates	process	0.70
M1 and nAChR convergent signaling	regulates	mechanism	0.70
ALS	activates	disease	0.65
Depression	contributes_to	disease	0.65
Spinocerebellar Ataxia	activates	disease	0.65
ALS	inhibits	disease	0.65
Inflammation	expressed_in	disease	0.65
Bipolar	expressed_in	disease	0.65
Bipolar	causes	disease	0.65
Neuroinflammation	expressed_in	disease	0.65
Als	expressed_in	disease	0.65
Cardiac	treats	disease	0.65
Cardiovascular	regulates	disease	0.65
Schizophrenia	expressed_in	disease	0.65
Diabetes	regulates	disease	0.65
Alzheimer	interacts_with	disease	0.65
Schizophrenia	causes	disease	0.65
Cancer	inhibits	disease	0.65
ALS	expressed_in	disease	0.65
Alzheimer	activates	disease	0.65
Als	interacts_with	disease	0.65
Cardiac	activates	disease	0.65
Parkinson	activates	disease	0.65
Amyotrophic Lateral Sclerosis	activates	disease	0.65
Neurodegeneration	activates	disease	0.65
Huntington	activates	disease	0.65
ALS	regulates	disease	0.65
Ataxia	activates	disease	0.65
Als	activates	disease	0.65
Ms	regulates	disease	0.65
Depression	inhibits	disease	0.65
Ms	activates	disease	0.65
Neuroblastoma	activates	disease	0.65
Cardiovascular	treats	disease	0.65
Heart Failure	associated_with	disease	0.65
Obesity	regulates	disease	0.65
Cancer	regulates	disease	0.65
Ms	inhibits	disease	0.65

Incoming (119)

Source	Relation	Type	Str
Cyclosporine A	inhibits	drug	0.95
30299659	dephosphorylates and triggers nuclear translocation of	paper	0.90
38890273	has reduced association with	paper	0.90
30299659	activates	paper	0.90
24713000	mediates	paper	0.90
29961886	is an inhibitor of	paper	0.90
11733061	plays a critical role in	paper	0.90
RCAN1	inhibits	protein	0.70
cytosolic calcium elevation	activates	process	0.70
Orexin	activates	neuropeptide	0.70
lysosomal calcium release	activates	process	0.70
GAPDH	activates	gene	0.60
ATG10	activates	gene	0.60
ATG12	activates	gene	0.60
BECN1	activates	gene	0.60
BAG3	activates	gene	0.60
BDNF	activates	gene	0.60
TREH	activates	gene	0.60
HUNTINGTIN	activates	gene	0.60
COMPLEMENT	regulates	gene	0.60
CAMKII	regulates	gene	0.60
RNA	activates	gene	0.60
SCABP3	activates	gene	0.60
HTT	activates	gene	0.60
LGALS3	interacts_with	gene	0.60
DRP1	activates	gene	0.60
CBL7	activates	gene	0.60
SMPD1	inhibits	gene	0.60
ATG	activates	gene	0.60
GENES	activates	gene	0.60
AMYOTROPHIC LATERAL SCLEROSIS	activates	gene	0.60
ROS	treats	gene	0.60
DEPRESSION	interacts_with	gene	0.60
AMYLOID	interacts_with	gene	0.60
ALZHEIMER	interacts_with	gene	0.60
SYNAPSE	interacts_with	gene	0.60
APOPTOSIS	expressed_in	gene	0.60
ALZHEIMER	expressed_in	gene	0.60
DEPRESSION	therapeutic_target	gene	0.60
AMYLOID	activates	gene	0.60
ASTROCYTES	activates	gene	0.60
ALZHEIMER	activates	gene	0.60
PPP3CB	interacts_with	gene	0.60
AND	inhibits	gene	0.60
GRIN2A	activates	gene	0.60
DNA	activates	gene	0.60
PPP3	activates	gene	0.60
PARKINSON	activates	gene	0.60
NEURODEGENERATIVE DISEASES	activates	gene	0.60
ALS	activates	gene	0.60

Targeting Hypotheses (7)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Spatiotemporal coupling between TRPML1-mediated lysosomal ca	0.705	neurodegeneration	What determines the specificity of calci
mTORC1 displacement from lysosomal surface enables calcineur	0.650	neurodegeneration	What determines the specificity of calci
Calmodulin isoform switching from CaMK to calcineurin activa	0.607	neurodegeneration	What determines the specificity of calci
PIKFYVE Inhibition Activates Aggregate Exocytosis via PI(3,5	0.584	neurodegeneration	How does PIKFYVE inhibition activate unc
Calcineurin-FUNDC1 Axis as a Master Switch for Mitophagy vs.	0.430	neurodegeneration	What determines organelle-specific autop

P2X7/P2Y12 Purinergic Signaling Connects Aβ Aggregation to S	0.423	neurodegeneration	How do perivascular cells specifically r
Reticulocalbin-2 bridges calcineurin to lysosomal membranes	0.360	neurodegeneration	What determines the specificity of calci

Mentioning Analyses (9)

Scientific analyses that reference this entity

Gene Regulatory Network Inference in Alzheimer's Disease

neurodegeneration | 2026-04-16 | 1 hypotheses Top: 0.661

What molecular mechanisms mediate HDAC9's effects on Aβ deposition and synaptic

neurodegeneration | 2026-04-14 | 0 hypotheses

What is the temporal sequence of sleep disruption versus amyloid-beta accumulati

neurodegeneration | 2026-04-12 | 0 hypotheses

Does tau aggregation specifically cause PS externalization in vesicles independe

neurodegeneration | 2026-04-11 | 0 hypotheses

Do stellate neurons express unique α7 nicotinic receptor subtypes that could ena

neurodegeneration | 2026-04-10 | 0 hypotheses

Experiments (1)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
PPP3/calcineurin-dependent TFEB dephosphorylation mechanism	exploratory	motoneuron degeneration	0.800	0.00	neuronal cell lines	proposed	N/A

Related Papers (0)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
No papers found

Debates (11)

Multi-agent debates referencing this entity

The study shows trehalose causes lysosomal membrane permeabilization (LMP) that

closed · Rounds: 4 · Score: 0.61 · 2026-04-21

While the study establishes that trehalose-induced lysosomal permeabilization ac

closed · Rounds: 4 · Score: 0.73 · 2026-04-21

The review covers various organelle-specific autophagy types but doesn't address

closed · Rounds: 4 · Score: 0.66 · 2026-04-21

The debate proposed α7-containing heteromers (α7β2) might be enriched in stellat

closed · Rounds: 4 · Score: 0.30 · 2026-04-21

The debate revealed a fundamental gap in understanding whether tau pathology dir

closed · Rounds: 4 · Score: 0.30 · 2026-04-21

Which transcription factors drive the gene regulatory networks that distinguish

closed · Rounds: 4 · Score: 0.70 · 2026-04-21

The debate highlighted the bidirectional relationship between sleep and neurodeg

closed · Rounds: 4 · Score: 0.50 · 2026-04-18

Is REST the master regulator of neuronal vulnerability in AD, or is it one of se

closed · Rounds: 4 · Score: 0.70 · 2026-04-16

The abstract shows HDAC9 overexpression reduces Aβ deposition and improves synap

closed · Rounds: 4 · Score: 0.95 · 2026-04-16

What are the critical protein expression changes and post-translational modifica

closed · Rounds: 4 · Score: 0.68 · 2026-04-12

Related Research

Hypotheses and analyses mentioning CALCINEURIN in their description or question text

P2X7/P2Y12 Purinergic Signaling Connects Aβ Aggregation to SPP1 Transcription vi

Score: 0.423 · neurodegeneration · 2026-04-22

## Mechanistic Overview P2X7/P2Y12 Purinergic Signaling Connects Aβ Aggregation to SPP1 Transcription via Calcineurin/NF

Reticulocalbin-2 bridges calcineurin to lysosomal membranes for Ca2+-dependent a

Score: 0.360 · neurodegeneration · 2026-04-21

## Mechanistic Overview Reticulocalbin-2 bridges calcineurin to lysosomal membranes for Ca2+-dependent activation starts