gene

MCU

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about MCU: 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.

226Connections

3Hypotheses

1Analyses

50Outgoing

50Incoming

6Experiments

1Debates

Summary

MCU is a gene implicated in neurodegeneration research. Key relationships include: activates, regulates, implicated in. Associated with AD, ALI, ALS. Connected to 92 entities in the SciDEX knowledge graph.

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🧬 Gene Info

Gene Symbol	MCU
Protein Type	Ion Channel
Target Class	Ion Channel
Function	MCU encodes a 351 amino acid protein with two transmembrane domains that form a highly selective calcium channel in the inner mitochondrial membrane.
Mechanism of Action	MCU inhibitors block the mitochondrial calcium uniporter channel, reducing excessive calcium accumulation in mitochondria that leads to oxidative stress, energy depletion, and cell death. This mechanism may protect against ischemic injury, neurodegeneration, and heart failure by preserving mitochondrial function and preventing apoptosis in calcium-sensitive tissues.
Druggability	Low (0.41)
Clinical Stage	Phase III
Molecular Weight	40 kDa
Amino Acids	351 aa
Pathways	Mitochondrial Calcium Buffering Enhancement via MC
UniProt ID	S4R3F5
Ensembl ID	ENSG00000156026
GeneCards	MCU
Human Protein Atlas	MCU
MCU	pore-forming subunit; oligomerizes into a tetramer or pentamer to create the calcium-conducting pore
Associated Diseases	AD, aging, ALI, Als
Known Drugs/Compounds	Ruthenium Red
Interactions	AGING, AMPK, AND, APOPTOSIS, App, ATP
SciDEX Target	View Target Profile (10 clinical trials)
SciDEX Hypotheses	Mitochondrial Calcium Buffering Enhancement via MC
KG Connections	226 knowledge graph edges
Databases	GeneCards NCBI Gene HPA STRING

🧬 3D Structure Comparison — MCU Experimental (PDB) vs Predicted (AlphaFold) — click to expand

📄 Experimental Structure

6DNF — X-ray / Cryo-EM

🔮 AI Predicted Structure

S4R3F5 — AlphaFold

Left: Experimental structure from RCSB PDB | Right: AI-predicted structure from AlphaFold | Powered by Mol*

Wiki Pages (2)

Knowledge base pages for this entity

Canonical Page

MCU Gene

gene · 960 words

→

MCU Protein

protein · 1045 words

→

Pathway Diagram

graph TD
    MCU["MCU"]
    MCU -->|"regulates"| Mitochondrial_Calcium_Bufferin["Mitochondrial Calcium Buffering Enhancement via MC"]
    MCU -->|"target for"| Cancer["Cancer"]
    MCU -->|"target for"| Neurodegeneration["Neurodegeneration"]
    MCU -->|"target for"| Stroke["Stroke"]
    MCU -->|"target for"| Ms["Ms"]
    MCU -->|"target for"| Heart_Failure["Heart Failure"]
    MCU -->|"target for"| Diabetes["Diabetes"]
    MCU -->|"activates"| Aging["Aging"]
    MCU -->|"activates"| Als["Als"]
    h_aa8b4952["h-aa8b4952"] -->|"target for"| MCU
    LETM1["LETM1"] -->|"regulates"| MCU
    OVERVIEW["OVERVIEW"] -->|"regulates"| MCU
    DES["DES"] -->|"activates"| MCU
    VDAC1["VDAC1"] -->|"activates"| MCU
    MITOPHAGY["MITOPHAGY"] -->|"activates"| MCU
    PARKIN["PARKIN"] -->|"activates"| MCU
    APOPTOSIS["APOPTOSIS"] -->|"activates"| MCU
    CANCER["CANCER"] -->|"inhibits"| MCU

Outgoing (171)

Target	Relation	Type	Str
Calcium	binds	compound	0.95
Mitochondrial Calcium	transports	compound	0.95
Mitochondrial Calcium	regulates	compound	0.95
Mitochondrial Calcium Uptake	mediates	process	0.95
MITOCHONDRIAL CALCIUM	regulates	entity	0.95
CYTOSOLIC CALCIUM	regulates	entity	0.95
Mitochondrial Calcium Exchange	mediates	process	0.95
MITOCHONDRIAL CALCIUM UPTAKE	mediates	entity	0.95
Mitochondrial Calcium Transport	mediates	process	0.95
calcium	regulates	compound	0.95
cytosolic calcium	upregulates	compound	0.90
Hepatic Fatty Acid Oxidation	upregulates	process	0.90
Intrahepatic Lipolysis	upregulates	process	0.90
Mitochondria	component_of	organelle	0.90
Succinate Dehydrogenase	regulates	enzyme	0.85
Isocitrate Dehydrogenase	regulates	enzyme	0.85
Α-Ketoglutarate Dehydrogenase	regulates	enzyme	0.85
Mitochondrial Calcium Uptake	involved_in	process	0.85
Alpha-Ketoglutarate Dehydrogenase	regulates	enzyme	0.85
isocitrate dehydrogenase	upregulates	protein	0.85
α-ketoglutarate dehydrogenase	upregulates	protein	0.85
succinate dehydrogenase	upregulates	protein	0.85
mitochondrial calcium uptake	modulates	process	0.85
Cell Survival	regulates	process	0.75
Mitochondrial Calcium Buffering Enhancement via MC	regulates	mechanism	0.70
amyloid beta	regulates	protein	0.70
Apoptosis	activates	pathway	0.70
Als	activates	disease	0.65
Cancer	therapeutic_target	disease	0.65
Stroke	therapeutic_target	disease	0.65
Neurodegeneration	therapeutic_target	disease	0.65
Ms	therapeutic_target	disease	0.65
Heart Failure	therapeutic_target	disease	0.65
Diabetes	therapeutic_target	disease	0.65
Aging	activates	disease	0.65
Ms	activates	disease	0.65
ALS	activates	disease	0.65
Stroke	regulates	disease	0.65
Heart Failure	regulates	disease	0.65
Stroke	associated_with	disease	0.65
Diabetes	associated_with	disease	0.65
Heart Failure	associated_with	disease	0.65
Cancer	associated_with	disease	0.65
Neurodegeneration	regulates	disease	0.65
Cancer	regulates	disease	0.65
Diabetes	regulates	disease	0.65
ALS	regulates	disease	0.65
Inflammation	associated_with	disease	0.65
Autoimmune	inhibits	disease	0.65
Cancer	inhibits	disease	0.65

Incoming (55)

Source	Relation	Type	Str
oleuropein	activates	chemical	0.90
h-aa8b4952	targets_gene	hypothesis	0.90
MICU1	interacts_with	protein	0.85
h-aa8b4952	targets	hypothesis	0.80
VDAC1	activates	gene	0.70
APOPTOSIS	activates	gene	0.70
INFLAMMATION	associated_with	gene	0.60
PARKIN	activates	gene	0.60
DRP1	activates	gene	0.60
MITOPHAGY	activates	gene	0.60
ATP	activates	gene	0.60
ATP	interacts_with	gene	0.60
CANCER	inhibits	gene	0.60
APOPTOSIS	inhibits	gene	0.60
STROKE	therapeutic_target	gene	0.60
CAMKII	activates	gene	0.60
AMPK	activates	gene	0.60
FUNDC1	associated_with	gene	0.60
FUNDC1	activates	gene	0.60
BRAIN INJURY	activates	gene	0.60
OVERVIEW	regulates	gene	0.60
OPA1	activates	gene	0.60
DES	activates	gene	0.60
LETM1	regulates	gene	0.60
MITOCHONDRIAL DYSFUNCTION	activates	gene	0.60
NEURODEGENERATION	regulates	gene	0.60
AGING	activates	gene	0.60
AND	inhibits	gene	0.60
AMPK	inhibits	gene	0.60
ATP	inhibits	gene	0.60
AMPK	regulates	gene	0.60
LETM1	interacts_with	entity	0.60
SIRT1	activates	gene	0.60
RNA	inhibits	gene	0.60
PINK1	activates	gene	0.60
ferroptosis	co_mentioned	pathway	0.55
GPX4	co_mentioned	gene	0.55
APP	regulates	gene	0.55
APP	associated_with	gene	0.50
LETM1	co_expressed_with	gene	0.50
DAB1	debate_co_mention	gene	0.45
HCN1	debate_co_mention	gene	0.45
IDH2	debate_co_mention	gene	0.45
MAP6	debate_co_mention	gene	0.45
excitotoxicity	debate_co_mention	process	0.45
IDH2	co_associated_with	gene	0.40
HCN1	co_associated_with	gene	0.40
MAP6	co_associated_with	gene	0.40
MAP6	co_discussed	gene	0.40
HCN1	co_discussed	gene	0.40

Targeting Hypotheses (3)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Mitochondrial Calcium Buffering Enhancement via MCU Modulati	0.650	neurodegeneration	Selective vulnerability of entorhinal co
MCU Calcium Overload via MFN2/GRP75/VDAC1 MAM Dysfunction	0.644	neurodegeneration	What upstream mechanisms cause TDP-43 to
Enhanced MCU Activity Primes mPTP Opening in Motor Neurons	0.620	neurodegeneration	What determines the specificity of TDP-4

Mentioning Analyses (1)

Scientific analyses that reference this entity

Selective vulnerability of entorhinal cortex layer II neurons in AD

neurodegeneration | 2026-04-01 | 7 hypotheses Top: 0.696

Experiments (6)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
s:** - Test MCU overexpression specifically in layer II neurons in hea	falsification	Neurodegeneration	0.400	0.50	mouse	proposed	$200,000
Exercise-BDNF-Mitophagy Biomarker Study in PD	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$6,550,000
Ferroptosis Validation in Parkinson's Disease	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$6,550,000
Experiment Design: Metal Ion-Synuclein-Mitochondria Axis in Parkinson'	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$5,460,000
MLCS Quantification in Parkinson's Disease	validation	Parkinson's Disease	0.400	0.50	human	proposed	$2,730,000
Wilson Disease Neurodegeneration: Mechanism and Therapeutic Response	clinical	Neurodegeneration	0.400	0.50	human	proposed	$7,500,000

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
Mitochondrial calcium uptake declines during aging and is directly activated by [PMID:39603237]	Gherardi G, Weiser A, Bermont F, Migliav	Cell Metab	2025	1
Cytosolic calcium regulates hepatic mitochondrial oxidation, intrahepatic lipoly [PMID:39153480]	LaMoia TE, Hubbard BT, Guerra MT, Nasiri	Cell Metab	2024	1
Mitochondrial calcium exchange in physiology and disease. [PMID:34698550]	Garbincius JF, Elrod JW	Physiol Rev	2022	1
Ceritinib Induces Mitochondrial Fragmentation in Thyroid Cancer Cells by Targeti [PMID:41805100]	Qin D, Ding W, Wu X, Peng C, Bo Y et al.	Drug Dev Res	2026	0
Deficient Cardiolipin Remodelling Alters Muscle Fibre Composition and Neuromuscu [PMID:41841200]	Matias C, Snider PL, Sierra Potchanant E	J Cachexia Sarcopenia Muscle	2026	0
Zn(2+)-Dependent Modulation of the Mitochondrial Ca(2+) Uniporter Underlies Resv [PMID:41932596]	Xing B, Li X, Wang B, Huang L, Wang Q et	Exp Cell Res	2026	0
SERCA2 Dysfunction Drives Vascular Calcification via Coupling with TSPO-MCU at M [PMID:41932666]	Pi S, Liu W, Zhao J, Chen H, Luo X et al	Pharmacol Res	2026	0
Berberine is a Novel Mitochondrial Calcium Uniporter Inhibitor that Disrupts MCU [PMID:39921279]	Zhao H, Chen S, Cao N, Wu W, Liu G, Gao	Advanced science (Weinheim, Ba	2025	0
Mitochondrial Calcium Uniporter Links Acetyl-CoA Metabolism and H3K27 Acetylatio [PMID:40712058]	Liu G, Zhang H, Chen S, Gao J, Zhao H, D	Cancer research	2025	0
Assessment of the Spatial Distribution of Moisture Content in Granular Material [PMID:31234567]	["Porzuczek J"]	Sensors (Basel, Switzerland)	2024	0
A vision-based real-time traffic flow monitoring system for road intersections. [PMID:36789012]	["Azimjonov J", "\u00d6zmen A", "Varan M	Multimedia tools and applicati	2023	0
Mitochondrial calcium cycling in neuronal function and neurodegeneration. [PMID:36760367]	Walters GC, Usachev YM	Frontiers in cell and developm	2023	0
The Mitochondrial Calcium Uniporter (MCU): Molecular Identity and Role in Human [PMID:37759703]	D'Angelo D, Rizzuto R	Biomolecules	2023	0
The Importance of Emotional Intelligence in University Athletes: Analysis of Its [PMID:36901234]	["Mercader-Rubio I", "\u00c1ngel N"]	International journal of envir	2023	0
Synergistic Antitumoral Effect of Epigenetic Inhibitors and Gemcitabine in Pancr [PMID:35890123]	["Maietta I", "Mart\u00ednez-P\u00e9rez	Pharmaceuticals (Basel, Switze	2022	0
The Genetic Architecture of Obsessive-Compulsive Disorder: Contribution of Liabi [PMID:34789012]	["Mahjani B", "Klei L", "Mattheisen M",	The American journal of psychi	2022	0
Controlled synthesis of silver-based ternary quantum dots with outstanding lumin [PMID:35678901]	["Mbaz G", "Parani S", "Oluwafemi O"]	Journal of fluorescence	2022	0
Multiple Primary Malignancies in Head and Neck Cancer: A University Hospital Exp [PMID:34567890]	["Batista MV", "Ulrich J", "Costa L", "R	Cureus	2021	0
Early treatment with sumatriptan prevents PACAP38-induced migraine: A randomised [PMID:33567890]	["Wienholtz N", "Christensen C", "Zhang	Cephalalgia : an international	2021	0
Severe vernal keratoconjunctivitis complicated by anaesthetic abuse [PMID:32456789]	Anchouche Sonia; Yin Jia	Canadian Journal of Ophthalmol	2020	0

Debates (1)

Multi-agent debates referencing this entity

Why do entorhinal cortex layer II stellate neurons die first in AD? Their unique

closed · Rounds: 6 · Score: 0.95 · 2026-04-10