gene

COX4I1

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about COX4I1: 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.

325Connections

1Hypotheses

1Analyses

50Outgoing

50Incoming

10Experiments

1Debates

Summary

COX4I1 is a gene implicated in neurodegeneration research. Key relationships include: associated with, activates, inhibits. Associated with Aging, Als, Cardiovascular. Connected to 130 entities in the SciDEX knowledge graph.

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🧬 Gene Info

Gene Symbol	COX4I1
Full Name	Cytochrome C Oxidase Subunit 4I1
Chromosome	16q24.1
Protein Type	Enzyme
Target Class	Enzyme
Function	encodes a critical subunit of the mitochondrial electron transport chain Complex IV (cytochrome c oxidase).
Mechanism of Action	Drugs targeting COX4I1 pathway would enhance electron transport chain efficiency or stabilize complex IV assembly, improving ATP production and reducing oxidative stress in mitochondria. These agents work by either promoting mitochondrial bioenergetics, acting as electron donors/acceptors, or preventing complex IV degradation in diseases with impaired oxidative phosphorylation.
Primary Expression	Brain, Heart, Skeletal Muscle
Druggability	Low (0.42)
Clinical Stage	Phase II
Pathways	Mitochondrial dynamics / bioenergetics
UniProt ID	P12074
NCBI Gene ID	1024
Ensembl ID	ENSG00000131043
GeneCards	COX4I1
Human Protein Atlas	COX4I1
Associated Diseases	Aging, Cardiovascular, Ischemia, neurodegeneration
Known Drugs/Compounds	Elamipretide (MTP131), Idebenone, Coenzyme Q10 (Ubiquinone), SS-31 (Szeto-Schiller peptide 31)
Interactions	AGING, AIF1, AMPK, ARC, ATF3, AUTOPHAGY
SciDEX Target	View Target Profile (7 clinical trials)
SciDEX Hypotheses	Near-infrared light therapy stimulates COX4-depend
KG Connections	325 knowledge graph edges
Databases	GeneCards HPA STRING

🔮 Predicted Structure: COX4I1 — AlphaFold P12074 Click to expand

AI-predicted structure from AlphaFold | Powered by Mol*

Wiki Pages (2)

Knowledge base pages for this entity

Canonical Page

COX4I1

gene · 1587 words

→

COX4I1 Protein — Cytochrome C Oxidase Subunit 4I1

protein · 576 words

→

Pathway Diagram

graph TD
    COX4I1["COX4I1"]
    COX4I1 -->|"inhibits"| Aging["Aging"]
    COX4I1 -->|"inhibits"| Ms["Ms"]
    COX4I1 -->|"inhibits"| Cardiovascular["Cardiovascular"]
    COX4I1 -->|"inhibits"| Mitophagy["Mitophagy"]
    COX4I1 -->|"inhibits"| Proteasome["Proteasome"]
    COX4I1 -->|"activates"| GRIA2["GRIA2"]
    h_fd1562a3["h-fd1562a3"] -->|"target for"| COX4I1
    MYO7A["MYO7A"] -->|"activates"| COX4I1
    MAP1LC3B["MAP1LC3B"] -->|"activates"| COX4I1
    OPTN["OPTN"] -->|"activates"| COX4I1
    PARKIN["PARKIN"] -->|"activates"| COX4I1
    PINK1["PINK1"] -->|"activates"| COX4I1
    XBP1["XBP1"] -->|"activates"| COX4I1
    ATF3["ATF3"] -->|"activates"| COX4I1
    TOMM20["TOMM20"] -->|"activates"| COX4I1

Outgoing (215)

Target	Relation	Type	Str
oxidative phosphorylation	involved_in	pathway	0.90
OXPHOS	involved_in	pathway	0.90
ATP synthesis	suppresses	process	0.80
cytochrome_c_oxidase	encodes	protein	0.80
ubiquitin-proteasome	participates_in	pathway	0.70
autophagy pathway	participates_in	pathway	0.70
ALS	protects_against	disease	0.65
Aging	activates	disease	0.65
Aging	associated_with	disease	0.65
Neurodegeneration	protects_against	disease	0.65
Inflammation	protects_against	disease	0.65
Cardiovascular	associated_with	disease	0.65
Neuroinflammation	protects_against	disease	0.65
Cardiovascular	inhibits	disease	0.65
Ms	inhibits	disease	0.65
Aging	inhibits	disease	0.65
Als	protects_against	disease	0.65
Ischemia	associated_with	disease	0.65
Cardiovascular	activates	disease	0.65
Cardiovascular	degrades	disease	0.65
Aging	degrades	disease	0.65
neurodegeneration	associated_with	disease	0.63
neural stem cells	regulates	cell_type	0.60
PRKN	associated_with	gene	0.60
GRIA2	activates	gene	0.60
PRKN	activates	gene	0.60
HSPD1	activates	gene	0.60
GAPDH	associated_with	gene	0.60
MAP1LC3A	associated_with	gene	0.60
PARKIN	associated_with	gene	0.60
SLC2A1	inhibits	gene	0.60
NRXN3	inhibits	gene	0.60
PRKAA1	inhibits	gene	0.60
BDNF	inhibits	gene	0.60
SOD1	inhibits	gene	0.60
NLGN2	inhibits	gene	0.60
CYCS	inhibits	gene	0.60
PDHA1	inhibits	gene	0.60
SOD2	protects_against	gene	0.60
CAT	inhibits	gene	0.60
SLC2A2	inhibits	gene	0.60
Autophagy	activates	pathway	0.60
Mitophagy	associated_with	pathway	0.60
Proteasome	associated_with	pathway	0.60
LC3B	activates	gene	0.60
Oxidative Stress	inhibits	pathway	0.60
AGING	inhibits	gene	0.60
Neuron	inhibits	cell_type	0.60
PKM	inhibits	gene	0.60
Bdnf	inhibits	protein	0.60

Incoming (110)

Source	Relation	Type	Str
h-fd1562a3	targets	hypothesis	0.90
Melamine	downregulates	compound	0.90
PS-COOH	downregulates	compound	0.90
PM10	downregulates	compound	0.85
melamine	downregulates	compound	0.85
Ps-Cooh	downregulates	compound	0.80
MITOPHAGY	inhibits	gene	0.60
PKM	inhibits	gene	0.60
ATG7	interacts_with	entity	0.60
BCL2L13	interacts_with	entity	0.60
BNIP3L	interacts_with	entity	0.60
GENES	inhibits	gene	0.60
CREB	protects_against	gene	0.60
GLUT4	protects_against	gene	0.60
OXIDATIVE STRESS	inhibits	gene	0.60
PER	protects_against	gene	0.60
NEURODEGENERATION	protects_against	gene	0.60
NEURODEGENERATIVE DISORDERS	protects_against	gene	0.60
NEUROINFLAMMATION	protects_against	gene	0.60
ATG7	protects_against	gene	0.60
BCL2	protects_against	gene	0.60
BNIP3L	protects_against	gene	0.60
BCL2L13	protects_against	gene	0.60
APOPTOSIS	associated_with	gene	0.60
MITOPHAGY	degrades	gene	0.60
MITOPHAGY	activates	gene	0.60
AMPK	activates	gene	0.60
UBIQUITIN	associated_with	gene	0.60
UBIQUITIN	activates	gene	0.60
HSP60	activates	gene	0.60
OPTINEURIN	activates	gene	0.60
NRXN3	inhibits	gene	0.60
LC3B	activates	gene	0.60
BDNF	associated_with	gene	0.60
CAT	associated_with	gene	0.60
NIX	associated_with	gene	0.60
GSK3B	inhibits	gene	0.60
INFLAMMATION	protects_against	gene	0.60
PDHA1	inhibits	gene	0.60
BDNF	inhibits	gene	0.60
PRKAA1	inhibits	gene	0.60
SOD2	protects_against	gene	0.60
SOD1	inhibits	gene	0.60
NLGN2	inhibits	gene	0.60
PSD95	protects_against	gene	0.60
CYCS	inhibits	gene	0.60
CAT	inhibits	gene	0.60
SLC2A2	inhibits	gene	0.60
SLC2A1	inhibits	gene	0.60
COX15	inhibits	gene	0.60

Targeting Hypotheses (1)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Near-infrared light therapy stimulates COX4-dependent mitoch	0.742	neurodegeneration	Mitochondrial transfer between astrocyte

Mentioning Analyses (1)

Scientific analyses that reference this entity

Mitochondrial transfer between astrocytes and neurons

neurodegeneration | 2026-04-01 | 7 hypotheses Top: 0.822

Experiments (10)

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
Proposed experiment from debate on Mitochondrial transfer between astr	falsification	Neurodegeneration	0.400	0.50	cell_line	proposed	$80,000
Mechanism: Selective Vulnerability of Dopaminergic Neurons in Parkinso	validation	Parkinson's Disease	0.400	0.50	human	proposed	$3,000,000
Ferroptosis Validation in Parkinson's Disease	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$6,550,000
GLP-1 Agonist Neuroprotection Mechanism in PD	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$6,550,000
Cytochrome Therapeutics	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$5,460,000
Peroxisomal Dysfunction Validation in Parkinson's Disease	validation	Parkinson's Disease	0.400	0.50	human	proposed	$2,280,000
Prodromal Parkinson's Disease Biomarker Development — Early Detection	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$6,550,000
Synaptic Mitochondrial Resilience Enhancement for 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
Increased mitophagy protects cochlear hair cells from aminoglycoside-induced dam [PMID:35471096]	Zhang Y, Fang Q, Wang H, Qi J, Sun S, Li	Autophagy	2023	1
BNIP3L/NIX degradation leads to mitophagy deficiency in ischemic brains. [PMID:32722981]	Wu X, Zheng Y, Liu M, Li Y, Ma S, Tang W	Autophagy	2021	1
SIRT5 regulation of ammonia-induced autophagy and mitophagy. [PMID:25700560]	Polletta L, Vernucci E, Carnevale I, Arc	Autophagy	2015	1
PRKAB2 as a tumor suppressor in renal cell carcinoma: inhibiting mitophagy via t [PMID:41612594]	Chen K, Zhang Y, Ruan H, Wei Z, Wang K,	Autophagy	2026	0
ROS-responsive nanogels for brain targeted delivery of icariin in the treatment [PMID:41197818]	["Li X", "Huang J", "Zhou Y", "Chen X",	International journal of pharm	2026	0
Single-Cell RNA Sequencing and Network Pharmacology Reveal the Potential Role of [PMID:41610872]	["Niu J", "Wang L", "Qi J", "Lu G"]	The journal of gene medicine	2026	0
Integrated Profiling of DEHP-Induced Hippocampal Neurotoxicity in Adult Female R [PMID:41600627]	Bai J, Li J, Tang L, Sun W, Gao F, Zhang	Toxics	2026	0
Functional and Molecular Characterization of Melamine-Induced Disruption of Huma [PMID:41596180]	["Luongo F", "Annunzi E", "Ponchia R", "	Antioxidants (Basel, Switzerla	2026	0
Exploring the lactate-metabolism related characteristics during the development [PMID:41815173]	Wang C, Zhang R, Li S, Kang Z, Xia S, Li	Translational cancer research	2026	0
Developmental toxicity of carboxylated microplastics in zebrafish mediated by mi [PMID:41265820]	["Li Y", "Ni Y", "Dong C", "Zhang J", "G	Environmental pollution (Barki	2026	0
Complex IV deficiency due to COX4I1 deep intronic and de novo variants results i [PMID:41203052]	Ugarteburu O, Farré-Tarrats L, Muñoz-Puj	Mitochondrion	2026	0
Bionanoconjugates in Neurodegeneration: Peptide-Nanoparticle Alliances for Next- [PMID:41199078]	["Ranjitha V", "Kumar A", "Kaalappa P"]	Pharmaceutical research	2025	0
810-nm Photobiomodulation Evokes Glutamate Release in Normal and Rotenone-Dysfun [PMID:39851493]	["Ravera S", "Farsetti E", "Maura G", "M	Cells	2025	0
Mongolian medicine Wulanwendusu-11 alleviates myocardial ischemia-reperfusion in [PMID:41586357]	["Wuyunsiqin", "Bai T", "Yang D", "Hashe	Frontiers in microbiology	2025	0
Near-Infrared Photoimmunotherapy in Brain Tumors-An Unexplored Frontier. [PMID:40430568]	["Yamaguchi H", "Okada M", "Otani T", "O	Pharmaceuticals (Basel, Switze	2025	0
Evaluation of local and systemic photobiomodulation in only single-implant inser [PMID:40531278]	["Pucca D", "Pinheiro S"]	Oral and maxillofacial surgery	2025	0
Comparison of the efficacy of 12 interventions in the treatment of diabetic foot [PMID:40821981]	["Hu X", "Meng H", "Liang J", "An H", "Z	PeerJ	2025	0
Exosomes as nanocarriers for brain-targeted delivery of therapeutic nucleic acid [PMID:40533746]	["Sanadgol N", "Abedi M", "Hashemzaei M"	Journal of nanobiotechnology	2025	0
Dose-dependent effects of transcranial photobiomodulation on brain temperature i [PMID:39370461]	["Weerasekera A", "Coelho D", "Ratai E",	Lasers in medical science	2024	0
Mystery of gamma wave stimulation in brain disorders. [PMID:39695746]	["Deng Q", "Wu C", "Parker E", "Zhu J",	Molecular neurodegeneration	2024	0

Debates (1)

Multi-agent debates referencing this entity

Mitochondrial transfer between astrocytes and neurons

closed · Rounds: 4 · Score: 0.95 · 2026-04-06

Related Research

Hypotheses and analyses mentioning COX4I1 in their description or question text

No additional research found