gene

CLOCK

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about CLOCK: 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.

1359Connections

25Hypotheses

16Analyses

50Outgoing

50Incoming

13Experiments

20Debates

Summary

CLOCK is a gene implicated in neurodegeneration research. Key relationships include: activates, regulates, associated with. Associated with ALS, Aging, Als. Connected to 641 entities in the SciDEX knowledge graph.

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🧬 Gene Info

Gene Symbol	CLOCK
Full Name	Circadian Locomotor Output Cycles Kaput
Chromosome	4q12
Protein Type	Transcription Factor
Target Class	Transcription Factor
Function	CLOCK is a bHLH-PAS transcription factor that functions as the master regulator of the circadian clock.
Mechanism of Action	Modulation of circadian transcriptional activity through protein-protein interaction disruption
Druggability	Low (0.35)
Clinical Stage	Approved
Pathways	Akt, Amyloid, Apoptosis, Autophagy, CIRCADIAN_RHYTHM
UniProt ID	O15516
NCBI Gene ID	9609
Ensembl ID	ENSG00000132266
OMIM	601851
GeneCards	CLOCK
Human Protein Atlas	CLOCK
Associated Diseases	aging, Als, Alzheimer
Known Drugs/Compounds	nicotinamide
Interactions	ACETYL-COA, Actin, AGING, AHR, AKT, ALOX12
SciDEX Target	View Target Profile (10 clinical trials)
SciDEX Hypotheses	Circadian Clock-Autophagy Synchronization Temporal Decoupling via Circadian Clock Reset Circadian-Synchronized Microbiome Intervention (+5 more)
KG Connections	1357 knowledge graph edges
Databases	GeneCards HPA STRING

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

📄 Experimental Structure

4F3L — X-ray / Cryo-EM

🔮 AI Predicted Structure

O15516 — AlphaFold

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

Wiki Pages (3)

Knowledge base pages for this entity

Canonical Page

Pathway Diagram

flowchart TD
    CLOCK(["CLOCK"])
    Cancer["Cancer"]
    Aging["Aging"]
    AGING(["AGING"])
    Als["Als"]
    METABOLIC_HEALTH["METABOLIC HEALTH"]
    autophagy["autophagy"]
    mitophagy["mitophagy"]
    mitochondrial_autophagy["mitochondrial autophagy"]
    cell_survival("cell survival")
    BMAL1(["BMAL1"])
    Period_genes(["Period genes"])
    Cryptochrome_genes(["Cryptochrome genes"])
    Circadian_Rhythms("Circadian Rhythms")
    Cellular_Metabolism("Cellular Metabolism")

    CLOCK -->|"associated with"| Cancer
    CLOCK -->|"associated with"| Aging
    CLOCK -->|"associated with"| AGING
    CLOCK -->|"activates"| Als
    CLOCK -->|"associated with"| Als
    CLOCK -->|"regulates"| METABOLIC_HEALTH
    CLOCK -->|"regulates"| autophagy
    CLOCK -->|"regulates"| mitophagy
    CLOCK -->|"regulates"| mitochondrial_autophagy
    CLOCK -->|"regulates"| cell_survival
    CLOCK -->|"interacts with"| BMAL1
    CLOCK -->|"activates"| Period_genes
    CLOCK -->|"activates"| Cryptochrome_genes
    CLOCK -->|"involved in"| Circadian_Rhythms
    CLOCK -->|"regulates"| Cellular_Metabolism

    style CLOCK fill:#006494,stroke:#4fc3f7,stroke-width:3px,color:#e0e0e0

Outgoing (951)

Target	Relation	Type	Str
CLOCK	encodes	protein	0.00
Aging	associated_with	disease	1.00
Cancer	associated_with	disease	1.00
AGING	associated_with	gene	1.00
Circadian Clock	component_of	pathway	0.96
Als	activates	disease	0.95
circadian rhythm	drives	process	0.95
Als	associated_with	disease	0.95
METABOLIC HEALTH	regulates	entity	0.95
Immune Cell Function	regulates	process	0.95
Circadian Rhythm Regulation	involved_in	process	0.90
Cellular Metabolism	regulates	process	0.90
Circadian Rhythms	involved_in	process	0.90
Cryptochrome genes	activates	gene	0.90
adiposity	modulates	phenotype	0.90
Circadian rhythm	regulates	pathway	0.90
LIPID METABOLISM	regulates	entity	0.90
Period genes	activates	gene	0.90
Circadian Gene Expression	involved_in	process	0.90
mitochondrial autophagy	regulates	pathway	0.90
Type 2 Diabetes Mellitus	associated_with	disease	0.90
autophagy	regulates	pathway	0.90
cell survival	regulates	phenotype	0.90
mitophagy	regulates	pathway	0.90
circadian rhythm disruption	involved_in	process	0.90
Circadian Rhythm Regulation	regulates	process	0.90
BMAL1	interacts_with	gene	0.90
CANCER	associated_with	gene	0.90
Obesity	activates	disease	0.85
CIRCADIAN OUTPUT GENES	regulates	gene	0.85
circadian regulation	participates_in	pathway	0.85
CELL DIVISION	modulates	entity	0.85
FOOD INTAKE	regulates	entity	0.85
Suprachiasmatic Nucleus	expressed_in	brain_region	0.85
PHOSPHOLIPID METABOLISM	regulates	entity	0.85
ADIPOSITY	regulates	entity	0.85
PARKINSON'S DISEASE	associated_with	entity	0.85
DNA REPAIR	modulates	pathway	0.85
ALZHEIMER'S DISEASE	associated_with	entity	0.85
Inflammation	regulates	disease	0.85
tumor microenvironment	modulates	process	0.80
Insomnia	associated_with	disease	0.80
Circadian Rhythm	associated_with	process	0.80
ATG7	regulates	gene	0.80
BECN1	regulates	gene	0.80
Circadian Rhythms	regulates	pathway	0.80
circadian rhythm	part_of	pathway	0.80
Circadian Rhythms	regulates	process	0.80
p65	phosphorylates	protein	0.80
DIABETES	associated_with	disease	0.80

Incoming (408)

Source	Relation	Type	Str
CLOCK	encodes	gene	0.00
h-019ad538	targets	hypothesis	0.90
h-828b3729	targets	hypothesis	0.90
h-0e0cc0c1	targets	hypothesis	0.90
h-b7898b79	targets	hypothesis	0.90
h-de52344d	targets_gene	hypothesis	0.90
Chronic Sleep Deprivation	causes	process	0.90
CK1D	phosphorylates	protein	0.90
BMAL1	associated_with	gene	0.90
OBSTRUCTIVE SLEEP APNEA SYNDROME	modulates	entity	0.85
Obstructive Sleep Apnea Syndrome	modulates	disease	0.75
OSAS	modulates	disease	0.75
BMAL1	expressed_in	gene	0.70
CRY2	expressed_in	gene	0.70
AGING	activates	gene	0.70
AGING	associated_with	gene	0.70
high-fat diet	regulates	drug	0.70
PER1	expressed_in	gene	0.70
GBM	associated_with	gene	0.70
APP/PS1	activates	gene	0.70
CK1_epsilon	regulates	protein	0.70
GSK3B	regulates	protein	0.70
PER	interacts_with	gene	0.70
CK1_delta	regulates	protein	0.70
BMAL1	activates	gene	0.70
nicotinamide	targets	drug	0.65
ATG7	activates	gene	0.65
ATG5	activates	gene	0.65
GBM	therapeutic_target	gene	0.60
HCRTR2	regulates	gene	0.60
HCRTR1	regulates	gene	0.60
CLOCK GENE	stabilizes	gene	0.60
APP	activates	gene	0.60
CHI3L1	regulates	gene	0.60
GAPDH	activates	gene	0.60
LOX	therapeutic_target	gene	0.60
PTEN	therapeutic_target	gene	0.60
GENES	inhibits	gene	0.60
HIF-1Α	activates	gene	0.60
EXERCISE	associated_with	gene	0.60
DNA	biomarker_for	gene	0.60
RNA	expressed_in	gene	0.60
NEURODEGENERATION	regulates	gene	0.60
DNA	associated_with	gene	0.60
GABA	associated_with	gene	0.60
ALZHEIMER DISEASE	activates	gene	0.60
APP	expressed_in	gene	0.60
NEURODEGENERATIVE DISEASES	protects_against	gene	0.60
NF-ΚB	activates	gene	0.60
DNA	encodes	gene	0.60

Targeting Hypotheses (25)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Circadian Clock-Autophagy Synchronization	0.763	neurodegeneration	Sleep disruption as cause and consequenc
HDAC3-Selective Inhibition for Clock Reset	0.710	neurodegeneration	Epigenetic clocks and biological aging i
Gamma entrainment corrects AD-related clock gene dysregulati	0.676	Alzheimer's disease	Gamma entrainment therapy to restore hip
PD genetic aging variants accelerating cell-type-specific ep	0.626	neurodegeneration	Genetic Aging Landscape Variants and Epi
Temporal Decoupling via Circadian Clock Reset	0.543	neurodegeneration	Microglia-astrocyte crosstalk amplificat

Circadian Clock Epigenetic Desynchronization Window	0.524	neurodegeneration	What is the optimal therapeutic window d
DNA Methylation Clock Drift at Glial Promoters	0.480	neurodegeneration	Comparative epigenetic signatures: DNA m
Clock Gene-Mediated Microglial Reprogramming	0.455	chronobiology	Can circadian interventions reverse micr
BMAL1-CLOCK regulation of miR-143/145 locks microglia into g	0.389	neuroinflammation	Do microglia actually switch between gly
TDP-43 Pathology Creates a Distinct Epigenetic Clock "Signat	0.387	-	Epigenetic clocks as biomarkers for Alzh
Ethnic and Metabolic Epigenetic Clock Divergence Explains Di	0.376	-	Epigenetic clocks as biomarkers for Alzh
Epigenetic Age Acceleration Moderates the Amyloid-to-Tau Con	0.343	-	Epigenetic clocks as biomarkers for Alzh
Multi-Clock Ensemble Discordance as a Parkinson's Disease Pr	0.323	-	Epigenetic clocks as biomarkers for Alzh
Epigenetic Clock Biomarker-Guided Combination Therapy	0.000	-	Epigenetic clocks and biological aging i
Multi-Cell Type Aging Clock Synchronization	0.000	-	Cell type vulnerability in Alzheimer's D
Timed Melatonin Administration Exploits Circadian Vulnerabil	0.000	-	Microglia-astrocyte crosstalk amplificat
Epigenetic Clock Reversal Through Targeted DNA Demethylation	0.000	-	Epigenetic clocks and biological aging i
Temporal Modulation of Microglial Circadian Rhythms	0.000	-	Synaptic pruning by microglia in early A
Epigenetic Clock Reversal via Metabolic Oscillator Coupling	0.000	-	Epigenetic reprogramming in aging neuron
CX3CR1-Cre-Driven BMAL1 Deletion as Microglial Circadian Clo	0.000	-	Can circadian interventions selectively
Circadian Rhythm Disruption via Microbiome-Clock Axis	0.000	-	Does reduced Prevotellaceae abundance ca
Circadian Rhythm Synchronization via Microbiome Entrainment	0.000	-	Gut-Brain Axis Therapeutics for Alzheime
Temporal Epigenetic Clock Synchronization Therapy	0.000	-	Epigenetic clocks and biological aging i
Temporal Epigenetic Switch Points (TESP)	0.000	-	Do different priming stimuli require dis
Circadian-Synchronized Microbiome Intervention	0.000	-	What are the mechanisms by which gut mic

Mentioning Analyses (16)

Scientific analyses that reference this entity

Does reduced Prevotellaceae abundance cause PD pathology or result from it?

neurodegeneration | 2026-04-11 | 7 hypotheses

What neural circuits encode and maintain multi-generational migratory route memo

spatial memory | 2026-04-08 | 7 hypotheses Top: 0.455

Do different priming stimuli require distinct therapeutic approaches or share co

immunology | 2026-04-08 | 8 hypotheses Top: 0.380

Can circadian interventions reverse microglial priming independent of sleep disr

chronobiology | 2026-04-08 | 7 hypotheses Top: 0.455

Neuroinflammation and microglial priming in early AD

neurodegeneration | 2026-04-04 | 7 hypotheses Top: 0.710

Experiments (13)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
Circadian gene expression effects of SD vs ketamine	exploratory	depression	0.950	0.00	C57BL/6J mice	proposed	N/A
CLOCK/BMAL1 regulation of ICC autophagy in GERD model	exploratory	gastroesophageal reflux diseas	0.900	0.00	primary esophageal interstitia	proposed	N/A
Proposed experiment from debate on Astrocytes adopt A1 (neurotoxic) an	falsification	Neurodegeneration	0.400	0.50	cell_line	proposed	$80,000
Proposed experiment from debate on Epigenetic clocks and biological ag	falsification	Neurodegeneration	0.400	0.50	cell_line	proposed	$100,000
Circadian-Vascular-Metabolic Syndrome (CVMS) Intervention Trial	clinical	Neurodegeneration	0.400	0.50	human	proposed	$3,900,000
Experiment Index	validation	Neurodegeneration	0.400	0.50	human	proposed	$2,280,000
Macroautophagy Dysfunction in PD - Experiment Design	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$5,460,000
N-of-1 Clinical Trial Design for CBS/PSP	clinical	ALS	0.400	0.50	human	proposed	$5,460,000
Normal Aging to Alzheimer's Disease Transition Trigger — Identifying t	validation	Alzheimer's Disease	0.400	0.50	human	proposed	$2,280,000
Proposed experiment from debate on Microglia activate astrocytes via I	falsification	Neurodegeneration	0.400	0.50	cell_line	proposed	$100,000
CRISPR Gene Correction Approaches for CBS/PSP	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$6,550,000
Epigenetic Dysregulation in Huntington's Disease — Therapeutic Targeti	validation	Neurodegeneration	0.400	0.50	human	completed	$3,000,000
Neural Oscillation Dysfunction Validation in Parkinson's Disease	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$5,460,000

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
Circadian Rhythms in Gastroenterology: The Biological Clock's Impact on Gut Heal [PMID:40588189]	Bishehsari F, Post Z, Swanson GR, Keshav	Gastroenterology	2025	1
From geroscience to precision geromedicine: Understanding and managing aging. [PMID:40250404]	Kroemer G, Maier AB, Cuervo AM, Gladyshe	Cell	2025	1
Circadian disruption, clock genes, and metabolic health. [PMID:39007272]	Schrader LA, Ronnekleiv-Kelly SM, Hogene	J Clin Invest	2024	1
Biomarkers of aging for the identification and evaluation of longevity intervent [PMID:37657418]	Moqri M, Herzog C, Poganik JR, Biomarker	Cell	2023	1
Effect of Electronic Prescribing Compared to Paper-Based (Handwritten) Prescribi [PMID:34433219]	Aluga D, Nnyanzi LA, King N, Okolie EA,	Appl Clin Inform	2021	1
Improved T-cell Receptor Diversity Estimates Associate with Survival and Respons [PMID:33177107]	Bortone DS, Woodcock MG, Parker JS, Vinc	Cancer Immunol Res	2021	1
Clocks, cancer, and chronochemotherapy. [PMID:33384351]	Sancar A, Van Gelder RN	Science	2021	1
Structurally diverse sesquiterpenoids from the aerial parts of Artemisia annua ( [PMID:32891001]	Qin DP, Li HB, Pang QQ, Huang YX, Pan DB	Bioorg Chem	2020	1
Mycobacterium Abscessus: A Rare Cause of Peri-Ductal Mastitis in Endemic Regions [PMID:32580856]	Shaikh A, Vohra LM	J Coll Physicians Surg Pak	2020	1
Spatiotemporal profile of postsynaptic interactomes integrates components of com [PMID:28671696]	Li J, Zhang W, Yang H, Howrigan DP, Wilk	Nat Neurosci	2017	1
Core Concept: The Internet of Things and the explosion of interconnectivity. [PMID:27702874]	Ornes S	Proc Natl Acad Sci U S A	2016	1
The scanning ion conductance microscope for cellular physiology. [PMID:23086993]	Lab MJ, Bhargava A, Wright PT, Gorelik J	Am J Physiol Heart Circ Physio	2013	1
Telomere dysfunction causes sustained inflammation in chronic obstructive pulmon [PMID:21885626]	Amsellem V, Gary-Bobo G, Marcos E, Maitr	Am J Respir Crit Care Med	2011	1
Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's diseas [PMID:21102463]	Franke A, McGovern DP, Barrett JC, Wang	Nat Genet	2010	1
Precision Neurodegeneration: Integrating Molecular Mechanisms, Biomarkers, and T [PMID:41833042]	["Lyu G", "Li D"]	CNS & neurological disorders d	2026	0
HDAC3 Preserves the primordial follicle reserve by epigenetically suppressing fe [PMID:41803516]	["Chen Z", "Guo J", "Gao M", "Wang H", "	Cellular and molecular life sc	2026	0
Epigenetics and the gut-brain axis: Insights into DNA methylation, aging, and Al [PMID:41886887]	Kumar V, Shukla R, Gangani S, Joseph R,	The Journal of pharmacology an	2026	0
Effects of circadian rhythms on antimicrobial peptide concentrations in lactatin [PMID:41923233]	Liang ZL, Nii T, Sugino T, Isobe N	BMC veterinary research	2026	0
Circadian synchronization between diet and gut microbiota in modulating host's h [PMID:41914045]	["Ma J", "Zhen Y", "Weng Y", "Lin J", "Z	Gut microbes	2026	0
Randomized controlled trial of resistance exercise and brain aging clocks. [PMID:41665740]	["Gonzalez-Gomez R", "Demnitz N", "Coron	GeroScience	2026	0

Debates (20)

Multi-agent debates referencing this entity

Extended debate: Metabolic Reprogramming to Reverse Senescence

closed · Rounds: 6 · Score: 0.95 · 2026-04-27

Hypothesis debate: Metabolic Reprogramming to Reverse Senescence

closed · Rounds: 4 · Score: 0.44 · 2026-04-27

Hypothesis debate: SASP Modulation Rather Than Cell Elimination

closed · Rounds: 4 · Score: 0.50 · 2026-04-26

Hypothesis debate: Metabolic Reprogramming to Reverse Senescence

closed · Rounds: 4 · Score: 0.50 · 2026-04-26

Hypothesis debate: Metabolic Reprogramming to Reverse Senescence

closed · Rounds: 4 · Score: 0.50 · 2026-04-26

Should metabolic reprogramming via SIRT1/NAD+/PGC-1alpha axis be prioritized to

closed · Rounds: 4 · Score: 0.81 · 2026-04-23

Investigate the therapeutic potential of clearing senescent cells (senolytics) t

closed · Rounds: 4 · Score: 0.75 · 2026-04-16

How does microglial priming contribute to early Alzheimer's disease pathology? F

closed · Rounds: 4 · Score: 0.80 · 2026-04-12

Investigate mechanistic links between early microglial priming states, neuroinfl

closed · Rounds: 4 · Score: 0.86 · 2026-04-12

Investigate mechanistic links between early microglial priming states, neuroinfl

closed · Rounds: 5 · Score: 0.95 · 2026-04-12

Related Research

Hypotheses and analyses mentioning CLOCK in their description or question text

CLOCK

Understanding Entity Pages

Summary

Wiki Pages (3)

Blood p-Tau217 as a Clock for Alzheimer's Disease Onset Timing

CLOCK Gene

CLOCK Protein

Pathway Diagram

Outgoing (951)

Incoming (408)

Targeting Hypotheses (25)

Mentioning Analyses (16)

Does reduced Prevotellaceae abundance cause PD pathology or result from it?

What neural circuits encode and maintain multi-generational migratory route memo

Do different priming stimuli require distinct therapeutic approaches or share co

Can circadian interventions reverse microglial priming independent of sleep disr

Neuroinflammation and microglial priming in early AD

Neuroinflammation and microglial priming in early Alzheimer's Disease

Senescent cell clearance as neurodegeneration therapy

Metabolic reprogramming in neurodegenerative disease

Sleep disruption as cause and consequence of neurodegeneration

Neuroinflammation resolution mechanisms and pro-resolving mediators

Digital biomarkers and AI-driven early detection of neurodegeneration

Autophagy-lysosome pathway convergence across neurodegenerative diseases

Microglia-astrocyte crosstalk amplification loops in neurodegeneration

Microglia-astrocyte crosstalk amplification loops in neurodegeneration

Digital biomarkers and AI-driven early detection of neurodegeneration

Sleep disruption as cause and consequence of neurodegeneration

Experiments (13)

Related Papers (20)

Debates (20)

Extended debate: Metabolic Reprogramming to Reverse Senescence

Hypothesis debate: Metabolic Reprogramming to Reverse Senescence

Hypothesis debate: SASP Modulation Rather Than Cell Elimination

Hypothesis debate: Metabolic Reprogramming to Reverse Senescence

Hypothesis debate: Metabolic Reprogramming to Reverse Senescence

Should metabolic reprogramming via SIRT1/NAD+/PGC-1alpha axis be prioritized to

Investigate the therapeutic potential of clearing senescent cells (senolytics) t

How does microglial priming contribute to early Alzheimer's disease pathology? F

Investigate mechanistic links between early microglial priming states, neuroinfl

Investigate mechanistic links between early microglial priming states, neuroinfl

Related Research

Circadian Clock Epigenetic Desynchronization Window

DNA Methylation Clock Drift at Glial Promoters

Clock Gene-Mediated Microglial Reprogramming

BMAL1-CLOCK regulation of miR-143/145 locks microglia into glycolytic priming

TDP-43 Pathology Creates a Distinct Epigenetic Clock "Signature Divergence" Dete

Ethnic and Metabolic Epigenetic Clock Divergence Explains Disparate AD Risk — Hi

Epigenetic Age Acceleration Moderates the Amyloid-to-Tau Conversion Cascade — A

Multi-Clock Ensemble Discordance as a Parkinson's Disease Prodrome Detector — Ep

Epigenetic Clock Biomarker-Guided Combination Therapy

Multi-Cell Type Aging Clock Synchronization

Timed Melatonin Administration Exploits Circadian Vulnerability of Microglial Ac

Epigenetic Clock Reversal Through Targeted DNA Demethylation

Temporal Modulation of Microglial Circadian Rhythms

Epigenetic Clock Reversal via Metabolic Oscillator Coupling

CX3CR1-Cre-Driven BMAL1 Deletion as Microglial Circadian Clock Ablation