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.

1348Connections

10Hypotheses

10Analyses

50Outgoing

50Incoming

13Experiments

16Debates

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
KG Connections	1347 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 (940)

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

Incoming (408)

Source	Relation	Type	Str
Chronic Sleep Deprivation	causes	process	0.90
h-828b3729	targets	hypothesis	0.90
h-019ad538	targets	hypothesis	0.90
h-de52344d	targets_gene	hypothesis	0.90
h-b7898b79	targets	hypothesis	0.90
CK1D	phosphorylates	protein	0.90
BMAL1	associated_with	gene	0.90
h-0e0cc0c1	targets	hypothesis	0.90
OBSTRUCTIVE SLEEP APNEA SYNDROME	modulates	entity	0.85
OSAS	modulates	disease	0.75
Obstructive Sleep Apnea Syndrome	modulates	disease	0.75
high-fat diet	regulates	drug	0.70
PER1	expressed_in	gene	0.70
CRY2	expressed_in	gene	0.70
GBM	associated_with	gene	0.70
AGING	associated_with	gene	0.70
PER	interacts_with	gene	0.70
AGING	activates	gene	0.70
APP/PS1	activates	gene	0.70
BMAL1	activates	gene	0.70
BMAL1	expressed_in	gene	0.70
ATG5	activates	gene	0.65
ATG7	activates	gene	0.65
nicotinamide	targets	drug	0.65
PTEN	inhibits	gene	0.60
AKT	inhibits	gene	0.60
PER2	expressed_in	gene	0.60
PI3K	inhibits	gene	0.60
MTOR	inhibits	gene	0.60
AKT	expressed_in	gene	0.60
PI3K	regulates	gene	0.60
SIRT1	regulates	gene	0.60
PER2	regulates	gene	0.60
UBIQUITIN	regulates	gene	0.60
UBR5	inhibits	gene	0.60
PER2	inhibits	gene	0.60
FASN	activates	gene	0.60
NFKBIA	activates	gene	0.60
PGC1A	activates	gene	0.60
LPL	activates	gene	0.60
CRY1	expressed_in	gene	0.60
PER2	activates	gene	0.60
NAMPT	regulates	gene	0.60
CRY2	associated_with	gene	0.60
CRY1	regulates	gene	0.60
CRY2	regulates	gene	0.60
NPAS2	associated_with	gene	0.60
PER3	associated_with	gene	0.60
FASN	regulates	gene	0.60
MYD88	inhibits	gene	0.60

Targeting Hypotheses (10)

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
Temporal Decoupling via Circadian Clock Reset	0.543	neurodegeneration	Microglia-astrocyte crosstalk amplificat
Epigenetic Age Acceleration Moderates the Amyloid-to-Tau Con	0.533	-	Epigenetic clocks as biomarkers for Alzh
Circadian Clock Epigenetic Desynchronization Window	0.524	neurodegeneration	What is the optimal therapeutic window d

TDP-43 Pathology Creates a Distinct Epigenetic Clock "Signat	0.483	-	Epigenetic clocks as biomarkers for Alzh
DNA Methylation Clock Drift at Glial Promoters	0.480	neurodegeneration	Comparative epigenetic signatures: DNA m
Ethnic and Metabolic Epigenetic Clock Divergence Explains Di	0.474	-	Epigenetic clocks as biomarkers for Alzh
BMAL1-CLOCK regulation of miR-143/145 locks microglia into g	0.389	neuroinflammation	Do microglia actually switch between gly
Multi-Clock Ensemble Discordance as a Parkinson's Disease Pr	0.377	-	Epigenetic clocks as biomarkers for Alzh

Mentioning Analyses (10)

Scientific analyses that reference this entity

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

neurodegeneration | 2026-04-11 | 0 hypotheses

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

spatial memory | 2026-04-08 | 0 hypotheses

Can circadian interventions reverse microglial priming independent of sleep disr

chronobiology | 2026-04-08 | 0 hypotheses

Neuroinflammation and microglial priming in early Alzheimer's Disease

neurodegeneration | 2026-04-04 | 14 hypotheses Top: 0.651

Senescent cell clearance as neurodegeneration therapy

neurodegeneration | 2026-04-04 | 7 hypotheses Top: 1.000

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	proposed	$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 (16)

Multi-agent debates referencing this entity

Hypothesis debate: SASP Modulation Rather Than Cell Elimination

closed · Rounds: 4 · Score: 0.00 · 2026-04-26

Hypothesis debate: Metabolic Reprogramming to Reverse Senescence

closed · Rounds: 4 · Score: 0.00 · 2026-04-26

Hypothesis debate: Metabolic Reprogramming to Reverse Senescence

closed · Rounds: 4 · Score: 0.00 · 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

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

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

closed · Rounds: 4 · Score: 0.95 · 2026-04-11

Can circadian interventions reverse microglial priming independent of sleep disr

closed · Rounds: 4 · Score: 0.95 · 2026-04-10

The paper describes memory-based migration routes maintained across generations

closed · Rounds: 4 · Score: 0.95 · 2026-04-09

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 (940)

Incoming (408)

Targeting Hypotheses (10)

Mentioning Analyses (10)

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

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

Can circadian interventions reverse microglial priming independent of sleep disr

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

Microglia-astrocyte crosstalk amplification loops in neurodegeneration

Experiments (13)

Related Papers (20)

Debates (16)

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

Investigate mechanistic links between early microglial priming states, neuroinfl

Investigate mechanistic links between early microglial priming states, neuroinfl

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

Can circadian interventions reverse microglial priming independent of sleep disr

The paper describes memory-based migration routes maintained across generations

Related Research

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

DNA Methylation Clock Drift at Glial Promoters

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

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

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