CLOCK

Chr 4

clock circadian regulator

Also known as: KAT13D, bHLHe8

NCBI Gene: 9575 ENSG00000134852 UniProt: O15516 OMIM: 601851

The protein encoded by this gene plays a central role in the regulation of circadian rhythms. The protein encodes a transcription factor of the basic helix-loop-helix (bHLH) family and contains DNA binding histone acetyltransferase activity. The encoded protein forms a heterodimer with ARNTL (BMAL1) that binds E-box enhancer elements upstream of Period (PER1, PER2, PER3) and Cryptochrome (CRY1, CRY2) genes and activates transcription of these genes. PER and CRY proteins heterodimerize and repress their own transcription by interacting in a feedback loop with CLOCK/ARNTL complexes. Polymorphisms in this gene may be associated with behavioral changes in certain populations and with obesity and metabolic syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

GeneReviews OMIM Research

GeneReviews OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

4090

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.25

LOEUF· LoF intol.

LOF

Mechanism· predicted

📖

GeneReview available — CLOCK

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.25LOEUF

pLI 1.000

Z-score 5.87

OE 0.13 (0.07–0.25)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.83Z-score

OE missense 0.76 (0.69–0.83)

334 obs / 442.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.13 (0.07–0.25)

0≤0.351.4

Missense OE?0.76 (0.69–0.83)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 7 / 53.1Missense obs/exp: 334 / 442.1Syn Z: 0.58

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

CLOCK · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

📖

GeneReview available — CLOCK

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Sleep QualityMeal TimingCircadian Rhythm

This Trial Examines How Last Meal Composition and Timing Affect Sleep Quality and Circadian Gene Expression Among Medical Residents. Recruitment Not Yet Started; Study Begins Dec 2025 and Ends Dec 2026.

ENROLLING BY INVITATION

NCT07339592Phase NAUniversity of JordanStarted 2025-12-01

High-Carbohydrate Last MealHigh-Protein Last MealBalanced Standard Dinner

Overweight , ObesityAntioxidant Status

Impact of Antioxidant-rich Supplementation on Skin Carotenoids Status, Antioxidant Status and Cardiometabolic Health in Overweight and Obese Individuals

NOT YET RECRUITING

NCT07748468Phase NANational University of SingaporeStarted 2026-08-15

Antioxidant-rich supplementation ElementAntioxidant-rich supplementation Optimal

Polymorphism, Restriction Fragment LengthObesity

Weight Loss and CLOCK 3111T/C Polymorphism

RECRUITING

NCT05750732Hacettepe UniversityStarted 2023-02-20

Weight loss diet

Parkinson DiseaseREM Sleep Behavior Disorder

Implementing a National Biobank of PD With WGS and Functional Assessment of Polygenic Inheritance by iPSC Technology

RECRUITING

NCT05721911IRCCS San RaffaeleStarted 2023-10-30