PER1

Chr 17

period circadian regulator 1

Also known as: PER, RIGUI, hPER

NCBI Gene: 5187ENSG00000179094UniProt: O15534

This gene is a member of the Period family of genes and is expressed in a circadian pattern in the suprachiasmatic nucleus, the primary circadian pacemaker in the mammalian brain. Genes in this family encode components of the circadian rhythms of locomotor activity, metabolism, and behavior. This gene is upregulated by CLOCK/ARNTL heterodimers but then represses this upregulation in a feedback loop using PER/CRY heterodimers to interact with CLOCK/ARNTL. Polymorphisms in this gene may increase the risk of getting certain cancers. Alternative splicing has been observed in this gene; however, these variants have not been fully described. [provided by RefSeq, Jan 2014]

247
ClinVar variants
19
Pathogenic / LP
0.00
pLI score
8
Active trials
Clinical Summary— PER1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.
📋
ClinVar Variants
19 Pathogenic / Likely Pathogenic· 191 VUS of 247 total submissions
💊
Clinical Trials
8 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.47LOEUF
pLI 0.000
Z-score 4.73
OE 0.31 (0.21–0.47)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.20Z-score
OE missense 0.98 (0.92–1.04)
751 obs / 766.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.31 (0.21–0.47)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.92–1.04)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.21
0≤1.21.6
LoF obs/exp: 17 / 54.8Missense obs/exp: 751 / 766.4Syn Z: -2.99

ClinVar Variant Classifications

247 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
VUS191
Likely Benign25
Benign12
19
Pathogenic
191
VUS
25
Likely Benign
12
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
19
0
19
Likely Pathogenic
0
0
0
0
0
VUS
0
179
12
0
191
Likely Benign
0
11
1
13
25
Benign
0
1
3
8
12
Total01913521247

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PER1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
FOXA3 induction under endoplasmic reticulum stress contributes to non-alcoholic fatty liver disease.
Liu C et al.·J Hepatol
2021
Chemical perturbations reveal that RUVBL2 regulates the circadian phase in mammals.
Ju D et al.·Sci Transl Med
2020
Disrupting Circadian Rhythm via the PER1-HK2 Axis Reverses Trastuzumab Resistance in Gastric Cancer.
Wang J et al.·Cancer Res
2022
Clinical Chronobiology: Circadian Rhythms in Health and Disease.
Tomatsu S et al.·Semin Neurol
2025Review
Chi3l1/YKL-40 is controlled by the astrocyte circadian clock and regulates neuroinflammation and Alzheimer's disease pathogenesis.
Lananna BV et al.·Sci Transl Med
2020
Quercetin-Loaded Bioglass Injectable Hydrogel Promotes m6A Alteration of Per1 to Alleviate Oxidative Stress for Periodontal Bone Defects.
Zhu H et al.·Adv Sci (Weinh)
2024
Discrete placental gene expression signatures accompany diabetic disease classifications during pregnancy.
Barrozo ER et al.·Am J Obstet Gynecol
2025
Human mood disorder risk gene Synaptotagmin-14 contributes to mania-like behaviors in mice.
Zhang Y et al.·Mol Psychiatry
2025
Experimental and clinical aspects of melatonin and clock genes in diabetes.
Peschke E et al.·J Pineal Res
2015Review
Circadian rhythm in gastrointestinal cancer: clinical applications and future perspectives.
Han J et al.·Ann Med
2025Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Obesity Type I and IIObesity and Overweight

Metabolic Investigation, Physical Performance, Physical Training At Different Times of the Day in Obese Women

ACTIVE NOT RECRUITING
NCT06601660Phase NAState University of Minas GeraisStarted 2024-09-16
Morning Physical TrainingNight Physical TrainingNo intervention
Mantle Cell LymphomaRefractory Lymphoma

Avo In R/R And Previously Untreated MCL

RECRUITING
NCT04855695Phase PHASE1, PHASE2Austin I KimStarted 2021-07-02
AcalabrutinibVenetoclaxObinutuzumab
Newly Diagnosed Multiple Myeloma

Expression-linked and R-ISS-adapted Stratification for First Line Therapy in Multiple Myeloma Patients

RECRUITING
NCT05665140Phase PHASE2, PHASE3University Hopsital Schleswig Holstein Campus LübeckStarted 2023-02-03
IsatuximabLenalidomideBortezomib
Congenital Adrenal Hyperplasia (CAH)

Fertility And Sexual Function In CAH: CALLIOPE

RECRUITING
NCT07099456University of Roma La SapienzaStarted 2024-11-01
Type 2 Diabetes Mellitus (T2DM)HypertensionObesity and Type 2 Diabetes

Eating Window and Sleep Disorders on Glycemic Control, Cardiovascular Risk, and Weight Loss

RECRUITING
NCT06735859Phase NAFederal University of São PauloStarted 2026-01-21
Comparison of eating windows intervention
Polycystic Ovary SyndromeDiminished Ovarian ReserveOvulation Disorder

Clinical Trial of Anovulatory Infertility

ENROLLING BY INVITATION
NCT06601452Phase EARLY_PHASE1Affiliated Hospital of Nanjing University of Chinese MedicineStarted 2024-09-30
a compound prescription of Chinese medicine
Circadian RhythmEnergy BalanceAppetitive Behavior

Timing and Resistance Exercise: Impact on Eating and Metabolism

NOT YET RECRUITING
NCT06549322Phase NANational Taiwan Normal UniversityStarted 2024-09-01
The exercise in morningThe exercise in evening
Pelvic Organ ProlapseFemale Urogenital Diseases

Pelvic Organs Prolapse Treatment Using Neodymium Laser

ACTIVE NOT RECRUITING
NCT05000957Phase NAMeLSyTech, LtdStarted 2021-10-03
Laser TreatmentBlood analysisСlinical urine test

External Resources

Links to major genomics databases and tools