PER2

Chr 2AD

period circadian regulator 2

Also known as: FASPS, FASPS1

NCBI Gene: 8864ENSG00000132326UniProt: O15055

The PER2 protein is a transcriptional repressor that forms a core component of the circadian clock, regulating approximately 24-hour rhythms in gene expression that control sleep, metabolism, body temperature, and other physiological processes through feedback loops in both central brain circuits and peripheral tissues. Mutations cause familial advanced sleep phase syndrome type 1, inherited in an autosomal dominant pattern. This gene shows high constraint against loss-of-function variants (LOEUF 0.347), indicating that such variants are likely to be pathogenic.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

?Advanced sleep phase syndrome, familial, 1MIM #604348
AD
8
Active trials
207
Pubs (1 yr)
86
P/LP submissions
1%
P/LP missense
0.35
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical Summary— PER2
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.71) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
84 unique Pathogenic / Likely Pathogenic· 172 VUS of 334 total submissions
💊
Clinical Trials
8 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.35LOEUF
pLI 0.715
Z-score 5.31
OE 0.21 (0.13–0.35)
Highly constrained

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

Missense Constraint
0.43Z-score
OE missense 0.96 (0.90–1.02)
706 obs / 738.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.21 (0.13–0.35)
0≤0.351.4
Missense OE0.96 (0.90–1.02)
0≤0.61.4
Synonymous OE1.04
0≤1.21.6
LoF obs/exp: 11 / 52.5Missense obs/exp: 706 / 738.6Syn Z: -0.50
DN
0.3892th %ile
GOF
0.4283th %ile
LOF
0.75top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.35

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

334 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic82
Likely Pathogenic2
VUS172
Likely Benign44
Benign16
Conflicting2
82
Pathogenic
2
Likely Pathogenic
172
VUS
44
Likely Benign
16
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
1
80
0
82
Likely Pathogenic
0
0
2
0
2
VUS
2
163
7
0
172
Likely Benign
0
18
7
19
44
Benign
0
5
0
11
16
Conflicting
—2
Total31879630318

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

View in ClinVar →

Protein Context — Lollipop Plot

PER2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Cystic Fibrosis

Circadian Rhythm Disorders in Children With Cystic Fibrosis Under CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) Modulators

RECRUITING
NCT06370962Hospices Civils de LyonStarted 2024-04-29
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
Obesity (Disorder)Morbid ObesityBariatric Sleeve Gastrectomy

Chrono-ALIGN: A Chronotype-Based Chrono-Nutrition Intervention in Post-Bariatric Patients

NOT YET RECRUITING
NCT07324044Phase NAKing Saud UniversityStarted 2026-01-01
Standard Post-Bariatric Care (Control)Early Time-Restricted Eating (eTRE)Chronotype-Based Chrono-Nutrition (CB-CN)
Fibromyalgia (FM)tDCSDuloxetine

Home-based Transcranial Direct Current Stimulation (tDCS) Compared to Duloxetine: Non-inferiority Clinical Trial (FIBROSTIM)

RECRUITING
NCT07203339Phase NAHospital de Clinicas de Porto AlegreStarted 2025-09-30
Transcranial direct current stimulation (tDCS) plus placebo.Duloxetine (60 mg) once dailyHome-based transcranial direct current stimulation
Critical Illness

The Effect of Continuous Versus Intermittent Enteral Nutrition on Metabolic Outcomes in Critically Ill Patients

RECRUITING
NCT07173504Phase NAGelderse Vallei HospitalStarted 2025-09-30
Intermittent enteral nutrition
Aging

The Fuel and Rhythm (FAR) Phase 2 Study

ACTIVE NOT RECRUITING
NCT05482711Phase NAUniversity of FloridaStarted 2023-01-10
Time Restricted Eating Intervention
Multiple Sclerosis

Understanding the Impact of Meal Timing on Neurological Health in Adults With Multiple Sclerosis

NOT YET RECRUITING
NCT07475377Phase NAUniversity of Alabama at BirminghamStarted 2026-05-01
Time Restricted EatingUnrestricted eating
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
PER2 regulates odontoblastic differentiation of dental papilla cells in vitro via intracellular ATP content and reactive oxygen species levels
Ma H et al.·PeerJ
2023
Period 2 Suppresses the Malignant Cellular Behaviors of Colorectal Cancer Through the Epithelial-Mesenchymal Transformation Process
Xiong Y et al.·Cancer Control
2022
Involvement of circadian clock protein PER2 in controlling sleep deprivation induced HMGB1 up-regulation by targeting p300 in the cortex
Zhang M et al.·Sci Rep
2025
Circadian Period 2 (Per2) downregulate inhibitor of differentiation 3 (Id3) expression via PTEN/AKT/Smad5 axis to inhibits glioma cell proliferation
Zhang Y et al.·Bioengineered
2022
Knockout of the circadian gene, Per2, disrupts corticosterone secretion and results in depressive-like behaviors and deficits in startle responses
Russell AL et al.·BMC Neurosci
2021
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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