FASPS1
MCID: ADV003
MIFTS: 43

Advanced Sleep Phase Syndrome, Familial, 1 (FASPS1)

Categories: Genetic diseases, Mental diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Advanced Sleep Phase Syndrome, Familial, 1

MalaCards integrated aliases for Advanced Sleep Phase Syndrome, Familial, 1:

Name: Advanced Sleep Phase Syndrome, Familial, 1 56 73 13 71
Familial Advanced Sleep Phase Syndrome 1 12 29 6
Fasps1 56 12 73
Advanced Sleep Phase Syndrome 1 12 15
Sleep Phase Syndrome, Advanced, Familial, Type 1 39
Sleep Disorders, Circadian Rhythm 43

Characteristics:

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
onset in childhood, but most noticeable in mid-teens and early adulthood


HPO:

31
advanced sleep phase syndrome, familial, 1:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0110011
OMIM 56 604348
OMIM Phenotypic Series 56 PS604348
MeSH 43 D020178
UMLS 71 C3807327

Summaries for Advanced Sleep Phase Syndrome, Familial, 1

UniProtKB/Swiss-Prot : 73 Advanced sleep phase syndrome, familial, 1: A disorder characterized by very early sleep onset and offset. Individuals are 'morning larks' with a 4 hours advance of the sleep, temperature and melatonin rhythms.

MalaCards based summary : Advanced Sleep Phase Syndrome, Familial, 1, also known as familial advanced sleep phase syndrome 1, is related to advanced sleep phase syndrome, familial, 3 and sleep disorder. An important gene associated with Advanced Sleep Phase Syndrome, Familial, 1 is PER2 (Period Circadian Regulator 2), and among its related pathways/superpathways are BMAL1-CLOCK,NPAS2 activates circadian gene expression and Transcriptional misregulation in cancer. The drugs Diphenhydramine and Promethazine have been mentioned in the context of this disorder. Affiliated tissues include brain, breast and liver, and related phenotypes are sleep-wake cycle disturbance and depressivity

Disease Ontology : 12 An advanced sleep phase syndrome that has material basis in heterozygous mutation in the PER2 gene on chromosome 2q37.

OMIM : 56 Advanced sleep phase syndrome is characterized by very early sleep onset and offset (summary by Jones et al., 1999). (604348)

Related Diseases for Advanced Sleep Phase Syndrome, Familial, 1

Graphical network of the top 20 diseases related to Advanced Sleep Phase Syndrome, Familial, 1:



Diseases related to Advanced Sleep Phase Syndrome, Familial, 1

Symptoms & Phenotypes for Advanced Sleep Phase Syndrome, Familial, 1

Human phenotypes related to Advanced Sleep Phase Syndrome, Familial, 1:

31
# Description HPO Frequency HPO Source Accession
1 sleep-wake cycle disturbance 31 hallmark (90%) HP:0006979
2 depressivity 31 HP:0000716
3 early chronotype 31 HP:0031873

Symptoms via clinical synopsis from OMIM:

56
Neurologic Behavioral Psychiatric Manifestations:
depression (in some patients)
early sleep onset (almost 4 hours advanced over controls)
early sleep offset (almost 4 hours advanced over controls)
short circadian rhythm cycle (tau)
'morning larks'

Metabolic Features:
melatonin rhythm phase-advanced by 3-4 hours
temperature rhythm phase-advanced by 3-4 hours

Clinical features from OMIM:

604348

Drugs & Therapeutics for Advanced Sleep Phase Syndrome, Familial, 1

Drugs for Advanced Sleep Phase Syndrome, Familial, 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show top 50) (show all 67)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Diphenhydramine Approved, Investigational Phase 4 147-24-0, 58-73-1 3100
2
Promethazine Approved, Investigational Phase 4 60-87-7 4927
3
Suvorexant Approved, Investigational Phase 4 1030377-33-3
4 Neurotransmitter Agents Phase 4
5 Hypnotics and Sedatives Phase 4
6 Orexin Receptor Antagonists Phase 4
7 Antioxidants Phase 4
8 Protective Agents Phase 4
9
Modafinil Approved, Investigational Phase 3 68693-11-8 4236
10 Central Nervous System Stimulants Phase 3
11 Cytochrome P-450 CYP3A Inducers Phase 3
12
Melatonin Approved, Nutraceutical, Vet_approved Phase 1 73-31-4 896
13 Central Nervous System Depressants Phase 1
14
Methylcobalamin Approved, Investigational 13422-55-4
15
Hydroxocobalamin Approved 13422-51-0 11953898 15589840
16
Dopamine Approved 51-61-6, 62-31-7 681
17
Risperidone Approved, Investigational 106266-06-2 5073
18
Eszopiclone Approved, Investigational 138729-47-2 969472
19
Hydrocortisone acetate Approved, Vet_approved 50-03-3
20
Hydrocortisone Approved, Vet_approved 50-23-7 5754
21
Zolpidem Approved 82626-48-0 5732
22
Caffeine Approved 58-08-2 2519
23
Methamphetamine Approved, Illicit 537-46-2 10836
24
Metronidazole Approved 443-48-1 4173
25
Fentanyl Approved, Illicit, Investigational, Vet_approved 437-38-7 3345
26
Sevoflurane Approved, Vet_approved 28523-86-6 5206
27
Ropivacaine Approved 84057-95-4 71273 175805
28
Glucagon Approved 16941-32-5
29
Folic acid Approved, Nutraceutical, Vet_approved 59-30-3 6037
30
Cyanocobalamin Approved, Nutraceutical 68-19-9 44176380
31
Cobalamin Experimental 13408-78-1 6857388
32 Vitamins
33 Trace Elements
34 Vitamin B 12
35 Hematinics
36 Nutrients
37 Vitamin B Complex
38 Vitamin B12
39 Vitamin B9
40 Folate
41 Micronutrients
42 Antipsychotic Agents
43 Tranquilizing Agents
44 Dopamine Agents
45 Psychotropic Drugs
46 Dopamine Antagonists
47 Serotonin Agents
48 Serotonin Antagonists
49 Hydrocortisone hemisuccinate
50 Hydrocortisone 17-butyrate 21-propionate

Interventional clinical trials:

(show top 50) (show all 82)
# Name Status NCT ID Phase Drugs
1 Are Patients Suffering From DSPS Show Compromising in Everyday Functions and Abilities (Attention and Concentration, Mood and Fatigue) Before Handling the Disorder? And Whether the Treatment Fixes the Disorder? Unknown status NCT02962037 Phase 4
2 Examination of the Effectiveness of Suvorexant in Improving Daytime Sleep in Shift Workers Completed NCT02491788 Phase 4 Suvorexant;Placebo
3 Assessments in Stress and Quality of Sleep/Life in Night-shift Nurses and Doctors Completed NCT02541747 Phase 4
4 Delayed Sleep Phase Syndrome in Adolescents and Young Adults. Sleep, Personality, Developmental History, Circadian Rhythm, Daytime Functioning and Treatment Completed NCT00834886 Phase 4
5 A Single Dose, Open-Label, Randomized Two-Period Crossover Study in Healthy Young Subjects to Assess the Absolute Bioavailability of Tasimelteon (HETLIOZ™) Completed NCT02130999 Phase 4 tasimelteon 20 mg capsule;tasimelteon 2 mg I.V.
6 Open-Label Safety Study of a 1-Year 20 mg Dose Regimen of Tasimelteon for Treatment of Non-24-Hour-Sleep-Wake Disorder (N24HSWD) in Blind Individuals With No Light Perception Unknown status NCT01218789 Phase 3 tasimelteon
7 A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of the Efficacy and Multiple-Dose Plasma Concentration-Time Profiles of Armodafinil (150, 200, and 250 mg) and PROVIGIL® (200 mg) in Patients With Chronic Shift Work Sleep Disorder Completed NCT00236080 Phase 3 PROVIGIL 200 mg;Armodafinil 250 mg;Armodafinil 200 mg;Armodafinil 150 mg;Placebo
8 A 12-Month, Open-Label, Flexible-Dosage (100 to 250 mg/Day) Extension Study of the Safety and Efficacy of Armodafinil (CEP-10953) in the Treatment of Patients With Excessive Sleepiness Associated With Narcolepsy, Obstructive Sleep Apnea/Hypopnea Syndrome, or Chronic Shift Work Sleep Disorder (With an Open-Ended Extension Period) Completed NCT00228553 Phase 3 Armodafinil 100 to 250 mg/day
9 Multicenter, Randomized, Double-blind, Placebo Controlled Trial of 2 mg Melatonin for Circadian Phase Adjustment and Improvement of Metabolic Control in Night Shift Workers Completed NCT02108353 Phase 3 Melatonin 2mg;Placebo
10 A 12 Week, Randomized, Double Blind, Placebo Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of CEP 10953 (150 mg) as Treatment for Adults With Excessive Sleepiness Associated With Chronic Shift Work Sleep Disorder Completed NCT00080288 Phase 3 Armodafinil 150 mg/day;Placebo
11 A 12-Month, Open-Label, Flexible-Dosage (100 to 250 mg/Day) Study of the Safety and Efficacy of CEP-10953 in the Treatment of Patients With Excessive Sleepiness Associated With Narcolepsy, Obstructive Sleep Apnea/Hypopnea Syndrome, or Chronic Shift Work Sleep Disorder (With an Open-Ended Extension Period) Completed NCT00078312 Phase 3 CEP-10953 (Armodafinil)
12 A Randomized Withdrawal Study to Demonstrate the Maintenance of Effect of 20 mg Tasimelteon in the Treatment of N24HSWD Completed NCT01430754 Phase 3 tasimelteon;Placebo
13 An Extension Open-Label Safety Study of a 24-month 20 mg Dose Regimen of Tasimelteon for the Treatment of Non-24-Hour Sleep-Wake Disorder (N24HSWD) in Blind Individuals With no Light Perception Who Have Enrolled in Other Tasimelteon Clinical Trials Completed NCT01429116 Phase 3 tasimelteon
14 A Multicenter, Randomized, Double-Mask, Placebo-Controlled, Parallel Study to Investigate the Efficacy and Safety of 20 mg Tasimelteon Versus Placebo in Totally Blind Subjects With N24HSWD Followed by an OLE Phase Completed NCT01163032 Phase 3 tasimelteon;Placebo
15 Diabetic Retinopathy: Effects of Melatonin Treatment on Visual Functions and Circadian Rhythm Recruiting NCT03478306 Phase 3 Melatonin 4 mg Tablet
16 The Clinical Utility of DLMO in the Treatment of Delayed Sleep-Wake Phase Disorder: A Randomized Trial Recruiting NCT03715465 Phase 3 Melatonin 0.5 MG
17 The Role of Palliative Care Interventions to Reduce Circadian Rhythm Disorders in Persons With Dementia: The Healthy Patterns Study Recruiting NCT03682185 Phase 3
18 An Evaluation of the Effects of Pharmaton® Caplets Film-coated Tablets on Mental Performance and Physical Fatigue in Nurses Working Night Shifts: a Double-blind, Placebo Controlled Pilot Trial Completed NCT02199847 Phase 2 Pharmaton® Caplets;Placebo
19 A Randomized, Double-blind, Placebo-controlled, Multi-center Study of the Effects of VEC-162 on Circadian Rhythm in Healthy Subjects Completed NCT00490945 Phase 2 VEC-162
20 Melatonin as a Circadian Clock Regulator, Neuromodulator and Myelo-protector in Adjuvant Breast Cancer Chemotherapy: a Randomized, Double-blind, Placebo-controlled Trial. Completed NCT03205033 Phase 2 Melatonin 20 MG Oral Capsule;Placebo oral capsule
21 A Randomized, Double-Blind, Placebo-Controlled, Parallel, Proof of Concept Study to Evaluate the Effectiveness of Ramelteon to Advance the Timing of Sleep in Individuals With Delayed Sleep Phase Syndrome (DSPS) Completed NCT00593736 Phase 2 Ramelteon;Ramelteon;Ramelteon;Placebo
22 A Double-Blind, Placebo-Controlled Study of Circadin™ for Non-24 Hour Sleep-Wake Disorder in Totally Blind Subjects Completed NCT00972075 Phase 2 melatonin (Circadin);placebo
23 Open-label Study to Investigate the Pharmacokinetics and Safety of Tasimelteon in Children and Adolescents Unknown status NCT02776215 Phase 1 tasimelteon
24 Synchronization and Desynchronization Between Circadian Rhythms in Patients With Delayed Sleep Phase Syndrome (DSPS) Unknown status NCT00282061 Phase 1 Melatonin
25 Sleep Enhancement Training Study for Experienced Shiftworkers Completed NCT00786357 Phase 1
26 Sleep Enhancement Training Study for Novice Shiftworkers Completed NCT00786266 Phase 1
27 A Phase One Treatment Trial of the Circadian Sleep Disturbance in Smith-Magenis Syndrome (SMS) Completed NCT00506259 Phase 1 dTR Melatonin (NIH CC PDS);Melatonin CR
28 The Impact of Night Nursing Activity on the Quality of Hospitalized Patients' Sleep Unknown status NCT03370354
29 Sleep Helsinki! CIRCADIAN SLEEP REGULATION IN ADOLESCENCE Unknown status NCT02964598
30 Circadian Integration of Photic and Non-photic Stimuli Unknown status NCT00387179 Melatonin;Methylxanthine
31 ROOM-LIGHT: Dynamic LED-light as Treatment for Depressed Patients in Inpatient Wards: A Feasibility Trial Unknown status NCT03363529
32 Early Development of Sleep-wake Cycles in Premature Infants and Its Impact on Neurodevelopmental Outcome Unknown status NCT01774318
33 Implementing and Sustaining a Transdiagnostic Sleep and Circadian Treatment Completed NCT03556878
34 Teen School-Night Sleep Extension: An Intervention Targeting the Circadian System Completed NCT04087603
35 Meal Distribution Across the Day in Female Nurses Working Shifts and Their Relationship With Nutritional Status Completed NCT02522195
36 Magnetoencephalographic Imaging of Sleepiness: The Effect of Armodafinil in Shift Work Sleep Disorder Completed NCT00688142
37 Effect of Vitamin B12 on the Human Circadian Pacemaker Completed NCT00120484 Vitamin B12
38 Actigraphic Analysis of Treatment Response in a Six Year Old Girl With Kabuki Syndrome Completed NCT00723580 risperidone
39 Effects of Daytime Eszopiclone Administration in Shift Workers on Overnight Wakefulness During a Subsequent Simulated Nightshift Completed NCT00900159 eszopiclone;matching placebo
40 Cross Sectional Study of Sleep-wake and Melatonin Patterns in Patients Treated for Craniopharyngiomas Compared to Matched Controls Completed NCT01881854
41 Determination of Protocol of Nocturnal Food Intake of Shift Workers: a Crossover Randomized and Controlled Study. Completed NCT03456219
42 Wake-sleep Cycle and Melatonin Secretion Dynamics Associated With 12 Hours Shift Work in French Nurses Completed NCT03153917
43 Impact of Shift Work on Risk of Cardiovascular Disease and Diabetes: A Cross-sectional Study Completed NCT02901860
44 Improving the Sleep and Circadian Rhythms of Mechanically Ventilated Patients Completed NCT01284140
45 The Effects of Bright Light on Adaptation to Night Work Among Nurses Completed NCT02978053
46 Does Zolpidem CR Treatment Change Clinical Outcomes in Elderly Hospitalized Patients With Dementia- A Pilot Study Completed NCT00814502 Zolpidem CR;Placebo
47 Fire Fighter Fatigue Management Program: Operation Healthy Sleep Completed NCT01988129
48 Sleep Disruption and ICU Delirium: Delirium Assessment and Monitoring Combined With the Evaluation of Sleep Using the Sedline Brain Function Monitor. Completed NCT01280097
49 Testing the Effectiveness of a Comprehensive Fatigue Management for the Police Completed NCT00246051
50 The Impact of Ergonomic Circadian Light on Hospitalized Stroke Patients in a Rehabilitation Unit Completed NCT02186392

Search NIH Clinical Center for Advanced Sleep Phase Syndrome, Familial, 1

Cochrane evidence based reviews: sleep disorders, circadian rhythm

Genetic Tests for Advanced Sleep Phase Syndrome, Familial, 1

Genetic tests related to Advanced Sleep Phase Syndrome, Familial, 1:

# Genetic test Affiliating Genes
1 Familial Advanced Sleep Phase Syndrome 1 29 PER2

Anatomical Context for Advanced Sleep Phase Syndrome, Familial, 1

MalaCards organs/tissues related to Advanced Sleep Phase Syndrome, Familial, 1:

40
Brain, Breast, Liver, Testes

Publications for Advanced Sleep Phase Syndrome, Familial, 1

Articles related to Advanced Sleep Phase Syndrome, Familial, 1:

(show all 12)
# Title Authors PMID Year
1
An hPer2 phosphorylation site mutation in familial advanced sleep phase syndrome. 56 6
11232563 2001
2
Familial advanced sleep-phase syndrome: A short-period circadian rhythm variant in humans. 56
10470086 1999
3
Optimal Melatonin Dose in Older Adults: A Clinical Review of the Literature. 61
31383052 2019
4
Sleep Disorders: Circadian Rhythm Sleep-Wake Disorders. 61
28845960 2017
5
[Definitions and clinical classifications of sleep disorders]. 61
22844797 2012
6
Sleep and epilepsy: common bedfellows. 61
21399510 2011
7
The roles of melatonin and light in the pathophysiology and treatment of circadian rhythm sleep disorders. 61
18628753 2008
8
Consistency and accuracy of the Medical Subject Headings thesaurus for electronic indexing and retrieval of chronobiologic references. 61
18075808 2007
9
Sleep and its disorders in older adults. 61
17118283 2006
10
Sleep disorders in psychiatry. 61
16979426 2006
11
Behavioral sleep medicine: a historical perspective. 61
15600134 2003
12
Appropriate use of benzodiazepines in insomnia: clinical update. 61
2071565 1991

Variations for Advanced Sleep Phase Syndrome, Familial, 1

ClinVar genetic disease variations for Advanced Sleep Phase Syndrome, Familial, 1:

6 ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 PER2 NM_022817.3(PER2):c.1984A>G (p.Ser662Gly)SNV Pathogenic 6345 rs121908635 2:239165644-239165644 2:238257003-238257003
2 PER2 NM_022817.3(PER2):c.595del (p.Leu199fs)deletion Pathogenic 634825 rs1559332542 2:239180130-239180130 2:238271489-238271489
3 PER2 NM_022817.3(PER2):c.2963C>T (p.Pro988Leu)SNV Uncertain significance 634824 rs1559323041 2:239161701-239161701 2:238253060-238253060

UniProtKB/Swiss-Prot genetic disease variations for Advanced Sleep Phase Syndrome, Familial, 1:

73
# Symbol AA change Variation ID SNP ID
1 PER2 p.Ser662Gly VAR_029080 rs121908635

Expression for Advanced Sleep Phase Syndrome, Familial, 1

Search GEO for disease gene expression data for Advanced Sleep Phase Syndrome, Familial, 1.

Pathways for Advanced Sleep Phase Syndrome, Familial, 1

GO Terms for Advanced Sleep Phase Syndrome, Familial, 1

Cellular components related to Advanced Sleep Phase Syndrome, Familial, 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nucleus GO:0005634 9.36 RPS3A PER3 PER2 NPAS2 MLX MDM2

Biological processes related to Advanced Sleep Phase Syndrome, Familial, 1 according to GeneCards Suite gene sharing:

(show all 15)
# Name GO ID Score Top Affiliating Genes
1 negative regulation of transcription by RNA polymerase II GO:0000122 9.95 PER3 PER2 MLX MDM2 CRY2 CRY1
2 negative regulation of transcription, DNA-templated GO:0045892 9.91 PER2 MLX MDM2 CRY2 CRY1 BHLHE41
3 regulation of circadian rhythm GO:0042752 9.69 PER2 CRY2 CRY1
4 rhythmic process GO:0048511 9.63 PER3 PER2 NPAS2 CRY2 CRY1 BHLHE41
5 response to light stimulus GO:0009416 9.62 PER3 PER2 CRY2 CRY1
6 entrainment of circadian clock by photoperiod GO:0043153 9.56 PER3 PER2 CRY2 CRY1
7 lipid storage GO:0019915 9.55 CRY2 CRY1
8 protein-chromophore linkage GO:0018298 9.54 CRY2 CRY1
9 negative regulation of circadian rhythm GO:0042754 9.54 PER2 CRY2 CRY1
10 response to glucagon GO:0033762 9.52 CRY1 CCNA2
11 negative regulation of glucocorticoid receptor signaling pathway GO:2000323 9.49 CRY2 CRY1
12 negative regulation of glucocorticoid secretion GO:2000850 9.48 CRY2 CRY1
13 blue light signaling pathway GO:0009785 9.46 CRY2 CRY1
14 circadian regulation of gene expression GO:0032922 9.43 PER3 PER2 NPAS2 CRY2 CRY1 BHLHE41
15 circadian rhythm GO:0007623 9.17 SERPINE1 PER3 PER2 NPAS2 CRY2 CRY1

Molecular functions related to Advanced Sleep Phase Syndrome, Familial, 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transcription factor binding GO:0008134 9.73 PER3 PER2 MLX CRY1
2 lyase activity GO:0016829 9.65 CRY2 CRY1 ADCY10
3 kinase binding GO:0019900 9.54 PER3 CRY2 CRY1
4 nuclear hormone receptor binding GO:0035257 9.46 CRY2 CRY1
5 transcription regulatory region sequence-specific DNA binding GO:0000976 9.43 PER3 PER2 CRY2
6 transcription corepressor binding GO:0001222 9.4 PER3 PER2
7 photoreceptor activity GO:0009881 9.32 CRY2 CRY1
8 blue light photoreceptor activity GO:0009882 9.16 CRY2 CRY1
9 DNA (6-4) photolyase activity GO:0003914 8.96 CRY2 CRY1
10 deoxyribodipyrimidine photo-lyase activity GO:0003904 8.62 CRY2 CRY1

Sources for Advanced Sleep Phase Syndrome, Familial, 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
Content
Loading form....