Advanced sleep phase syndrome 1

Summary

Advanced sleep phase syndrome 1 (MONDO:0011442) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 11

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	advanced sleep phase syndrome 1
Mondo ID	MONDO:0011442
OMIM	604348
DOID	DOID:0110011
UMLS	C3807327
MedGen	813657
GARD	0015368
Is cancer (heuristic)	no

Also known as: advanced sleep phase syndrome caused by mutation in PER2 · advanced sleep phase syndrome type 1 · advanced sleep phase syndrome, familial, 1 · advanced sleep phase syndrome, familial, type 1 · FASPS1 · PER2 advanced sleep phase syndrome

Data availability: 11 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › advanced sleep phase syndrome › advanced sleep phase syndrome 1

Related subtypes (3): advanced sleep phase syndrome 2, advanced sleep phase syndrome 3, advance sleep phase syndrome, familial, 4

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

11 retrieved; paginated sample, class counts are floors:

8 uncertain significance, 2 pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
6345	NM_022817.3(PER2):c.1984A>G (p.Ser662Gly)	PER2	Pathogenic	no assertion criteria provided
634825	NM_022817.3(PER2):c.595del (p.Leu199fs)	PER2	Pathogenic	criteria provided, single submitter
977454	NM_022817.3(PER2):c.1793A>G (p.Asn598Ser)	PER2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2434645	NM_022817.3(PER2):c.14C>G (p.Ala5Gly)	PER2	Uncertain significance	criteria provided, single submitter
2434646	NM_022817.3(PER2):c.1202G>A (p.Arg401His)	PER2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2434647	NM_022817.3(PER2):c.2542G>A (p.Ala848Thr)	PER2	Uncertain significance	criteria provided, single submitter
2434649	NM_022817.3(PER2):c.3376C>T (p.His1126Tyr)	PER2	Uncertain significance	criteria provided, single submitter
2434650	NM_022817.3(PER2):c.293+1G>T	PER2	Uncertain significance	criteria provided, single submitter
3891936	NM_022817.3(PER2):c.2530G>A (p.Val844Met)	PER2	Uncertain significance	criteria provided, single submitter
3891937	NM_022817.3(PER2):c.2620G>A (p.Ala874Thr)	PER2	Uncertain significance	criteria provided, single submitter
634824	NM_022817.3(PER2):c.2963C>T (p.Pro988Leu)	PER2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
PER2	Supportive	Autosomal dominant	advanced sleep phase syndrome	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PER2	Orphanet:164736	Familial advanced sleep-phase syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PER2	HGNC:8846	ENSG00000132326	O15055	Period circadian protein homolog 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PER2	Period circadian protein homolog 2	Transcriptional repressor which forms a core component of the circadian clock.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PER2	Transcription factor	no		PAS, PAS_fold_3, Period_circadian-like_C

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
mucosa of paranasal sinus	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PER2	296	ubiquitous	marker	oocyte, mucosa of paranasal sinus, secondary oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PER2	1,945

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PER2	O15055	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Phosphorylation of CLOCK, acetylation of BMAL1 (ARNTL) at target gene promoters	1	878.5×	0.002	PER2
Phosphorylation and nuclear translocation of the CRY:PER:kinase complex	1	815.7×	0.002	PER2
The CRY:PER:kinase complex represses transactivation by the BMAL:CLOCK (ARNTL:CLOCK) complex	1	713.8×	0.002	PER2
Phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) activates expression of core clock genes	1	475.8×	0.003	PER2
Degradation of CRY and PER proteins	1	219.6×	0.005	PER2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of glutamate uptake involved in transmission of nerve impulse	1	8426.0×	0.002	PER2
lactate biosynthetic process	1	5617.3×	0.002	PER2
negative regulation of fat cell proliferation	1	2808.7×	0.003	PER2
negative regulation of circadian rhythm	1	2106.5×	0.003	PER2
neural retina development	1	936.2×	0.003	PER2
glycogen biosynthetic process	1	936.2×	0.003	PER2
white fat cell differentiation	1	842.6×	0.003	PER2
regulation of vasoconstriction	1	802.5×	0.003	PER2
entrainment of circadian clock by photoperiod	1	732.7×	0.003	PER2
regulation of neurogenesis	1	401.2×	0.005	PER2
regulation of insulin secretion	1	391.9×	0.005	PER2
gluconeogenesis	1	324.1×	0.006	PER2
negative regulation of protein ubiquitination	1	285.6×	0.006	PER2
regulation of circadian rhythm	1	259.3×	0.006	PER2
response to ischemia	1	251.5×	0.006	PER2
circadian rhythm	1	244.2×	0.006	PER2
circadian regulation of gene expression	1	234.1×	0.006	PER2
fatty acid metabolic process	1	193.7×	0.007	PER2
positive regulation of cold-induced thermogenesis	1	163.6×	0.007	PER2
regulation of cell cycle	1	74.6×	0.015	PER2
chromatin remodeling	1	73.0×	0.015	PER2
negative regulation of DNA-templated transcription	1	31.6×	0.033	PER2
negative regulation of transcription by RNA polymerase II	1	17.7×	0.056	PER2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PER2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
PER2	5	Binding:5

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	PER2

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
PER2	5	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.