Advanced sleep phase syndrome 3

Summary

Advanced sleep phase syndrome 3 (MONDO:0014814) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 9

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	advanced sleep phase syndrome 3
Mondo ID	MONDO:0014814
OMIM	616882
DOID	DOID:0110013
UMLS	C4225169
MedGen	909447
GARD	0016165
Is cancer (heuristic)	no

Also known as: advanced sleep phase syndrome caused by mutation in PER3 · advanced sleep phase syndrome type 3 · advanced sleep phase syndrome, familial, 3 · advanced sleep phase syndrome, familial, type 3 · FASPS3 · PER3 advanced sleep phase syndrome

Data availability: 9 ClinVar variants.

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 3

Related subtypes (3): advanced sleep phase syndrome 1, advanced sleep phase syndrome 2, 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

9 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 3 conflicting classifications of pathogenicity, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
224889	NM_001289862.1(PER3):c.[1243C>G;1250A>G]		Pathogenic	no assertion criteria provided
753405	NM_001377275.1(PER3):c.2299C>T (p.Pro767Ser)	LOC126805604	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
242410	NM_001377275.1(PER3):c.1243C>G (p.Pro415Ala)	PER3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
242411	NM_001377275.1(PER3):c.1250A>G (p.His417Arg)	PER3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4079520	NM_001377275.1(PER3):c.2325_2329dup (p.Pro777fs)	LOC126805604	Uncertain significance	criteria provided, single submitter
1342644	NM_001377275.1(PER3):c.3550-1G>A	PER3	Uncertain significance	criteria provided, single submitter
2359547	NM_001377275.1(PER3):c.1715A>C (p.Asn572Thr)	PER3	Uncertain significance	criteria provided, multiple submitters, no conflicts
3065260	NM_001377275.1(PER3):c.171G>C (p.Met57Ile)	PER3	Uncertain significance	criteria provided, single submitter
3891938	NM_001377275.1(PER3):c.150_151del (p.Arg50fs)	PER3	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PER3	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
PER3	HGNC:8847	ENSG00000049246	P56645	Period circadian protein homolog 3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PER3	Period circadian protein homolog 3	Originally described as 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)
PER3	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
cerebellar vermis	1
parietal pleura	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PER3	278	ubiquitous	marker	sural nerve, parietal pleura, cerebellar vermis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PER3	898

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PER3	P56645	54.62

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	PER3
Phosphorylation and nuclear translocation of the CRY:PER:kinase complex	1	815.7×	0.002	PER3
The CRY:PER:kinase complex represses transactivation by the BMAL:CLOCK (ARNTL:CLOCK) complex	1	713.8×	0.002	PER3
Phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) activates expression of core clock genes	1	475.8×	0.003	PER3
Degradation of CRY and PER proteins	1	219.6×	0.005	PER3

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 circadian sleep/wake cycle, sleep	1	2407.4×	0.002	PER3
entrainment of circadian clock by photoperiod	1	732.7×	0.003	PER3
circadian regulation of gene expression	1	234.1×	0.007	PER3
protein stabilization	1	66.9×	0.019	PER3
negative regulation of transcription by RNA polymerase II	1	17.7×	0.056	PER3

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PER3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	PER3

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)
PER3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.