Circadian rhythm sleep disorder, delayed sleep phase type

Summary

Circadian rhythm sleep disorder, delayed sleep phase type (MONDO:0024377) is a disease with 1 cohort gene and 12 clinical trials. Top therapeutic interventions include melatonin and lemborexant.

At a glance

• Cohort genes: 1
• ClinVar variants: 2
• Clinical trials: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	circadian rhythm sleep disorder, delayed sleep phase type
Mondo ID	MONDO:0024377
DOID	DOID:0111141
ICD-10-CM	G47.21
SNOMED CT	28011000119104, 80623000
UMLS	C0393770
MedGen	97962
Is cancer (heuristic)	no

Also known as: delayed sleep phase syndrome · DSPS · sleep wake schedule disorder, delayed phase type

Data availability: 2 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › sleep disorder › sleep-wake disorder › circadian rhythm sleep disorder › circadian rhythm sleep disorder, delayed sleep phase type

Related subtypes (7): advanced sleep phase syndrome, non-24-hour sleep-wake syndrome, rapid eye movement sleep disorder, circadian rhythm sleep disorder, advanced sleep phase type, circadian rhythm sleep disorder, irregular sleep wake type, circadian rhythm sleep disorder, jet lag type, circadian rhythm sleep disorder, shift work type

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

2 retrieved; paginated sample, class counts are floors:

1 association, 1 association; risk factor

ClinVar	Variant (HGVS)	Gene	Classification	Review
427574	NM_004075.5(CRY1):c.1657+3A>C	CRY1	association; risk factor	no assertion criteria provided
1344736	NM_004075.5(CRY1):c.825+1G>A	CRY1	association	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

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

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
CRY1	HGNC:2384	ENSG00000008405	Q16526	Cryptochrome-1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CRY1	Cryptochrome-1	Transcriptional repressor which forms a core component of the circadian clock.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CRY1	Other/Unknown	no		Cryptochrome/DNA_photolyase_1, Cryptochr/Photolyase_FAD-bd, DNA_photolyase_N

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
cartilage tissue	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CRY1	294	ubiquitous	marker	oocyte, secondary oocyte, cartilage tissue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CRY1	2,644

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CRY1	Q16526	85.32

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	CRY1
Phosphorylation and nuclear translocation of the CRY:PER:kinase complex	1	815.7×	0.002	CRY1
The CRY:PER:kinase complex represses transactivation by the BMAL:CLOCK (ARNTL:CLOCK) complex	1	713.8×	0.002	CRY1
Phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) activates expression of core clock genes	1	475.8×	0.003	CRY1
Degradation of CRY and PER proteins	1	219.6×	0.005	CRY1

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
blue light signaling pathway	1	8426.0×	0.001	CRY1
negative regulation of glucocorticoid secretion	1	8426.0×	0.001	CRY1
negative regulation of nuclear receptor-mediated glucocorticoid signaling pathway	1	2407.4×	0.003	CRY1
negative regulation of circadian rhythm	1	2106.5×	0.003	CRY1
response to glucagon	1	1685.2×	0.003	CRY1
negative regulation of G protein-coupled receptor signaling pathway	1	1203.7×	0.003	CRY1
regulation of DNA damage checkpoint	1	1123.5×	0.003	CRY1
response to light stimulus	1	887.0×	0.003	CRY1
signal transduction in response to DNA damage	1	802.5×	0.003	CRY1
negative regulation of gluconeogenesis	1	802.5×	0.003	CRY1
positive regulation of gluconeogenesis	1	766.0×	0.003	CRY1
entrainment of circadian clock by photoperiod	1	732.7×	0.003	CRY1
lipid storage	1	543.6×	0.003	CRY1
gluconeogenesis	1	324.1×	0.005	CRY1
response to activity	1	324.1×	0.005	CRY1
negative regulation of protein ubiquitination	1	285.6×	0.005	CRY1
regulation of circadian rhythm	1	259.3×	0.005	CRY1
circadian rhythm	1	244.2×	0.005	CRY1
circadian regulation of gene expression	1	234.1×	0.005	CRY1
response to insulin	1	230.8×	0.005	CRY1
positive regulation of protein ubiquitination	1	213.3×	0.005	CRY1
glucose homeostasis	1	130.6×	0.008	CRY1
negative regulation of DNA-templated transcription	1	31.6×	0.033	CRY1
negative regulation of transcription by RNA polymerase II	1	17.7×	0.056	CRY1

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
CRY1	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
CRY1	2	Binding:2

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	CRY1

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)
CRY1	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 12.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	6
PHASE4	4
PHASE3	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06874855	PHASE4	RECRUITING	Lemborexant in Delayed Sleep Phase Syndrome
NCT00834886	PHASE4	COMPLETED	Randomized Controlled Trial on the Treatment Effects of Melatonin and Light Therapy on Delayed Sleep Phase Syndrome
NCT02962037	PHASE4	UNKNOWN	Are Patients Suffering From DSPS Show Compromising in Everyday Functions and Abilities Before Handling the Disorder?
NCT05463861	PHASE4	COMPLETED	Lemborexant in Delayed Sleep Phase Syndrome
NCT03715465	PHASE3	COMPLETED	The Clinical Utility of Measuring the Circadian Clock in Treatment of Delayed Sleep-Wake Phase Disorder
NCT00282061	PHASE1	UNKNOWN	Synchronization and Desynchronization Between Circadian Rhythms in Patients With Delayed Sleep Phase Syndrome (DSPS)
NCT04792697	Not specified	RECRUITING	Experimental Manipulation of Sleep and Circadian Rhythms and the Role Played on Reward Function in Teens
NCT06471374	Not specified	RECRUITING	Pathophysiology of Circadian Rhythm Delayed Sleep Wake Phase Disorder
NCT01419938	Not specified	COMPLETED	Does Cognitive Behaviour Therapy (CBT) Improve the Effect of Light Therapy
NCT03956745	Not specified	TERMINATED	Biomarkers for Circadian Timing in Healthy Adults
NCT03980340	Not specified	TERMINATED	Breath Biomarkers for Sleep Loss and Circadian Timing
NCT04690504	Not specified	COMPLETED	Validation of Circadian Biomarkers in Patients With Sleep Disorders

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
MELATONIN	4	4
LEMBOREXANT	4	2