Advance sleep phase syndrome, familial, 4

disease
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Also known as FASPS4

Summary

Advance sleep phase syndrome, familial, 4 (MONDO:0031044) is a disease with 1 cohort gene.

At a glance

  • Cohort genes: 1
  • ClinVar variants: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical nameadvance sleep phase syndrome, familial, 4
Mondo IDMONDO:0031044
OMIM620015
DOIDDOID:0061006
UMLSC5774204
MedGen1823977
GARD0025682
Is cancer (heuristic)no

Also known as: advance sleep phase syndrome, familial, 4 · FASPS4

Data availability: 3 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary diseaseadvanced sleep phase syndromeadvance sleep phase syndrome, familial, 4

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

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

3 retrieved; paginated sample, class counts are floors:

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

ClinVarVariant (HGVS)GeneClassificationReview
1702937NM_003920.5(TIMELESS):c.3241C>T (p.Arg1081Ter)TIMELESSPathogenicno assertion criteria provided
2672272NM_003920.5(TIMELESS):c.2515G>A (p.Asp839Asn)TIMELESSConflicting classifications of pathogenicitycriteria provided, conflicting classifications
3065705NM_003920.5(TIMELESS):c.909+5G>ATIMELESSUncertain significancecriteria provided, single submitter

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

SubsetGenes
multi_evidence1

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
TIMELESSHGNC:11813ENSG00000111602Q9UNS1Protein timeless homologclinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
TIMELESSProtein timeless homologPlays an important role in the control of DNA replication, maintenance of replication fork stability, maintenance of genome stability throughout normal DNA replication, DNA repair and in the regulation 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.

FamilyGenesFoldFDR
Other/Unknown11.8×0.558

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
TIMELESSOther/UnknownnoTimeless_N, TIMELESS_PAB, Timeless

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)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)1
unknown0

Top tissues across cohort

TissueCohort genes
embryo1
ganglionic eminence1
ventricular zone1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
TIMELESS215ubiquitousmarkerventricular zone, embryo, ganglionic eminence

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
TIMELESS2,560

Structural data

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

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
TIMELESSQ9UNS19

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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.

PathwayCohort genesFoldFDRSample cohort genes
Processing of DNA double-strand break ends1114.2×0.009TIMELESS

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 termCohort genesFoldFDRSample cohort genes
cellular response to bleomycin15617.3×0.001TIMELESS
replication fork arrest14213.0×0.001TIMELESS
detection of abiotic stimulus13370.4×0.001TIMELESS
cellular response to cisplatin13370.4×0.001TIMELESS
cell cycle phase transition12808.7×0.001TIMELESS
cellular response to hydroxyurea11404.3×0.002TIMELESS
DNA replication checkpoint signaling11296.3×0.002TIMELESS
branching morphogenesis of an epithelial tube1732.7×0.003TIMELESS
replication fork processing1421.3×0.005TIMELESS
positive regulation of double-strand break repair via homologous recombination1383.0×0.005TIMELESS
morphogenesis of an epithelium1343.9×0.005TIMELESS
positive regulation of double-strand break repair1343.9×0.005TIMELESS
regulation of circadian rhythm1259.3×0.006TIMELESS
circadian rhythm1244.2×0.006TIMELESS
lung development1198.3×0.006TIMELESS
DNA repair163.8×0.019TIMELESS
DNA damage response153.5×0.021TIMELESS
cell division146.2×0.023TIMELESS
negative regulation of DNA-templated transcription131.6×0.032TIMELESS

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

SymbolMoleculesMax phase
TIMELESS00

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):

TierDefinitionGenesSymbols
AApproved (phase 4 drug)0
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug1TIMELESS

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
TIMELESS0

Clinical trials & evidence

Clinical trials

Clinical trials: 0.