CSNK1D

Chr 17AD

casein kinase 1 delta

Also known as: ASPS, CKI-delta, CKId, CKIdelta, FASPS2, HCKID

NCBI Gene: 1453ENSG00000141551UniProt: P48730

This gene is a member of the casein kinase I (CKI) gene family whose members have been implicated in the control of cytoplasmic and nuclear processes, including DNA replication and repair. The encoded protein may also be involved in the regulation of apoptosis, circadian rhythm, microtubule dynamics, chromosome segregation, and p53-mediated effects on growth. The encoded protein is highly similar to the mouse and rat CK1 delta homologs. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2014]

Primary Disease Associations & Inheritance

Advanced sleep-phase syndrome, familial, 2MIM #615224
AD
UniProtAdvanced sleep phase syndrome, familial, 2
75
ClinVar variants
24
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— CSNK1D
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
24 Pathogenic / Likely Pathogenic· 38 VUS of 75 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.23LOEUF
pLI 0.996
Z-score 4.00
OE 0.05 (0.02–0.23)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.70Z-score
OE missense 0.53 (0.46–0.61)
136 obs / 258.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.05 (0.02–0.23)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.53 (0.46–0.61)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.25
0≤1.21.6
LoF obs/exp: 1 / 20.6Missense obs/exp: 136 / 258.2Syn Z: -2.09

ClinVar Variant Classifications

75 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic3
VUS38
Likely Benign11
Benign2
21
Pathogenic
3
Likely Pathogenic
38
VUS
11
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
19
0
21
Likely Pathogenic
0
0
3
0
3
VUS
0
29
9
0
38
Likely Benign
0
2
2
7
11
Benign
0
0
0
2
2
Total03333975

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CSNK1D · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Advanced sleep-phase syndrome, familial, 2

MIM #615224

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
CSNK1D inhibition suppresses head and neck squamous cell carcinoma progression through SHH and PTCH1 pathway.
Yang L et al.·Cell Death Dis
2025
Centrosome amplification-related signature correlated with immune microenvironment and treatment response predicts prognosis and improves diagnosis of hepatocellular carcinoma by integrating machine learning and single-cell analyses.
Liu Y et al.·Hepatol Int
2024
Migraine in monogenic disorders: Shedding light on new therapeutic targets.
Mascarella D et al.·Cephalalgia
2025Review
A novel CSNK1Dvariant in pediatric advanced sleep-wake phase syndrome.
Pisanò G et al.·Sleep Med
2025Case report
Genetic variants associated with sleep disorders.
Kripke DF et al.·Sleep Med
2015
Upregulation of Stress-Induced Protein Kinase CK1 Delta is associated with a Poor Prognosis for patients with Hepatocellular Carcinoma.
Zhang H et al.·Genet Test Mol Biomarkers
2021Cohort
The impact of Mendelian sleep and circadian genetic variants in a population setting.
Weedon MN et al.·PLoS Genet
2022
Casein kinase 1 family member CSNK1E can regulate proliferation and migration in hepatocellular carcinoma.
Zhou J et al.·J Cancer Res Clin Oncol
2025
Identifying prognostic hub genes and key pathways in pediatric adrenocortical tumors through RNA sequencing and Co-expression analysis.
Veronez LC et al.·Mol Cell Endocrinol
2024
Dysregulation of Circadian Clock Genes Associated with Tumor Immunity and Prognosis in Patients with Colon Cancer.
He Y et al.·Comput Math Methods Med
2022Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools