CSNK1E

Chr 22

casein kinase 1 epsilon

Also known as: CKIe, CKIepsilon, HCKIE

NCBI Gene: 1454ENSG00000213923UniProt: P49674OMIM: 600863

The encoded protein is a serine/threonine kinase that phosphorylates key substrates in Wnt signaling pathways and serves as a central component of the circadian clock by regulating PER1 and PER2 phosphorylation, nuclear transport, and degradation. Mutations cause autosomal dominant familial advanced sleep phase syndrome, characterized by very early sleep and wake times. This gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to have severe consequences.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.14
Clinical Summary— CSNK1E
⚡
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
23 unique Pathogenic / Likely Pathogenic· 35 VUS of 79 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.14LOEUF
pLI 0.999
Z-score 4.23
OE 0.00 (0.00–0.14)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
3.18Z-score
OE missense 0.47 (0.41–0.55)
136 obs / 287.8 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.00 (0.00–0.14)
0≤0.351.4
Missense OE0.47 (0.41–0.55)
0≤0.61.4
Synonymous OE0.97
0≤1.21.6
LoF obs/exp: 0 / 20.8Missense obs/exp: 136 / 287.8Syn Z: 0.24
DN
0.5575th %ile
GOF
0.4382th %ile
LOF
0.68top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.14

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

79 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic3
VUS35
Benign3
Conflicting1
20
Pathogenic
3
Likely Pathogenic
35
VUS
3
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
19
0
20
Likely Pathogenic
0
0
3
0
3
VUS
0
34
1
0
35
Likely Benign
0
0
0
0
0
Benign
0
0
2
1
3
Conflicting
—1
Total13425162

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

View in ClinVar →

Protein Context — Lollipop Plot

CSNK1E · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients