CSNK1E

Chr 22

casein kinase 1 epsilon

Also known as: CKIe, CKIepsilon, HCKIE

NCBI Gene: 1454 ENSG00000213923 UniProt: P49674 OMIM: 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.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a serine/threonine protein kinase and a member of the casein kinase I protein family, whose members have been implicated in the control of cytoplasmic and nuclear processes, including DNA replication and repair. The encoded protein is found in the cytoplasm as a monomer and can phosphorylate a variety of proteins, including itself. This protein has been shown to phosphorylate period, a circadian rhythm protein. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Feb 2014]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.14

Clinical Summary— CSNK1E

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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.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 34 VUS of 55 total submissions

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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 OE?0.00 (0.00–0.14)

0≤0.351.4

Missense OE?0.47 (0.41–0.55)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 0 / 20.8Missense obs/exp: 136 / 287.8Syn Z: 0.24

This gene — mechanism propensity

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

55 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS34

Benign3

Pathogenic

VUS

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	0	0	1
Likely Pathogenic	0	0	0	0	0
VUS	0	34	0	0	34
Likely Benign	0	0	0	0	0
Benign	0	0	2	1	3
Total	1	34	2	1	38

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

View in ClinVar →

22 pathogenic / likely-pathogenic (of 24) ClinVar copy-number / structural variants overlap CSNK1E — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →