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…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.14

LOEUF· LoF intol.

LOF

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in CSNK1E?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 69

691 rare PASS variants

Rare truncating (LoF)

1 in 1,600

80 rare PASS variants

Rare synonymous (reference)

1 in 120

374 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CSNK1E. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 140	1 in 1,500
South Asian	~43k	1 in 71	1 in 3,300
Remaining (unassigned)	~30k	1 in 69	1 in 1,300
European (Finnish)	~27k	1 in 210	1 in 1,100
Admixed American	~22k	1 in 79	1 in 1,800
African / African American	~21k	1 in 110	1 in 1,700
East Asian	~20k	1 in 90	1 in 1,200
Ashkenazi Jewish	~13k	1 in 400	≈ 1 in 3,000
Middle Eastern	~2,884	1 in 65	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 9 coding exons well covered in gnomAD exomes and genomes.? see exons ↓