CILK1

Chr 6ADAR

ciliogenesis associated kinase 1

Also known as: CED6, ECO, EJM10, ICK, LCK2, MRK, hICK

NCBI Gene: 22858ENSG00000112144UniProt: Q9UPZ9

Eukaryotic protein kinases are enzymes that belong to a very extensive family of proteins which share a conserved catalytic core common with both serine/threonine and tyrosine protein kinases. This gene encodes an intestinal serine/threonine kinase harboring a dual phosphorylation site found in mitogen-activating protein (MAP) kinases. The protein localizes to the intestinal crypt region and is thought to be important in intestinal epithelial cell proliferation and differentiation. Alternative splicing has been observed at this locus and two variants, encoding the same isoform, have been identified. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

{Epilepsy, juvenile myoclonic, susceptibility to, 10}MIM #617924
AD
Cranioectodermal dysplasia 6MIM #621337
AR
Endocrine-cerebroosteodysplasiaMIM #612651
AR
280
ClinVar variants
16
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CILK1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
16 Pathogenic / Likely Pathogenic· 140 VUS of 280 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.61LOEUF
pLI 0.000
Z-score 3.42
OE 0.40 (0.27–0.61)
Tolerant

Typical tolerance to LoF variation

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.
1.24Z-score
OE missense 0.81 (0.73–0.90)
276 obs / 340.2 exp
Tolerant

Mild missense constraint

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.0.40 (0.27–0.61)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.81 (0.73–0.90)
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.1.06
0≤1.21.6
LoF obs/exp: 15 / 37.7Missense obs/exp: 276 / 340.2Syn Z: -0.50

ClinVar Variant Classifications

280 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic5
VUS140
Likely Benign98
Benign18
Conflicting8
11
Pathogenic
5
Likely Pathogenic
140
VUS
98
Likely Benign
18
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
2
8
0
11
Likely Pathogenic
1
1
3
0
5
VUS
3
119
15
3
140
Likely Benign
1
8
31
58
98
Benign
0
3
13
2
18
Conflicting
—8
Total61337063280

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

View in ClinVar →

Protein Context — Lollipop Plot

CILK1 · 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

{Epilepsy, juvenile myoclonic, susceptibility to, 10}

MIM #617924

Molecular basis of disorder known

Autosomal dominant

Cranioectodermal dysplasia 6

MIM #621337

Molecular basis of disorder known

Autosomal recessive

Endocrine-cerebroosteodysplasia

MIM #612651

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — CILK1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
An Epilepsy-Associated CILK1 Variant Compromises KATNIP Regulation and Impairs Primary Cilia and Hedgehog Signaling.
Limerick A et al.·Cells
2024
Human disease variants of KATNIP fail to support CILK1 activation and control of primary cilia.
Carpenter EH et al.·J Cell Sci
2025
A homozygous frameshift variant in the CILK1 gene causes cranioectodermal dysplasia.
Sezer A et al.·Eur J Hum Genet
2025Case report
Functional Alterations in Ciliogenesis-Associated Kinase 1 (CILK1) that Result from Mutations Linked to Juvenile Myoclonic Epilepsy.
Wang EJ et al.·Cells
2020Functional
Molecular basis underlying the ciliary defects caused by IFT52 variations found in skeletal ciliopathies.
Ishida Y et al.·Mol Biol Cell
2022
An Overview of Drug-Resistant Epilepsies Based on Advances in Genetics: A Cohort Study.
Kılıç B et al.·Neurol India
2026Review
The carboxyl-terminal region of SDCCAG8 comprises a functional module essential for cilia formation as well as organ development and homeostasis.
Tsutsumi R et al.·J Biol Chem
2022Functional
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