CILK1
protein-codingciliogenesis associated kinase 1
Gene summary
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]
- ICK
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~60.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0005308
Submitter: ClinGen
The *CILK1* gene is located on chromosome 6 at 6p12.1 and encodes a ciliogenesis-associated kinase 1 that is important for regulating primary cilia formation, length, and intraflagellar transport. Multiple disease entities have been reported in association with this gene: Epilepsy, juvenile myoclonic susceptibility to 10 (MIM:617924); Cranioectodermal dysplasia 6 (MIM: 621337); and Endocrine-cerebroosteodysplasia (MIM:612651). Per criteria outlined by the ClinGen Lumping and Splitting Working Group, there was evidence of differences in molecular mechanism and inheritance pattern between Epilepsy, juvenile myoclonic susceptibility to 10 and the other assertions. Therefore, the following disease entities have been lumped into one disease entity: Cranioectodermal dysplasia 6, and Endocrine-cerebroosteodysplasia. The Epilepsy, juvenile myoclonic susceptibility to 10 assertion has been split and will be curated by the Epilepsy GCEP. Ciliopathy-*CILK1* was first reported in 2009 (Lahiry et al., 2009, PMID: 19185282). Four unique variants (three missense, one frameshift) from five probands across three publications have been identified (PMID: 19185282, 27069622, 40615527). The mechanism of disease is loss-of-function. This gene-disease relationship is also supported by animal models, rescue, functional alteration, and biochemical evidence (PMIDs: 19185282, 27069622, 27466187, 40615527). In summary, there is definitive evidence supporting the relationship between *CILK1* and autosomal recessive ciliopathy-*CILK1*. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Kidney Cystic and Ciliopathy Disorders GCEP on November 26th, 2025 (SOP Version 11).
Inheritance Pattern: AD
Disease ID:MONDO:0009696
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0012980
Submitter: Genomics England PanelApp
Inheritance Pattern: AR
Disease ID:MONDO:0012980
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0012980
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0012980
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Endocrine; Genitourinary; Musculoskeletal; Neurologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CILK1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014920.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 5 | 69 | 1 | 75 | ||
| missense | 2 | 1 | 136 | 17 | 156 | |
| nonsense | 3 | 7 | 10 | |||
| start loss | 0 | |||||
| frameshift | 1 | 1 | 2 | |||
| splice donor/acceptor (+/-2bp) | 1 | 2 | 3 | |||
| Total | 3 | 5 | 151 | 86 | 1 | 246 |
Highest pathogenic variant AF is 0.000004956918
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055735.1 | 13 | MANE Select | |
| Ensembl | ENSP00000501692.1 | 13 | MANE Select | |
| RefSeq | NP_001362326.1 | 13 | Standard | |
| RefSeq | NP_001362327.1 | 13 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- protein phosphorylation
- signal transduction
- multicellular organism development
- regulation of gene expression
- intracellular signal transduction
Molecular Function
- magnesium ion binding
- protein kinase activity
- protein serine/threonine kinase activity
- protein binding
- ATP binding
Cellular Component
- fibrillar center
- nucleus
- cytoplasm
- cytosol
- cilium
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000356971
- Coding exons
- 13
- Length
- 60524
- Individuals with no LoFs
- 125712
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 36
- Defined
- 125748
- p
- 0.000143
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.24 | 276 | 340 | 0.811 | 0.0000183 | 4123 |
| Missense (PolyPhen) | 76 | 106.5 | 0.71359 | 1297 | ||
| Synonymous | -0.500 | 131 | 124 | 1.06 | 0.00000666 | 1237 |
| Loss of Function | 3.42 | 15 | 37.7 | 0.398 | 0.00000248 | 388 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00031 | 0.00031 | rare |
| Latino/Admixed American | 0.00026 | 0.00026 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00043 | 0.00044 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000097 | 0.000097 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Required for ciliogenesis (PubMed:24797473). Phosphorylates KIF3A (By similarity). Involved in the control of ciliary length (PubMed:24853502). Regulates the ciliary localization of SHH pathway components as well as the localization of IFT components at ciliary tips (By similarity). May play a key role in the development of multiple organ systems and particularly in cardiac development (By similarity). Regulates intraflagellar transport (IFT) speed and negatively regulates cilium length in a cAMP and mTORC1 signaling-dependent manner and this regulation requires its kinase activity (By similarity). {ECO:0000250|UniProtKB:Q62726, ECO:0000250|UniProtKB:Q9JKV2, ECO:0000269|PubMed:24797473, ECO:0000269|PubMed:24853502}.;
- Disease
- DISEASE: Endocrine-cerebroosteodysplasia (ECO) [MIM:612651]: Previously unidentified neonatal lethal recessive disorder with multiple anomalies involving the endocrine, cerebral, and skeletal systems. {ECO:0000269|PubMed:19185282, ECO:0000269|PubMed:24797473, ECO:0000269|PubMed:24853502, ECO:0000269|PubMed:29539279}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Juvenile myoclonic epilepsy 10 (EJM10) [MIM:617924]: A form of juvenile myoclonic epilepsy, a subtype of idiopathic generalized epilepsy generally characterized by afebrile seizures with onset in adolescence (rather than in childhood) and myoclonic jerks, which usually occur after awakening and are triggered by sleep deprivation and fatigue. EJM10 is an autosomal dominant seizure disorder with variable manifestations, even within families. Affected individuals have febrile, myoclonic, tonic- clonic, or absence seizures, although several seizure types can occur in the same individual. Some patients have onset of seizures in the first years of life. {ECO:0000269|PubMed:29539279}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.0861
Intolerance Scores
- LoFtool
- 0.665
- RVIS EVS
- -0.2
- RVIS percentile EVS
- 39.11
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.654
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |