CILK1

ciliogenesis associated kinase 1

Basic information

Region (hg38): 6:53001279-53061824

Previous symbols: [ "ICK" ]

Links

ENSG00000112144

∙ NCBI:22858 ∙ OMIM:612325 ∙ HGNC:21219 ∙ Uniprot:Q9UPZ9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

endocrine-cerebro-osteodysplasia syndrome (Moderate), mode of inheritance: AR
juvenile myoclonic epilepsy (Supportive), mode of inheritance: AD
endocrine-cerebro-osteodysplasia syndrome (Supportive), mode of inheritance: AR
endocrine-cerebro-osteodysplasia syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epilepsy, juvenile myoclonic, susceptibility to, 10; Endocrine-cerebroosteodysplasia	AD/AR	General	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	Craniofacial; Endocrine; Genitourinary; Musculoskeletal; Neurologic	19185282; 29539279

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CILK1 gene.

not_provided (172 variants)
not_specified (84 variants)
CILK1-related_disorder (14 variants)
Epilepsy,_juvenile_myoclonic,_susceptibility_to,_10 (10 variants)
Endocrine-cerebro-osteodysplasia_syndrome (9 variants)
Dysplastic_corpus_callosum (2 variants)
Congenital_ocular_coloboma (2 variants)
Microphthalmia (2 variants)
Short_rib-polydactyly_syndrome (1 variants)
Cranioectodermal_dysplasia (1 variants)
CRANIOECTODERMAL_DYSPLASIA_6 (1 variants)
See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CILK1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000014920.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			5 clinvar	54 clinvar	2 clinvar	61
missense	2 clinvar	1 clinvar	117 clinvar	14 clinvar	2 clinvar	136
nonsense		1 clinvar	6 clinvar			7
start loss						0
frameshift	1 clinvar		1 clinvar			2
splice donor/acceptor (+/-2bp)		1 clinvar	2 clinvar			3
Total	3	3	131	68	4

Highest pathogenic variant AF is 0.000004956918

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CILK1	protein_coding	protein_coding	ENST00000356971	13	60524

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000134	1.00	125712	0	36	125748	0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.24	276	340	0.811	0.0000183	4123
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000568	0.000568
Ashkenazi Jewish	0.00	0.00
East Asian	0.000435	0.000435
Finnish	0.00	0.00
European (Non-Finnish)	0.0000970	0.0000967
Middle Eastern	0.000435	0.000435
South Asian	0.0000327	0.0000327
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

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

Haploinsufficiency Scores

pHI: 0.225
hipred: Y
hipred_score: 0.756
ghis: 0.518

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.654

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Ick
Phenotype: growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); craniofacial phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); skeleton phenotype; renal/urinary system phenotype; digestive/alimentary phenotype; limbs/digits/tail phenotype;

Gene ontology

Biological process: protein phosphorylation;signal transduction;multicellular organism development;regulation of gene expression;intracellular signal transduction;intraciliary anterograde transport;intraciliary retrograde transport;intraciliary transport;cilium assembly
Cellular component: fibrillar center;nucleus;cytoplasm;cytosol;cilium;ciliary basal body;ciliary tip;ciliary base
Molecular function: magnesium ion binding;protein kinase activity;protein serine/threonine kinase activity;protein binding;ATP binding