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Intellectual disability

Gene: CCNK

Amber List (moderate evidence)
CCNK (cyclin K)
EnsemblGeneIds (GRCh38): ENSG00000090061
EnsemblGeneIds (GRCh37): ENSG00000090061
OMIM: 603544, Gene2Phenotype
CCNK is in 2 panels

1 review

Ida Ertmanska (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There are at least 3 unrelated individuals reported in literature with de novo missense variants in CCNK, diagnosed with Intellectual developmental disorder with hypertelorism and distinctive facies. There are also several individuals reported with deletions affecting CCNK among other genes - these deletions are generally associated with a more severe phenotype. Functional evidence for this gene-disease association includes zebrafish and mouse knockdowns, which recapitulate features of human disease. Based on the available evidence, this gene should be promoted to Green for Intellectual disability.
Created: 24 Nov 2025, 12:12 p.m. | Last Modified: 24 Nov 2025, 12:13 p.m.
Panel Version: 9.190
PMID: 30122539 Fan et al., 2018
Report of 3 unrelated Chinese individuals with de novo heterozygous copy number loss of CCNK in an overlapping 14q32.3 region (with several other genes being deleted) and 1 African American individual harbouring a de novo CCNK variant c.331A>G (p.Lys111Glu) - variant not present in gnomAD v4; Revel score = 0.52. Common phenotype: developmental delay and moderate (1/4) to severe (3/4) intellectual disability (DD/ID), language defects, distinctive facial dysmorphism. 4/4 cases confirmed as de novo.
Functional evidence: Ccnk knockdown in zebrafish resulted in defective brain development, small eyes, and curly spinal cord; defects were partially rescued by WT CCNK mRNA but not by the c.331A>G mRNA variant.

PMID: 35063350 Rouxel et al., 2022
ID B5 - 1.5 yr old female, het for a missense variant in CCNK (variant not specified); phenotype: distinctive facial features matching CDK13-deficient patients, neuropsychological assessment not conducted; high methylation variant pathogenicity (MVP) score - methylation score matched individuals with pathogenic CDK13 variants; CDK13 forms a complex with cyclin K (encoded by CCNK).

PMID: 37597256 Dai et al., 2023
Report of 2 new (P1 & P3) and 3 previously reported cases. Seq method: exome seq + Sanger.
Patient 1 - Chinese Female 1 y 4 mo; het for c.556T>C, p.(Trp186Arg) - de novo; Moderate DD/ID, distinctive facial features, congenital cardiac defects. Variant not reported in gnomAD v4.
Patient 3 - Chinese Female 5 y 4 mo; het for c.772T>C, p.(Tyr258His) - de novo; Mild DD/ID (IQ 59 - WPPSI scale), facial dysmorphisms. Variant not reported in gnomAD v4.
Functional evidence: Ccnk +/- knockdown mouse model showed deficient neural progenitor cell proliferation and enhanced apoptotic cell death.

PMID: 41101726 Xiol et al., Oct 2025 - online ahead of print
Report of an 11yr old girl with a de novo CCNK missense variant c.549A>C, p.(Gln183His) - not in gnomAD v4.1.0, Revel score = 0.43; phenotype: mild intellectual disability (WISC-V at 10yrs showed IQ of 69), subtle dysmorphism (hypertelorism, depressed/broad nasal bridge), ventriculomegaly, delayed motor milestones & hypotonia.

CCNK pLI score = 1.00 - predicted to be extremely intolerant to LoF. CCNK is putatively associated with AD Intellectual developmental disorder with hypertelorism and distinctive facies, MIM:618147 (OMIM accessed 24th Nov 2025).
Sources: Literature
Created: 24 Nov 2025, 10:44 a.m. | Last Modified: 24 Nov 2025, 12:14 p.m.
Panel Version: 9.190

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
?Intellectual developmental disorder with hypertelorism and distinctive facies, OMIM:618147; intellectual developmental disorder with hypertelorism and distinctive facies, MONDO:0029143

Publications

Created: 24 Nov 2025, 10:44 a.m.
Last Modified: 24 Nov 2025, 12:14 p.m.
Panel version: 9.190

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Amber
  • Literature
Phenotypes
  • ?Intellectual developmental disorder with hypertelorism and distinctive facies, OMIM:618147
  • intellectual developmental disorder with hypertelorism and distinctive facies, MONDO:0029143
Tags
Q4_25_promote_green
OMIM
603544
Clinvar variants
Variants in CCNK
Penetrance
None
Publications
Panels with this gene

History Filter Activity

24 Nov 2025, Gel status: 2

Set Phenotypes

Ida Ertmanska (Genomics England Curator)

Phenotypes for gene: CCNK were changed from ?Intellectual developmental disorder with hypertelorism and distinctive facies, OMIM:618147 to ?Intellectual developmental disorder with hypertelorism and distinctive facies, OMIM:618147; intellectual developmental disorder with hypertelorism and distinctive facies, MONDO:0029143

24 Nov 2025, Gel status: 2

Entity classified by Genomics England curator

Ida Ertmanska (Genomics England Curator)

Gene: ccnk has been classified as Amber List (Moderate Evidence).

24 Nov 2025, Gel status: 1

Created, Added New Source, Added Tag, Set mode of inheritance, Set publications, Set Phenotypes

Ida Ertmanska (Genomics England Curator)

gene: CCNK was added gene: CCNK was added to Intellectual disability. Sources: Literature Q4_25_promote_green tags were added to gene: CCNK. Mode of inheritance for gene: CCNK was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: CCNK were set to 30122539; 35063350; 37597256; 41101726 Phenotypes for gene: CCNK were set to ?Intellectual developmental disorder with hypertelorism and distinctive facies, OMIM:618147 Review for gene: CCNK was set to GREEN