Table 1 Overview of CDKs and cyclins involved in developmental disorders
From: Cyclin-dependent kinases and rare developmental disorders
Gene | CDK or cyclin subfamily; CDK or cyclin main partner(s) | Disease (phenotype MIM number) | Inheritance | Mutations | Functional impact (mechanism) | References |
|---|---|---|---|---|---|---|
CDK5 | Atypical; p25/p35 | Lissencephaly 7 with cerebellar hypoplasia (616342) | Autosomal Recessive | Splice site | Loss of function (NMD) | [7] |
CDK6 | Cell Cycle; D-type cyclins (CCND1,2,3) | Primary microcephaly 12 (616080) | Autosomal Recessive | Missense | Loss of function (misslocalization) | [8] |
CDK8 | Transcriptional; Cyclin C (CCNC) | Intellectual developmental disorder with hypotonia and behavioral abnormalities (618748) | Autosomal Dominant | Missense in kinase domain | Loss of function (dominant negative effects?) | [9] |
CDK10 | Transcriptional; Cyclin M (CCNQ) | Al Kaissi syndrome (617694) | Autosomal Recessive | - Splice sites - Deletions - Frameshift | Loss of function (NMD) Misslocalization? | |
CDK13 | Transcriptional; Cyclin K (CCNK) | Congenital heart defects, dysmorphic facial features, intellectual developmental disorder (617360) | Autosomal Dominant | - Missense - Splice site - Nonsense - Frameshift | Loss of function (dominant negative effects? haploinsufficiency?) | |
CDK19 | Transcriptional; Cyclin C (CCNC) | Bilateral congenital retinal folds, microcephaly and mild mental retardation (unavailable) | Autosomal Dominant | Chromosomal pericentric inversion | Haploinsufficiency | [21] |
CCND2 | Cell Cycle; CDK6 | Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3 (615938) | Autosomal Dominant | - Missense - Nonsense | Gain of function (stabilization) | [22] |
CCNK | Transcriptional; CDK12 and CDK13 | Intellectual developmental disorder with hypertelorism and distinctive facies (618147) | Autosomal Dominant | - Deletion - Missense | Loss of function (haploinsufficiency) | [23] |
CCNO | Atypical; unknown | Primary ciliary dyskinesia 29 (615872) | Autosomal Recessive | -Frameshift - Missense - Nonsense | Loss of function (truncations, 1 missense) | |
CCNQ | Transcriptional; CDK10 | STAR syndrome (300707) | X-linked Dominant | - Deletions - Splice site - Frameshift | Loss of function |