CDKL5
Homo sapiens
Gene Name: cyclin-dependent kinase-like 5
Aliases: STK9
Chromosome No: X
Chromosome Band: Xp22.13
Genetic Category: Syndromic-Rare Single Gene variant--Rare single gene variant/syndromic-Multigenic CNV-Functional
Associated Syndrome(s): Early infantile epileptic encephalopathy-2,Rett syndrome
Aliases: STK9
Chromosome No: X
Chromosome Band: Xp22.13
Genetic Category: Syndromic-Rare Single Gene variant--Rare single gene variant/syndromic-Multigenic CNV-Functional
Associated Syndrome(s): Early infantile epileptic encephalopathy-2,Rett syndrome
Summary Statistics:
ASD Reports: 67
Recent Reports: 10
Annotated variants: 139
Associated CNVs: 12
Evidence score: 4
ASD Reports: 67
Recent Reports: 10
Annotated variants: 139
Associated CNVs: 12
Evidence score: 4
| Associated Disorders: |
|
Relevance to Autism
This gene has been identified with syndromic autism, where a subpopulation of individuals with a given syndrome develop autism. In particular, studies have found that rare mutations in the CDKL5 gene are identified with Rett syndrome. In addition, CDKL5 mutations have also been identified with epilepsy and Angelman syndrome.
Molecular Function
This gene is a member of Ser/Thr protein kinase family and encodes a phosphorylated protein with protein kinase activity.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Mutations of CDKL5 cause a severe neurodevelopmental disorder with infantile spasms and mental retardation.
Rett syndrome
Positive Association
De novo mutations in epileptic encephalopathies.
Epilepsy
IS, LGS, DD, ID, ASD, ADHD
Support
Autism spectrum disorder and comorbid neurodevelopmental disorders (ASD-NDDs): Clinical and genetic profile of a pediatric cohort
ASD
Epilepsy/seizures
Support
Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test.
ASD, ID, epilepsy/seizures
Support
The impact of inversions across 33,924 families with rare disease from a national genome sequencing project
DD, ID, epilepsy/seizures
Support
Analysis of the effects of rare variants on splicing identifies alterations in GABAA receptor genes in autism spectrum disorder individuals.
ASD, SCZ
Support
Behavioral impulsivity is associated with pupillary alterations and hyperactivity in CDKL5 mutant mice
Developmental and epileptic encephalopathy 2
Support
Neurological Diseases With Autism Spectrum Disorder: Role of ASD Risk Genes.
ASD
Epilepsy/seizures
Support
Perirhinal cortex abnormalities impair hippocampal plasticity and learning in Scn2a, Fmr1, and Cdkl5 autism mouse models
ASD
Support
Gene Mutation Analysis in 253 Chinese Children with Unexplained Epilepsy and Intellectual/Developmental Disabilities.
DD, ID, epilepsy/seizures
Support
Prevalence and phenotypic impact of rare potentially damaging variants in autism spectrum disorder
ASD
Support
Diagnostic Targeted Resequencing in 349 Patients with Drug-Resistant Pediatric Epilepsies Identifies Causative Mutations in 30 Different Genes.
Epilepsy/seizures
West syndrome
Support
Phenotypic and genetic analysis of children with unexplained neurodevelopmental delay and neurodevelopmental comorbidities in a Chinese cohort using trio-based whole-exome sequencing
ASD, ADHD, DD, ID, epilepsy/seizures
Support
CDKL5 gene status in female patients with epilepsy and Rett-like features: two new mutations in the catalytic domain.
Epilepsy
Support
Cdkl5 mutant zebrafish shows skeletal and neuronal alterations mimicking human CDKL5 deficiency disorder
Developmental and epileptic encephalopathy 2
Support
The combination of whole-exome sequencing and copy number variation sequencing enables the diagnosis of rare neurological disorders.
Epilepsy/seizures
DD, microcephaly, stereotypies
Support
Unveiling genetic insights: Array-CGH and WES discoveries in a cohort of 122 children with essential autism spectrum disorder
ASD
Support
Integrated analysis of whole-exome sequencing and transcriptome profiling in males with autism spectrum disorders.
ASD
Support
Genome sequencing of 320 Chinese children with epilepsy: a clinical and molecular study
DD, epilepsy/seizures
Support
Clinical exome sequencing: results from 2819 samples reflecting 1000 families.
Early infantile epileptic encephalopathy-2
DD, epilepsy/seizures
Support
Biallelic variants identified in 36 Pakistani families and trios with autism spectrum disorder
ASD
ID
Support
Application of array comparative genomic hybridization in 102 patients with epilepsy and additional neurodevelopmental disorders.
Epilepsy
ASD, DD, ID
Support
Genetic analysis using targeted exome sequencing of 53 Vietnamese children with developmental and epileptic encephalopathies
DD, epilepsy/seizures
Support
Targeted resequencing of 358 candidate genes for autism spectrum disorder in a Chinese cohort reveals diagnostic potential and genotype-phenotype c...
ASD
Support
The genetic landscape of autism spectrum disorder in an ancestrally diverse cohort
ASD
Support
Large-scale discovery of novel genetic causes of developmental disorders.
DD
Support
Confirming the contribution and genetic spectrum of de novo mutation in infantile spasms: Evidence from a Chinese cohort
Epilepsy/seizures
ASD, DD
Support
The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies.
DD, seizures
Support
Validation of targeted next-generation sequencing panels in a cohort of Polish patients with epilepsy: assessing variable performance across clinical endophenotypes and uncovering novel genetic varian
Epilepsy/seizures
ID
Support
Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders.
ASD
Support
Not Just Loss-of-Function Variations: Identification of a Hypermorphic Variant in a Patient With a CDKL5 Missense Substitution
DD, epilepsy/seizures
Support
Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.
ASD
Support
Genomic insights from a deeply phenotyped highly consanguineous neurodevelopmental disorders cohort
DD
Epilepsy/seizures
Support
Neurodevelopmental and neurobehavioral characteristics in males and females with CDKL5 duplications.
ASD, DD, ID
ADHD, OCD, sensory integration disorder
Support
De novo variants in neurodevelopmental disorders-experiences from a tertiary care center
DD, epilepsy/seizures
Support
De novo genic mutations among a Chinese autism spectrum disorder cohort.
ASD
Support
Clinical Utility of Proband Only Clinical Exome Sequencing in Neurodevelopmental Disorders
ASD, DD, epilepsy/seizures
Support
Cortical Visual Impairment in CDKL5 Deficiency Disorder
Developmental and epileptic encephalopathy 2
Support
High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies.
Epilepsy/seizures
DD/ID
Support
Autistic-relevant behavioral phenotypes of a mouse model of cyclin-dependent kinase-like 5 deficiency disorder
Developmental and epileptic encephalopathy 2
ASD
Support
Clinical features and gene mutational spectrum of CDKL5-related diseases in a cohort of Chinese patients.
DD, epilepsy
Autistic features
Support
Next Generation Sequencing of 134 Children with Autism Spectrum Disorder and Regression
ASD
Developmental regression
Support
Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior.
ASD
Support
CDKL5 deficiency in adult glutamatergic neurons alters synaptic activity and causes spontaneous seizures via TrkB signaling
Epilepsy/seizures
Support
Novel preclinical model for CDKL5 deficiency disorder
Developmental and epileptic encephalopathy 2
Support
Targeted sequencing and functional analysis reveal brain-size-related genes and their networks in autism spectrum disorders.
ASD
Support
Enhanced hippocampal LTP but normal NMDA receptor and AMPA receptor function in a rat model of CDKL5 deficiency disorder
Support
Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.
Epilepsy
ID, ASD, DD
Support
Neuronal hyperexcitability and ion channel dysfunction in CDKL5-deficiency patient iPSC-derived cortical organoids
Developmental and epileptic encephalopathy 2
Support
Phenotypic manifestations between male and female children with CDKL5 mutations.
Early infantile epileptic encephalopathy-2
Autistic features, stereotypic hand movements
Support
Mutations in HECW2 are associated with intellectual disability and epilepsy.
ID, epilepsy/seizures
Recent Recommendation
CDKL5 ensures excitatory synapse stability by reinforcing NGL-1-PSD95 interaction in the postsynaptic compartment and is impaired in patient iPSC-d...
Recent Recommendation
Extrasynaptic N-methyl-D-aspartate (NMDA) receptor stimulation induces cytoplasmic translocation of the CDKL5 kinase and its proteasomal degradation.
Recent Recommendation
A girl with early-onset epileptic encephalopathy associated with microdeletion involving CDKL5.
Recent Recommendation
Mutations in MEF2C from the 5q14.3q15 microdeletion syndrome region are a frequent cause of severe mental retardation and diminish MECP2 and CDKL5 ...
Recent Recommendation
Incorporating Functional Information in Tests of Excess De Novo Mutational Load.
Recent Recommendation
A novel mutation in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene associated with a severe Rett phenotype.
Rett syndrome
Recent Recommendation
Loss of CDKL5 impairs survival and dendritic growth of newborn neurons by altering AKT/GSK-3 signaling.
Recent Recommendation
Novel mutations in the CDKL5 gene, predicted effects and associated phenotypes.
Rett syndrome, Angelman syndrome
Recent Recommendation
GluD1 is a common altered player in neuronal differentiation from both MECP2-mutated and CDKL5-mutated iPS cells.
Recent Recommendation
CDKL5 mutations cause infantile spasms, early onset seizures, and severe mental retardation in female patients.
Epilepsy
Rare
Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
GEN046R010
inframe_indel
c.del678_691ins683_673
p.Gly228_Pro231delinsAlaProSer
Unknown
GEN046R026
frameshift_variant
c.510_511dup
p.Tyr171CysfsTer58
Unknown
Simplex
GEN046R028
inframe_deletion
c.1455_1460del
p.Ala486_Lys487del
Familial
Maternal
Simplex
GEN046R051
frameshift_variant
c.890_891dup
p.Gln298PhefsTer53
De novo
Multiplex
GEN046R062
missense_variant
c.104C>T
p.Thr35Ile
De novo
Simplex
GEN046R063
missense_variant
c.1940C>T
p.Pro647Leu
Familial
Maternal
Simplex
GEN046R067a
2KB_upstream_variant
c.-163+1683_-163+1684insGTAGAGCT
Familial
Both parents
Unknown
GEN046R068a
2KB_upstream_variant
c.-163+1683_-163+1684insGTAGAGCT
Familial
Both parents
Unknown
GEN046R081
frameshift_variant
c.1292_1293del
p.Thr431LysfsTer31
De novo
Simplex
GEN046R125
missense_variant
c.532C>T
p.Arg178Trp
Familial
Maternal
Simplex
GEN046R127
frameshift_variant
c.2009_2012dup
p.Thr672ArgfsTer12
Unknown
Simplex
GEN046R135
missense_variant
c.761A>G
p.His254Arg
Familial
Maternal
Simplex
GEN046R136
missense_variant
c.2482G>C
p.Asp828His
Familial
Maternal
Simplex
GEN046R137
missense_variant
c.1178C>T
p.Thr393Ile
Familial
Maternal
Simplex
Common
No Common Variants Available
