HELP     Sign In
Search

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
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
Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders.
ASD
Support
Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.
ASD
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
High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies.
Epilepsy/seizures
DD/ID
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
Targeted sequencing and functional analysis reveal brain-size-related genes and their networks in autism spectrum disorders.
ASD
Support
Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.
Epilepsy
ID, ASD, DD
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
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
Analysis of the effects of rare variants on splicing identifies alterations in GABAA receptor genes in autism spectrum disorder individuals.
ASD, SCZ
Support
Neurological Diseases With Autism Spectrum Disorder: Role of ASD Risk Genes.
ASD
Epilepsy/seizures
Support
Gene Mutation Analysis in 253 Chinese Children with Unexplained Epilepsy and Intellectual/Developmental Disabilities.
DD, ID, epilepsy/seizures
Support
Diagnostic Targeted Resequencing in 349 Patients with Drug-Resistant Pediatric Epilepsies Identifies Causative Mutations in 30 Different Genes.
Epilepsy/seizures
West syndrome
Support
CDKL5 gene status in female patients with epilepsy and Rett-like features: two new mutations in the catalytic domain.
Epilepsy
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
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
Application of array comparative genomic hybridization in 102 patients with epilepsy and additional neurodevelopmental disorders.
Epilepsy
ASD, DD, ID
Support
Targeted resequencing of 358 candidate genes for autism spectrum disorder in a Chinese cohort reveals diagnostic potential and genotype-phenotype c...
ASD
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
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.

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN046R001 
 frameshift_variant 
 c.183del 
 p.Met63CysfsTer13 
  
  
  
 GEN046R002 
 splice_site_variant 
 G>A 
 p.? 
 De novo 
 NA 
  
 GEN046R003 
 intron_variant 
 C>G 
  
  
  
  
 GEN046R004 
 missense_variant 
 c.2378T>C 
 p.Val793Ala 
  
  
  
 GEN046R005 
 intron_variant 
 IVS11-42_50del9 
  
 Unknown 
  
  
 GEN046R006 
 splice_site_variant 
 G>T 
 p.? 
  
  
  
 GEN046R007 
 splice_site_variant 
 A>G 
  
  
  
  
 GEN046R008 
 splice_site_variant 
 G>A 
 p.? 
  
  
  
 GEN046R009 
 frameshift_variant 
 c.2363_2367del 
 p.Lys788IlefsTer11 
  
  
  
 GEN046R010 
 inframe_variant 
 c.del678_691ins683_673 
 p.Gly228_Pro231delinsAlaProSer 
 Unknown 
  
  
 GEN046R011 
 stop_gained 
 c.175C>T 
 p.Arg59Ter 
  
  
  
 GEN046R012 
 missense_variant 
 c.539C>T 
 p.Pro180Leu 
  
  
  
 GEN046R013 
 splice_site_variant 
 c.145+2T>C 
  
 De novo 
 NA 
  
 GEN046R014 
 missense_variant 
 c.215T>C 
 p.Ile72Thr 
 De novo 
 NA 
  
 GEN046R015 
 stop_gained 
 c.1648C>T 
 p.Arg550Ter 
 De novo 
 NA 
  
 GEN046R016 
 frameshift_variant 
 c.-161del 
  
 Unknown 
  
 Unknown 
 GEN046R017 
 frameshift_variant 
 c.902_903dup 
 p.Leu302AspfsTer49 
 De novo 
 NA 
  
 GEN046R018 
 missense_variant 
 c.380A>G 
 p.His127Arg 
 De novo 
 NA 
  
 GEN046R019 
 splice_site_variant 
 c.2376+5G>A 
  
 De novo 
 NA 
  
 GEN046R020 
 missense_variant 
 c.2767C>T 
 p.Arg923Cys 
 Familial 
 Maternal 
  
 GEN046R021 
 missense_variant 
 c.2372A>C 
 p.Gln791Pro 
 Familial 
 Maternal 
  
 GEN046R022 
 missense_variant 
 c.1196A>C 
 p.Asn399Thr 
  
  
  
 GEN046R023 
 missense_variant 
 c.950A>G 
 p.His317Arg 
 Familial 
 Maternal 
 Simplex 
 GEN046R024 
 copy_number_loss 
  
  
 De novo 
 NA 
  
 GEN046R025 
 copy_number_loss 
  
  
 De novo 
 NA 
  
 GEN046R026 
 frameshift_variant 
 c.510_511dup 
 p.Tyr171CysfsTer58 
 Unknown 
  
 Simplex 
 GEN046R027 
 copy_number_loss 
 c.747del 
 p.Pro250GlnfsTer17 
 De novo 
 NA 
 Simplex 
 GEN046R028 
 inframe_deletion 
 c.1455_1460del 
 p.Ala486_Lys487del 
 Familial 
 Maternal 
 Simplex 
 GEN046R029 
 missense_variant 
 c.2389G>A 
 p.Asp797Asn 
 Familial 
 Paternal 
 Unknown 
 GEN046R030 
 5_prime_UTR_variant 
  
  
 Unknown 
  
 Unknown 
 GEN046R031 
 intron_variant 
 c.403+27A>G 
  
 Unknown 
  
 Unknown 
 GEN046R032 
 synonymous_variant 
 c.1278A>C 
 p.Ser426= 
 Unknown 
  
 Unknown 
 GEN046R033 
 splice_site_variant 
 c.464-2A>G 
  
 De novo 
 NA 
  
 GEN046R034 
 missense_variant 
 c.433C>T 
 p.His145Tyr 
 Familial 
 Maternal 
  
 GEN046R035 
 missense_variant 
 c.545T>C 
 p.Leu182Pro 
 De novo 
 NA 
  
 GEN046R036 
 stop_gained 
 c.2564C>G 
 p.Ser855Ter 
 De novo 
 NA 
  
 GEN046R037 
 frameshift_variant 
 c.1926del 
 p.Gln643AsnfsTer15 
 De novo 
 NA 
  
 GEN046R038 
 missense_variant 
 c.533G>A 
 p.Arg178Gln 
 De novo 
 NA 
  
 GEN046R039 
 missense_variant 
 c.620G>A 
 p.Gly207Glu 
 De novo 
 NA 
  
 GEN046R040 
 frameshift_variant 
 c.1926del 
 p.Gln643AsnfsTer15 
 Unknown 
  
  
 GEN046R041 
 missense_variant 
 c.1741C>T 
 p.His581Tyr 
 Unknown 
  
  
 GEN046R042 
 missense_variant 
 c.2572C>T 
 p.Arg858Cys 
 Unknown 
  
  
 GEN046R043 
 stop_gained 
 c.1390C>T 
 p.Gln464Ter 
 De novo 
 NA 
  
 GEN046R044 
 missense_variant 
 c.638G>A 
 p.Gly213Glu 
 De novo 
 NA 
  
 GEN046R045 
 missense_variant 
 c.379C>T 
 p.His127Tyr 
 De novo 
 NA 
  
 GEN046R046 
 frameshift_variant 
 c.1111del 
 p.Ala372LeufsTer121 
 De novo 
 NA 
  
 GEN046R047 
 splice_site_variant 
 NM_003159.2:ISV13+A>G 
 p.? 
 De novo 
 NA 
  
 GEN046R048 
 frameshift_variant 
 c.1713dup 
 p.Lys572GlufsTer9 
 De novo 
 NA 
  
 GEN046R049 
 splice_site_variant 
 NM_003159.2:ISV6+1A>G 
 p.? 
 De novo 
 NA 
  
 GEN046R050 
 stop_gained 
 c.1375C>T 
 p.Gln459Ter 
 De novo 
 NA 
  
 GEN046R051 
 frameshift_variant 
 c.890_891dup 
 p.Gln298PhefsTer53 
 De novo 
 NA 
 Multiplex 
 GEN046R052 
 missense_variant 
 c.533G>A 
 p.Arg178Gln 
 De novo 
 NA 
  
 GEN046R053 
 frameshift_variant 
 c.2360del 
 p.Lys787ArgfsTer16 
 De novo 
 NA 
  
 GEN046R054 
 frameshift_variant 
 c.234del 
 p.Arg80ValfsTer33 
 De novo 
 NA 
  
 GEN046R055 
 copy_number_gain 
  
  
 Familial 
 Maternal 
 Simplex 
 GEN046R056 
 copy_number_gain 
  
  
 Familial 
 Paternal 
 Unknown 
 GEN046R057 
 copy_number_gain 
  
  
 Familial 
 Maternal 
 Simplex 
 GEN046R058 
 copy_number_gain 
  
  
 Unknown 
  
 Unknown 
 GEN046R059 
 copy_number_gain 
  
  
 Unknown 
  
 Unknown 
 GEN046R060 
 copy_number_gain 
  
  
 Unknown 
  
 Unknown 
 GEN046R061 
 copy_number_gain 
  
  
 Familial 
 Maternal 
 Extended multiplex 
 GEN046R062 
 missense_variant 
 c.104C>T 
 p.Thr35Ile 
 De novo 
 NA 
 Simplex 
 GEN046R063 
 missense_variant 
 c.1940C>T 
 p.Pro647Leu 
 Familial 
 Maternal 
 Simplex 
 GEN046R064 
 frameshift_variant 
 c.2315del 
 p.Lys772ArgfsTer12 
 De novo 
 NA 
  
 GEN046R065 
 stop_gained 
 c.528G>A 
 p.Trp176Ter 
 De novo 
 NA 
  
 GEN046R066 
 stop_gained 
 c.400C>T 
 p.Arg134Ter 
 De novo 
 NA 
 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 
 GEN046R069 
 intron_variant 
 c.-163+1863G>A 
  
  
  
 Unknown 
 GEN046R070 
 stop_gained 
 c.2854C>T 
 p.Arg952Ter 
 De novo 
 NA 
  
 GEN046R071 
 stop_gained 
 c.2854C>T 
 p.Arg952Ter 
 Familial 
 Maternal 
  
 GEN046R072 
 missense_variant 
 c.119C>A 
 p.Ala40Glu 
 De novo 
 NA 
 Simplex 
 GEN046R073 
 stop_gained 
 c.858C>A 
 p.Tyr286Ter 
 De novo 
 NA 
  
 GEN046R074 
 translocation 
  
  
 De novo 
 NA 
  
 GEN046R075 
 stop_gained 
 c.2641C>T 
 p.Gln881Ter 
 De novo 
 NA 
  
 GEN046R076 
 missense_variant 
 c.587C>T 
 p.Ser196Leu 
 De novo 
 NA 
  
 GEN046R077 
 frameshift_variant 
 c.1449_1452dup 
 p.Lys485AspfsTer11 
 De novo 
 NA 
  
 GEN046R078 
 frameshift_variant 
 c.1247_1248del 
 p.Glu416ValfsTer2 
 Unknown 
  
  
 GEN046R079 
 frameshift_variant 
 c.2635_2636del 
 p.Leu879GlufsTer30 
 Unknown 
  
  
 GEN046R080 
 missense_variant 
 c.1939C>A 
 p.Pro647Thr 
 Familial 
  
 Simplex 
 GEN046R081 
 frameshift_variant 
 c.1292_1293del 
 p.Thr431LysfsTer31 
 De novo 
 NA 
 Simplex 
 GEN046R082 
 missense_variant 
 c.532C>T 
 p.Arg178Trp 
 De novo 
 NA 
 Simplex 
 GEN046R083 
 stop_gained 
 c.2112C>G 
 p.Tyr704Ter 
 De novo 
 NA 
 Simplex 
 GEN046R084 
 stop_gained 
 c.2854C>T 
 p.Arg952Ter 
 Familial 
 Maternal 
  
 GEN046R085 
 frameshift_variant 
 c.1247_1248del 
 p.Glu416ValfsTer2 
 De novo 
 NA 
  
 GEN046R086 
 missense_variant 
 c.1700C>T 
 p.Thr567Met 
 Familial 
 Maternal 
  
 GEN046R087 
 missense_variant 
 c.238C>T 
 p.Arg80Cys 
 Familial 
 Maternal 
  
 GEN046R088 
 frameshift_variant 
 c.163_166del 
 p.Glu55ArgfsTer20 
 De novo 
 NA 
  
 GEN046R089 
 frameshift_variant 
 c.282dup 
 p.Asn95LysfsTer16 
 De novo 
 NA 
  
 GEN046R090 
 frameshift_variant 
 c.1111del 
 p.Ala372LeufsTer121 
 De novo 
 NA 
  
 GEN046R091 
 splice_site_variant 
 c.100-2A>G 
  
 De novo 
 NA 
  
 GEN046R092 
 missense_variant 
 c.401G>C 
 p.Arg134Pro 
 De novo 
 NA 
  
 GEN046R093 
 missense_variant 
 c.58G>C 
 p.Gly20Arg 
 De novo 
 NA 
  
 GEN046R094 
 missense_variant 
 c.119C>G 
 p.Ala40Gly 
 De novo 
 NA 
  
 GEN046R095 
 copy_number_loss 
  
  
 De novo 
 NA 
  
 GEN046R096 
 frameshift_variant 
 c.2635_2636del 
 p.Leu879GlufsTer30 
 De novo 
 NA 
  
 GEN046R097 
 stop_gained 
 c.1670C>G 
 p.Ser557Ter 
 Unknown 
  
  
 GEN046R098 
 frameshift_variant 
 c.849dup 
 p.Asp284Ter 
 De novo 
 NA 
  
 GEN046R099 
 stop_gained 
 c.1519C>T 
 p.Gln507Ter 
 De novo 
 NA 
  
 GEN046R100 
 missense_variant 
 c.1387A>G 
 p.Lys463Glu 
 Unknown 
  
 Unknown 
 GEN046R101 
 copy_number_loss 
  
  
 De novo 
 NA 
 Unknown 
 GEN046R102 
 missense_variant 
 c.80T>C 
 p.Val27Ala 
 De novo 
 NA 
 Simplex 
 GEN046R103 
 splice_site_variant 
 c.99+2C>A 
  
 De novo 
 NA 
 Simplex 
 GEN046R104 
 splice_site_variant 
 c.403+1G>T 
  
 De novo 
 NA 
 Simplex 
 GEN046R105 
 stop_gained 
 c.1675C>T 
 p.Arg559Ter 
 De novo 
 NA 
 Simplex 
 GEN046R106 
 frameshift_variant 
 c.1731_1732del 
 p.Met577IlefsTer3 
 De novo 
 NA 
 Simplex 
 GEN046R107 
 missense_variant 
 c.134A>T 
 p.Lys45Met 
 Unknown 
  
  
 GEN046R108 
 frameshift_variant 
 c.1136_1139del 
 p.Leu379ProfsTer113 
 Unknown 
  
  

Common

No Common Variants Available
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
X
Deletion
 7
 
X
Duplication
 6
 
X
Deletion
 1
 
X
Deletion
 4
 
X
Deletion-Duplication
 1
 
X
Deletion
 1
 
X
Duplication
 1
 
X
Duplication
 1
 
X
Deletion
 2
 
X
Deletion
 1
 
X
Deletion
 1
 
X
Deletion-Duplication
 18
 

Model Summary

CDKL5 regulates signal transduction pathways and mediates autistic-like phenotypes and together establish a causal role for Cdkl5 loss-of-function in neurodevelopmental disorders.

References

Type
Title
Author, Year
Primary
Loss of CDKL5 disrupts kinome profile and event-related potentials leading to autistic-like phenotypes in mice.
Primary
Heterozygous CDKL5 Knockout Female Mice Are a Valuable Animal Model for CDKL5 Disorder.
Additional
Altered NMDAR signaling underlies autistic-like features in mouse models of CDKL5 deficiency disorder.

M_CDKL5_1_KO_HE

Model Type: Genetic
Model Genotype: Hemizygous
Mutation: Homologous recombination mediated deletion of exon 6 of Cdkl5 leading to shift in reading frame and premature truncation within N-terminal kinase domain.
Allele Type: Targeted (Knock Out)
Strain of Origin: Not specified
Genetic Background: C57BL/6
ES Cell Line: Not specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_CDKL5_2_KO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Homologous recombination mediated deletion of exon 6 of Cdkl5 leading to shift in reading frame and premature truncation within N-terminal kinase domain.
Allele Type: Targeted (Knock Out)
Strain of Origin: Not specified
Genetic Background: C57BL/6
ES Cell Line: Not specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_CDKL5_3_KO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Exon 4 of CDKL5 was deleted by flanking by loxP sites 806 bp upstream and 347 bp downstream of the exon, followed bycrerecombination, and an intermediate FRT-flanked neomycin resistance cassette that followed the second loxP site was deleted byflprecombinase.
Allele Type: Targeted (Knock Out)
Strain of Origin: (C57BL/6 x 129P2/OlaHsd)F1
Genetic Background: C57BL/6N*C57BL/6J
ES Cell Line: Not specified
Mutant ES Cell Line: A8
Model Source: 24838000

M_CDKL5_4_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Exon 4 of CDKL5 was deleted by flanking by loxP sites 806 bp upstream and 347 bp downstream of the exon, followed bycrerecombination, and an intermediate FRT-flanked neomycin resistance cassette that followed the second loxP site was deleted byflprecombinase.
Allele Type: Targeted (Knock Out)
Strain of Origin: (C57BL/6 x 129P2/OlaHsd)F1
Genetic Background: C57BL/6N*C57BL/6J
ES Cell Line: Not specified
Mutant ES Cell Line: A8
Model Source: 24838000

M_CDKL5_5_CKO_HM

Model Type: Genetic
Model Genotype: Hemizygous
Mutation: The Cdkl5 floxed mouse line with Cre-dependent excision of exon 7 (formerly exon 6) was crossed with Dlx5/6-Cre to generate mice with selective ablation of Cdkl5 in forebrain inhibitory GABAergic neurons.
Allele Type: Conditional knockout
Strain of Origin:
Genetic Background: C59BL/6J
ES Cell Line:
Mutant ES Cell Line:
Model Source: Jackson Laboratories, Stock No. 008199

M_CDKL5_6_KI

Model Type: Genetic
Model Genotype: Hemizygous
Mutation: CDKL5 R59X knock-in mice (Jackson laboratory, stock number Stock No. 028856) were generated by ES cell electroporation of targeting vector was designed to insert a frt-flanked neomycin resistance cassette downstream of exon 5, and a single-nucleotide change of C to T, leading to a nonsense mutation at arginine 59 (R59X) of the Cdkl5 gene. The neomycin cassette was later excised by Flp recombination through breeding with B6.Cg-Tg(ACTFLPe)9205Dym/J mice. R59X is an ASD-patient-associated nonsense mutation of the kinase domain of CDKL5.
Allele Type: ASD LOF Knockin
Strain of Origin: BALB/c*B6.Cg-Tg(ACTFLPe)9205Dym/J
Genetic Background: C57BL/6J
ES Cell Line: C57BL/6N
Mutant ES Cell Line:
Model Source: Jackson Laboratories, Stock No. 000664

M_CDKL5_7_CKO_HM

Model Type: Genetic
Model Genotype: Hemizygous
Mutation: Cdkl5^fl/fl;Nex-Cre CKO mice were generated by crossing Cdkl5 floxed mouse line with Cre-dependent excision of exon 7 (based on revised Cdkl5 gene nomenclature; formerly exon 6) using Nex-Cre [Goebbels et al., 2006; RRID: MGI: 4429523), to selectively ablate Cdkl5 in forebrain glutamatergic neurons.
Allele Type: Conditional knockout
Strain of Origin: sv129:C57BL/6
Genetic Background: C57BL/6
ES Cell Line: C57BL/6N
Mutant ES Cell Line:
Model Source: Klaus-Armin Nave (Max Planck Institute of Experimental Medicine, Gottingen, Germany); Lazzerini Denchi (The Scripps Research Institute); PMID 28674172

M_CDKL5_1_KO_HE

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Motor coordination and balance1
Decreased
Description: Decreased motor coordination indicated by lower latency to fall
Exp Paradigm: Male mice: accelerating rotarod assay
 Accelerating rotarod test
 9-12 weeks
General locomotor activity1
Increased
Description: Increased motor activity indicative of hyperactivity
Exp Paradigm: Male mice: home cage activity, zero maze test, social approach test
 Home cage behavior
 9-12 weeks
Event related potential (erp) in electroencephalography (eeg)1
Decreased
Description: Decreased low-frequency event related neuronal oscillations t delta, theta, and alpha, but no change in beta, low gamma and high gamma
Exp Paradigm: Male mice: time-frequency analysis of erp recordings
 Event related potential (erp)
 9-12 weeks
Event related potential (erp) in electroencephalography (eeg)1
Decreased
Description: Decreased auditory evoked event related potentials with decreased amplitude of n1 and p2 peaks and increase in latency of p2 peak
Exp Paradigm: Male mice: event related potential measurements using tripolar electrodes with white-noise stimuli
 Event related potential (erp)
 9-12 weeks
Nest building behavior1
Decreased
Description: Decreased nesting behavior in home-cage
Exp Paradigm: Male mice: observation of nest building
 Nest building assay
 4-5 weeks
Social interaction1
Decreased
Description: Decreased sociability demonstrated by reduced social preference for social chamber, decreased time sniffing novel stimulus, and less time interacting
Exp Paradigm: Male mice: three-chambered social approach test
 Three-chamber social approach test
 9-12 weeks
Anxiety1
Decreased
Description: Decreased anxiety related behavior demonstrated by more time spent in open areas and less time in closed areas
Exp Paradigm: Male mice: zero maze test
 Elevated zero maze test
 9-12 weeks
Cued or contextual fear conditioning1
Decreased
Description: Decreased cued and contextual fear memory indicated by less freezing after reexposing to shock box
Exp Paradigm: Male mice: cued/contextual fear conditioning
 Fear conditioning test
 9-12 weeks
Protein phosphorylation1
Decreased
Description: Decreased phosphorylation of akt and mtor
Exp Paradigm: Phosphorylation of akt-mtor
 Western blot
 Unreported
Protein modification process1
Decreased
Description: Decreased phosphorylation of adenosine monophosphate activated protein kinase (ampk), protein kinase a (pka) and akt substrates in striatum, somatosensory cortex, and hippocampus
Exp Paradigm: Kinome profile
 Western blot
 Unreported
General characteristics1
 No change
 General observations
 Unreported
Protein expression level evidence1
 No change
 Western blot
 Unreported
Brain morphology1
 No change
 Histology
 Unreported
Brain size1
 No change
 Histology
 Unreported
Electroencephalogram (eeg): signature of seizure/epilepsy1
 No change
 Electroencephalogram (eeg)
 9-12 weeks
Seizures1
 No change
 Electroencephalogram (eeg)
 9-12 weeks
Olfaction1
 No change
 Olfactory discrimination test
 9-12 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Immune response, Maternal behavior, Physiological parameters, Repetitive behavior

M_CDKL5_2_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
General characteristics1
 No change
 General observations
 Unreported
Brain morphology1
 No change
 NA
 Unreported
 Not Reported: Circadian sleep/wake cycle, Communications, Emotion, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

M_CDKL5_3_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
General locomotor activity: ambulatory activity1
Increased
Description: Mutants travelled longer distances compared with controls.
Exp Paradigm: NA
 Open field test
 3-4 months
Swimming ability1
Decreased
Description: Mutants show a decrease in average swim speed although the maximum swim speed was not altered compared with controls. mutants show an increase in floating behavior compared with controls.
Exp Paradigm: NA
 Morris water maze test
 3-4 months
General locomotor activity1
Increased
Description: Mutants travelled at higher average speed compared with controls.
Exp Paradigm: NA
 Open field test
 3-4 months
Motor learning1
Decreased
Description: Mutants show decrease in motor learning skills over consecutive trials compared with controls.
Exp Paradigm: NA
 Accelerating rotarod test
 3-4 months
Motor coordination and balance1
Decreased
Description: Mutants show decreased latency to fall from the rotarod and increase in passive rotations compared with controls.
Exp Paradigm: NA
 Accelerating rotarod test
 3-4 months
Dendritic architecture: dendritic length1
Decreased
Description: Mutants show decreased dendritic length compared to controls.
Exp Paradigm: NA
 Golgi-cox staining
 3-4 months
Dendritic architecture: spine turnover1
Decreased
Description: Mutants show a higher number of filopodia like immature spines and a decrease in mature spines compared with controls.
Exp Paradigm: NA
 Golgi-cox staining
 3-4 months
Dendritic architecture: spine density1
Decreased
Description: Mutants show reduced dendritic spine density compared with controls.
Exp Paradigm: NA
 Golgi-cox staining
 3-4 months
Dendritic architecture: dendritic tree complexity1
Decreased
Description: Mutants show decreased dendritic branching compared to controls.
Exp Paradigm: NA
 Golgi-cox staining
 3-4 months
Synaptic morphology1
Decreased
Description: Mutants show a decrease in the number of psd-95 puncta compared with controls.
Exp Paradigm: NA
 Golgi-cox staining
 3-4 months
Vertical jumping or back flipping1
Increased
Description: Mutants show an increase in jumping in the home cage compared with controls, indicating the jumping is not induced by a stressful situation.
Exp Paradigm: NA
 Home cage behavior
 3-4 months
Vertical jumping or back flipping1
Increased
Description: Mutants show an increase in jumping in the corners of the open field compared with controls.
Exp Paradigm: NA
 Open field test
 3-4 months
Repetitive digging1
Decreased
Description: Mutants show reduction in the number of total marbles buried compared with controls.
Exp Paradigm: NA
 Marble-burying test
 3-4 months
Olfaction1
Decreased
Description: Mutants needed more time to find the buried cookie compared with controls, indicating olfactory impairment.
Exp Paradigm: NA
 Buried food test
 3 month
Nest building behavior1
Decreased
Description: Mutants show impaired nest-building behavior compared with controls.
Exp Paradigm: NA
 Nest building assay
 3-4 months
Size/growth1
Decreased
Description: Mutants show lower average weight than controls.
Exp Paradigm: NA
 Body weight measurement
 3.5 months
Cued or contextual fear conditioning: passive avoidance1
Decreased
Description: Mutants show a decrease in step-through latency compared with controls.
Exp Paradigm: NA
 Passive avoidance test
 3-4 months
Spatial reference memory1
Decreased
Description: Mutants show increased latency and reduced frequency to enter the target quadrant, and swam a larger distance from the target quadrant, during the probe test compared with controls.
Exp Paradigm: NA
 Morris water maze test
 3-4 months
Spatial learning1
Decreased
Description: Mutants show reduced ability to learn the location of the platform during the acquisition phase compared to controls.
Exp Paradigm: NA
 Morris water maze test
 3-4 months
Signaling: pi3k/ akt1
Decreased
Description: Juvenile mice show reduction in p-akt-ser473 and beta-catenin levels in the hippocampus and cerebellum compared with controls. young adult mutant mice show reduction in p-akt-ser473 and beta-catenin levels in the hippocampus compared with controls.
Exp Paradigm: NA
 Western blot
 3 weeks, 8 weeks
Signaling: mapk1
Decreased
Description: Mutants show decreased levels of erk1 and 2 in the hippocampal and cerebellar extracts compared with controls. mutants show decreased levels of phosphoryated-msk1, a downstream target of erk1/2, compared with controls. young adult mutant mice show decreased levels of erk1,2 and phosphorylated-msk1 in the hippocampus compared with controls.
Exp Paradigm: NA
 Western blot
 3-4 months, 8 weeks
Targeted expression1
Decreased
Description: Mutants show reduction in the total protein levels of cdkl5 in the cortex, hippocampus and cerebellum, compared to controls.
Exp Paradigm: NA
 Western blot
 3-4 months
Size/growth1
 No change
 Body weight measurement
 2 months
Anxiety1
 No change
 Open field test
 3-4 months
Thigmotaxis1
 No change
 Morris water maze test
 3-4 months
Signaling: mapk1
 No change
 Western blot
 3 weeks
Signaling: pi3k/ akt1
 No change
 Western blot
 3-4 months
 Not Reported: Circadian sleep/wake cycle, Communications, Immune response, Maternal behavior, Neurophysiology, Physiological parameters, Seizure

M_CDKL5_4_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
General locomotor activity: ambulatory activity1
Increased
Description: Mutants travelled longer distances compared with controls.
Exp Paradigm: NA
 Open field test
 3-4 months
Swimming ability1
Decreased
Description: Mutants show a decrease in average swim speed although the maximum swim speed was not altered compared with controls. mutants show an increase in floating behavior compared with controls.
Exp Paradigm: NA
 Morris water maze test
 3-4 months
General locomotor activity1
Increased
Description: Mutants travelled at higher average speed compared with controls.
Exp Paradigm: NA
 Open field test
 3-4 months
Motor learning1
Decreased
Description: Mutants show decrease in motor learning skills over consecutive trials compared with controls.
Exp Paradigm: NA
 Accelerating rotarod test
 3-4 months
Motor coordination and balance1
Decreased
Description: Mutants show decreased latency to fall from the rotarod and increase in passive rotations compared with controls.
Exp Paradigm: NA
 Accelerating rotarod test
 3-4 months
Dendritic architecture: dendritic length1
Decreased
Description: Mutants show decreased dendritic length compared to controls.
Exp Paradigm: NA
 Golgi-cox staining
 3-4 months
Dendritic architecture: spine turnover1
Decreased
Description: Mutants show a higher number of filopodia like immature spines and a decrease in mature spines compared with controls.
Exp Paradigm: NA
 Golgi-cox staining
 3-4 months
Dendritic architecture: spine density1
Decreased
Description: Mutants show reduced dendritic spine density compared with controls.
Exp Paradigm: NA
 Golgi-cox staining
 3-4 months
Dendritic architecture: dendritic tree complexity1
Decreased
Description: Mutants show decreased dendritic branching compared to controls.
Exp Paradigm: NA
 Golgi-cox staining
 3-4 months
Synaptic morphology1
Decreased
Description: Mutants show a decrease in the number of psd-95 puncta compared with controls.
Exp Paradigm: NA
 Golgi-cox staining
 3-4 months
Vertical jumping or back flipping1
Increased
Description: Mutants show an increase in jumping in the home cage compared with controls, indicating the jumping is not induced by a stressful situation.
Exp Paradigm: NA
 Home cage behavior
 3-4 months
Vertical jumping or back flipping1
Increased
Description: Mutants show an increase in jumping in the corners of the open field compared with controls.
Exp Paradigm: NA
 Open field test
 3-4 months
Repetitive digging1
Decreased
Description: Mutants show reduction in the number of total marbles buried compared with controls.
Exp Paradigm: NA
 Marble-burying test
 3-4 months
Olfaction1
Decreased
Description: Mutants needed more time to find the buried cookie compared with controls, indicating olfactory impairment.
Exp Paradigm: NA
 Buried food test
 3 month
Nest building behavior1
Decreased
Description: Mutants show impaired nest-building behavior compared with controls.
Exp Paradigm: NA
 Marble-burying test
 3-4 months
Size/growth1
Decreased
Description: Mutants show lower average weight than controls.
Exp Paradigm: NA
 Body weight measurement
 3.5 months
Cued or contextual fear conditioning: passive avoidance1
Decreased
Description: Mutants show a decrease in step-through latency compared with controls.
Exp Paradigm: NA
 Passive avoidance test
 3-4 months
Spatial reference memory1
Decreased
Description: Mutants show increased latency and reduced frequency to enter the target quadrant, and swam a larger distance from the target quadrant, during the probe test compared with controls.
Exp Paradigm: NA
 Morris water maze test
 3-4 months
Spatial learning1
Decreased
Description: Mutants show reduced ability to learn the location of the platform during the acquisition phase compared to controls.
Exp Paradigm: NA
 Morris water maze test
 3-4 months
Signaling: pi3k/ akt1
Decreased
Description: Juvenile mice show reduction in p-akt-ser473 and beta-catenin levels in the hippocampus and cerebellum compared with controls. young adult mutant mice show reduction in p-akt-ser473 and beta-catenin levels in the hippocampus compared with controls.
Exp Paradigm: NA
 Western blot
 3 weeks
Signaling: mapk1
Decreased
Description: Mutants show decreased levels of erk1 and 2 in the hippocampal and cerebellar extracts compared with controls. mutants show decreased levels of phosphoryated-msk1, a downstream target of erk1/2, compared with controls. young adult mutant mice show decreased levels of erk1,2 and phosphorylated-msk1 in the hippocampus compared with controls.
Exp Paradigm: NA
 Western blot
 3-4 months, 8 weeks
Targeted expression1
Decreased
Description: Mutants show reduction in the total protein levels of cdkl5 in the cortex, hippocampus and cerebellum, compared to controls.
Exp Paradigm: NA
 Western blot
 3-4 months
Size/growth1
 No change
 Body weight measurement
 2 months
Anxiety1
 No change
 Open field test
 3-4 months
Thigmotaxis1
 No change
 Morris water maze test
 3-4 months
Signaling: mapk1
 No change
 Western blot
 3 weeks, 8 weeks
Signaling: pi3k/ akt1
 No change
 Western blot
 3-4 months
 Not Reported: Circadian sleep/wake cycle, Communications, Immune response, Maternal behavior, Neurophysiology, Physiological parameters, Seizure

M_CDKL5_5_CKO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Neuroreceptor levels: glutamate receptors: nmda receptors1
Increased
Description: Mutants show increase in the protein levels of glun1 and glun2b nmda receptors at the postsynaptic membrane.
Exp Paradigm: Brain
 Western blot
 9-12 weeks
Presynaptic function: paired-pulse facilitation1
Increased
Description: Mutants show increased facilitation of vsdi responses in the molecular layer, granule cell layer, and hilus of the dentate gyrus at 200 and 400microamp stimulation.
Exp Paradigm: Hippocampal slices
 Voltage sensitive dye imaging (vsdi)
 9-12 weeks
Miniature post synaptic current frequency: excitatory1
Increased
Description: Mutants show increased mepsc frequency with decreased interevent intervals.
Exp Paradigm: Ca1 pyramidal neurons
 Whole-cell patch clamp
 9-12 weeks
Repetitive digging1
Increased
Description: Mutants spent more time digging.
Exp Paradigm: NA
 Observation of repetitive behavior
 9-12 weeks
Social scent marking or recognition1
Decreased
Description: Mutants spent less time sniffing a social scent.
Exp Paradigm: NA
 Olfactory habituation-dishabituation test
 9-12 weeks
Social interaction1
Decreased
Description: Mutants spent less time in direct interaction with a social stimulus.
Exp Paradigm: NA
 Reciprocal social interaction test
 9-12 weeks
Social approach1
Decreased
Description: Mutants spent less time sniffing the cylinder with the social stimulus.
Exp Paradigm: NA
 Three-chamber social approach test
 9-12 weeks
Cognitive flexibility1
Decreased
Description: Mutants show increase in the number of errors during the reversal probe phase. mutants show increase in the number of visits to the original target in the reversal probe phase.
Exp Paradigm: NA
 Barnes maze test
 9-12 weeks
Targeted expression1
Decreased
Description: Mutants show decreased cdkl5 protein expression in the striatum.
Exp Paradigm: Striatum
 Western blot
 9-12 weeks
Size/growth1
 No change
 Body weight measurement
 P2-p14
Anxiety1
 No change
 Zero maze test
 9-12 weeks
Spatial reference memory1
 No change
 Barnes maze test
 9-12 weeks
Spatial working memory1
 No change
 Y-maze test
 9-12 weeks
Targeted expression1
 No change
 Western blot
 9-12 weeks
General locomotor activity: ambulatory activity1
 No change
 Home cage behavior
 9-12 weeks
Motor coordination and balance1
 No change
 Accelerating rotarod test
 9-12 weeks
Neuroreceptor levels: glutamate receptors: ampa receptors1
 No change
 Western blot
 9-12 weeks
Neuroreceptor levels: glutamate receptors: nmda receptors1
 No change
 Western blot
 9-12 weeks
Decay kinetics of miniature post synaptic currents1
 No change
 Whole-cell patch clamp
 9-12 weeks
Miniature post synaptic current amplitude: excitatory1
 No change
 Whole-cell patch clamp
 9-12 weeks
Miniature post synaptic current amplitude: inhibitory1
 No change
 Whole-cell patch clamp
 9-12 weeks
Miniature post synaptic current frequency: inhibitory1
 No change
 Whole-cell patch clamp
 9-12 weeks
Network excitability1
 No change
 Voltage sensitive dye imaging (vsdi)
 9-12 weeks
Synaptic transmission: excitatory1
 No change
 Whole-cell patch clamp
 9-12 weeks
Synaptic transmission: inhibitory1
 No change
 Whole-cell patch clamp
 9-12 weeks
Olfaction1
 No change
 Olfactory habituation-dishabituation test
 9-12 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Immune response, Maternal behavior, Physiological parameters, Seizure

M_CDKL5_6_KI

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Neuroreceptor levels: glutamate receptors: nmda receptors1
Increased
Description: Mutants show increase in the protein levels of glun2b nmda receptors at the postsynaptic membrane.
Exp Paradigm: Brain
 Western blot
 9-12 weeks
Social interaction1
Decreased
Description: Mutants show decrease in total time spent in dyadic social interaction.
Exp Paradigm: NA
 Reciprocal social interaction test
 9-12 weeks
Spatial working memory1
Decreased
Description: Mutants show decrease in the number of spontaneous alternations or transitions.
Exp Paradigm: NA
 Y-maze test
 9-12 weeks
Targeted expression1
Decreased
Description: Mutants show loss of full length cdkl5 protein expression in the cortex.
Exp Paradigm: Cerebral cortex
 Western blot
 9-12 weeks
Neuroreceptor levels: glutamate receptors: ampa receptors1
 No change
 Western blot
 9-12 weeks
Neuroreceptor levels: glutamate receptors: nmda receptors1
 No change
 Western blot
 9-12 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Maternal behavior, Motor phenotype, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory

M_CDKL5_7_CKO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Presynaptic function: paired-pulse facilitation1
Decreased
Description: Mutants show lack of facilitation of vsdi responses in the molecular layer, granule cell layer, and hilus of the dentate gyrus at 400microamp stimulation and in the hilus at 200microamp and shows depression in the granular cell layer and molecular cell layer at 200microamp.
Exp Paradigm: Hippocampal slices
 Voltage sensitive dye imaging (vsdi)
 9-12 weeks
Network excitability1
 No change
 Voltage sensitive dye imaging (vsdi)
 9-12 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / ultrastructure / cytoarchitecture, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior


Interactor Symbol Interactor Name Interactor Organism Entrez ID Uniprot ID Interaction Type Evidence Reference
C9ORF86 RAB, member RAS oncogene family-like 6 55684 Q3YEC7 IP; LC-MS/MS
Huttlin EL , et al. 2015
CDKL5 cyclin-dependent kinase-like 5 6792 O76039 Metabolic labeling with 32P
Bertani I , et al. 2006
DHX16 DEAH (Asp-Glu-Ala-His) box polypeptide 16 8449 O60231 IP; LC-MS/MS
Huttlin EL , et al. 2015
DHX38 DEAH (Asp-Glu-Ala-His) box polypeptide 38 9785 Q92620 IP; LC-MS/MS
Huttlin EL , et al. 2015
HDGFRP3 Hepatoma-derived growth factor-related protein 3 50810 Q9Y3E1 IP; LC-MS/MS
Huttlin EL , et al. 2015
KIAA1704 KIAA1704 55425 Q8IXQ4 IP; LC-MS/MS
Huttlin EL , et al. 2015
KLHL20 kelch-like family member 20 27252 Q9Y2M5 IP; LC-MS/MS
Huttlin EL , et al. 2015
MACF1 microtubule-actin crosslinking factor 1 23499 Q9UPN3 IP; LC-MS/MS
Huttlin EL , et al. 2015
MECP2 methyl CpG binding protein 2 (Rett syndrome) 4204 P51608 GST; IP/WB; Metabolic labeling with 32P
Mari F , et al. 2005
MEF2C myocyte enhancer factor 2C 4208 Q06413 Luciferase reporter assay
Zweier M , et al. 2010
MLH1 mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli) 4292 P40692 Y2H
Sakai Y , et al. 2011
MYCN v-myc myelocytomatosis viral related oncogene, neuroblastoma derived (avian) 4613 P04198 ChIP; qRT-PCR; Luciferase reporter assay; ChIP-qPCR
Valli E , et al. 2012
NLGN1 neuroligin 1 22871 Q8N2Q7 IP/WB; in vitro kinase assay
Ricciardi S , et al. 2012
SERPINB8 Serpin B8 5271 P50452 IP; LC-MS/MS
Huttlin EL , et al. 2015
SPTBN4 spectrin, beta, non-erythrocytic 4 57731 Q9H254 Y2H
Sakai Y , et al. 2011
TACC3 transforming, acidic coiled-coil containing protein 3 10460 Q9Y6A5 Y2H
Sakai Y , et al. 2011
Dnmt1 DNA methyltransferase (cytosine-5) 1 13433 P13864 GST; MS; Metabolic labeling with 32P
Kameshita I , et al. 2008
FMR1 fragile X mental retardation 1 14265 P35922 HITS-CLIP
Darnell JC , et al. 2011
NFY Nuclear transcription factor Y subunit alpha 18044 P23708 ChIP-Seq
Vitezic M , et al. 2014
PP1 Serine/threonine-protein phosphatase PP1-gamma catalytic subunit 19047 P63087 IP/WB; Electrophysiology; Immunofluorescence; qRT-PCR; in vitro phosphatase assay
La Montanara P , et al. 2015
SP1 trans-acting transcription factor 1 20683 O89090 ChIP-Seq
Vitezic M , et al. 2014
MIB1 mindbomb E3 ubiquitin protein ligase 1 307594 D3ZUV2 Affinity chromatography; LC-MS/MS
Mertz J , et al. 2015
Rac1 RAS-related C3 botulinum substrate 1 19353 P63001 GST
Chen Q , et al. 2010

HELP
Copyright © 2017 MindSpec, Inc.