CDKL5

Protein identityUniProt · HPA

UniProt accession

O76039

Gene

CDKL5

Ensembl

ENSG00000008086

Chromosome

X

Canonical length

960 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Nucleoplasm

OverviewNCBI Gene

This gene is a member of Ser/Thr protein kinase family and encodes a phosphorylated protein with protein kinase activity. Mutations in this gene have been associated with X-linked infantile spasm syndrome (ISSX), also known as X-linked West syndrome, and Rett syndrome (RTT). Alternate transcriptional splice variants have been characterized. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

960 residues, UniProt reviewed canonical sequence.

>O76039|CDKL5
     1  MKIPNIGNVM NKFEILGVVG EGAYGVVLKC RHKETHEIVA IKKFKDSEEN EEVKETTLRE
    61  LKMLRTLKQE NIVELKEAFR RRGKLYLVFE YVEKNMLELL EEMPNGVPPE KVKSYIYQLI
   121  KAIHWCHKND IVHRDIKPEN LLISHNDVLK LCDFGFARNL SEGNNANYTE YVATRWYRSP
   181  ELLLGAPYGK SVDMWSVGCI LGELSDGQPL FPGESEIDQL FTIQKVLGPL PSEQMKLFYS
   241  NPRFHGLRFP AVNHPQSLER RYLGILNSVL LDLMKNLLKL DPADRYLTEQ CLNHPTFQTQ
   301  RLLDRSPSRS AKRKPYHVES STLSNRNQAG KSTALQSHHR SNSKDIQNLS VGLPRADEGL
   361  PANESFLNGN LAGASLSPLH TKTYQASSQP GSTSKDLTNN NIPHLLSPKE AKSKTEFDFN
   421  IDPKPSEGPG TKYLKSNSRS QQNRHSFMES SQSKAGTLQP NEKQSRHSYI DTIPQSSRSP
   481  SYRTKAKSHG ALSDSKSVSN LSEARAQIAE PSTSRYFPSS CLDLNSPTSP TPTRHSDTRT
   541  LLSPSGRNNR NEGTLDSRRT TTRHSKTMEE LKLPEHMDSS HSHSLSAPHE SFSYGLGYTS
   601  PFSSQQRPHR HSMYVTRDKV RAKGLDGSLS IGQGMAARAN SLQLLSPQPG EQLPPEMTVA
   661  RSSVKETSRE GTSSFHTRQK SEGGVYHDPH SDDGTAPKEN RHLYNDPVPR RVGSFYRVPS
   721  PRPDNSFHEN NVSTRVSSLP SESSSGTNHS KRQPAFDPWK SPENISHSEQ LKEKEKQGFF
   781  RSMKKKKKKS QTVPNSDSPD LLTLQKSIHS ASTPSSRPKE WRPEKISDLQ TQSQPLKSLR
   841  KLLHLSSASN HPASSDPRFQ PLTAQQTKNS FSEIRIHPLS QASGGSSNIR QEPAPKGRPA
   901  LQLPGQMDPG WHVSSVTRSA TEGPSYSEQL GAKSGPNGHP YNRTNRSRMP NLNDLKETAL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CDKL5 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.57

Highest tissue expression

13 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CDKL5.

Disease | AllUniProt

Conditions CDKL5 is implicated in, by any mechanism.

• Developmental and epileptic encephalopathy 2 (DEE2) MIM:300672

Disease | GeneticClinVar

590 pathogenic / likely-pathogenic of 1,714 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Developmental and epileptic encephalopathy, 2
• Angelman syndrome-like
• CDKL5 disorder
• Atypical Rett syndrome
• Inborn genetic diseases

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.23

gnomAD pLI

1

gnomAD missense Z

2.74

DepMap mean gene effect

0.05

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• modulation of chemical synaptic transmission
• neuron migration
• positive regulation of axon extension
• positive regulation of dendrite morphogenesis
• positive regulation of Rac protein signal transduction
• regulation of cilium assembly
• regulation of dendrite development
• regulation of postsynapse organization

Molecular functions

• ATP binding
• cyclin-dependent protein serine/threonine kinase activity
• kinase activity
• protein kinase activity
• protein serine kinase activity
• protein serine/threonine kinase activity
• small GTPase binding

Cellular components

• centrosome
• ciliary basal body
• ciliary tip
• dendrite cytoplasm
• dendritic growth cone
• glutamatergic synapse
• nucleoplasm
• nucleus

Protein domainsUniProt · Pfam · InterPro

• Protein kinase domain
• Serine/threonine-protein kinase, active site
• Protein kinase-like domain superfamily
• Protein kinase, ATP binding site
• Cyclin-dependent kinase
• Protein kinase domain

KeywordsUniProt

• ATP-binding
• Cell projection
• Chromosomal rearrangement
• Cytoplasm
• Cytoskeleton
• Epilepsy
• Intellectual disability
• Kinase
• Nucleotide-binding
• Nucleus
• Phosphoprotein
• Serine/threonine-protein kinase
• Transferase

InteractionsUniProt · HPA

Protein binding partners of CDKL5 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• MECP2
• MLH1