Human Disease Model Report: developmental and epileptic encephalopathy 2

General Information

Name

developmental and epileptic encephalopathy 2

FlyBase ID

FBhh0001644

Disease Ontology Term

developmental and epileptic encephalopathy 2

Parent Disease

developmental and epileptic encephalopathy

OMIM

DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 2; DEE2

Overview

This report describes developmental and epileptic encephalopathy 2 (DEE2); DEE2 exhibits X-linked dominant inheritance. The human gene implicated in this disease is CDKL5, which encodes a serine/threonine protein kinase. There is a single orthologous gene in Drosophila, Dmel\Cdkl, for which multiple genetic reagents have been generated. The fly gene is the single ortholog of 5 paralogous genes in human.

Loss of Drosophila Cdkl causes a semi-lethal phenotype in pupae, killing 90% of the animals just prior to eclosion. The mutant flies that survive show climbing defects, heat-induced seizures, reduced longevity, and hearing loss. Dmel\Cdkl is expressed primarily in the peripheral nervous system.

A UAS construct of the human Hsap\CDKL5 gene has been introduced into flies; heterologous rescue (functional complementation) has been demonstrated. The redundancy of the CDKL system in vertebrates complicates investigations into disease-implicated genetic variants. It is proposed that Drosophila Cdkl provides a relevant DEE2 model for variants affecting the kinase domain, but not for those affecting the C-terminal tail.

[updated Aug. 2025 by FlyBase; FBrf0222196]

Disease Summary Information

Parent Disease Summary: developmental and epileptic encephalopathy

Symptoms and phenotype

Specific Disease Summary: developmental and epileptic encephalopathy 2

OMIM report

[DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 2; DEE2](https://omim.org/entry/300672)

Human gene(s) implicated

[CYCLIN-DEPENDENT KINASE-LIKE 5; CDKL5](https://omim.org/entry/300203)

Symptoms and phenotype

Developmental and epileptic encephalopathy 2 (DEE2) is an X-linked dominant severe neurologic disorder characterized by onset of seizures in the first months of life and severe global developmental delay resulting in impaired intellectual development and poor motor control. Other features include lack of speech development, subtle dysmorphic facial features, sleep disturbances, gastrointestinal problems, and stereotypic hand movements. [from MIM:300672; 2025.08.26]

(OMIM, 2013-)

Genetics

Developmental and epileptic encephalopathy 2 (DEE2) is caused by mutation in the CDKL5 gene. [from MIM:300672; 2025.08.26]

(OMIM, 2013-)

Cellular phenotype and pathology

Molecular information

CDKL5 encodes a serine/threonine protein kinase. [GeneCards, CDKL5; 2025.08.26]

(FlyBase Curators, 2013-)

The CDKL kinase domain is conserved across all eukaryotic species; a long C-terminal region present in CDKL5 is specific to vertebrates (Martin-Carrascosa, et al., 2025; pubmed:40371392; FBrf0262381).

(FlyBase Curators, 2013-)

External links

Gene2Function (human gene): CDKL5
Gene Cards: CDKL5
GeneReviews, NCBI Bookshelf: CDKL5 Deficiency Disorder
MedlinePlus (gene): CDKL5
MARRVEL (human gene): CDKL5
NCBI MedGen: Developmental and epileptic encephalopathy, 2 (DEE2)
NCBI (Entrez) gene: CDKL5; cyclin dependent kinase like 5

Disease synonyms

CDKL5 deficiency disorder

CDKL5-related developmental and epileptic encephalopathy

DEE2

EIEE2

epileptic encephalopathy, early infantile, 2

Related Diseases

Related human health report(s)

neurodevelopmental disorder, CDKL2-related

neurodevelopmental disorder (postulated), CDKL1-related

Related Specific Diseases

OMIM phenotypic series

Developmental and epileptic encephalopathy

Disease

Associated Human gene(s)

Drosophila model

Human transgene in Drosophila

[DEE2](https://omim.org/entry/300672)

[CDKL5](https://omim.org/entry/300203)

developmental and epileptic encephalopathy 2

[DEE4](https://omim.org/entry/612164)

[STXBP1](https://omim.org/entry/602926)

developmental and epileptic encephalopathy 4

[DEE7](https://omim.org/entry/613720)

[KCNQ2](https://omim.org/entry/602235)

developmental and epileptic encephalopathy 7

[DEE11](https://omim.org/entry/613721)

[SCN2A](https://omim.org/entry/182390)

developmental and epileptic encephalopathy 11

[DEE13](https://omim.org/entry/614558)

[SCN8A](https://omim.org/entry/600702)

developmental and epileptic encephalopathy 13

[DEE14](https://omim.org/entry/614959)

[KCNT1](https://omim.org/entry/608167)

developmental and epileptic encephalopathy 14

[DEE17](https://omim.org/entry/615473)

[GNAO1](https://omim.org/entry/139311)

developmental and epileptic encephalopathy 17

[DEE25](https://omim.org/entry/615905)

[SLC13A5](https://omim.org/entry/608305)

developmental and epileptic encephalopathy 25, with amelogenesis imperfecta

[DEE34](https://omim.org/entry/616645)

[SLC12A5](https://omim.org/entry/606726)

developmental and epileptic encephalopathy 34

[DEE44](https://omim.org/entry/617132)

[UBA5](https://omim.org/entry/610552)

developmental and epileptic encephalopathy 44

[DEE47](https://omim.org/entry/617166)

[FGF12](https://omim.org/entry/601513)

developmental and epileptic encephalopathy 47

[DEE57](https://omim.org/entry/617771)

[KCNT2](https://omim.org/entry/610044)

developmental and epileptic encephalopathy 57

[DEE64](https://omim.org/entry/618004)

[RHOBTB2](https://omim.org/entry/607352)

developmental and epileptic encephalopathy 64

[DEE87](https://omim.org/entry/618916)

[CDK19](https://omim.org/entry/614720)

developmental and epileptic encephalopathy 87

[DEE96](https://omim.org/entry/619340)

[NSF](https://omim.org/entry/601633)

developmental and epileptic encephalopathy 96

[DEE109](https://omim.org/entry/620145)

[FZR1](https://omim.org/entry/603619)

developmental and epileptic encephalopathy 109

[DRVT](https://omim.org/entry/607208)

[SCN1A](https://omim.org/entry/182389)

developmental and epileptic encephalopathy 6

Ortholog Information

Human gene(s) in FlyBase

Hsap\CDKL5

Human gene (HGNC)

Symbol / Name

CDKL5; cyclin dependent kinase like 5

D. melanogaster ortholog (based on DIOPT)

Dmel\Cdkl

(DIOPT, 2013-)

Comments on ortholog(s)

Many to one: 5 human genes to 1 Drosophila gene.

Other mammalian ortholog(s) used

D. melanogaster Gene Information (1)

Dmel\Cdkl

Gene Snapshot

Cyclin dependent kinase-like (Cdkl) encodes a member of the Cyclin Dependent Kinases family. The gene is expressed widely in sensory neurons, except photoreceptors. The loss of function of Cdkl leads to climbing defects, hearing loss, reduced lifespan and heat induced seizures. [Date last reviewed: 2025-05-22]

Molecular function (GO)

Cellular component (GO)