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FB2026_01
,
released March 12, 2026
This report describes developmental and epileptic encephalopathy 44, a subtype of developmental and epileptic encephalopathy that exhibits autosomal dominant inheritance. The human gene implicated is UBA5, which encodes ubiquitin like modifier activating enzyme 5, a member of the E1-like ubiquitin-activating enzyme family. There is one high-scoring fly ortholog, Dmel\Uba5, for which multiple genetic reagents, including amorphic alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis, have been generated.
UAS constructs of the human Hsap\UBA5 gene have been introduced into flies, including wild-type and variants implicated in human disease. See the 'Disease-Implicated Variants' table below. Heterologous rescue (functional complementation) has been demonstrated for the Dmel\Uba5 embryonic lethal phenotype. Variants implicated in human disease, when expressed in flies mutant for Dmel\Uba5, fell into three classes based on efficacy of rescuing the lethal phenotype, and presence of other phenotypes including decreased lifespan and bang-sensitivity in adults.
Amorphic mutations in Dmel\Uba5 are almost entirely embryonic lethal, with a few escapers surviving to the first larval instar,
[updated Dec. 2023 by FlyBase; FBrf0222196]
[DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 44; DEE44](https://omim.org/entry/617132)
[UBIQUITIN-LIKE MODIFIER-ACTIVATING ENZYME 5; UBA5](https://omim.org/entry/610552)
Developmental and epileptic encephalopathy-44 (DEE44) is an autosomal recessive neurologic disorder characterized by the onset of refractory infantile spasms or myoclonus usually in the first weeks or months of life, up to about 12 months of age. Affected infants may have normal or mildly delayed development before the onset of seizures, but thereafter show developmental stagnation and severe neurologic impairment. EEG in some patients shows hypsarrhythmia, consistent with a clinical diagnosis of West syndrome. Additional features include poor feeding and poor overall growth with microcephaly, axial hypotonia with peripheral hypertonia or spasticity, abnormal movements, limited eye contact, and profoundly impaired intellectual development with absent language. Many patients require tube feeding, and some die in childhood (summary by Muona et al., 2016, pubmed: 2754567; Colin et al., 2016, pubmed:27545681). [from MIM:617132; 2023.12.20]
Developmental and epileptic encephalopathy 44 (DEE44) is caused by compound heterozygous mutation in the UBA5 gene on chromosome 3q22. [from MIM:617132; 2023.12.20]
The UBA5 (Ubiquitin Like Modifier Activating Enzyme 5) gene encodes a member of the E1-like ubiquitin-activating enzyme family. This protein activates ubiquitin-fold modifier 1, a ubiquitin-like post-translational modifier protein, via the formation of a high-energy thioester bond. [provided by RefSeq, Feb 2016]
One to one (1 human to 1 Drosophila); UBA5 has one high-scoring Drosophila ortholog, Uba5.
High-scoring ortholog of human UBA5 (1 Drosophila to 1 human).