This report describes developmental and epileptic encephalopathy 118 (DEE118); DEE118 exhibits autosomal dominant inheritance. TMEM63B encodes transmembrane protein 63B, an osmolarity-activated cation channel. There is a single Drosophila ortholog, Dmel\Tmem63, for which amorphic alleles, RNAi-targeting constructs, alleles caused by insertional mutagenesis, and regulated expression constructs have been generated.
Multiple UAS constructs of the human Hsap\TMEM63B gene have been introduced into flies, including wild-type TMEM63B and two disease-associated variants; see the 'Disease-Implicated Variants' table below. Developing-eye-specific expression of either variant is lethal before adulthood; expression of wild-type Hsap\TMEM63B has no observable eye phenotypes or effects on viability.
Heterologous rescue (functional complementation) has been demonstrated in a separate study: expression of Hsap\TMEM63B in Tmem63 mutant flies rescues their defects in humidity sensing and moisture attraction.
[updated Jul. 2025 by FlyBase; FBrf0222196]
[DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 118; DEE118](https://omim.org/entry/621250)
[TRANSMEMBRANE PROTEIN 63B; TMEM63B](https://omim.org/entry/619952)
Developmental and epileptic encephalopathy-118 (DEE118) is characterized by early-onset refractory epilepsy, severe global developmental delay usually with absent speech, hypotonia evolving to spastic quadriparesis, nystagmus, cortical visual impairment, and hematologic abnormalities. The disorder is progressive. [from MIM:621250; 2025.07.30]
Seventeen unrelated individuals exhibited early-onset developmental and epileptic encephalopathy (DEE), all associated with white matter disease, corpus callosum abnormalities, and variable cortical, cerebellar, and hematological abnormalities (Vetro et al., 2023; pubmed:37421948; FBrf0257232).
Developmental and epileptic encephalopathy-118 (DEE118) is caused by heterozygous mutation in the TMEM63B gene. [from MIM:621250; 2025.07.30]
Ten distinct de novo heterozygous mutations in the gene TMEM63B were identified among 17 patients with early-onset developmental and epileptic encephalopathy (Vetro et al., 2023; pubmed:37421948; FBrf0257232).
Brain imaging shows dysmorphic lateral ventricles, thin corpus callosum, white matter signal abnormalities, and cerebral cortical and cerebellar atrophy. [from MIM:621250; 2025.07.30]
TMEM63B is predicted to enable calcium activated cation channel activity; mechanosensitive ion channel activity; and osmolarity-sensing cation channel activity. Predicted to be involved in cation transmembrane transport. Located in actin cytoskeleton and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
Many to one (3 human to 1 Drosophila); TMEM63B has one high-scoring Drosophila ortholog, Tmem63.
High-scoring ortholog of human TMEM63A, TMEM63B, TMEM63C (1 Drosophila to 3 human).
