This report describes neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity. The human gene implicated is TMX2, which encodes thioredoxin related transmembrane protein 2. There is one high-scoring fly ortholog, Dmel\Tmx2, for which multiple genetic reagents, including classical alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
The human gene TMX2 has not been introduced into flies.
Pan-glial RNAi knockdown of Dmel\Tmx2 results in locomotor deficits, a 'bang-sensitive' seizure phenotype, reduced viability at pharate adult stages, and decreased lifespan in adult survivors. Pan-neuronal RNAi knockdown of Dmel\Tmx2 does not result in locomotor or seizure phenotypes.
[updated Aug. 2026 by FlyBase; FBrf0222196]
[NEURODEVELOPMENTAL DISORDER WITH MICROCEPHALY, CORTICAL MALFORMATIONS, AND SPASTICITY; NEDMCMS](https://omim.org/entry/618730)
[THIOREDOXIN-RELATED TRANSMEMBRANE PROTEIN 2; TMX2](https://omim.org/entry/616715)
Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity (NEDMCMS) is an autosomal recessive disorder characterized by severe to profound global developmental delay, early-onset seizures, microcephaly, and polymicrogyria and/or cerebral atrophy on brain imaging. Most affected individuals are unable to walk or speak and have profoundly impaired intellectual development, as well as axial hypotonia and peripheral spasticity. Rare individuals may be less severely affected (summary by Vandervore et al., 2019, pubmed:31735293). [from MIM:618730; 2026.08.14]
Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity (NEDMCMS) is caused by homozygous or compound heterozygous mutation in the TMX2 gene on chromosome 11q12. [from MIM:618730; 2026.08.14]
TMX2 is a member of the thioredoxin (TXN) gene family (Meng et al., 2003, pubmed:12670024). TMX2 encodes an endoplasmic reticulum (ER) protein that functions in posttranslational protein modification and folding. It localizes to ER mitochondria-associated membranes (MAMs), where it is involved with calcium flux and cellular redox homeostasis (summary by Vandervore et al., 2019, pubmed:31735293). [from MIM:616715; 2026.08.14]
One to one (1 human to 1 Drosophila); TMX2 has one high-scoring Drosophila ortholog, Tmx2.
High-scoring ortholog of human TMX2 (1 Drosophila to 1 human).
