This report describes neurodevelopmental disorder with behavioral abnormalities and childhood onset spastic paraplegia. The human gene implicated is TBCB, which encodes tubulin folding cofactor B, which is involved in alpha-tubulin synthesis and degradation There is one high-scoring fly ortholog, Dmel\Tbcb, for which multiple genetic reagents, including classical alleles, RNAi-targeting constructs, alleles caused by insertional mutagenesis, and an allele representing a disease-implicated variant have been generated.
The human gene TBCB has not been introduced into flies.
Pan-neuronal RNAi knockdown of Dmel\Tbcb resulted in impaired locomoter activity and a shorter lifespan. A mutant allele of Dmel\Tbcb representing a pathogenic variant associated with human disease results in semilethality, shorter lifespan, and decreased locomotor activity.
[updated Aug. 2026 by FlyBase; FBrf0222196]
[NEURODEVELOPMENTAL DISORDER WITH BEHAVIORAL ABNORMALITIES AND CHILDHOOD-ONSET SPASTIC PARAPLEGIA; NEDBSPG](https://omim.org/entry/621382)
[TUBULIN FOLDING COFACTOR B; TBCB](https://omim.org/entry/601303)
Neurodevelopmental disorder with behavioral abnormalities and childhood-onset spastic paraplegia (NEDBSPG) is an autosomal recessive disorder characterized by mild global developmental delay apparent from infancy, with mildly delayed walking and speech acquisition, mildly impaired intellectual development (in some patients), and behavioral abnormalities, most commonly autism spectrum disorder. Affected individuals develop age-dependent, slowly progressive spastic paraplegia late in the first decade, resulting in gait abnormalities, but remain ambulatory. Brain imaging may be normal or show thin corpus callosum and decreased white matter. The phenotype can also be classified as a 'complicated' form of spastic paraplegia (SPG) (Bratman Morag et al., 2025, pubmed:40856104). [from MIM:621382; 2026.08.05]
Neurodevelopmental disorder with behavioral abnormalities and childhood-onset spastic paraplegia (NEDBSPG) is caused by homozygous mutation in the TBCB gene on chromosome 19q13. [from MIM:621382; 2026.08.05]
The TBCB gene encodes tubulin folding cofactor B, which is involved in alpha-tubulin synthesis and degradation. Along with TBCE (MIM:604934), TBCB regulates tubulin heterodimer dynamics and neuronal axonal growth (summary by Bratman Morag et al., 2025, pubmed:40856104). [from MIM:601303; 2026.08.05]
One to one (1 human to 1 Drosophila); TBCB has one high-scoring Drosophila ortholog, Tbcb.
High-scoring ortholog of human TBCB (1 Drosophila to 1 human).
