TUBG1

TUBG1 is the gene that encodes gamma-tubulin 1, a highly conserved protein that is a core component of the microtubule nucleation machinery in eukaryotic cells. Gamma-tubulin forms part of the gamma-tubulin ring complex (gamma-TuRC), which templates the minus ends of microtubules and initiates their assembly at microtubule-organizing centers such as centrosomes.

In human cells, gamma-TuRC is composed of gamma-tubulin and several gamma-tubulin complex proteins (GCP2–GCP6), along with additional centrosomal factors such as NEDD1. The complex localizes to centrosomes and spindle poles during cell division and is essential for proper mitotic spindle formation, spindle orientation, and accurate chromosome segregation. Gamma-tubulin also contributes to non-centrosomal microtubule organization in certain differentiated cell types.

Expression of TUBG1 is widespread across tissues, and its activity is regulated throughout the cell cycle, including regulation of complex assembly, localization, and activity by phosphorylation and interacting proteins. Disruption of gamma-tubulin function impairs microtubule nucleation and centrosome biology, leading to defects in cell division and tissue development in model systems.

Clinical significance: variants in TUBG1 have been associated with neurodevelopmental disorders in humans, including microcephaly and related brain malformations. The pathogenic mechanisms are thought to involve impaired microtubule nucleation and mitotic spindle function, reducing neural progenitor proliferation and affecting brain development. Ongoing research aims to clarify the spectrum of TUBG1-related conditions and the precise molecular consequences of different variants.

See also: gamma-tubulin, gamma-tubulin ring complex, GCP proteins.