DYNC1H1

DYNC1H1 is the gene that encodes cytoplasmic dynein 1 heavy chain 1, a core component of the cytoplasmic dynein-1 motor complex. Dynein-1 is a minus-end directed microtubule motor that powers retrograde transport of organelles, signaling endosomes, and other cargos within most cell types, with particularly critical roles in neurons for long-range intracellular movement.

The dynein-1 heavy chain contains an N-terminal motor domain that hydrolyzes ATP and binds microtubules, and a C-terminal tail that mediates dimerization and interactions with other dynein subunits, the dynactin complex, and various cargo adapters. Proper assembly with intermediate and light chains and with dynactin is essential for processive movement and cargo specificity.

In humans, DYNC1H1 is broadly expressed but has prominent importance in the nervous system. Its activity supports retrograde transport in axons and is involved in neuronal development, migration, and survival. Disruptions of dynein-1 function can thus impact brain development and neuronal connectivity.

Clinical significance of DYNC1H1 mutations spans a spectrum of neurodevelopmental and neuromuscular disorders. Pathogenic variants have been linked to brain malformations such as lissencephaly and other cortical development disorders, as well as to intellectual disability and autism features. Neuromuscular phenotypes include spinal muscular atrophy with lower extremity predominance and Charcot–Marie–Tooth disease type 2O. These conditions illustrate the essential role of dynein-1 in intracellular transport and neural development.

Research continues to define the range of DYNC1H1-related phenotypes and the precise mechanisms by which specific mutations disrupt dynein function and cargo handling.