UNC13A

UNC13A is a human gene that encodes a protein also called UNC13A. This protein plays a critical role in neurotransmitter release, specifically functioning as a presynaptic protein involved in synaptic vesicle priming.

UNC13A is a member of the Munc13 family of proteins, which are essential for synaptic transmission. Munc13 proteins act as priming factors, enabling synaptic vesicles to become fusion-competent and ready for release upon arrival of an action potential. They achieve this by interacting with other proteins in the presynaptic active zone, including RIMs (Rab3-interacting molecules) and Munc18-1.

The UNC13A protein contains several conserved domains, including a C1 domain, which binds diacylglycerol (DAG), a regulator of protein kinase C (PKC) activity and vesicle priming. It also possesses MUN (Munc13 N-terminal) domains and C2 domains, which mediate calcium-dependent phospholipid binding. These domains contribute to the complex interactions required for efficient vesicle priming and neurotransmitter release.

Mutations in the UNC13A gene have been linked to various neurological disorders, particularly neurodevelopmental disorders. These disorders can manifest as intellectual disability, epilepsy, autism spectrum disorder, and other neurological symptoms. The specific clinical presentation often depends on the nature and location of the mutation within the gene. Research into the function of UNC13A and the impact of its mutations is ongoing, with the aim of developing targeted therapies for these disorders.

Defects in UNC13A's function lead to impaired synaptic transmission, disrupting the communication between neurons and contributing to the pathogenesis of these neurological conditions. The study of UNC13A provides valuable insights into the molecular mechanisms underlying synaptic function and the development of neurological disorders.