UNC13B

UNC13B is a human protein-coding gene that encodes Munc13-2, a member of the Munc13 family of presynaptic active zone proteins. The UNC13B gene plays a crucial role in neurotransmitter release by regulating synaptic vesicle priming, the step that prepares vesicles for Ca2+-triggered exocytosis.

The Munc13 family proteins contain conserved domains, including a MUN domain and C2 domains, which participate in interactions with the SNARE machinery and in calcium sensing. In neurons, UNC13B is expressed predominantly in the central nervous system, with higher expression in certain brain regions, suggesting a role at excitatory synapses.

Functionally, UNC13B works with other active zone components such as Rab3, RIM, and syntaxin-1 to control vesicle docking and priming, thereby influencing the probability of neurotransmitter release and aspects of short-term synaptic plasticity. The protein contributes to the efficiency and timing of neurotransmission, which are essential for normal neural communication.

Genetic and functional studies in model organisms indicate that Munc13 proteins are essential for proper synaptic transmission. In vertebrates, UNC13B is one of several Munc13 paralogs, and there is evidence for partial redundancy among family members. Disruption of Munc13-2 in experimental models leads to defects in synaptic function, supporting its critical role in neurotransmission.

Clinical relevance: Variants in UNC13B have been investigated in studies of neurological and neurodevelopmental disorders, but associations remain tentative and require further validation. UNC13B is frequently cited in discussions of presynaptic mechanisms and synaptic vesicle priming.