Pathogenic UNC13A variants cause a neurodevelopmental syndrome by impairing synaptic function

This article speaks on the UNC13A gene that is responsible for information transfer between neurons. It usually contains neurodevelopmental syndrome which is known to cause seizures, tremors and even early (childhood) death. There are three mechanisms that are known to be examined and they consist of “reduction in synaptic strength caused by reduced UNC13A protein expression, increased neurotransmission caused by UNC13A gain-of-function and impaired regulation of neurotransmission by second messenger signalling” (Pathogenic UNC13A variants cause a neurodevelopmental syndrome by impairing synaptic function, 2025).  

There are various different types of UNC13A variants that present neurodevelopmental deficiencies. There are three subdivisions of this, let’s start with part A. This is known to compromise variants, sometimes over 50%. This leads to reduced synaptic strength which results in early seizures and developmental delay. Part B are usually heterozygous variants, they increase neurotransmission. This also leads to movement disorders and seizures. Part C is more mild and known to be caused by a heterozygous variant as well. Usually in this case there is little development impairment, seizures and there seems to be a dominant inheritance pattern across generations.

Asadollahi, R., Ahmad, A., Boonsawat, P., Shahanoor Hinzen, J., Lohse, M., Bouazza-Arostegui, B., Sun, S., Utesch, T., Sommer, J. D., Ilic, D., Padmanarayana, M., Fischermanns, K., Ranjan, M., Boll, M., Ka, C., Piton, A., Mattioli, F., Isidor, B., Õunap, K., … Lipstein, N. (2025, October 22). Pathogenic UNC13A variants cause a neurodevelopmental syndrome by impairing synaptic function. Nature News. https://www.nature.com/articles/s41588-025-02361-5#Sec10

Account - genecards suite. (n.d.). https://www.genecards.org/cgi-bin/carddisp.pl?gene=UNC13A