Table 6.

Important TARDBP mutations associated with ALS onset.

Mutation	Pathogenicity	Type of Mutation	Biological Effect	Citation
M337V	ALS Pathogenic	Substitution	Production of an abnormal TDP-43 protein that aggregates abnormally and accumulates in motor neurons, ultimately leading to their degeneration and death, and thus contributing to ALS development.	[150,154,155]
A315T	ALS Pathogenic	Substitution	Transgenic mice carrying the A315T mutation of TDP-43 may succumb to early death due to digestive complications before fully manifesting neurological signs associated with ALS, suggesting it also influences their digestive systems and may contribute to their early demise. Although the exact mechanisms underlying gastrointestinal complications remain poorly understood, experts speculate that abnormal TDP-43 protein build-up in intestinal cells may lead to dysfunction and damage.	[156]
A382T	Possible ALS Pathogenic	Substitution	Unknown mechanism.	[157,158]