Relevance to Autism

LMTK3 was identified as an ASD candidate gene based on having a p-value < 0.001 following DeNovoWEST analysis of de novo variants in 16,877 ASD trios from the Simons Simplex Collection, the Autism Sequencing Consortium, the MSSNG cohort, and the SPARK cohort in Zhou et al., 2022; among the de novo variants observed in ASD cases in this analysis were two de novo loss-of-function variants and two damaging de novo missense variants (defined as having a REVEL score > 0.5). Inoue et al., 2014 demonstrated that Lmtk3-knockout mice exhibited behavioral abnormalities (locomotor hyperactivity, reduced anxiety, and decreased depression-like behavior) and impaired endocytotic trafficking of NMDA receptors, while Montrose et al., 2019 demonstrated that Lmtk3-knockout mice displayed behavioral abnormalities (including hypersociability, PPI defects, and impaired cognitive function), severely impaired long-term potentiation induction, and abnormal GluA1 trafficking after AMPA stimulation.

Molecular Function

Predicted to enable protein kinase activity. Predicted to be involved in protein phosphorylation. Predicted to be located in Golgi membrane; axon; and dendrite. Predicted to be integral component of membrane. Involved in endocytic trafficking of N-methyl-D-aspartate receptors (NMDAR) in neurons.

External Links

References