Relevance to Autism

A de novo in-frame deletion variant in the TAOK1 gene was identified in an ASD proband from the Autism Sequencing Consortium (De Rubeis et al., 2014). Dulovic-Mahlow et al., 2019 described eight individuals with de novo TAOK1 variants who presented with a neurodevelopmental disorder characterized by developmental delay and muscular hypotonia; autism was reported in two individuals. Three novel de novo variants in the TAOK1 gene (two likely gene-disruptive variants, one missense variant predicted to be probably damaging as defined by an MPC score > 2) were identified in ASD probands from the Autism Sequencing Consortium in Satterstrom et al., 2020; subsequent TADA analysis of de novo variants from the Simons Simplex Collection and the Autism Sequencing Consortium and protein-truncating variants from iPSYCH in this report identified TAOK1 as a candidate gene with a false discovery rate between 0.05 and 0.1 (0.05 < FDR 0.1). Additional de novo loss-of-function variants and potentially damaging missense variants in the TAOK1 gene were reported in ASD probands from the Simons Simplex Collection and the SPARK cohort in Zhou et al., 2022; a two-stage analysis of rare de novo and inherited coding variants in 42,607 ASD cases, including 35,130 new cases from the SPARK cohort, in this report identified TAOK1 as a gene reaching exome-wide significance (P < 2.5E-06). Elkhateeb et al., 2025 recently reported 50 individuals with TAOK1 variants with associated phenotypes, including neurodevelopmental abnormalities (100%), macrocephaly (83%), and hypotonia (58%); autism spectrum disorder or autistic traits were reported in 31% of individuals with TAOK1 variants in this report.

Molecular Function

Serine/threonine-protein kinase involved in various processes such as p38/MAPK14 stress-activated MAPK cascade, DNA damage response and regulation of cytoskeleton stability.

External Links

References