Relevance to Autism

De novo variants in the MINK1 gene have been identified in ASD probands, including two de novo missense variants in probands from the Simons Simplex Collection and the Autism Sequencing Consortium (Iossifov et al., 2014; Sanders et al., 2015; Yuen et al., 2017; Turner et al., 2017; Satterstrom et al., 2020), while a de novo post-zygotic missense variant in this gene that was predicted to be damaging was identified in brain tissue from an ASD brain donor from the Harvard Brain Tissue Resource Center (Woodbury-Smith et al., 2022). Functional assessment of the ASD-associated p.Cys269Arg missense variant, which was originally identified in a proband from the Simons Simplex Collection, in Drosophila using an overexpression-based strategy in Macrogliese et al., 2022 demonstrated that flies overexpressing MINK1-p.Cys269Arg failed to reduce the expected viability to the extent of the corresponding reference allele upon overexpression, indicating a loss-of-function effect.

Molecular Function

This gene encodes a serine/threonine kinase belonging to the germinal center kinase (GCK) family. The protein is structurally similar to the kinases that are related to NIK and may belong to a distinct subfamily of NIK-related kinases within the GCK family. Studies of the mouse homolog indicate an up-regulation of expression in the course of postnatal mouse cerebral development and activation of the cJun N-terminal kinase (JNK) and the p38 pathways.

External Links

References