Relevance to Autism

A de novo missense variant in the MAPK8IP1 gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014; functional assessment of this variant by a high throughput Massively Parallel Splicing Assay (MaPSY) in Rhine et al., 2022 demonstrated that this variant disrupted splicing, and this functional effect was further validated by RT-PCR. Additional rare de novo non-coding variation in this gene has also been observed in ASD probands (Turner et al., 2016; Yuen et al., 2017).

Molecular Function

This gene encodes a regulator of the pancreatic beta-cell function. It is highly similar to JIP-1, a mouse protein known to be a regulator of c-Jun amino-terminal kinase (Mapk8). This protein has been shown to prevent MAPK8 mediated activation of transcription factors, and to decrease IL-1 beta and MAP kinase kinase 1 (MEKK1) induced apoptosis in pancreatic beta cells. This protein also functions as a DNA-binding transactivator of the glucose transporter GLUT2. RE1-silencing transcription factor (REST) is reported to repress the expression of this gene in insulin-secreting beta cells. This gene is found to be mutated in a type 2 diabetes family, and thus is thought to be a susceptibility gene for type 2 diabetes.

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