Relevance to Autism

De novo damaging missense variants in the TRAPPC9 gene were identified in ASD probands from the Simons Simplex Collection and the Autism Sequencing Consortium (De Rubeis et al., 2014; Iossifov et al., 2014). Rare inherited loss-of-function and damaging missense variants in this gene were observed in ASD probands from the Simons Simplex Collection in Krumm et al. 201 and in a cohort of Chinese ASD probands in Guo et al., 2017. Transmission and De Novo Association (TADA) analysis of a combined cohort consisting of Chinese ASD probands and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium, in Guo et al., 2017 identified TRAPPC9 as an ASD candidate gene with a PTADA of 0.000561. A novel compound heterozygous mutation in the TRAPPC9 gene (consisting of a paternally-inherited frameshift variant and a maternally-inherited splice-site variant) was identified in a female proband diagnosed with ASD and her older brother, who presented with intellectual disability, born to healthy and non-consanguineous Thai parents (Hnoonual et al., 2019).

Molecular Function

Functions as an activator of NF-kappa-B through increased phosphorylation of the IKK complex. May function in neuronal cells differentiation. May play a role in vesicular transport from endoplasmic reticulum to Golgi. Homozygous mutations in the TRAPPC9 gene are associated with a form of autosomal recessive mental retardation (MRT13; OMIM 613192), a disorder characterized by postnatal microcephaly and white matter abnormalities (Mochida et al., 2009; Philippe et al., 2009; Mir et al., 2009; Kakar et al., 2012; Marangi et al., 2013).

External Links

References