Relevance to Autism

Homozygous mutations in the TBC1D23 gene were shown to be responsible for pontocerebellar hypoplasia type 11 (PCH11; OMIM 617695), an autosomal recessive neurodevelopmental disorder characterized by severely delayed psychomotor development with intellectual disability and poor speech, microcephaly, dysmorphic features, and hypoplasia of the pons and cerebellum on brain imaging (Marin-Valencia et al., 2017; Ivanova et al., 2017). All six affected individuals described in Marin-Valencia et al., 2017 presented with delayed or absent social development. Ivanova et al., 2017 reported that four of the seven affected individuals in their study presented with stereotypic movements (two of whom also presented with autistic behavior), in addition to two individuals that presented with poor communication and interaction and persistent repetitive motor behavior.

Molecular Function

Putative Rab GTPase-activating protein which plays a role in vesicular trafficking. Involved in endosome-to-Golgi trafficking. Acts as a bridging protein by binding simultaneously to golgins, including GOLGA1 and GOLGA4, located at the trans-Golgi, and to the WASH complex, located on endosome-derived vesicles. Plays a role in brain development, including in cortical neuron positioning. May also be important for neurite outgrowth, possibly through its involvement in membrane trafficking and cargo delivery, 2 processes that are essential for axonal and dendritic growth.

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