A number of predicted loss-of-function and damaging missense variants in the SPARCL1 gene, including a de novo LoF variant, were observed in ASD probands from the Autism Sequencing Consortium (De Rubeis et al., 2014). The protein encoded by the SPARCL1 gene, hevin, was shown to induce thalamocortical synapse formation by bridging neurexin 1 -alpha and neuroligin 1-beta following secretion from astrocytes (Singh et al., 2016). Functional analysis of the ASD-associated SPARCL1 p.Trp647Arg missense variant in Taketomi et al., 2022 demonstrated that this mutation impaired normal Hevin secretion and resulted in accumulation of protein in the endoplasmic reticulum, leading to activation of unfolded protein responses.
Molecular Function
Predicted to enable calcium ion binding activity; collagen binding activity; and extracellular matrix binding activity. Predicted to be involved in anatomical structure development and regulation of synapse organization. Located in extracellular space.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Synaptic, transcriptional and chromatin genes disrupted in autism.
