De novo nonsense variants in the HERC1 gene have been identified in a Japanese ASD proband (Hashimoto et al., 2016) and in an ASD proband from the Autism Sequencing Consortium (Satterstrom et al., 2020), while an inherited nonsense variant in this gene was observed in an ASD proband from the iHART cohort (Ruzzo et al., 2019). Additional de novo variants in this gene were identified in ASD probands from the Simons Simplex Collection (Iossifov et al., 2014). Limited social interaction had previously been observed in an individual with MDFPMR (Nguyen et al., 2016). Roy et al., 2021 found that HERC1 exhibited high expression in the anterodorsal thalamus (AD) of mice, and that knockdown of HERC1 in AD thalamus resulted in memory deficits and neuronal hyperexcitability, phenotypes that were also observed in AD thalamus-specific PTCHD1 knock-down mice.
Molecular Function
This gene encodes a member of the HERC protein family. This protein stimulates guanine nucleotide exchange on ARF1 and Rab proteins. This protein may be involved in membrane transport processes. Biallelic variants in the HERC1 gene are responsible for macrocephaly, dysmorphic facies, and psychomotor retardation (MDFPMR; OMIM 617011), an autosomal recessive neurodevelopmental disorder characterized by large head and somatic overgrowth apparent at birth followed by global developmental delay (Ortega-Recalde et al., 2015; Nguyen et al., 2016; Aggarwal et al. 2016; Schwarz et al., 2020).
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Whole-exome sequencing and neurite outgrowth analysis in autism spectrum disorder.
A splice site mutation in HERC1 leads to syndromic intellectual disability with macrocephaly and facial dysmorphism: Further delineation of the phenotypic spectrum
