A recurrent de novo missense variant in the PACS2 gene (p.Glu209Lys) was identified in 14 unrelated individuals presenting with neonatal-onset developmental and epileptic encephalopathy (Olson et al., 2018); in addition to recurrent phenotypes such as epilepsy and developmental delay/intellectual disability, three cases in this report presented with autism spectrum disorder/autistic disorder, and six cases presented with stereotypies. A de novo probably damaging missense variant in the PACS2 gene was observed in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014.
Molecular Function
Multifunctional sorting protein that controls the endoplasmic reticulum (ER)-mitochondria communication, including the apposition of mitochondria with the ER and ER homeostasis. In addition, in response to apoptotic inducer, translocates BIB to mitochondria, which initiates a sequence of events including the formation of mitochondrial truncated BID, the release of cytochrome c, the activation of caspase-3 thereby causing cell death. May also be involved in ion channel trafficking, directing acidic cluster-containing ion channels to distinct subcellular compartments.
External Links
References
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Type of Disorder
Associated Disorders
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Primary
A Recurrent De Novo PACS2 Heterozygous Missense Variant Causes Neonatal-Onset Developmental Epileptic Encephalopathy, Facial Dysmorphism, and Cereb...
