Relevance to Autism

Al-Amri et al., 2022 identified homozygous truncating mutations in the PDZD8 gene in two independent consanguineous families from the Arabian peninsula in which affected individuals presented with syndromic intellectual disability with autistic features; furthermore, mice homozygous for a premature truncation codon in Pdzd8 exhibited restricted growth, structural brain alterations, spontaneous stereotypic behavior, decreased anxiety-like behavior, and impairments in long-term spatial memory and TBS-induced long term potentiation, while Drosphila melanogaster with knockdown of the PDZD8 ortholog exhibited impaired long-term courtship-based memory. A third consanguineous family from Afghanistan with a biallelic nonsense variant in the PDZD8 gene was recently reported in Pantiru et al., 2025; both siblings with this biallelic variant in this family were diagnosed with ASD (according to DSM-5 criteria using CARS and ADOS-2) and presented with developmental delay, severe intellectual disability, and dysmorphic features. Pantiru et al., 2025 also further characterized PDZD8-deficient mice (Pdzd8-tm1b) and observed increases in locomotor activity and metabolic rate and decreased plasma triglyceride levels in males.

Molecular Function

Predicted to enable lipid binding activity and metal ion binding activity. Involved in several processes, including mitochondrial calcium ion homeostasis; mitochondrion-endoplasmic reticulum membrane tethering; and regulation of cell morphogenesis. Located in endoplasmic reticulum membrane and mitochondria-associated endoplasmic reticulum membrane. In neurons, involved in the regulation of dendritic Ca2+ dynamics by regulating mitochondrial Ca2+ uptake in neurons (Hirabayashi et al., 2017).

External Links

References