Aliases: LPPR4, LPR4, PHP1, PRG-1, PRG1
Chromosome No: 1
Chromosome Band: 1p21.3-p21.2
Genetic Category: Functional-Rare single gene variant-Rare single gene variant/Functional
ASD Reports: 7
Recent Reports: 2
Annotated variants: 7
Associated CNVs: 8
Evidence score: 2
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Relevance to Autism
Li et al., 2023 reported three unrelated patients presenting with a neurodevelopmental disorder caused by PLPPR4 haploinsufficiency that was characterized by mild intellectual disability, language delay or disorder, motor delay, and autistic behavior (including a diagnosis of autism spectrum disorder in one patient); subsequent functional characterization of iPSC-derived neurons from a patient with a de novo heterozygous PLPPR4 deletion demonstrated reduced density of dendritic protrusions, shorter neurites, and reduced axon length. Additional de novo variants in this gene, including a de novo loss-of-function variant and two de novo missense variants, have been reported in ASD probands (Satterstrom et al., 2020; Zhou et al., 2022; Trost et al., 2022). PLPPR4 +/- mice were shown to display abnormal function in cortical networks, reduced resilience in stress-related behaviors, reduced social interaction, and a significant decrease in prepulse inhibition compared to wild-type mice in Vogt et al., 2015. Schneider et al., 2017 demonstrated that PLPPR4 -/- mice displayed increased ambulation, increased speed of locomotion, increased anxiety and stereotypic behaviors including rearing, leaning, and self-grooming.
Molecular Function
The protein encoded by this gene belongs to the lipid phosphate phosphatase (LPP) family. LPPs catalyze the dephosphorylation of a number of bioactive lipid mediators that regulate a variety of cell functions. This protein is specifically expressed in neurons. It is located in the membranes of outgrowing axons and has been shown to be important for axonal outgrowth during development and regenerative sprouting.
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