PLPPR4phospholipid phosphatase related 4
Autism Reports / Total Reports
4 / 7Rare Variants / Common Variants
7 / 0Aliases
PLPPR4, LPPR4, LPR4, PHP1, PRG-1, PRG1Associated Syndromes
-Chromosome Band
1p21.3-p21.2Associated Disorders
-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.
External Links
SFARI Genomic Platforms
Reports related to PLPPR4 (7 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Primary | Molecular cause and functional impact of altered synaptic lipid signaling due to a prg-1 gene SNP | Vogt J , et al. (2015) | No | - |
| 2 | Support | Plasticity-Related Gene 1 Affects Mouse Barrel Cortex Function via Strengthening of Glutamatergic Thalamocortical Transmission | Unichenko P , et al. (2016) | No | - |
| 3 | Recent Recommendation | Altered synaptic phospholipid signaling in PRG-1 deficient mice induces exploratory behavior and motor hyperactivity resembling psychiatric disorders | Schneider P , et al. (2017) | No | - |
| 4 | Support | Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism | Satterstrom FK et al. (2020) | Yes | - |
| 5 | Support | - | Zhou X et al. (2022) | Yes | - |
| 6 | Support | - | Trost B et al. (2022) | Yes | - |
| 7 | Recent Recommendation | - | Li H et al. (2023) | Yes | Epilepsy/seizures |
Rare Variants (7)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| - | - | copy_number_loss | De novo | - | - | 37550884 | Li H et al. (2023) | |
| G>T | - | missense_variant | De novo | - | - | 36368308 | Trost B et al. (2022) | |
| c.4C>T | p.Gln2Ter | stop_gained | De novo | - | - | 37550884 | Li H et al. (2023) | |
| c.223-1G>T | - | splice_site_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.408+2T>C | p.? | splice_site_variant | Unknown | - | - | 37550884 | Li H et al. (2023) | |
| c.894A>G | p.Arg298= | synonymous_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.1394C>A | p.Ser465Tyr | missense_variant | De novo | - | - | 31981491 | Satterstrom FK et al. (2020) |
Common Variants
No common variants reported.
SFARI Gene score
Suggestive Evidence
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.
Score Delta: Score remained at 3
criteria met
See SFARI Gene'scoring criteriaThe literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.
7/1/2023
Increased from to 3
Description
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.
10/1/2019
Decreased from 5 to
New Scoring Scheme
Description
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.
Reports Added
[New Scoring Scheme]10/1/2017
Increased from to 5
Description
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.