PLPP1
protein-codingphospholipid phosphatase 1, the group of Phospholipid phosphatases|MicroRNA protein coding host genes
Gene summary
The protein encoded by this gene is a member of the phosphatidic acid phosphatase (PAP) family. PAPs convert phosphatidic acid to diacylglycerol, and function in synthesis of glycerolipids and in phospholipase D-mediated signal transduction. This enzyme is an integral membrane glycoprotein that plays a role in the hydrolysis and uptake of lipids from extracellular space. Alternate splicing results in multiple transcript variants of this gene. [provided by RefSeq, May 2013]
- PPAP2A
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~110.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PLPP1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003711.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 33 | 1 | 34 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 36 | 1 | 0 | 37 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003702.2 | 6 | MANE Select | |
| Ensembl | ENSP00000302229.8 | 6 | MANE Select | |
| RefSeq | NP_795714.1 | 6 | Standard | |
| Ensembl | ENSP00000264775.5 | 6 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| plpp1b | Danio rerio | Structure: intersegmental vessel Quality: decreased functionality abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Fc gamma R-mediated phagocytosis - Homo sapiens (human)
- Glycerolipid metabolism - Homo sapiens (human)
- Ether lipid metabolism - Homo sapiens (human)
- Glycerophospholipid metabolism - Homo sapiens (human)
- Choline metabolism in cancer - Homo sapiens (human)
Biological Process
- protein dephosphorylation
- lipid metabolic process
- phospholipid metabolic process
- protein kinase C-activating G protein-coupled receptor signaling pathway
- negative regulation of cell population proliferation
Molecular Function
- phosphatidate phosphatase activity
- phosphatase activity
- sphingosine-1-phosphate phosphatase activity
- lipid phosphatase activity
Cellular Component
- plasma membrane
- integral component of plasma membrane
- membrane
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000264775
- Coding exons
- 6
- Length
- 110197
- Individuals with no LoFs
- 125736
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 9
- Defined
- 125745
- p
- 0.0000358
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.541 | 134 | 153 | 0.877 | 0.00000766 | 1843 |
| Missense (PolyPhen) | 41 | 59.399 | 0.69025 | 707 | ||
| Synonymous | 0.579 | 53 | 58.6 | 0.904 | 0.00000324 | 555 |
| Loss of Function | 2.35 | 4 | 13.2 | 0.302 | 6.86e-7 | 169 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Broad-specificity phosphohydrolase that dephosphorylates exogenous bioactive glycerolipids and sphingolipids. Catalyzes the conversion of phosphatidic acid (PA) to diacylglycerol (DG). Pivotal regulator of lysophosphatidic acid (LPA) signaling in the cardiovascular system. Major enzyme responsible of dephosphorylating LPA in platelets, which terminates signaling actions of LPA. May control circulating, and possibly also regulate localized, LPA levels resulting from platelet activation. It has little activity towards ceramide-1-phosphate (C-1-P) and sphingosine-1-phosphate (S-1-P). The relative catalytic efficiency is LPA > PA > S-1-P > C-1-P. It's down-regulation may contribute to the development of colon adenocarcinoma. {ECO:0000269|PubMed:12909631}.;
Intolerance Scores
- RVIS EVS
- -0.25
- RVIS percentile EVS
- 35.75
Essentials
- Essential (gene trap)
- N