PLD3 Gene: Phospholipase D Family Member 3
Genetic insights into PLD3 and its role in Alzheimer's disease and cellular signaling
Gene Information Card
| Symbol | PLD3 |
|---|---|
| Full Name | phospholipase D family member 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 19q13.2 |
| NCBI Gene ID | 23646 ncbi.nlm.nih.gov/gene/23646 |
| Ensembl ID | ENSG00000105220 |
| UniProt ID | Q8IV08 |
| OMIM ID | 615698 |
| HGNC ID | 17158 |
| Aliases | HU-K4, PLD3_HUMAN, AD15 |
Description
PLD3 (phospholipase D family member 3) encodes a 5'-3' exonuclease involved in RNA processing and lipid metabolism. It is highly expressed in the brain and has been implicated in late-onset Alzheimer's disease through rare coding variants that may alter protein function. PLD3 is also involved in endosomal trafficking and immune signaling.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alzheimer's disease, late-onset | Rare coding variants (e.g., p.Val232Met) may impair exonuclease activity, leading to altered amyloid precursor protein processing and increased Aβ accumulation. | OMIM 615698; ClinVar; NCBI Gene |
| Spinocerebellar ataxia, autosomal recessive | Biallelic loss-of-function mutations in PLD3 cause a neurodegenerative disorder with cerebellar atrophy. | OMIM 615698; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 45.2 | High |
| Testis | 12.8 | Medium |
| Lung | 8.5 | Medium |
| Liver | 3.1 | Low |
| Heart | 2.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 38.7 | Neuronal model |
| HEK293 (embryonic kidney) | 22.1 | Common overexpression system |
| HeLa (cervical carcinoma) | 15.3 | Epithelial |
| HepG2 (hepatocellular carcinoma) | 4.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.694G>A (p.Val232Met) | Missense | 0.2% in European populations | Associated with increased Alzheimer's disease risk; may reduce exonuclease activity |
| c.1075C>T (p.Arg359Cys) | Missense | Rare | Reported in Alzheimer's disease; functional impact uncertain |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Likely loss of function; associated with spinocerebellar ataxia |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations (e.g., start loss) cause spinocerebellar ataxia with cerebellar atrophy.
Gain of Function (GOF)
No evidence for gain-of-function mutations in PLD3.
Dominant Negative (DN)
Rare missense variants (e.g., p.Val232Met) may act in a dominant-negative manner to impair PLD3 function in Alzheimer's disease.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004527 - exonuclease activity | • GO:0004630 - phospholipase D activity |
| • GO:0005737 - cytoplasm | • GO:0005768 - endosome |
| • GO:0016020 - membrane | • GO:0042981 - regulation of apoptotic process |
Pathways
• Alzheimer's disease - amyloid processing (Reactome: R-HSA-977225)
• Phospholipid metabolism (Reactome: R-HSA-1483206)
• Endosomal trafficking (Reactome: R-HSA-199991)
Protein Summary
PLD3 is a 490-amino acid protein with 5'-3' exonuclease activity and phospholipase D activity. It localizes to endosomes and the endoplasmic reticulum, where it processes RNA and modulates lipid signaling. In the brain, PLD3 interacts with amyloid precursor protein and influences Aβ production. Loss of function is linked to neurodegeneration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PLD3 Knockout HEK293 Cell Line | EDJ-KQ3738 | Human | 23646 | Details Get a Quote |
| PLD3 Knockout A-549 Cell Line | EDJ-KQ25789 | Human | 23646 | Details Get a Quote |
| PLD3 Knockout HCT 116 Cell Line | EDJ-KQ25790 | Human | 23646 | Details Get a Quote |
| PLD3 Knockout HeLa Cell Line | EDJ-KQ25791 | Human | 23646 | Details Get a Quote |
| PLD3 Knockout HAP1 Cell Line | EDC07809 | Human | 23646 | Details Get a Quote |
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