LPIN1 Gene: Lipin-1, Phosphatidate Phosphatase, and Its Role in Lipid Metabolism and Disease
A comprehensive biomedical overview of LPIN1, including gene structure, function, expression, associated diseases, mutations, and clinical significance.
Gene Information Card
| Symbol | LPIN1 |
|---|---|
| Full Name | Lipin 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 2p25.1 |
| NCBI Gene ID | 23175 ncbi.nlm.nih.gov/gene/23175 |
| Ensembl ID | ENSG00000134524 |
| UniProt ID | Q15393 |
| OMIM ID | 605518 |
| HGNC ID | HGNC:14453 |
| Aliases | LIPIN1, PAP1, lipin-1, phosphatidate phosphatase LPIN1 |
Description
LPIN1 encodes lipin-1, a phosphatidate phosphatase (PAP) enzyme that catalyzes the dephosphorylation of phosphatidate to diacylglycerol, a key step in triglyceride and phospholipid biosynthesis. Lipin-1 also functions as a transcriptional coactivator, regulating lipid metabolism genes. Mutations in LPIN1 are associated with acute recurrent rhabdomyolysis and lipodystrophy. The gene is widely expressed, with highest levels in skeletal muscle, adipose tissue, and liver.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Acute recurrent rhabdomyolysis (AR) | Loss-of-function mutations lead to reduced PAP activity, impairing lipid metabolism and membrane integrity, causing muscle breakdown. | ClinVar, OMIM (605518) |
| Lipodystrophy, familial partial, type 1 (FPLD1) | Mutations may disrupt lipin-1 function in adipocyte differentiation and lipid storage, leading to abnormal fat distribution. | OMIM (605518), ClinVar |
| Metabolic syndrome (susceptibility) | Altered LPIN1 expression or activity may contribute to insulin resistance and dyslipidemia. | NCBI Gene, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | High (nTPM ~ 50-100) | High |
| Adipose tissue | High (nTPM ~ 30-60) | High |
| Liver | Moderate (nTPM ~ 10-30) | Moderate |
| Heart | Moderate (nTPM ~ 10-20) | Moderate |
| Kidney | Low (nTPM < 10) | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | Moderate | Hepatocyte cell line |
| A549 (lung) | Low | Epithelial cell line |
| C2C12 (myoblast) | High | Muscle cell line |
| 3T3-L1 (adipocyte precursor) | High | Adipocyte differentiation model |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.229C>T (p.Arg77Ter) | Nonsense | Rare | Loss of function, associated with rhabdomyolysis |
| c.1465C>T (p.Arg489Trp) | Missense | Rare | Impaired PAP activity, linked to lipodystrophy |
| c.1801G>A (p.Gly601Arg) | Missense | Rare | Reduced enzyme activity, possible dominant-negative effect |
| c.2290C>T (p.Arg764Ter) | Nonsense | Rare | Loss of function, severe phenotype |
Mutation functional classification
Loss of Function (LOF)
Most LPIN1 mutations are loss-of-function, leading to reduced or absent PAP activity, causing rhabdomyolysis and lipodystrophy.
Gain of Function (GOF)
No clear gain-of-function mutations reported; some variants may increase activity but are not clinically characterized.
Dominant Negative (DN)
Certain missense mutations may exert dominant-negative effects by interfering with dimerization or substrate binding, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • phosphatidate phosphatase activity | • phospholipid biosynthetic process |
| • triglyceride biosynthetic process | • lipid homeostasis |
| • transcription coactivator activity | • nucleus |
| • endoplasmic reticulum | • cytoplasm |
Pathways
• Glycerolipid metabolism
• Phospholipid metabolism
• PPAR signaling pathway
• Insulin signaling pathway
• Adipocytokine signaling pathway
Protein Summary
Lipin-1 is a bifunctional protein: as a phosphatidate phosphatase, it converts phosphatidate to diacylglycerol, a precursor for triglycerides and phospholipids. As a transcriptional coactivator, it interacts with PPARγ and other transcription factors to regulate genes involved in lipid metabolism and adipogenesis. The protein is predominantly cytoplasmic but translocates to the nucleus upon dephosphorylation. Mutations cause metabolic disorders, highlighting its critical role in energy homeostasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LPIN1 Knockout HEK293 Cell Line | EDJ-KQ532 | Human | 23175 | Details Get a Quote |
| LPIN1 Knockout A-549 Cell Line | EDJ-KQ20230 | Human | 23175 | Details Get a Quote |
| LPIN1 Knockout HCT 116 Cell Line | EDJ-KQ20232 | Human | 23175 | Details Get a Quote |
| LPIN1 Knockout HeLa Cell Line | EDJ-KQ20233 | Human | 23175 | Details Get a Quote |
| LPIN1（g.11944582G>A） Point Mutation in HEK293T Cell Line | EDC90761 | Human | 23175 | Details Get a Quote |
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