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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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LPIN3
lipin 3
Chromosome 20 · 20q12
NCBI Gene: 64900Ensembl: ENSG00000132793.13HGNC: HGNC:14451UniProt: Q9BQK8
28PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cytosolphosphatidate phosphatase activityfatty acid catabolic processtriglyceride biosynthetic processcataractnarcolepsymajor depressive disordermultiple sclerosis
✦AI Summary

LPIN3 (lipin 3) is a magnesium-dependent phosphatidate phosphatase that catalyzes the conversion of phosphatidic acid to diacylglycerol, regulating fatty acid and lipid metabolism 1. Beyond its canonical enzymatic function, LPIN3 has emerged as a key regulator in multiple disease contexts. In colorectal cancer, LPIN3 promotes tumor growth by activating β-catenin signaling and suppressing CD8+ T cell-mediated anti-tumor immunity through reduced antigen presentation 2. In acetaminophen-induced liver injury, LPIN3 acts protectively by directly inhibiting JAK1 phosphorylation, thereby suppressing hepatocyte ferroptosis and pyroptosis via the JAK1-STAT3 axis 1. LPIN3 also plays a role in viral infections; knockdown of LPIN3 reduces SARS-CoV-2 replication by disrupting glycerophospholipid metabolism 3. Genetically, LPIN3 variants are associated with metabolic diseases and dementia susceptibility, with rs150562240 identified as a shared causal variant across dementia, Alzheimer's disease, and atherosclerosis 4. Unlike LPIN1 mutations which cause severe rhabdomyolysis, LPIN3 mutations are rarely associated with primary muscular manifestations 5. The protein contains a cell-penetrating peptide sequence enabling potential therapeutic applications 6.

Sources cited
1
LPIN3 promotes colorectal cancer growth by activating β-catenin signaling and suppressing CD8+ T cell-mediated cytotoxicity
PMID: 40042548
2
LPIN3 deficiency promotes hepatocyte ferroptosis and pyroptosis via JAK1-STAT3 pathway during acetaminophen-induced acute liver injury; Lipin3 directly interacts with JAK1 to suppress its phosphorylation
PMID: 41071519
3
LPIN3 mutations are not major causes of muscular manifestations unlike LPIN1; LPIN3-P24L variant is functional in yeast complementation assay
PMID: 22481384
4
Rs150562240 in LPIN3 is identified as a shared causal variant across dementia, Alzheimer's disease and atherosclerosis
PMID: 35675752
5
LPIN3 contains a novel cell-penetrating peptide sequence (RRKRRRRRK) from its nuclear localization sequence with potential drug delivery applications
PMID: 23263658
6
LPIN3 knockdown reduces SARS-CoV-2 replication by affecting glycerophospholipid metabolism pathway
PMID: 35874954
Disease Associationsⓘ20
cataractOpen Targets
0.32Weak
narcolepsyOpen Targets
0.30Weak
major depressive disorderOpen Targets
0.27Weak
multiple sclerosisOpen Targets
0.19Weak
alcohol drinkingOpen Targets
0.14Weak
response to statinOpen Targets
0.08Suggestive
neoplasmOpen Targets
0.07Suggestive
androgenetic alopeciaOpen Targets
0.06Suggestive
metabolic diseaseOpen Targets
0.06Suggestive
diabetic eye diseaseOpen Targets
0.06Suggestive
neutrophil immunodeficiency syndromeOpen Targets
0.06Suggestive
colorectal carcinomaOpen Targets
0.06Suggestive
Blackfan-Diamond anemiaOpen Targets
0.05Suggestive
HypercholesterolemiaOpen Targets
0.05Suggestive
X-linked severe congenital neutropeniaOpen Targets
0.05Suggestive
Hallux valgusOpen Targets
0.05Suggestive
immunodeficiency 88Open Targets
0.05Suggestive
physical activityOpen Targets
0.05Suggestive
neutropenia, severe congenital, 2, autosomal dominantOpen Targets
0.05Suggestive
neutropenia, severe congenital, 1, autosomal dominantOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CDS1Protein interaction96%GPD1Protein interaction96%GPD2Protein interaction96%GNPATProtein interaction96%CDS2Protein interaction96%AGPAT1Protein interaction96%
Tissue Expression6 tissues
Liver
100%
Heart
76%
Ovary
59%
Lung
26%
Bone Marrow
2%
Brain
1%
Gene Interaction Network
Click a node to explore
LPIN3CDS1GPD1GPD2GNPATCDS2AGPAT1
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q9BQK8
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.00LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.83 [0.69–1.00]
RankingsWhere LPIN3 stands among ~20K protein-coding genes
  • #12,381of 20,598
    Most Researched28
  • #9,599of 17,882
    Most Constrained (LOEUF)1.00
Genes detectedLPIN3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
LPIN3 promotes colorectal cancer growth by dampening intratumoral CD8
PMID: 40042548
Cancer Immunol Immunother · 2025
1.00
2
Lipin3 deficiency promotes hepatocyte ferroptosis and pyroptosis via activating JAK1-STAT3 pathway during acetaminophen induced acute liver injury.
PMID: 41071519
Mol Biomed · 2025
0.90
3
Study of LPIN1, LPIN2 and LPIN3 in rhabdomyolysis and exercise-induced myalgia.
PMID: 22481384
J Inherit Metab Dis · 2012
0.80
4
A suggested shared aetiology of dementia - a colocalization study.
PMID: 35675752
Neurobiol Aging · 2022
0.70
5
Identification of a novel cell-penetrating peptide from human phosphatidate phosphatase LPIN3.
PMID: 23263658
Mol Cells · 2012
0.60