LPIN2 Gene

LPIN2 (Lipin 2) is a protein encoding gene located on chromosome 18p11.3 and encodes the phosphatidic acid phosphatase LIPIN2. Phosphatidic acid phosphatase LIPIN2 acts as a magnesium-dependent phosphatidate phosphatase enzyme that catalyzes the conversion of phosphatidic acid to diacylglycerol during the biosynthesis of triglycerides, phosphatidylcholine, and phosphatidylethanolamine in the endoplasmic membrane of the reticulum. This phosphatase plays an important role in controlling fatty acid metabolism at various levels and also acts as a nuclear transcriptional coactivator for PPARGC1A (PPARGC1A stands for "peroxisome proliferator-activated gamma receptor coactivator 1-alpha" and is the master regulator of mitochondrial biogenesis. PGC-1α is also the master regulator of gluconeogenesis in the liver by inducing increased gene expression for gluconeogenesis).

Animal studies suggest that the LPIN2 gene plays a role in normal adipose tissue development. The LPIN2 gene is a candidate gene for human lipodystrophy, which is characterized by loss of body fat, fatty liver, hypertriglyceridemia, and insulin resistance.

Diseases associated with LPIN2 include.

• Majeed syndrome (MJDS)

and

• chronic recurrent multifocal osteomyelitis.

In Majeed syndrome, there is a disturbance in phosphatidic acid phosphatase activity leading to dysregulation of the immune system. This is due to abnormal activation of the NLRP3 inflammasome and overproduction of proinflammatory cytokines, including IL-1β.

1. Ferguson PJ et al (2005) Homozygous mutations in LPIN2 are responsible for the syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anemia (Majeed syndrome). J Med Genet 42: 551-557.
2. Ferguson PJ et al (2021) Majeed syndrome: A Review of the Clinical, Genetic and Immunologic Features. Biomolecules 28;11(3):367.
3. Majeed HA et al. (2001) The syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anemia: report of a new family and a review. Europ. J. Pediat. 160: 705-710.
4. Majeed HA et al. (2000) On mice and men: an autosomal recessive syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anemia. (Letter) J Pediat 137: 441-442.