Alt. symbols: KIAA0249

Approved name: lipin 2
Alt. names: phosphatidate phosphatase LPIN2

Location: 18p11.31: 2885296 - 3013144 (-)
Gene type: protein_coding, 9 transcripts.

Scores: LoFtool: 0.319000 | pLI: 0.67351297 | LOEUF: 0.510

HGNC: 14450

NCBI: 9663, RefSeq: NG_007507.1

Ensembl: ENSG00000101577.11

LRG_174 | Status: public

OMIM: 605519

Expression | ProteinAtlas

Lipin-2 is a magnesium-dependent phosphatidate phosphatase that catalyzes the conversion of phosphatidic acid to DAG during triglyceride, phosphatidylcholine and phosphatidylethanolamine biosynthesis in the ER. It has been reported to control proinflammatory signaling induced by saturated fatty acids in macrophages (PMID: 22334674). Lipin-2 also restricts overphosphorylation of MAPK kinases such as ERK, p38, and JNK to act as a negative regulator of the NLRP3 inflammasome (PMID: 28031477). In addition to their function as lipid metabolizing enzymes, lipins contain nuclear localization signals and can act as transcriptional cofactors that modulate the activity of key transcription factors such as PPARalpha, PPARgamma, or sterol regulatory element-binding protein 1 (SREBP1) (PMID: 24133206).

Biallelic nonsense, missense, frameshift, splice site and large intragenic deletion mutations in LPIN2, encoding lipin-2, are associated with Majeed syndrome [OMIM: 609628], an AR disorder with three cardinal features: Chronic recurrent multifocal osteomyelitis (CRMO), congenital dyserythropoietic anemia (CDA), and skin inflammation. The CRMO begins in infancy and continues relentlessly leading to retarded growth or joint contractures or both, while CDA is variable in severity and characterised by microcytosis. Neutrophilic dermatosis or cutaneous pustulosis are the most common reported inflammatory skin phenotype and patients may also have recurrent fevers. Labs are notable for elevations in ESR and CRP and patients respond to IL-1 inhibition (PMID: 15994876). Lipin-2 depletion reduces cellular cholesterol levels, which increases ion currents through the ATP‐activated P2X7 receptor and subsequent NLRP3 inflammasome activation with mature IL‐1beta release. However, the CRMO phenotype associated with both LPIN2 and IL1RN apparently arises via an NLRP3 inflammasome-independent pathway whereby LPS‐stimulated M2‐MDMs from patients promote accelerated osteoclastogenesis through changes in macrophage phosphorylation patterns that could largely be reversed by IL‐1 inhibition (PMID: 33314777). [Load More]