Ormdl3

ORMDL3 (Orosomucoid like 3) also known as Sphingolipid Biosynthesis Regulator 3, is a protein encoded by the ORMDL3 gene of the same name located on chromosome 17q21.1. Mutations of the ORMDL3 gene are associated with childhood asthma, among others (Moffatt MF et al. 2007).

ORMDL3 plays an inhibitory role in sphingolipid synthesis. It also plays a role in the regulation of Ca2 + levels in the endoplasmic reticulum (ER). ER plays an important role in the generation, signaling, function and storage of intracellular Ca2 +. There are channels that control the release of Ca2 + from the ER into the cytoplasm. Furthermore, certain pumps (sarcoendoplasmic reticulum Ca2 + ATPase = SERCA) return cytoplasmic Ca2 + back into the ER. Dysregulation of Ca2 + plays a key role in various pathological conditions such as asthma and Alzheimer's disease (Green KN et al. (2008). Furthermore, mutations in the ORMDL3 gene are associated with inflammatory diseases like Crohn's disease, type 1 diabetes and rheumatoid arthritis (Kurreeman FA et al. 2012).

1. Davis D et al (2018) Orm/ORMDL proteins: Gate guardians and master regulators". Advances in Biological Regulation. Sphingolipid Signaling in Chronic Disease. 70: 3–18.
2. Green KN et al. (2008). Linking calcium to Abeta and Alzheimer's disease. Neuron 59: 190-194.
3. Kurreeman FA et al. (2012) Use of a multiethnic approach to identify rheumatoid arthritis-susceptibility loci, 1p36 and 17q12 American Journal of Human Genetics. 90: 524–532.
4. Moffatt MF et al (2007) Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma (PDF). Nature 448: 470-473.
5. Verlaan DJ et al (2009) Allele-specific chromatin remodeling in the ZPBP2/GSDMB/ORMDL3 locus associated with the risk of asthma and autoimmune disease. American Journal of Human Genetics. 85: 377–393.