Chromosome 17q21 contains a cluster of genes including ORMDL3 and GSDMB, which
have been highly linked to asthma in genome-wide association studies. ORMDL3 is
localized to the endoplasmic reticulum and regulates downstream pathways including
sphingolipids, metalloproteases, remodeling genes, and chemokines. ORMDL3 inhibits
serine palmitoyl-CoA transferase, the rate-limiting enzyme for sphingolipid biosynthesis. In
addition, ORMDL3 activates the ATF6α branch of the unfolded protein response which …