The short mRNA isoform of the immunoglobulin superfamily, member 1 gene encodes an intracellular glycoprotein

摘要

Mutations in the immunoglobulin superfamily, member 1 gene (IGSF1/Igsf1) cause an X-linked form of central hypothyroidism. The canonical form of IGSF1 is a transmembrane glycoprotein with 12 immunoglobulin (Ig) loops. The protein is co-translationally cleaved into two sub-domains. The carboxyl-terminal domain (CTD), which contains the last 7 Ig loops, is trafficked to the plasma membrane. Most pathogenic mutations in IGSF1 map to the portion of the gene encoding the CTD. IGSF1/Igsf1 encodes a variety of transcripts. A little studied, but abundant splice variant encodes a truncated form of the protein, predicted to contain the first 2 Ig loops of the full-length IGSF1. The protein (hereafter referred to as IGSF1 isoform 2 or IGSF1-2) is likely retained in most individuals with IGSF1 mutations. [...]