The transport of proteins from the endoplasmic reticulum to the Golgi requires the assembly of a Coat Protein II (COPII) complex at certain sites on the membrane. These are known as endoplasmic reticulum exit sites (ERES) or transitional ER sites. The SEC16A gene encodes a peripheral membrane protein that is responsible for COPII vesicles coating, defining the transitional ER sites, endoplasmic reticulum organization and regulating secretory cargo traffic from the endoplasmic reticulum to the Golgi apparatus. The protein is recruited to the ER membrane by SAR1 and it has been found to interact with the COPII components SEC23A and SEC13.
The SEC16A gene is located on the long arm of chromosome 9. It spans a length of 44.4 kb of DNA and its coding sequence is spread across 37 exons. The gene encodes a 233.5 kDa protein product composed of 2179 amino acids. Several additional isoforms of the SEC16A protein exist due to alternatively spliced transcript variants. While the gene is ubiquitously expressed in the human body, overexpression is seen in the bone, bone marrow stromal cells, peripheral blood mononuclear cells and pancreas.
Monies et al. (2017) described the genomic landscape of Saudi Arabia based on the findings of 1000 diagnostic panels and exomes. One patient, a 12-year-old female from a consanguineous family, presented with microcephaly, fine/gross motor delay, speech delay, flat feet, short stature, small fingers and abnormal nails. Whole exome sequencing helped identify a homozygous mutation (c.3820C>T, p.R1274C) in exon 5 of the patient’s SEC16A gene. This gene mutation was considered a candidate for pathogenicity as it was a novel variant located within the autozygome and predicted to be deleterious; and the gene is found to be involved in cell proliferation. Additional studies are required to independently confirm this association.