AP1S1 Gene

The AP1S1 gene (APIS1 stands for Adaptor Related Protein Complex 1 Subunit Sigma 1) is a protein-coding gene located on chromosome 7q22.1. The protein encoded by this gene is part of the clathrin-coat assembly complex, which links clathrin to receptors in coated vesicles. These vesicles are involved in endocytosis and Golgi processing. This protein, together with beta-prime-adaptin, gamma-adaptin, and the AP47 middle (mu) chain, forms the AP-1 assembly protein complex located in the Golgi vesicle.

Apparently, different mutations in AP1S1 lead to different phenotypes. At one time, loss of AP1S1 function can lead to a defect in the intestinal epithelial barrier and a non-syndromic form of congenital diarrhea, while other truncating AP1S1 mutations cause MEDNIK syndrome, which is characterized by mental retardation, enteropathy, deafness, neuropathy, ichthyosis, and keratoderma. In the case of the patient of Incecik F et al (2018) with MEDNIK syndrome, sequencing of the AP1S1 gene revealed a homozygous insertion c.364dupG (NM_001283.4) resulting in a frameshift of the reading frame (p.D122Gfs*18).

1. Incecik F et al. (2018) MEDNIK syndrome with a frame shift causing mutation in AP1S1 gene and literature review of the clinical features. Metab Brain Dis 33:2065-2068.
2. Klee KMC et al (2020) AP1S1 missense mutations cause a congenital enteropathy via an epithelial barrier defect. Hum Genet 139:1247-1259.
3. Martinelli D et al. (2014) AP1S1 defect causing MEDNIK syndrome: a new adaptinopathy associated with defective copper metabolism. Annals of the New York Academy of Sciences 1314: 55-63.
4. Martinelli D et al. (2013) MEDNIK syndrome: a novel defect of copper metabolism treatable by zinc acetate therapy. Brain 136: 872-881