The SERPINB8 gene encodes a protein belonging to the high molecular weight serine proteinase inhibitor (SERPIN) superfamily. Members of this family contain a highly-conserved surface-exposed reactive site loop (RSL), which interacts with the target protease to form tight, irreversible complexes. In addition to the RSL, the SERPINB8 protein contains two hydrophobic regions in close proximity to the N terminus, believed to be important for secretion and allowing SERPINB8 to reside either intracellularly or extracellularly.
SERPINs are responsible for a diverse set of intracellular and extracellular functions including cellular differentiation, tumor suppression, apoptosis, and cell migration. While the specific function of SERPINB8 has not been fully characterized, recent knockdown studies in human keratinocytes have shown that in the absence of SERPINB8, there is a cell-cell adhesion defect, which is heightened by mechanical stress. The gene has thus been implicated in Peeling Skin Syndrome 5 (PSS5), a genodermatosis characterized by superficial peeling of the dorsal and palmar skin of the hands and feet.
The gene is located on the long arm of chromosome 8 and spans a length of 49.8 kb of DNA. Its coding sequence is spread across 11 exons and it encodes a 42.7 kDa protein product composed of 374 amino acids. Several additional isoforms of the SERPINB8 gene exist due to alternatively spliced transcript variants. The gene is overexpressed in the skin, monocytes, peripheral blood mononuclear cells and platelets. So far only 3 mutations in the SERPINB8 gene have been associated with PSS5.
Pigors et al. (2016) described a 5-year-old boy and his 3-year-old sister from a consanguineous Tunisian family exhibiting superficial peeling of small areas of the palmar and dorsal faces of the hands and feet, with an underlying erythema. Homozygosity mapping and WES of the patients helped identify a novel homozygous c.947delA (p.Lys316Serfs*90) mutation in exon 7 of the SERPINB8 gene. As it was located in the last exon of the gene, it was not expected to lead to nonsense-mediated decay but to instead result in the loss of the reactive site loop of SERPINB8, crucial for forming the SERPINB8-protease complex.
Pigors et al. (2016) described a female UAE patient exhibiting superficial peeling of small areas of the palmar and dorsal faces of the hands extending to the lower arms and feet, with an underlying erythema. A homozygous c.2T>C (p.Met1?) mutation was detected in exon 2 of the SERPINB8 gene from the patient. It was predicted to result in an N-terminal truncated protein.
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