Ap1s3 gene

AP1S3 is the acronym for "Adaptor protein complex 1, sigma-1C subunit one gene, which is located on chromosome 2q36.1. The gene encodes a subunit of adaptor protein complex 1 (AP-1).

AP1S3 mutations are also detected in pustular psoriasis generalisata, acrodermatitis continua suppurativa, and pustulosis palmaris et plantaris (Setta-Kaffetzi N et al. 2014).

The detected mutations lead to autoreactive inflammation via overexpression of IL36 (Setta-Kaffetzi N et al. 2014).

In a larger study (n=67 patients), the coding exons of IL36RN, CARD14 and AP1S3 were sequenced - 61 with GPP, two with acute generalized exanthematous pustulosis (AGEP) and four with acrodermatitis continua suppurativa (Hallopeau). The majority of patients (GPP/ 64 %) did not carry rare variants in any of the three genes. Biallelic and monoallelic IL36RN mutations were found in 15 (24%) and 5 (8%) patients with GPP, respectively. The only significant genotype-phenotype correlation observed in IL36RN mutation carriers was early age at disease onset. Additional rare CARD14 or AP1S3 variants were identified in 15% of IL36RN mutation carriers (Mössner R et al. 2018)

1. Mössner R et al. (2018) The genetic basis for most patients with pustular skin disease remains elusive. Br J Dermatol 178:740-748.
2. Setta-Kaffetzi N et al. (2014) AP1S3 mutations are associated with pustular psoriasis and impaired Toll-like receptor 3 trafficking. Am J Hum Genet 94: 790-797