This variant, formerly titled SUSCEPTIBILITY TO ATOPY, SUSCEPTIBILITY TO ATOPIC DERMATITIS 6, and SUSCEPTIBILITY TO ASTHMA, has been reclassified as a polymorphism based on its frequency in the ExAC database (Hamosh, 2017).
In exon 14 of the SPINK5 gene, Walley et al. (2001) found a single-nucleotide polymorphism (SNP), a 1258G-A transition, that caused a missense change, glu420-to-lys. They found significant associations of maternally derived alleles between atopy (147050), atopic dermatitis (605845), asthma (600807), and the total serum IgE and lys420. Paternally derived alleles tended to be less often associated with disease than maternal alleles. SPINK5 is at the distal end of a cytokine cluster that extends from D5S490 (134 cM from the 'top' of the chromosome) to CSF1R (164770) at position 153 cM. Walley et al. (2001) emphasized that it was not clear from their study whether the SPINK5 polymorphism was primarily associated with atopic dermatitis, asthma, or the general atopic state.
Kato et al. (2003) analyzed the E420K polymorphism in 124 Japanese patients with atopic dermatitis and 110 controls and found that the GG genotype (E/E) was significantly less frequent (p = 0.023) in the atopic dermatitis group.
Hamosh (2017) noted that the 1258G-A variant was found in 61,019 of 120,144 alleles and in 16,138 homozygotes in the ExAC database, with an allele frequency of 0.5079 (July 31, 2017).
