NTHL1 D239Y is produced as a consequence of a single nucleotide polymorphism (SNP) rs3087468 in the NTHL1 gene. The frequency of this polymorphism varies in different populations. Substitution of aspartic acid residue at position 239 with tyrosine results in an NTHL1 protein that is still able to bind to damaged DNA but appears to have impaired glycosylase activity. Expression of NTHL1 D239Y in non-transformed human and mouse mammary epithelial cells increases genomic instability and leads to neoplastic transformation, acting as a dominant negative for wild-type NTHL1, through competition for substrate binding (Galick et al. 2013). It is uncertain if heterozygosity for NTHL1 D239Y polymorphism increases predisposition to cancer.