Found in high concentrations in potato tuber peel and 1-2 mm of the outer cortex tissue , PPO is used in the potato as a defense against insect predation, leading to enzymatic browning from tissue damage. [ citation needed ] Damage in the skin tissue of potato tuber causes a disruption of cell compartmentation, resulting in browning. The brown or black pigments are produced from the reaction of PPO quinone products with amino acid groups in the tuber.  In potatoes, PPO genes are not only expressed in potato tubers, but also in leaves, petioles , flowers and roots. 
In a Serbian patient with nephronophthisis-16 (NPHP16; 615382), Hoff et al. (2013) identified a homozygous -G transition in exon 6 of the ANKS6 gene, resulting in a gln441-to-arg (Q441R) substitution at a highly conserved residue. The unaffected parents were heterozygous for the mutation. The patient had polycystic kidney disease resulting in chronic renal failure in early childhood, but did not have heart or liver abnormalities. Although the Q441R mutation did not alter the interaction of ANKS6 with other NPHP proteins or its ciliary localization, the mutant protein was unable to rescue the renal phenotype in Xenopus knockdown embryos, supporting its pathogenicity.
While research efforts to develop therapeutic drugs to target hypoxia-associated tumor cells have been ongoing for many years, there has not yet been any breakthrough that has shown selectivity and effectiveness at targeting HIF1A pathways to decrease tumor progression and angiogenesis.  Successful therapeutic approaches in the future may also be highly case-specific to particular cancers and individuals, and seem unlikely to be widely applicable due to the genetically heterogenous nature of the many cancer types and subtypes.