Solute carrier family 30 (zinc transporter), member 8, also known as SLC30A8, is a human gene that codes for a zinctransporter related to insulin secretion in humans. Certain alleles of this gene may increase the risk for developing type 2 diabetes, but a loss-of-function mutation appears to greatly reduce the risk of diabetes.
12 rare variants in SLC30A8 have been identified through the sequencing or genotyping of approximately 150,000 individuals from 5 different ancestry groups. SLC30A8 contains a common variant (p.Trp325Arg), which is associated with T2D risk and levels of glucose and proinsulin. Individuals carrying protein-truncating variants collectively had 65% reduced risk of T2D. Additionally, non-diabetic individuals from Iceland harboring a frameshift variant p. Lys34Serfs*50 demonstrated reduced glucose levels. Earlier functional studies of SLC30A8 suggested that reduced zinc transport increased T2D risk. Conversely, loss-of-function mutations in humans indicate that SLC30A8 haploinsufficiency protects against T2D. Therefore, ZnT8 inhibition can serve as a therapeutic strategy in preventing T2D.
Chimienti F, Devergnas S, Favier A, Seve M (2004). "Identification and cloning of a beta-cell-specific zinc transporter, ZnT-8, localized into insulin secretory granules.". Diabetes53 (9): 2330–7. doi:10.2337/diabetes.53.9.2330. PMID15331542.