Zinc transporter 8

From Wikipedia, the free encyclopedia
AliasesSLC30A8, ZNT8, ZnT-8, solute carrier family 30 member 8
External IDsOMIM: 611145 MGI: 2442682 HomoloGene: 13795 GeneCards: SLC30A8
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 8: 116.95 – 117.18 MbChr 15: 52.16 – 52.2 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse

Zinc transporter 8 (ZNT8) is a protein that in humans is encoded by the SLC30A8 gene.[5] ZNT8 is a zinc transporter related to insulin secretion in humans. Certain alleles of the SLC30A8 gene may increase the risk for developing type 2 diabetes, but a loss-of-function mutation appears to greatly reduce the risk of diabetes.[6]

Clinical significance[edit]

Association with type 2 diabetes (T2D)[edit]

Twelve 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.[7][8][9] 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.[6] Earlier functional studies of SLC30A8 suggested that reduced zinc transport increased T2D risk.[10][11] 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.[6]

See also[edit]


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000164756 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000022315 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Entrez Gene: SLC30A8 solute carrier family 30 (zinc transporter), member 8".
  6. ^ a b c Flannick, Jason; et al. (2014). "Loss-of-function mutations in SLC30A8 protect against type 2 diabetes". Nature Genetics. 46 (4): 357–363. doi:10.1038/ng.2915. PMC 4051628. PMID 24584071.
  7. ^ Dupis, J.; et al. (Feb 2010). "New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk". Nature Genetics. 42 (2): 105–16. doi:10.1038/ng.520. PMC 3018764. PMID 20081858.
  8. ^ Strawbridge, R.J.; et al. (October 2011). "Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes". Diabetes. 60 (10): 2624–34. doi:10.2337/db11-0415. PMC 3178302. PMID 21873549.
  9. ^ Morris, A.P.; et al. (Sep 2012). "Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes". Nature Genetics. 44 (9): 981–90. doi:10.1038/ng.2383. PMC 3442244. PMID 22885922.
  10. ^ Nicolson, T.J.; et al. (Sep 2009). "Insulin storage and glucose homeostasis in mice null for the granule zinc transporter ZnT8 and studies of the type 2 diabetes–associated variants". Diabetes. 58 (9): 2070–83. doi:10.2337/db09-0551. PMC 2731533. PMID 19542200.
  11. ^ Rutter, G.A.; et al. (2010). "Think zinc: new roles for zinc in the control of insulin secretion". Islets. 2 (1): 49–50. doi:10.4161/isl.2.1.10259. PMID 21099294.

Further reading[edit]

External links[edit]