SLC30A8

Solute carrier family 30 (zinc transporter), member 8
Identifiers
Symbols	SLC30A8 ; ZNT8; ZnT-8
External IDs	OMIM: 611145 MGI: 2442682 HomoloGene: 13795 IUPHAR: 1128 GeneCards: SLC30A8 Gene
Gene ontology Molecular function • zinc ion transmembrane transporter activity • zinc ion binding • protein homodimerization activity Cellular component • Golgi apparatus • plasma membrane • integral component of membrane • cytoplasmic membrane-bounded vesicle • secretory granule • transport vesicle membrane • secretory granule membrane Biological process • zinc ion transport • cellular zinc ion homeostasis • response to glucose • insulin secretion • positive regulation of insulin secretion • sequestering of zinc ion • response to interferon-gamma • glucose homeostasis • transmembrane transport • regulation of vesicle-mediated transport • regulation of sequestering of zinc ion • response to interleukin-1 • zinc ion transmembrane transport Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	169026	239436
Ensembl	ENSG00000164756	ENSMUSG00000022315
UniProt	Q8IWU4	Q8BGG0
RefSeq (mRNA)	NM_001172811	NM_172816
RefSeq (protein)	NP_001166282	NP_766404
Location (UCSC)	Chr 8: 117.96 – 118.19 Mb	Chr 15: 52.3 – 52.34 Mb
PubMed search	[1]	[2]

Solute carrier family 30 (zinc transporter), member 8, also known as SLC30A8, is a human gene that codes for a zinc transporter 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.

Clinical significance

Association with type 2 diabetes (T2D)

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.

See also

• Solute carrier family

Further reading

• Chimienti F, Favier A, Seve M (2006). "ZnT-8, a pancreatic beta-cell-specific zinc transporter.". Biometals 18 (4): 313–7. doi:10.1007/s10534-005-3687-9. PMID 16158222. 
• Hartley JL, Temple GF, Brasch MA (2001). "DNA cloning using in vitro site-specific recombination.". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863. 
• Wiemann S, Weil B, Wellenreuther R et al. (2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs.". Genome Res. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166.  CS1 maint: Explicit use of et al. (link)
• Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.  CS1 maint: Explicit use of et al. (link)
• Seve M, Chimienti F, Devergnas S, Favier A (2004). "In silico identification and expression of SLC30 family genes: an expressed sequence tag data mining strategy for the characterization of zinc transporters' tissue expression.". BMC Genomics 5 (1): 32. doi:10.1186/1471-2164-5-32. PMC 428573. PMID 15154973. 
• 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.". Diabetes 53 (9): 2330–7. doi:10.2337/diabetes.53.9.2330. PMID 15331542. 
• Gerhard DS, Wagner L, Feingold EA et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.  CS1 maint: Explicit use of et al. (link)
• Wiemann S, Arlt D, Huber W et al. (2004). "From ORFeome to biology: a functional genomics pipeline.". Genome Res. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336.  CS1 maint: Explicit use of et al. (link)
• Mehrle A, Rosenfelder H, Schupp I et al. (2006). "The LIFEdb database in 2006.". Nucleic Acids Res. 34 (Database issue): D415–8. doi:10.1093/nar/gkj139. PMC 1347501. PMID 16381901.  CS1 maint: Explicit use of et al. (link)
• Sladek R, Rocheleau G, Rung J et al. (2007). "A genome-wide association study identifies novel risk loci for type 2 diabetes.". Nature 445 (7130): 881–5. doi:10.1038/nature05616. PMID 17293876.  CS1 maint: Explicit use of et al. (link)
• Wenzlau JM, Juhl K, Yu L et al. (2007). "The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes.". Proc. Natl. Acad. Sci. U.S.A. 104 (43): 17040–5. doi:10.1073/pnas.0705894104. PMC 2040407. PMID 17942684.  CS1 maint: Explicit use of et al. (link)

External links

• Type 2 diabetes genes mapped out, BBC News article